Zoonoses

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

A single dose of oral acoziborole resulted in a greater than 95% cure or probable cure rate for human African trypanosomiasis (HAT), also known as sleeping sickness, according to results from a clinical trial testing a one-dose experimental drug.

The drug has “the potential to revolutionize treatment” for the disease, which remains endemic in sub-Saharan Africa, said Antoine Tarral, MD, head of the human African trypanosomiasis clinical program at the Drugs for Neglected Diseases initiative, based in Geneva, and senior author of the study, in a press release.

“It’s fantastic news, because it’s the first time that with one single administration you can treat the disease,” he told this news organization. “It’s the first drug we can use without hospitalization. ... All the previous medications needed hospitalization, and therefore we could not treat the population early before they started expressing symptoms.”

The World Health Organization “has been working for decades for such a possibility to implement a new strategy for this disease,” Dr. Tarral said.

Current (2019) WHO guidelines recommend oral fexinidazole as first-line treatment for any stage of the disease. The 10-day course often requires hospitalization and skilled staff. Previous recommendations required disease-staging with cerebrospinal fluid (CSF) sampling and 7 days of intramuscular pentamidine for early-stage disease or nifurtimox-eflornithine combination therapy (NECT) with hospitalization for late-stage disease.

By contrast, acoziborole, which was codeveloped by the DND initiative and Sanofi, “is administered in a single dose and is effective across every stage of the disease, thereby eliminating the many barriers currently in place for people most vulnerable to the diseases, such as invasive treatments and long travel distances to a hospital or clinic, and opening the door to screen-and-treat approaches at the village level,” Dr. Tarral said in the statement.

“Today, and in the future, we will have less and less support to do this long and costly diagnostic process and treatment in the hospital,” he said in an interview. “This development means we can go for a simple test and a simple treatment, which means we can meet the WHO 2030 goal for ending transmission of this disease.”

Results from the multicenter, prospective, open-label, single-arm, noncomparative, phase 2/3 study were published in The Lancet.
 

Pragmatic study design

Sleeping sickness is caused by Trypanosoma brucei gambiense (gambiense HAT). It is transmitted by the tsetse fly and mostly fatal when left untreated.

The study enrolled 208 adults and adolescents (167 with late-stage, and 41 with early-stage or intermediate-stage disease) from 10 hospitals in the Democratic Republic of the Congo and Guinea. All patients were treated with acoziborole 960 mg – an unusual study design.

“Due to the substantial decline in incidence, enrolling patients with gambiense HAT into clinical trials is challenging,” the authors wrote. “Following advice from the European Medicines Agency, this study was designed as an open-label, single-arm trial with no comparator or control group.”

After 18 months of follow-up, treatment success, defined as absence of trypanosomes and less than 20 white blood cells per mcL of CSF, occurred in 159 (95.2%) of the late-stage patients, and 100% of the early- and intermediate-stage patients, “which was similar to the estimated historical results for NECT,” the authors noted.

Serious treatment-emergent adverse events were reported in 21 (10%) of patients, “but none of these events were considered drug-related,” they added.

The DND initiative and the WHO are currently nearing completion of a much larger, double-blind, placebo-controlled trial of acoziborole to “increase the safety database,” Dr. Tarral explained.

“Purists will say that acoziborole has not been evaluated according to current standards, because the study was not a randomized trial, there was no control group, and the number of participants was small,” said Jacques Pépin, MD, from the University of Sherbrooke (Que.), in a linked commentary.

“But these were difficult challenges to overcome, considering the drastic reduction in the number of patients with HAT and dispersion over a vast territory, particularly in the Democratic Republic of the Congo. For these reasons, the authors took a pragmatic approach instead,” he wrote.
 

A potential new tool for eradication of sleeping sickness

“This is really an exciting development, which will be useful in the drive for eradication/interruption of transmission of this disease,” Dr. Pépin told this news organization.

Dr. Pépin treated around 1,000 trypanosomiasis patients during an outbreak in Zaire in the early 1980s. Because the asymptomatic incubation period for the disease can be several months or even years, “the core strategy for controlling the disease is active screening,” he said in an interview.

“You try to convince the whole population of endemic villages to show up on a given day, and then you have a mobile team of nurses who examine everybody, trying to find those with early trypanosomiasis. This includes physical examination for lymph nodes in the neck, but also a blood test whose results are available within minutes,” he said.

“Until now, these persons with a positive serology would undergo additional and labor-intensive examinations of blood to try to find trypanosomes and prove that they have the disease. So far those with a positive serology and negative parasitological assays (‘serological suspects’) were left untreated, because the treatments were toxic and cumbersome, and because a substantial but unknown proportion of these ‘suspects’ just have a false positive of their serological test, without having the disease,” Dr. Pépin said.

“Now with acoziborole, which seems to have little serious toxicity ... and can be given as a single-dose oral med, it might be reasonable to treat the ‘serological suspects,’ ” he said.

“Take it one step further, it might be possible to do the serological test only and treat all individuals with a positive serology without bothering to do parasitological assays. This is what they call ‘test-and-treat’ strategy. It would make sense, provided that we are sure that the drug is very well tolerated.”

Dr. Pépin added that he is “just slightly worried” about three patients described in the paper who had psychiatric adverse events 3 months after treatment. “If that happens to patients who indeed have trypanosomiasis, that’s a reasonable price to pay considering the toxicity of other drugs,” he said. “If that happens to serological suspects, many of whom don’t have any disease, this becomes a preoccupation.”

But Dr. Tarral said, “We have no indication that the drug can provoke psychiatric symptoms. In fact, the psychiatric symptoms did not emerge – they re-emerged after 3 months due to some patients’ refusal to be followed up.”

“We included patients in very advanced stages of the disease, and these symptoms are considered disease sequelae,” Dr. Tarral said. “The majority of patients who have such psychiatric symptoms need follow-up after treatment. If not, they can relapse very early. There were a lot of patients who had such symptoms and the investigators proposed they should be followed by a psychiatrist and some of them refused. And due to that only three of our patients had this relapse, and they were cured after psychiatric support.”

The study was funded through the DND initiative and was supported by grants from the Bill & Melinda Gates Foundation; UK Aid; the Federal Ministry of Education and Research through Kreditanstalt für Wiederaufbau, Germany; the Swiss Agency for Development and Cooperation; Médecins Sans Frontières; the Dutch Ministry of Foreign Affairs; the Norwegian Agency for Development Cooperation; the Stavros Niarchos Foundation; the Spanish Agency for International Development Cooperation; and the Banco Bilbao Vizcaya Argentaria Foundation.

A number of study investigators, including Dr. Tarral, report employment at the DND initiative. Other investigators report fees from the DND initiative for the statistical report, consulting fees from CEMAG, D&A Pharma, Inventiva, and OT4B Pharma. The Swiss Tropical and Public Health Institute acted as a service provider for the DND initiative by monitoring the study sites. Dr. Pépin declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A single dose of oral acoziborole resulted in a greater than 95% cure or probable cure rate for human African trypanosomiasis (HAT), also known as sleeping sickness, according to results from a clinical trial testing a one-dose experimental drug.

The drug has “the potential to revolutionize treatment” for the disease, which remains endemic in sub-Saharan Africa, said Antoine Tarral, MD, head of the human African trypanosomiasis clinical program at the Drugs for Neglected Diseases initiative, based in Geneva, and senior author of the study, in a press release.

“It’s fantastic news, because it’s the first time that with one single administration you can treat the disease,” he told this news organization. “It’s the first drug we can use without hospitalization. ... All the previous medications needed hospitalization, and therefore we could not treat the population early before they started expressing symptoms.”

The World Health Organization “has been working for decades for such a possibility to implement a new strategy for this disease,” Dr. Tarral said.

Current (2019) WHO guidelines recommend oral fexinidazole as first-line treatment for any stage of the disease. The 10-day course often requires hospitalization and skilled staff. Previous recommendations required disease-staging with cerebrospinal fluid (CSF) sampling and 7 days of intramuscular pentamidine for early-stage disease or nifurtimox-eflornithine combination therapy (NECT) with hospitalization for late-stage disease.

By contrast, acoziborole, which was codeveloped by the DND initiative and Sanofi, “is administered in a single dose and is effective across every stage of the disease, thereby eliminating the many barriers currently in place for people most vulnerable to the diseases, such as invasive treatments and long travel distances to a hospital or clinic, and opening the door to screen-and-treat approaches at the village level,” Dr. Tarral said in the statement.

“Today, and in the future, we will have less and less support to do this long and costly diagnostic process and treatment in the hospital,” he said in an interview. “This development means we can go for a simple test and a simple treatment, which means we can meet the WHO 2030 goal for ending transmission of this disease.”

Results from the multicenter, prospective, open-label, single-arm, noncomparative, phase 2/3 study were published in The Lancet.
 

Pragmatic study design

Sleeping sickness is caused by Trypanosoma brucei gambiense (gambiense HAT). It is transmitted by the tsetse fly and mostly fatal when left untreated.

The study enrolled 208 adults and adolescents (167 with late-stage, and 41 with early-stage or intermediate-stage disease) from 10 hospitals in the Democratic Republic of the Congo and Guinea. All patients were treated with acoziborole 960 mg – an unusual study design.

“Due to the substantial decline in incidence, enrolling patients with gambiense HAT into clinical trials is challenging,” the authors wrote. “Following advice from the European Medicines Agency, this study was designed as an open-label, single-arm trial with no comparator or control group.”

After 18 months of follow-up, treatment success, defined as absence of trypanosomes and less than 20 white blood cells per mcL of CSF, occurred in 159 (95.2%) of the late-stage patients, and 100% of the early- and intermediate-stage patients, “which was similar to the estimated historical results for NECT,” the authors noted.

Serious treatment-emergent adverse events were reported in 21 (10%) of patients, “but none of these events were considered drug-related,” they added.

The DND initiative and the WHO are currently nearing completion of a much larger, double-blind, placebo-controlled trial of acoziborole to “increase the safety database,” Dr. Tarral explained.

“Purists will say that acoziborole has not been evaluated according to current standards, because the study was not a randomized trial, there was no control group, and the number of participants was small,” said Jacques Pépin, MD, from the University of Sherbrooke (Que.), in a linked commentary.

“But these were difficult challenges to overcome, considering the drastic reduction in the number of patients with HAT and dispersion over a vast territory, particularly in the Democratic Republic of the Congo. For these reasons, the authors took a pragmatic approach instead,” he wrote.
 

A potential new tool for eradication of sleeping sickness

“This is really an exciting development, which will be useful in the drive for eradication/interruption of transmission of this disease,” Dr. Pépin told this news organization.

Dr. Pépin treated around 1,000 trypanosomiasis patients during an outbreak in Zaire in the early 1980s. Because the asymptomatic incubation period for the disease can be several months or even years, “the core strategy for controlling the disease is active screening,” he said in an interview.

“You try to convince the whole population of endemic villages to show up on a given day, and then you have a mobile team of nurses who examine everybody, trying to find those with early trypanosomiasis. This includes physical examination for lymph nodes in the neck, but also a blood test whose results are available within minutes,” he said.

“Until now, these persons with a positive serology would undergo additional and labor-intensive examinations of blood to try to find trypanosomes and prove that they have the disease. So far those with a positive serology and negative parasitological assays (‘serological suspects’) were left untreated, because the treatments were toxic and cumbersome, and because a substantial but unknown proportion of these ‘suspects’ just have a false positive of their serological test, without having the disease,” Dr. Pépin said.

“Now with acoziborole, which seems to have little serious toxicity ... and can be given as a single-dose oral med, it might be reasonable to treat the ‘serological suspects,’ ” he said.

“Take it one step further, it might be possible to do the serological test only and treat all individuals with a positive serology without bothering to do parasitological assays. This is what they call ‘test-and-treat’ strategy. It would make sense, provided that we are sure that the drug is very well tolerated.”

Dr. Pépin added that he is “just slightly worried” about three patients described in the paper who had psychiatric adverse events 3 months after treatment. “If that happens to patients who indeed have trypanosomiasis, that’s a reasonable price to pay considering the toxicity of other drugs,” he said. “If that happens to serological suspects, many of whom don’t have any disease, this becomes a preoccupation.”

But Dr. Tarral said, “We have no indication that the drug can provoke psychiatric symptoms. In fact, the psychiatric symptoms did not emerge – they re-emerged after 3 months due to some patients’ refusal to be followed up.”

“We included patients in very advanced stages of the disease, and these symptoms are considered disease sequelae,” Dr. Tarral said. “The majority of patients who have such psychiatric symptoms need follow-up after treatment. If not, they can relapse very early. There were a lot of patients who had such symptoms and the investigators proposed they should be followed by a psychiatrist and some of them refused. And due to that only three of our patients had this relapse, and they were cured after psychiatric support.”

The study was funded through the DND initiative and was supported by grants from the Bill & Melinda Gates Foundation; UK Aid; the Federal Ministry of Education and Research through Kreditanstalt für Wiederaufbau, Germany; the Swiss Agency for Development and Cooperation; Médecins Sans Frontières; the Dutch Ministry of Foreign Affairs; the Norwegian Agency for Development Cooperation; the Stavros Niarchos Foundation; the Spanish Agency for International Development Cooperation; and the Banco Bilbao Vizcaya Argentaria Foundation.

A number of study investigators, including Dr. Tarral, report employment at the DND initiative. Other investigators report fees from the DND initiative for the statistical report, consulting fees from CEMAG, D&A Pharma, Inventiva, and OT4B Pharma. The Swiss Tropical and Public Health Institute acted as a service provider for the DND initiative by monitoring the study sites. Dr. Pépin declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A single dose of oral acoziborole resulted in a greater than 95% cure or probable cure rate for human African trypanosomiasis (HAT), also known as sleeping sickness, according to results from a clinical trial testing a one-dose experimental drug.

The drug has “the potential to revolutionize treatment” for the disease, which remains endemic in sub-Saharan Africa, said Antoine Tarral, MD, head of the human African trypanosomiasis clinical program at the Drugs for Neglected Diseases initiative, based in Geneva, and senior author of the study, in a press release.

“It’s fantastic news, because it’s the first time that with one single administration you can treat the disease,” he told this news organization. “It’s the first drug we can use without hospitalization. ... All the previous medications needed hospitalization, and therefore we could not treat the population early before they started expressing symptoms.”

The World Health Organization “has been working for decades for such a possibility to implement a new strategy for this disease,” Dr. Tarral said.

Current (2019) WHO guidelines recommend oral fexinidazole as first-line treatment for any stage of the disease. The 10-day course often requires hospitalization and skilled staff. Previous recommendations required disease-staging with cerebrospinal fluid (CSF) sampling and 7 days of intramuscular pentamidine for early-stage disease or nifurtimox-eflornithine combination therapy (NECT) with hospitalization for late-stage disease.

By contrast, acoziborole, which was codeveloped by the DND initiative and Sanofi, “is administered in a single dose and is effective across every stage of the disease, thereby eliminating the many barriers currently in place for people most vulnerable to the diseases, such as invasive treatments and long travel distances to a hospital or clinic, and opening the door to screen-and-treat approaches at the village level,” Dr. Tarral said in the statement.

“Today, and in the future, we will have less and less support to do this long and costly diagnostic process and treatment in the hospital,” he said in an interview. “This development means we can go for a simple test and a simple treatment, which means we can meet the WHO 2030 goal for ending transmission of this disease.”

Results from the multicenter, prospective, open-label, single-arm, noncomparative, phase 2/3 study were published in The Lancet.
 

Pragmatic study design

Sleeping sickness is caused by Trypanosoma brucei gambiense (gambiense HAT). It is transmitted by the tsetse fly and mostly fatal when left untreated.

The study enrolled 208 adults and adolescents (167 with late-stage, and 41 with early-stage or intermediate-stage disease) from 10 hospitals in the Democratic Republic of the Congo and Guinea. All patients were treated with acoziborole 960 mg – an unusual study design.

“Due to the substantial decline in incidence, enrolling patients with gambiense HAT into clinical trials is challenging,” the authors wrote. “Following advice from the European Medicines Agency, this study was designed as an open-label, single-arm trial with no comparator or control group.”

After 18 months of follow-up, treatment success, defined as absence of trypanosomes and less than 20 white blood cells per mcL of CSF, occurred in 159 (95.2%) of the late-stage patients, and 100% of the early- and intermediate-stage patients, “which was similar to the estimated historical results for NECT,” the authors noted.

Serious treatment-emergent adverse events were reported in 21 (10%) of patients, “but none of these events were considered drug-related,” they added.

The DND initiative and the WHO are currently nearing completion of a much larger, double-blind, placebo-controlled trial of acoziborole to “increase the safety database,” Dr. Tarral explained.

“Purists will say that acoziborole has not been evaluated according to current standards, because the study was not a randomized trial, there was no control group, and the number of participants was small,” said Jacques Pépin, MD, from the University of Sherbrooke (Que.), in a linked commentary.

“But these were difficult challenges to overcome, considering the drastic reduction in the number of patients with HAT and dispersion over a vast territory, particularly in the Democratic Republic of the Congo. For these reasons, the authors took a pragmatic approach instead,” he wrote.
 

A potential new tool for eradication of sleeping sickness

“This is really an exciting development, which will be useful in the drive for eradication/interruption of transmission of this disease,” Dr. Pépin told this news organization.

Dr. Pépin treated around 1,000 trypanosomiasis patients during an outbreak in Zaire in the early 1980s. Because the asymptomatic incubation period for the disease can be several months or even years, “the core strategy for controlling the disease is active screening,” he said in an interview.

“You try to convince the whole population of endemic villages to show up on a given day, and then you have a mobile team of nurses who examine everybody, trying to find those with early trypanosomiasis. This includes physical examination for lymph nodes in the neck, but also a blood test whose results are available within minutes,” he said.

“Until now, these persons with a positive serology would undergo additional and labor-intensive examinations of blood to try to find trypanosomes and prove that they have the disease. So far those with a positive serology and negative parasitological assays (‘serological suspects’) were left untreated, because the treatments were toxic and cumbersome, and because a substantial but unknown proportion of these ‘suspects’ just have a false positive of their serological test, without having the disease,” Dr. Pépin said.

“Now with acoziborole, which seems to have little serious toxicity ... and can be given as a single-dose oral med, it might be reasonable to treat the ‘serological suspects,’ ” he said.

“Take it one step further, it might be possible to do the serological test only and treat all individuals with a positive serology without bothering to do parasitological assays. This is what they call ‘test-and-treat’ strategy. It would make sense, provided that we are sure that the drug is very well tolerated.”

Dr. Pépin added that he is “just slightly worried” about three patients described in the paper who had psychiatric adverse events 3 months after treatment. “If that happens to patients who indeed have trypanosomiasis, that’s a reasonable price to pay considering the toxicity of other drugs,” he said. “If that happens to serological suspects, many of whom don’t have any disease, this becomes a preoccupation.”

But Dr. Tarral said, “We have no indication that the drug can provoke psychiatric symptoms. In fact, the psychiatric symptoms did not emerge – they re-emerged after 3 months due to some patients’ refusal to be followed up.”

“We included patients in very advanced stages of the disease, and these symptoms are considered disease sequelae,” Dr. Tarral said. “The majority of patients who have such psychiatric symptoms need follow-up after treatment. If not, they can relapse very early. There were a lot of patients who had such symptoms and the investigators proposed they should be followed by a psychiatrist and some of them refused. And due to that only three of our patients had this relapse, and they were cured after psychiatric support.”

The study was funded through the DND initiative and was supported by grants from the Bill & Melinda Gates Foundation; UK Aid; the Federal Ministry of Education and Research through Kreditanstalt für Wiederaufbau, Germany; the Swiss Agency for Development and Cooperation; Médecins Sans Frontières; the Dutch Ministry of Foreign Affairs; the Norwegian Agency for Development Cooperation; the Stavros Niarchos Foundation; the Spanish Agency for International Development Cooperation; and the Banco Bilbao Vizcaya Argentaria Foundation.

A number of study investigators, including Dr. Tarral, report employment at the DND initiative. Other investigators report fees from the DND initiative for the statistical report, consulting fees from CEMAG, D&A Pharma, Inventiva, and OT4B Pharma. The Swiss Tropical and Public Health Institute acted as a service provider for the DND initiative by monitoring the study sites. Dr. Pépin declared no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The annual cost of Lyme disease in the United States could be nearly $970 million, according to new research. But not all cases of Lyme disease are equally costly. Costs for patients with disseminated Lyme disease were more than twice as high as those for patients with localized disease.

Lyme_tick_CDC_photo_web.jpg

“These findings emphasize the importance of early and accurate diagnosis to reduce both illness and its associated personal and societal costs,” the study’s authors write. The analysis was published  in Emerging Infectious Diseases. The authors are from the Centers for Disease Control and Prevention, the Yale School of Public Health, and the Departments of Health of Minnesota, Maryland, and New York State.

Lyme disease is the most reported vector-borne disease in the United States; an estimated 476,000 Americans are diagnosed with the infection every year. Though the highest incidences are in the Northeast and in Minnesota and Wisconsin, the CDC has recorded cases in all 50 states. Over the past 20 years, estimates of the total cost of treating Lyme disease have varied from $203 million to nearly $1.3 billion. A major limitation to these studies, however, is that they may not accurately identify patients with Lyme disease or capture many of the nonmedical costs associated with treatment, the authors write, such as costs associated with time taken off work and travel to appointments.

To better capture the comprehensive cost of Lyme disease in the United States, researchers conducted a prospective study from September 2014 to January 2016 and followed reported cases in four states with high rates of Lyme disease: Connecticut, Maryland, Minnesota, and New York. The team conducted monthly patient surveys and queried billing codes from participants’ clinicians to estimate both the personal expenses and societal costs – such as total costs to the health care system – of Lyme disease.

Participants were variously assigned to one of three categories: those with confirmed local disease (such as patients with erythema migrans); those with confirmed disseminated disease, with symptoms including arthritis, lymphocytic meningitis, and encephalomyelitis; and those with probable cases with reported symptoms.

The researchers surveyed 901 participants with clinician-diagnosed Lyme disease: 402 with localized disease, 238 with disseminated disease, and 261 with probable cases. Nearly all participants (94%) were White, 57% were men, and 71% had an annual household income above $60,000. About 28% of participants were younger than 18 years, 16% were aged 18-45 years, 36% were aged 46-65, and 19% were older than 65 years. For most participants (68%), complete medical cost data were available. Those data were used to calculate societal costs.

Costs per patient varied dramatically, from $0.46 to $30,628. On average, patients spent $1,252 during the study period on expenses related to Lyme disease treatment, including expenses associated with travel and time taken off work. The median cost to patients was notably smaller, at $244. Patients with disseminated disease had the highest median ($358) and mean ($1,692) costs, followed by participants with probable disease (median, $315; mean, $1,277). Participants with localized disease had the lowest median ($170) and mean ($1,070) costs.

Societal costs ranged from $54 to $122,766 per patient; the median was $690, and the mean was $2,032. Multiplying these numbers by the estimated cases diagnosed nationally each year, researchers determined that the total cost of Lyme disease in the United States is between $345 million and $968 million.

The study “pointed out the tremendous variability in costs” associated with Lyme disease treatment, Brian Fallon, MD, MPH, director of the Lyme and Tick-Borne Diseases Research Center at the Columbia University Irving Medical Center, New York, told this news organization. He was not involved with the research. Some patients continued having health expenses after the end of the study, which means their costs would be even higher, he noted. Though most patients fully recovered after 1 year, about 4% still reported symptoms, and 3% were still incurring costs.

Fallon_Brian_NY_web.jpg

Aucott_John_MD_web.jpg

A version of this article first appeared on Medscape.com.

The annual cost of Lyme disease in the United States could be nearly $970 million, according to new research. But not all cases of Lyme disease are equally costly. Costs for patients with disseminated Lyme disease were more than twice as high as those for patients with localized disease.

Lyme_tick_CDC_photo_web.jpg

“These findings emphasize the importance of early and accurate diagnosis to reduce both illness and its associated personal and societal costs,” the study’s authors write. The analysis was published  in Emerging Infectious Diseases. The authors are from the Centers for Disease Control and Prevention, the Yale School of Public Health, and the Departments of Health of Minnesota, Maryland, and New York State.

Lyme disease is the most reported vector-borne disease in the United States; an estimated 476,000 Americans are diagnosed with the infection every year. Though the highest incidences are in the Northeast and in Minnesota and Wisconsin, the CDC has recorded cases in all 50 states. Over the past 20 years, estimates of the total cost of treating Lyme disease have varied from $203 million to nearly $1.3 billion. A major limitation to these studies, however, is that they may not accurately identify patients with Lyme disease or capture many of the nonmedical costs associated with treatment, the authors write, such as costs associated with time taken off work and travel to appointments.

To better capture the comprehensive cost of Lyme disease in the United States, researchers conducted a prospective study from September 2014 to January 2016 and followed reported cases in four states with high rates of Lyme disease: Connecticut, Maryland, Minnesota, and New York. The team conducted monthly patient surveys and queried billing codes from participants’ clinicians to estimate both the personal expenses and societal costs – such as total costs to the health care system – of Lyme disease.

Participants were variously assigned to one of three categories: those with confirmed local disease (such as patients with erythema migrans); those with confirmed disseminated disease, with symptoms including arthritis, lymphocytic meningitis, and encephalomyelitis; and those with probable cases with reported symptoms.

The researchers surveyed 901 participants with clinician-diagnosed Lyme disease: 402 with localized disease, 238 with disseminated disease, and 261 with probable cases. Nearly all participants (94%) were White, 57% were men, and 71% had an annual household income above $60,000. About 28% of participants were younger than 18 years, 16% were aged 18-45 years, 36% were aged 46-65, and 19% were older than 65 years. For most participants (68%), complete medical cost data were available. Those data were used to calculate societal costs.

Costs per patient varied dramatically, from $0.46 to $30,628. On average, patients spent $1,252 during the study period on expenses related to Lyme disease treatment, including expenses associated with travel and time taken off work. The median cost to patients was notably smaller, at $244. Patients with disseminated disease had the highest median ($358) and mean ($1,692) costs, followed by participants with probable disease (median, $315; mean, $1,277). Participants with localized disease had the lowest median ($170) and mean ($1,070) costs.

Societal costs ranged from $54 to $122,766 per patient; the median was $690, and the mean was $2,032. Multiplying these numbers by the estimated cases diagnosed nationally each year, researchers determined that the total cost of Lyme disease in the United States is between $345 million and $968 million.

The study “pointed out the tremendous variability in costs” associated with Lyme disease treatment, Brian Fallon, MD, MPH, director of the Lyme and Tick-Borne Diseases Research Center at the Columbia University Irving Medical Center, New York, told this news organization. He was not involved with the research. Some patients continued having health expenses after the end of the study, which means their costs would be even higher, he noted. Though most patients fully recovered after 1 year, about 4% still reported symptoms, and 3% were still incurring costs.

Fallon_Brian_NY_web.jpg

Aucott_John_MD_web.jpg

A version of this article first appeared on Medscape.com.

The annual cost of Lyme disease in the United States could be nearly $970 million, according to new research. But not all cases of Lyme disease are equally costly. Costs for patients with disseminated Lyme disease were more than twice as high as those for patients with localized disease.

Lyme_tick_CDC_photo_web.jpg

“These findings emphasize the importance of early and accurate diagnosis to reduce both illness and its associated personal and societal costs,” the study’s authors write. The analysis was published  in Emerging Infectious Diseases. The authors are from the Centers for Disease Control and Prevention, the Yale School of Public Health, and the Departments of Health of Minnesota, Maryland, and New York State.

Lyme disease is the most reported vector-borne disease in the United States; an estimated 476,000 Americans are diagnosed with the infection every year. Though the highest incidences are in the Northeast and in Minnesota and Wisconsin, the CDC has recorded cases in all 50 states. Over the past 20 years, estimates of the total cost of treating Lyme disease have varied from $203 million to nearly $1.3 billion. A major limitation to these studies, however, is that they may not accurately identify patients with Lyme disease or capture many of the nonmedical costs associated with treatment, the authors write, such as costs associated with time taken off work and travel to appointments.

To better capture the comprehensive cost of Lyme disease in the United States, researchers conducted a prospective study from September 2014 to January 2016 and followed reported cases in four states with high rates of Lyme disease: Connecticut, Maryland, Minnesota, and New York. The team conducted monthly patient surveys and queried billing codes from participants’ clinicians to estimate both the personal expenses and societal costs – such as total costs to the health care system – of Lyme disease.

Participants were variously assigned to one of three categories: those with confirmed local disease (such as patients with erythema migrans); those with confirmed disseminated disease, with symptoms including arthritis, lymphocytic meningitis, and encephalomyelitis; and those with probable cases with reported symptoms.

The researchers surveyed 901 participants with clinician-diagnosed Lyme disease: 402 with localized disease, 238 with disseminated disease, and 261 with probable cases. Nearly all participants (94%) were White, 57% were men, and 71% had an annual household income above $60,000. About 28% of participants were younger than 18 years, 16% were aged 18-45 years, 36% were aged 46-65, and 19% were older than 65 years. For most participants (68%), complete medical cost data were available. Those data were used to calculate societal costs.

Costs per patient varied dramatically, from $0.46 to $30,628. On average, patients spent $1,252 during the study period on expenses related to Lyme disease treatment, including expenses associated with travel and time taken off work. The median cost to patients was notably smaller, at $244. Patients with disseminated disease had the highest median ($358) and mean ($1,692) costs, followed by participants with probable disease (median, $315; mean, $1,277). Participants with localized disease had the lowest median ($170) and mean ($1,070) costs.

Societal costs ranged from $54 to $122,766 per patient; the median was $690, and the mean was $2,032. Multiplying these numbers by the estimated cases diagnosed nationally each year, researchers determined that the total cost of Lyme disease in the United States is between $345 million and $968 million.

The study “pointed out the tremendous variability in costs” associated with Lyme disease treatment, Brian Fallon, MD, MPH, director of the Lyme and Tick-Borne Diseases Research Center at the Columbia University Irving Medical Center, New York, told this news organization. He was not involved with the research. Some patients continued having health expenses after the end of the study, which means their costs would be even higher, he noted. Though most patients fully recovered after 1 year, about 4% still reported symptoms, and 3% were still incurring costs.

Fallon_Brian_NY_web.jpg

Aucott_John_MD_web.jpg

A version of this article first appeared on Medscape.com.

Testing the DNA of antimicrobial-resistant Plasmodium falciparum in the blood of travelers from malaria-endemic regions may help researchers monitor how drug resistance changes over time, a study from Canada reports.

“Malaria remains the deadliest vector-borne infectious disease worldwide. Plasmodium spp., most commonly P. falciparum, are responsible for [approximately] 229 million cases and 500,000 deaths from malaria annually,” the authors write in Emerging Infectious Diseases.

“Our findings demonstrate an absence of genetic markers of resistance to the most powerful antimalarials on the planet – the artemisinins – in potentially deadly malaria imported primarily from sub-Saharan Africa over time. This is good news,” senior study author Andrea K. Boggild, MD, MSc, DTMH, told this news organization.

“We also showed that over 90% of falciparum malaria imports were resistant to the proguanil component of the fixed drug combination atovaquone-proguanil, a popular oral antimalarial that is first-line treatment for uncomplicated malaria in Canada,” Dr. Boggild, an associate professor in the department of medicine at the University of Toronto, Canada, added in an email. “We documented no genetic markers of atovaquone resistance.”
 

Search for global patterns of emerging drug resistance

Dr. Boggild, the medical director of the tropical disease unit at Toronto General Hospital, and colleagues analyzed 243 whole-blood specimens that contained P. falciparum and no other Plasmodium species from the malaria biobank at the Public Health Ontario Laboratory in Toronto. They analyzed specimens from the years 2008-2009, 2013-2014, and 2017-2018 from patients ranging in age from 3 to 88 years. Of the 186 patients with a documented travel history, 81 had traveled in West Africa, the most common region, and 40 in Nigeria, the most common country. Five specimens came from travelers to Southeast Asia, and one came from a traveler to the Caribbean.

The researchers extracted DNA from whole blood and detected the parasite’s DNA by real-time quantitative polymerase chain reaction (qPCR). They analyzed 23 different single-nucleotide polymorphisms (SNPs) in six genes, and quantified the prevalence of resistance markers, including genes that provoke resistance to the most common antimalarial drugs: chloroquine, mefloquine, atovaquone/proguanil, and the artemisinins.

They analyzed SNPs at atpase6 (pfATPase6), pfcrt (chloroquine resistance transporter, cytb (cytochrome b), dhfr (dihydrofolate reductase), dhps (dihydropteroate synthetase), mdr1 (multidrug resistance protein) and mdr1 copy number, and kelch13 (kelch protein gene on chromosome 13).

Over time, they detected increasing mutant genotypes for dhfr S108N (P = .001) and dhps A613T (P = .029) but decreasing mutant genotypes for mdr1 N86Y (P < .001), D1246Y (P = .003), pfcrt K76T (P = .011), and pfcrt 74-75 (P = .014). They found no kelch13 mutations. They detected fewer mutations indicating chloroquine resistance over time, suggesting less chloroquine pressure in specimens from travelers to Africa, but mutations that provided proguanil resistance increased.

“Antimalarial resistance – particularly resistance to the powerful artemisinins – continues to expand globally, and it is important to conduct routine surveillance for resistant parasites in order to inform appropriate prevention and treatment guidelines,” Dr. Boggild explained. “It cannot be presumed that a drug’s efficacy will be durable over time given the global landscape of antimalarial resistance.”

Dr. Boggild acknowledged limitations to the study, including incomplete travel history in about half of the patients, relatively few patients from Southeast Asia, and the small sample set.

“Clinicians caring for travelers before or after travel should familiarize themselves with the options for malaria prevention and treatment and understand the risk–benefit profile of each drug,” Dr. Boggild advised. 

“Resistance to proguanil means that we are reliant on the partner drug atovaquone for the antimalarial action of this formulation, which is effective only when taken with food,” she added.

Anne N. Cowell, MD, MPH, of the division of infectious diseases at the University of California, San Diego, was not surprised by the findings.

“The study demonstrates how quickly malaria parasites adapt and evolve to survive changes in malaria treatment,” Dr. Cowell, who was not involved in the study, told this news organization.

“These changes reflect changing malaria treatment and thus drug pressure during the time period,” she said in an email. “Because the majority of the clinical samples with a known travel history came from West Africa, and there was no clear evidence of artemisinin resistance in the area during the final time period studied, it is not surprising that they did not find kelch13 resistance mutations.

“The increase in mutations associated with proguanil resistance is concerning because atovaquone-proguanil is frequently used for prophylaxis during travel,” Dr. Cowell added. “There is no widespread evidence of resistance in travelers at this time, but it warrants monitoring.”

Sean C. Murphy, MD, PhD, an associate professor of laboratory medicine and the director of the malaria molecular diagnostic laboratory at the University of Washington in Seattle, also was not surprised by the study’s results.

“It may be just a matter of time before evidence of artemisinin resistance crops up among returning travelers,” he said in an email. “When that happens, we may lose the opportunity to easily use common go-to drugs like atovaquone/proguanil to treat these patients.

“The biggest takeaway of this study is the reminder that drug-resistant malaria (including the future potential for artemisinin-resistant malaria) is just an airplane flight or two away from nonendemic places like Canada and the United States,” Dr. Murphy noted. He was not involved with this Canadian study.

“Continued investment is needed to support malaria control, drug resistance monitoring, and vaccine efforts in order to fight this relentless, terrible parasite,” he urged.

The Project Initiation Fund of Public Health Ontario funded the study. The study authors, Dr. Cowell, and Dr. Murphy have disclosed no relevant financial relationships.  

A version of this article first appeared on Medscape.com.

Testing the DNA of antimicrobial-resistant Plasmodium falciparum in the blood of travelers from malaria-endemic regions may help researchers monitor how drug resistance changes over time, a study from Canada reports.

“Malaria remains the deadliest vector-borne infectious disease worldwide. Plasmodium spp., most commonly P. falciparum, are responsible for [approximately] 229 million cases and 500,000 deaths from malaria annually,” the authors write in Emerging Infectious Diseases.

“Our findings demonstrate an absence of genetic markers of resistance to the most powerful antimalarials on the planet – the artemisinins – in potentially deadly malaria imported primarily from sub-Saharan Africa over time. This is good news,” senior study author Andrea K. Boggild, MD, MSc, DTMH, told this news organization.

“We also showed that over 90% of falciparum malaria imports were resistant to the proguanil component of the fixed drug combination atovaquone-proguanil, a popular oral antimalarial that is first-line treatment for uncomplicated malaria in Canada,” Dr. Boggild, an associate professor in the department of medicine at the University of Toronto, Canada, added in an email. “We documented no genetic markers of atovaquone resistance.”
 

Search for global patterns of emerging drug resistance

Dr. Boggild, the medical director of the tropical disease unit at Toronto General Hospital, and colleagues analyzed 243 whole-blood specimens that contained P. falciparum and no other Plasmodium species from the malaria biobank at the Public Health Ontario Laboratory in Toronto. They analyzed specimens from the years 2008-2009, 2013-2014, and 2017-2018 from patients ranging in age from 3 to 88 years. Of the 186 patients with a documented travel history, 81 had traveled in West Africa, the most common region, and 40 in Nigeria, the most common country. Five specimens came from travelers to Southeast Asia, and one came from a traveler to the Caribbean.

The researchers extracted DNA from whole blood and detected the parasite’s DNA by real-time quantitative polymerase chain reaction (qPCR). They analyzed 23 different single-nucleotide polymorphisms (SNPs) in six genes, and quantified the prevalence of resistance markers, including genes that provoke resistance to the most common antimalarial drugs: chloroquine, mefloquine, atovaquone/proguanil, and the artemisinins.

They analyzed SNPs at atpase6 (pfATPase6), pfcrt (chloroquine resistance transporter, cytb (cytochrome b), dhfr (dihydrofolate reductase), dhps (dihydropteroate synthetase), mdr1 (multidrug resistance protein) and mdr1 copy number, and kelch13 (kelch protein gene on chromosome 13).

Over time, they detected increasing mutant genotypes for dhfr S108N (P = .001) and dhps A613T (P = .029) but decreasing mutant genotypes for mdr1 N86Y (P < .001), D1246Y (P = .003), pfcrt K76T (P = .011), and pfcrt 74-75 (P = .014). They found no kelch13 mutations. They detected fewer mutations indicating chloroquine resistance over time, suggesting less chloroquine pressure in specimens from travelers to Africa, but mutations that provided proguanil resistance increased.

“Antimalarial resistance – particularly resistance to the powerful artemisinins – continues to expand globally, and it is important to conduct routine surveillance for resistant parasites in order to inform appropriate prevention and treatment guidelines,” Dr. Boggild explained. “It cannot be presumed that a drug’s efficacy will be durable over time given the global landscape of antimalarial resistance.”

Dr. Boggild acknowledged limitations to the study, including incomplete travel history in about half of the patients, relatively few patients from Southeast Asia, and the small sample set.

“Clinicians caring for travelers before or after travel should familiarize themselves with the options for malaria prevention and treatment and understand the risk–benefit profile of each drug,” Dr. Boggild advised. 

“Resistance to proguanil means that we are reliant on the partner drug atovaquone for the antimalarial action of this formulation, which is effective only when taken with food,” she added.

Anne N. Cowell, MD, MPH, of the division of infectious diseases at the University of California, San Diego, was not surprised by the findings.

“The study demonstrates how quickly malaria parasites adapt and evolve to survive changes in malaria treatment,” Dr. Cowell, who was not involved in the study, told this news organization.

“These changes reflect changing malaria treatment and thus drug pressure during the time period,” she said in an email. “Because the majority of the clinical samples with a known travel history came from West Africa, and there was no clear evidence of artemisinin resistance in the area during the final time period studied, it is not surprising that they did not find kelch13 resistance mutations.

“The increase in mutations associated with proguanil resistance is concerning because atovaquone-proguanil is frequently used for prophylaxis during travel,” Dr. Cowell added. “There is no widespread evidence of resistance in travelers at this time, but it warrants monitoring.”

Sean C. Murphy, MD, PhD, an associate professor of laboratory medicine and the director of the malaria molecular diagnostic laboratory at the University of Washington in Seattle, also was not surprised by the study’s results.

“It may be just a matter of time before evidence of artemisinin resistance crops up among returning travelers,” he said in an email. “When that happens, we may lose the opportunity to easily use common go-to drugs like atovaquone/proguanil to treat these patients.

“The biggest takeaway of this study is the reminder that drug-resistant malaria (including the future potential for artemisinin-resistant malaria) is just an airplane flight or two away from nonendemic places like Canada and the United States,” Dr. Murphy noted. He was not involved with this Canadian study.

“Continued investment is needed to support malaria control, drug resistance monitoring, and vaccine efforts in order to fight this relentless, terrible parasite,” he urged.

The Project Initiation Fund of Public Health Ontario funded the study. The study authors, Dr. Cowell, and Dr. Murphy have disclosed no relevant financial relationships.  

A version of this article first appeared on Medscape.com.

Testing the DNA of antimicrobial-resistant Plasmodium falciparum in the blood of travelers from malaria-endemic regions may help researchers monitor how drug resistance changes over time, a study from Canada reports.

“Malaria remains the deadliest vector-borne infectious disease worldwide. Plasmodium spp., most commonly P. falciparum, are responsible for [approximately] 229 million cases and 500,000 deaths from malaria annually,” the authors write in Emerging Infectious Diseases.

“Our findings demonstrate an absence of genetic markers of resistance to the most powerful antimalarials on the planet – the artemisinins – in potentially deadly malaria imported primarily from sub-Saharan Africa over time. This is good news,” senior study author Andrea K. Boggild, MD, MSc, DTMH, told this news organization.

“We also showed that over 90% of falciparum malaria imports were resistant to the proguanil component of the fixed drug combination atovaquone-proguanil, a popular oral antimalarial that is first-line treatment for uncomplicated malaria in Canada,” Dr. Boggild, an associate professor in the department of medicine at the University of Toronto, Canada, added in an email. “We documented no genetic markers of atovaquone resistance.”
 

Search for global patterns of emerging drug resistance

Dr. Boggild, the medical director of the tropical disease unit at Toronto General Hospital, and colleagues analyzed 243 whole-blood specimens that contained P. falciparum and no other Plasmodium species from the malaria biobank at the Public Health Ontario Laboratory in Toronto. They analyzed specimens from the years 2008-2009, 2013-2014, and 2017-2018 from patients ranging in age from 3 to 88 years. Of the 186 patients with a documented travel history, 81 had traveled in West Africa, the most common region, and 40 in Nigeria, the most common country. Five specimens came from travelers to Southeast Asia, and one came from a traveler to the Caribbean.

The researchers extracted DNA from whole blood and detected the parasite’s DNA by real-time quantitative polymerase chain reaction (qPCR). They analyzed 23 different single-nucleotide polymorphisms (SNPs) in six genes, and quantified the prevalence of resistance markers, including genes that provoke resistance to the most common antimalarial drugs: chloroquine, mefloquine, atovaquone/proguanil, and the artemisinins.

They analyzed SNPs at atpase6 (pfATPase6), pfcrt (chloroquine resistance transporter, cytb (cytochrome b), dhfr (dihydrofolate reductase), dhps (dihydropteroate synthetase), mdr1 (multidrug resistance protein) and mdr1 copy number, and kelch13 (kelch protein gene on chromosome 13).

Over time, they detected increasing mutant genotypes for dhfr S108N (P = .001) and dhps A613T (P = .029) but decreasing mutant genotypes for mdr1 N86Y (P < .001), D1246Y (P = .003), pfcrt K76T (P = .011), and pfcrt 74-75 (P = .014). They found no kelch13 mutations. They detected fewer mutations indicating chloroquine resistance over time, suggesting less chloroquine pressure in specimens from travelers to Africa, but mutations that provided proguanil resistance increased.

“Antimalarial resistance – particularly resistance to the powerful artemisinins – continues to expand globally, and it is important to conduct routine surveillance for resistant parasites in order to inform appropriate prevention and treatment guidelines,” Dr. Boggild explained. “It cannot be presumed that a drug’s efficacy will be durable over time given the global landscape of antimalarial resistance.”

Dr. Boggild acknowledged limitations to the study, including incomplete travel history in about half of the patients, relatively few patients from Southeast Asia, and the small sample set.

“Clinicians caring for travelers before or after travel should familiarize themselves with the options for malaria prevention and treatment and understand the risk–benefit profile of each drug,” Dr. Boggild advised. 

“Resistance to proguanil means that we are reliant on the partner drug atovaquone for the antimalarial action of this formulation, which is effective only when taken with food,” she added.

Anne N. Cowell, MD, MPH, of the division of infectious diseases at the University of California, San Diego, was not surprised by the findings.

“The study demonstrates how quickly malaria parasites adapt and evolve to survive changes in malaria treatment,” Dr. Cowell, who was not involved in the study, told this news organization.

“These changes reflect changing malaria treatment and thus drug pressure during the time period,” she said in an email. “Because the majority of the clinical samples with a known travel history came from West Africa, and there was no clear evidence of artemisinin resistance in the area during the final time period studied, it is not surprising that they did not find kelch13 resistance mutations.

“The increase in mutations associated with proguanil resistance is concerning because atovaquone-proguanil is frequently used for prophylaxis during travel,” Dr. Cowell added. “There is no widespread evidence of resistance in travelers at this time, but it warrants monitoring.”

Sean C. Murphy, MD, PhD, an associate professor of laboratory medicine and the director of the malaria molecular diagnostic laboratory at the University of Washington in Seattle, also was not surprised by the study’s results.

“It may be just a matter of time before evidence of artemisinin resistance crops up among returning travelers,” he said in an email. “When that happens, we may lose the opportunity to easily use common go-to drugs like atovaquone/proguanil to treat these patients.

“The biggest takeaway of this study is the reminder that drug-resistant malaria (including the future potential for artemisinin-resistant malaria) is just an airplane flight or two away from nonendemic places like Canada and the United States,” Dr. Murphy noted. He was not involved with this Canadian study.

“Continued investment is needed to support malaria control, drug resistance monitoring, and vaccine efforts in order to fight this relentless, terrible parasite,” he urged.

The Project Initiation Fund of Public Health Ontario funded the study. The study authors, Dr. Cowell, and Dr. Murphy have disclosed no relevant financial relationships.  

A version of this article first appeared on Medscape.com.

Owning an outdoor cat as a child is associated with an increased risk of psychotic experiences in adulthood – but only in males, new research suggests.

Investigators found male children who owned cats that went outside had a small, but significantly increased, risk of psychotic experiences in adulthood, compared with their counterparts who had no cat during childhood or who had an indoor cat.

Paquin_Vincent_CAN_web.jpg

The suspected culprit is not the cat itself but rather exposure to Toxoplasma gondii, a common parasite carried by rodents and sometimes found in cat feces. The study adds to a growing evidence showing exposure to T. gondii may be a risk factor for schizophrenia and other psychotic disorders.

“These are small pieces of evidence but it’s interesting to consider that there might be combinations of risk factors at play,” lead author Vincent Paquin, MD, psychiatry resident at McGill University, Montreal, said in an interview.

“And even if the magnitude of the risk is small at the individual level,” he added, “cats and Toxoplasma gondii are so present in our society that if we add up all these small potential effects then it becomes a potential public health question.”

The study was published online Jan. 30, 2022, in the Journal of Psychiatric Research.
 

Inconsistent evidence

T. gondii infects about 30% of the human population and is usually transmitted by cats. Most infections are asymptomatic, but T. gondii can cause toxoplasmosis in humans, which has been linked to increased risk of schizophrenia, suicide attempts, and more recently, mild cognitive impairment.

Although some studies show an association between cat ownership and increased risk of mental illness, the research findings have been inconsistent.

“The evidence has been mixed about the association between cat ownership and psychosis expression, so our approach was to consider whether specific factors or combinations of factors could explain this mixed evidence,” Dr. Paquin said.

For the study, 2206 individuals aged 18-40 years completed the Community Assessment of Psychic Experiences (CAPE-42) and a questionnaire to gather information about cat ownership at any time between birth and age 13 and if the cats lived exclusively indoors (nonhunting) or if they were allowed outside (rodent hunting).

Participants were also asked about the number of residential moves between birth and age 15, date and place of birth, lifetime history of head trauma, and tobacco smoking history.

Rodent-hunting cat ownership was associated with higher risk of psychosis in male participants, compared with owning no cat or a nonhunting cat. When the investigators added head trauma and residential moves to rodent-hunting cat ownership, psychosis risk was elevated in both men and women.

Independent of cat ownership, younger age, moving more than three times as a child, a history of head trauma, and being a smoker were all associated with higher psychosis risk.

King_Suzanne_CAN_web.jpg

The study wasn’t designed to explore potential biological mechanisms to explain the sex differences in psychosis risk seen among rodent-hunting cat owners, but “one possible explanation based on the animal model literature is that the neurobiological effects of parasitic exposure may be greater with male sex,” senior author Suzanne King, PhD, professor of psychiatry at McGill, said in an interview.

The new study is part of a larger, long-term project called EnviroGen, led by Dr. King, examining the environmental and genetic risk factors for schizophrenia.
 

Need for replication

Commenting on the findings, E. Fuller Torrey, MD, who was among the first researchers to identify a link between cat ownership, T. gondii infection, and schizophrenia, said the study is “an interesting addition to the studies of cat ownership in childhood as a risk factor for psychosis.”

Of the approximately 10 published studies on the topic, about half suggest a link between cat ownership and psychosis later in life, said Dr. Torrey, associate director for research at the Stanley Medical Research Institute in Rockville, Md.

“The Canadian study is interesting in that it is the first study that separates exposure to permanently indoor cats from cats that are allowed to go outdoors, and the results were positive only for outdoor cats,” Dr. Torrey said.

The study has limitations, Dr. Torrey added, including its retrospective design and the use of a self-report questionnaire to assess psychotic experiences in adulthood.

Also commenting on findings, James Kirkbride, PhD, professor of psychiatric and social epidemiology, University College London, noted the same limitations.

Dr. Kirkbride is the lead author of a 2017 study that showed no link between cat ownership and serious mental illness that included nearly 5,000 people born in 1991 or 1992 and followed until age 18. In this study, there was no link between psychosis and cat ownership during pregnancy or at ages 4 or 10 years.

“Researchers have long been fascinated with the idea that cat ownership may affect mental health. This paper may have them chasing their own tail,” Dr. Kirkbride said.

“Evidence of any association is limited to certain subgroups without a strong theoretical basis for why this may be the case,” he added. “The retrospective and cross-sectional nature of the survey also raise the possibility that the results are impacted by differential recall bias, as well as the broader issues of chance and unobserved confounding.”

Dr. King noted that recall bias is a limitation the researchers highlighted in their study, but “considering the exposures are relatively objective and factual, we do not believe the potential for recall bias is substantial.”

“Nonetheless, we strongly believe that replication of our results in prospective, population-representative cohorts will be crucial to making firmer conclusions,” he added.

The study was funded by grants from the Quebec Health Research Fund. The study authors and Dr. Kirkbride disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Owning an outdoor cat as a child is associated with an increased risk of psychotic experiences in adulthood – but only in males, new research suggests.

Investigators found male children who owned cats that went outside had a small, but significantly increased, risk of psychotic experiences in adulthood, compared with their counterparts who had no cat during childhood or who had an indoor cat.

Paquin_Vincent_CAN_web.jpg

The suspected culprit is not the cat itself but rather exposure to Toxoplasma gondii, a common parasite carried by rodents and sometimes found in cat feces. The study adds to a growing evidence showing exposure to T. gondii may be a risk factor for schizophrenia and other psychotic disorders.

“These are small pieces of evidence but it’s interesting to consider that there might be combinations of risk factors at play,” lead author Vincent Paquin, MD, psychiatry resident at McGill University, Montreal, said in an interview.

“And even if the magnitude of the risk is small at the individual level,” he added, “cats and Toxoplasma gondii are so present in our society that if we add up all these small potential effects then it becomes a potential public health question.”

The study was published online Jan. 30, 2022, in the Journal of Psychiatric Research.
 

Inconsistent evidence

T. gondii infects about 30% of the human population and is usually transmitted by cats. Most infections are asymptomatic, but T. gondii can cause toxoplasmosis in humans, which has been linked to increased risk of schizophrenia, suicide attempts, and more recently, mild cognitive impairment.

Although some studies show an association between cat ownership and increased risk of mental illness, the research findings have been inconsistent.

“The evidence has been mixed about the association between cat ownership and psychosis expression, so our approach was to consider whether specific factors or combinations of factors could explain this mixed evidence,” Dr. Paquin said.

For the study, 2206 individuals aged 18-40 years completed the Community Assessment of Psychic Experiences (CAPE-42) and a questionnaire to gather information about cat ownership at any time between birth and age 13 and if the cats lived exclusively indoors (nonhunting) or if they were allowed outside (rodent hunting).

Participants were also asked about the number of residential moves between birth and age 15, date and place of birth, lifetime history of head trauma, and tobacco smoking history.

Rodent-hunting cat ownership was associated with higher risk of psychosis in male participants, compared with owning no cat or a nonhunting cat. When the investigators added head trauma and residential moves to rodent-hunting cat ownership, psychosis risk was elevated in both men and women.

Independent of cat ownership, younger age, moving more than three times as a child, a history of head trauma, and being a smoker were all associated with higher psychosis risk.

King_Suzanne_CAN_web.jpg

The study wasn’t designed to explore potential biological mechanisms to explain the sex differences in psychosis risk seen among rodent-hunting cat owners, but “one possible explanation based on the animal model literature is that the neurobiological effects of parasitic exposure may be greater with male sex,” senior author Suzanne King, PhD, professor of psychiatry at McGill, said in an interview.

The new study is part of a larger, long-term project called EnviroGen, led by Dr. King, examining the environmental and genetic risk factors for schizophrenia.
 

Need for replication

Commenting on the findings, E. Fuller Torrey, MD, who was among the first researchers to identify a link between cat ownership, T. gondii infection, and schizophrenia, said the study is “an interesting addition to the studies of cat ownership in childhood as a risk factor for psychosis.”

Of the approximately 10 published studies on the topic, about half suggest a link between cat ownership and psychosis later in life, said Dr. Torrey, associate director for research at the Stanley Medical Research Institute in Rockville, Md.

“The Canadian study is interesting in that it is the first study that separates exposure to permanently indoor cats from cats that are allowed to go outdoors, and the results were positive only for outdoor cats,” Dr. Torrey said.

The study has limitations, Dr. Torrey added, including its retrospective design and the use of a self-report questionnaire to assess psychotic experiences in adulthood.

Also commenting on findings, James Kirkbride, PhD, professor of psychiatric and social epidemiology, University College London, noted the same limitations.

Dr. Kirkbride is the lead author of a 2017 study that showed no link between cat ownership and serious mental illness that included nearly 5,000 people born in 1991 or 1992 and followed until age 18. In this study, there was no link between psychosis and cat ownership during pregnancy or at ages 4 or 10 years.

“Researchers have long been fascinated with the idea that cat ownership may affect mental health. This paper may have them chasing their own tail,” Dr. Kirkbride said.

“Evidence of any association is limited to certain subgroups without a strong theoretical basis for why this may be the case,” he added. “The retrospective and cross-sectional nature of the survey also raise the possibility that the results are impacted by differential recall bias, as well as the broader issues of chance and unobserved confounding.”

Dr. King noted that recall bias is a limitation the researchers highlighted in their study, but “considering the exposures are relatively objective and factual, we do not believe the potential for recall bias is substantial.”

“Nonetheless, we strongly believe that replication of our results in prospective, population-representative cohorts will be crucial to making firmer conclusions,” he added.

The study was funded by grants from the Quebec Health Research Fund. The study authors and Dr. Kirkbride disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Owning an outdoor cat as a child is associated with an increased risk of psychotic experiences in adulthood – but only in males, new research suggests.

Investigators found male children who owned cats that went outside had a small, but significantly increased, risk of psychotic experiences in adulthood, compared with their counterparts who had no cat during childhood or who had an indoor cat.

Paquin_Vincent_CAN_web.jpg

The suspected culprit is not the cat itself but rather exposure to Toxoplasma gondii, a common parasite carried by rodents and sometimes found in cat feces. The study adds to a growing evidence showing exposure to T. gondii may be a risk factor for schizophrenia and other psychotic disorders.

“These are small pieces of evidence but it’s interesting to consider that there might be combinations of risk factors at play,” lead author Vincent Paquin, MD, psychiatry resident at McGill University, Montreal, said in an interview.

“And even if the magnitude of the risk is small at the individual level,” he added, “cats and Toxoplasma gondii are so present in our society that if we add up all these small potential effects then it becomes a potential public health question.”

The study was published online Jan. 30, 2022, in the Journal of Psychiatric Research.
 

Inconsistent evidence

T. gondii infects about 30% of the human population and is usually transmitted by cats. Most infections are asymptomatic, but T. gondii can cause toxoplasmosis in humans, which has been linked to increased risk of schizophrenia, suicide attempts, and more recently, mild cognitive impairment.

Although some studies show an association between cat ownership and increased risk of mental illness, the research findings have been inconsistent.

“The evidence has been mixed about the association between cat ownership and psychosis expression, so our approach was to consider whether specific factors or combinations of factors could explain this mixed evidence,” Dr. Paquin said.

For the study, 2206 individuals aged 18-40 years completed the Community Assessment of Psychic Experiences (CAPE-42) and a questionnaire to gather information about cat ownership at any time between birth and age 13 and if the cats lived exclusively indoors (nonhunting) or if they were allowed outside (rodent hunting).

Participants were also asked about the number of residential moves between birth and age 15, date and place of birth, lifetime history of head trauma, and tobacco smoking history.

Rodent-hunting cat ownership was associated with higher risk of psychosis in male participants, compared with owning no cat or a nonhunting cat. When the investigators added head trauma and residential moves to rodent-hunting cat ownership, psychosis risk was elevated in both men and women.

Independent of cat ownership, younger age, moving more than three times as a child, a history of head trauma, and being a smoker were all associated with higher psychosis risk.

King_Suzanne_CAN_web.jpg

The study wasn’t designed to explore potential biological mechanisms to explain the sex differences in psychosis risk seen among rodent-hunting cat owners, but “one possible explanation based on the animal model literature is that the neurobiological effects of parasitic exposure may be greater with male sex,” senior author Suzanne King, PhD, professor of psychiatry at McGill, said in an interview.

The new study is part of a larger, long-term project called EnviroGen, led by Dr. King, examining the environmental and genetic risk factors for schizophrenia.
 

Need for replication

Commenting on the findings, E. Fuller Torrey, MD, who was among the first researchers to identify a link between cat ownership, T. gondii infection, and schizophrenia, said the study is “an interesting addition to the studies of cat ownership in childhood as a risk factor for psychosis.”

Of the approximately 10 published studies on the topic, about half suggest a link between cat ownership and psychosis later in life, said Dr. Torrey, associate director for research at the Stanley Medical Research Institute in Rockville, Md.

“The Canadian study is interesting in that it is the first study that separates exposure to permanently indoor cats from cats that are allowed to go outdoors, and the results were positive only for outdoor cats,” Dr. Torrey said.

The study has limitations, Dr. Torrey added, including its retrospective design and the use of a self-report questionnaire to assess psychotic experiences in adulthood.

Also commenting on findings, James Kirkbride, PhD, professor of psychiatric and social epidemiology, University College London, noted the same limitations.

Dr. Kirkbride is the lead author of a 2017 study that showed no link between cat ownership and serious mental illness that included nearly 5,000 people born in 1991 or 1992 and followed until age 18. In this study, there was no link between psychosis and cat ownership during pregnancy or at ages 4 or 10 years.

“Researchers have long been fascinated with the idea that cat ownership may affect mental health. This paper may have them chasing their own tail,” Dr. Kirkbride said.

“Evidence of any association is limited to certain subgroups without a strong theoretical basis for why this may be the case,” he added. “The retrospective and cross-sectional nature of the survey also raise the possibility that the results are impacted by differential recall bias, as well as the broader issues of chance and unobserved confounding.”

Dr. King noted that recall bias is a limitation the researchers highlighted in their study, but “considering the exposures are relatively objective and factual, we do not believe the potential for recall bias is substantial.”

“Nonetheless, we strongly believe that replication of our results in prospective, population-representative cohorts will be crucial to making firmer conclusions,” he added.

The study was funded by grants from the Quebec Health Research Fund. The study authors and Dr. Kirkbride disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The recently published “Clinical Practice Guidelines for the Prevention and Management of Tick-Borne Illness,” from the Wilderness Medical Society, are a good compilation of treatment suggestions but are not, in fact, new recommendations, lead author Benjamin Ho, MD, of Southern Wisconsin Emergency Associates in Janesville, acknowledged in an interview.

Dr. Ho emphasized that the focus of the report was on “practitioners who practice in resource-limited settings” and are “the group’s way of solidifying a ... standard of practice” for such physicians. Dr. Ho also said that, while “a lot of the recommendations aren’t well supported, the risk-benefit ratio, we believe, supports the recommendations.”

The article first reviewed the different types of ticks and their distribution in the United States, the specific pathogen associated with each, the disease it causes, and comments about seasonal variations in biting behavior. Another table outlines the most common clinical syndromes, typical lab findings, recommended diagnostic testing, and antibiotic treatments. A third section contains images of different types of ticks and photos of ticks in various life-cycle stages and different levels of engorgement.

The authors were careful to note: “Several tick species are able to carry multiple pathogens. In one study, nearly 25% of Ixodes were coinfected with some combination of the bacteria or parasites causing Lyme disease, anaplasmosis, or babesiosis. Although TBI [tick-borne illness] diagnosis is not the focus of this [clinical practice guideline], providers should be aware of high rates of coinfection; the presence of one TBI should in many instances prompt testing for others.”

In terms of recommendations for preventing TBIs, the authors challenge the suggestion of wearing light-colored clothing. For repellents, they recommend DEET, picaridin, and permethrin. And they also give instructions for laundering clothing and removing ticks.

[embed:render:related:node:233159]

One recommendation is controversial: that of providing single-dose doxycycline as prophylaxis against Lyme disease. Dr. Ho stresses that this was only for “high-risk” tick bites, defined as a tick bite from an identified Ixodes vector species in which the tick was attached for at least 36 hours and that occurred in an endemic area.

The recommendation for prophylactic doxycycline originated with an article by Robert Nadelman and colleagues in the New England Journal of Medicine and has been strongly challenged by ILADS (International Lyme and Associated Diseases Society) physicians, including Daniel Cameron, MD, and others.

Sam Donta, MD, a recent member of the Department of Health & Human Services Tick-borne Working Group and a member of the Infectious Disease Society of America, said in an interview: “The problem with the one-dose doxycycline is you may not begin to develop symptoms until 2 months later.” It might mask the early symptoms of Lyme. “My impression is that the doxycycline – even the single dose – might have abrogated the ability to see an immune response. The idea, though, if you’ve had a tick bite, is to do nothing and to wait for symptoms to develop. That becomes a little bit more complex. But even then, you could choose to follow the patient and see the patient in 2 weeks and then get blood testing.”

Dr. Donta added: “I think the screening test is inadequate. So you have to go directly to the Western blot. And you have to do both the IgM and IgG” and look for specific bands.

Dr. Donta emphasized that patients should be encouraged to save any ticks that were attached and that, if at all possible, ticks should be sent to a reference lab for testing before committing a patient to a course of antibiotics. There is no harm in that brief delay, he said, and most labs can identify an array of pathogens.

The Wilderness Society guidelines on TBIs provide a good overview for clinicians practicing in limited resource settings and mirror those from the IDSA.

Dr. Ho and Dr. Donta reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The recently published “Clinical Practice Guidelines for the Prevention and Management of Tick-Borne Illness,” from the Wilderness Medical Society, are a good compilation of treatment suggestions but are not, in fact, new recommendations, lead author Benjamin Ho, MD, of Southern Wisconsin Emergency Associates in Janesville, acknowledged in an interview.

Dr. Ho emphasized that the focus of the report was on “practitioners who practice in resource-limited settings” and are “the group’s way of solidifying a ... standard of practice” for such physicians. Dr. Ho also said that, while “a lot of the recommendations aren’t well supported, the risk-benefit ratio, we believe, supports the recommendations.”

The article first reviewed the different types of ticks and their distribution in the United States, the specific pathogen associated with each, the disease it causes, and comments about seasonal variations in biting behavior. Another table outlines the most common clinical syndromes, typical lab findings, recommended diagnostic testing, and antibiotic treatments. A third section contains images of different types of ticks and photos of ticks in various life-cycle stages and different levels of engorgement.

The authors were careful to note: “Several tick species are able to carry multiple pathogens. In one study, nearly 25% of Ixodes were coinfected with some combination of the bacteria or parasites causing Lyme disease, anaplasmosis, or babesiosis. Although TBI [tick-borne illness] diagnosis is not the focus of this [clinical practice guideline], providers should be aware of high rates of coinfection; the presence of one TBI should in many instances prompt testing for others.”

In terms of recommendations for preventing TBIs, the authors challenge the suggestion of wearing light-colored clothing. For repellents, they recommend DEET, picaridin, and permethrin. And they also give instructions for laundering clothing and removing ticks.

[embed:render:related:node:233159]

One recommendation is controversial: that of providing single-dose doxycycline as prophylaxis against Lyme disease. Dr. Ho stresses that this was only for “high-risk” tick bites, defined as a tick bite from an identified Ixodes vector species in which the tick was attached for at least 36 hours and that occurred in an endemic area.

The recommendation for prophylactic doxycycline originated with an article by Robert Nadelman and colleagues in the New England Journal of Medicine and has been strongly challenged by ILADS (International Lyme and Associated Diseases Society) physicians, including Daniel Cameron, MD, and others.

Sam Donta, MD, a recent member of the Department of Health & Human Services Tick-borne Working Group and a member of the Infectious Disease Society of America, said in an interview: “The problem with the one-dose doxycycline is you may not begin to develop symptoms until 2 months later.” It might mask the early symptoms of Lyme. “My impression is that the doxycycline – even the single dose – might have abrogated the ability to see an immune response. The idea, though, if you’ve had a tick bite, is to do nothing and to wait for symptoms to develop. That becomes a little bit more complex. But even then, you could choose to follow the patient and see the patient in 2 weeks and then get blood testing.”

Dr. Donta added: “I think the screening test is inadequate. So you have to go directly to the Western blot. And you have to do both the IgM and IgG” and look for specific bands.

Dr. Donta emphasized that patients should be encouraged to save any ticks that were attached and that, if at all possible, ticks should be sent to a reference lab for testing before committing a patient to a course of antibiotics. There is no harm in that brief delay, he said, and most labs can identify an array of pathogens.

The Wilderness Society guidelines on TBIs provide a good overview for clinicians practicing in limited resource settings and mirror those from the IDSA.

Dr. Ho and Dr. Donta reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The recently published “Clinical Practice Guidelines for the Prevention and Management of Tick-Borne Illness,” from the Wilderness Medical Society, are a good compilation of treatment suggestions but are not, in fact, new recommendations, lead author Benjamin Ho, MD, of Southern Wisconsin Emergency Associates in Janesville, acknowledged in an interview.

Dr. Ho emphasized that the focus of the report was on “practitioners who practice in resource-limited settings” and are “the group’s way of solidifying a ... standard of practice” for such physicians. Dr. Ho also said that, while “a lot of the recommendations aren’t well supported, the risk-benefit ratio, we believe, supports the recommendations.”

The article first reviewed the different types of ticks and their distribution in the United States, the specific pathogen associated with each, the disease it causes, and comments about seasonal variations in biting behavior. Another table outlines the most common clinical syndromes, typical lab findings, recommended diagnostic testing, and antibiotic treatments. A third section contains images of different types of ticks and photos of ticks in various life-cycle stages and different levels of engorgement.

The authors were careful to note: “Several tick species are able to carry multiple pathogens. In one study, nearly 25% of Ixodes were coinfected with some combination of the bacteria or parasites causing Lyme disease, anaplasmosis, or babesiosis. Although TBI [tick-borne illness] diagnosis is not the focus of this [clinical practice guideline], providers should be aware of high rates of coinfection; the presence of one TBI should in many instances prompt testing for others.”

In terms of recommendations for preventing TBIs, the authors challenge the suggestion of wearing light-colored clothing. For repellents, they recommend DEET, picaridin, and permethrin. And they also give instructions for laundering clothing and removing ticks.

[embed:render:related:node:233159]

One recommendation is controversial: that of providing single-dose doxycycline as prophylaxis against Lyme disease. Dr. Ho stresses that this was only for “high-risk” tick bites, defined as a tick bite from an identified Ixodes vector species in which the tick was attached for at least 36 hours and that occurred in an endemic area.

The recommendation for prophylactic doxycycline originated with an article by Robert Nadelman and colleagues in the New England Journal of Medicine and has been strongly challenged by ILADS (International Lyme and Associated Diseases Society) physicians, including Daniel Cameron, MD, and others.

Sam Donta, MD, a recent member of the Department of Health & Human Services Tick-borne Working Group and a member of the Infectious Disease Society of America, said in an interview: “The problem with the one-dose doxycycline is you may not begin to develop symptoms until 2 months later.” It might mask the early symptoms of Lyme. “My impression is that the doxycycline – even the single dose – might have abrogated the ability to see an immune response. The idea, though, if you’ve had a tick bite, is to do nothing and to wait for symptoms to develop. That becomes a little bit more complex. But even then, you could choose to follow the patient and see the patient in 2 weeks and then get blood testing.”

Dr. Donta added: “I think the screening test is inadequate. So you have to go directly to the Western blot. And you have to do both the IgM and IgG” and look for specific bands.

Dr. Donta emphasized that patients should be encouraged to save any ticks that were attached and that, if at all possible, ticks should be sent to a reference lab for testing before committing a patient to a course of antibiotics. There is no harm in that brief delay, he said, and most labs can identify an array of pathogens.

The Wilderness Society guidelines on TBIs provide a good overview for clinicians practicing in limited resource settings and mirror those from the IDSA.

Dr. Ho and Dr. Donta reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A Maryland woman came down with a severe tropical infection called melioidosis from her freshwater home aquarium, says a report in Emerging Infectious Diseases describing a new route of transmission. Melioidosis is caused by the bacteria Burkholderia pseudomallei in soil or water.

Until last year, almost all U.S. cases of melioidosis were from people who lived or traveled to disease-endemic areas. It has been a rare infection in the United States.

But this is not the first case of melioidosis from an unusual source. Earlier in 2021, CDC and state epidemiologists traced an outbreak of melioidosis in Georgia, Kansas, Minnesota, and Texas to B pseudomallei in a bottle of “Better Homes & Gardens Lavender & Chamomile Essential Oil Infused Aromatherapy Room Spray with Gemstones.”

In the aquarium case, the patient was a 56-year-old woman with diabetes and rheumatologic disease. She had been on immunosuppressives (methotrexate, azathioprine, and prednisone) until 1 month before she became symptomatic. She was hospitalized for fever and pneumonia.

Multiple blood cultures obtained on days 1-4 grew B. pseudomallei, but she had no evidence of endocarditis or intravascular seeding. Despite weeks of meropenem (Merrem), she developed evidence of a lung abscess, and trimethoprim/sulfamethoxazole (Bactrim) was added. Ultimately, the patient required a 12-week course of antibiotics.

CDC epidemiologist Patrick Dawson, PhD, first author of the report, told this news organization that although outbreak investigators always ask about pet ownership, they have not explicitly asked about fish. In this case, the patient did not volunteer exposure to the fish.

When state epidemiologists visited the patient’s home, “one of the first things they saw was a few aquariums,” Dr. Dawson said. Seeing the water and knowing “that most freshwater tropical fish in the U.S. are imported from Southeast Asia” led them to culture specifically for B. pseudomallei, which can be difficult for the microbiology lab to identify.

From there, Dr. Dawson explained, “The Maryland Department of Health sent a team to the local pet store” but did not find any of the bacteria there. (The patient had bought her fish 6 months earlier.) The investigators then worked with the national brand “to identify where they had actually sourced the fish from.”

Two retailers supply almost all of U.S. guppies and plants. While investigators could not find an exact matching isolate after so many months had elapsed, they found a positive PCR for B. pseudomallei in a water sample from imported fish in Los Angeles.

Dr. Dawson said tropical fish are imported from southeast Asia and typically come from small family fish farms. The fish import industry has “certain products that they add to the water to hopefully kill any bacteria.” He was unaware whether this included antibiotics but suggested, “we would have seen many more cases [of antibiotic resistance] by now” if it did.

In general advice for the public, Dr. Dawson said, “I would recommend washing hands before and after contact with the aquarium. If you have cuts or wounds on your hands, it’s really important to wear gloves if you have to go clean or maintain the aquarium and you’re putting your hands in the water, just for that extra layer of protection. It’s probably a strong idea to just avoid that altogether if someone’s immunocompromised. And not letting young children under 5 years old clean aquariums.” These are the “simplest things to do to protect yourself.”

Stephen A. Smith, DVM, PhD, a professor in the Aquatic Medicine Program at Virginia-Maryland College of Veterinary Medicine, Blacksburg, also stressed the importance of careful hand hygiene when caring for aquariums. He said that the filter, filter floss, biofilm, charcoal, and gravel might have exceptionally high concentrations of bacteria. Dr. Smith also recommended gloves when cleaning aquariums and not doing this task if immunocompromised.

Dr. Smith, who was not involved in the CDC study, shared a broader perspective, noting that “the reason why it’s important to federal regulators is that [B. pseudomallei] is a tier 1 select agent. And so, when that was isolated, it sent up all the red flags.” The far more common Mycobacterium marinum, or fish handler’s disease, is not reportable.

Mycobacterium marinum is another pathogen of concern that can be acquired from aquariums. These infections typically occur as nodular lesions on the arms and require months of therapy.

Dr. Smith stressed the importance of physicians eliciting a careful exposure history as the key to diagnosing zoonoses. For most exotic aquarium animals, he noted, “They’re caught in the wild wherever they are. They’re transported to a major hub to transport to the U.S., and a lot of times, we don’t have quarantine for those animals.”

Aquatic zoonoses (infections from water) are important because an estimated 11.5 million U.S. households have pet fish, totaling about 139 million freshwater fish, Dr. Smith said.

Many infections also occur in the course of water sports – or even hiking and getting a cut or abrasion wet from a stream or lake. Aeromonas hydrophila can cause life-threatening infections. Vibrio vulnificus infections from salt-water injuries can cause sepsis and characteristic hemorrhagic bullae – large, discolored blisters filled with body fluid – during the summer. And eating contaminated shellfish has a 50%-60% death rate.

Other exposures to water-loving bacteria happen during fishing or cleaning/preparing fish. For example, Streptococcus iniae has caused cellulitis, arthritis, endocarditis, and meningitis following superficial or puncture injuries, notably from cleaning tilapia.

Other infections from contact with fish include Erysipelothrix rhusiopathiae (primarily skin infections) and gastroenteritis from Plesiomonas shigelloides, Campylobacter spp, and Salmonella spp.

Each of these zoonoses illustrates the importance of a careful exposure history when there’s an atypical presentation or an infection that is not responding promptly to empiric treatment. The aquarium case broadens the differential to include melioidosis, a serious disease from southeast Asia.

Dr. Dawson and Dr. Smith have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A Maryland woman came down with a severe tropical infection called melioidosis from her freshwater home aquarium, says a report in Emerging Infectious Diseases describing a new route of transmission. Melioidosis is caused by the bacteria Burkholderia pseudomallei in soil or water.

Until last year, almost all U.S. cases of melioidosis were from people who lived or traveled to disease-endemic areas. It has been a rare infection in the United States.

But this is not the first case of melioidosis from an unusual source. Earlier in 2021, CDC and state epidemiologists traced an outbreak of melioidosis in Georgia, Kansas, Minnesota, and Texas to B pseudomallei in a bottle of “Better Homes & Gardens Lavender & Chamomile Essential Oil Infused Aromatherapy Room Spray with Gemstones.”

In the aquarium case, the patient was a 56-year-old woman with diabetes and rheumatologic disease. She had been on immunosuppressives (methotrexate, azathioprine, and prednisone) until 1 month before she became symptomatic. She was hospitalized for fever and pneumonia.

Multiple blood cultures obtained on days 1-4 grew B. pseudomallei, but she had no evidence of endocarditis or intravascular seeding. Despite weeks of meropenem (Merrem), she developed evidence of a lung abscess, and trimethoprim/sulfamethoxazole (Bactrim) was added. Ultimately, the patient required a 12-week course of antibiotics.

CDC epidemiologist Patrick Dawson, PhD, first author of the report, told this news organization that although outbreak investigators always ask about pet ownership, they have not explicitly asked about fish. In this case, the patient did not volunteer exposure to the fish.

When state epidemiologists visited the patient’s home, “one of the first things they saw was a few aquariums,” Dr. Dawson said. Seeing the water and knowing “that most freshwater tropical fish in the U.S. are imported from Southeast Asia” led them to culture specifically for B. pseudomallei, which can be difficult for the microbiology lab to identify.

From there, Dr. Dawson explained, “The Maryland Department of Health sent a team to the local pet store” but did not find any of the bacteria there. (The patient had bought her fish 6 months earlier.) The investigators then worked with the national brand “to identify where they had actually sourced the fish from.”

Two retailers supply almost all of U.S. guppies and plants. While investigators could not find an exact matching isolate after so many months had elapsed, they found a positive PCR for B. pseudomallei in a water sample from imported fish in Los Angeles.

Dr. Dawson said tropical fish are imported from southeast Asia and typically come from small family fish farms. The fish import industry has “certain products that they add to the water to hopefully kill any bacteria.” He was unaware whether this included antibiotics but suggested, “we would have seen many more cases [of antibiotic resistance] by now” if it did.

In general advice for the public, Dr. Dawson said, “I would recommend washing hands before and after contact with the aquarium. If you have cuts or wounds on your hands, it’s really important to wear gloves if you have to go clean or maintain the aquarium and you’re putting your hands in the water, just for that extra layer of protection. It’s probably a strong idea to just avoid that altogether if someone’s immunocompromised. And not letting young children under 5 years old clean aquariums.” These are the “simplest things to do to protect yourself.”

Stephen A. Smith, DVM, PhD, a professor in the Aquatic Medicine Program at Virginia-Maryland College of Veterinary Medicine, Blacksburg, also stressed the importance of careful hand hygiene when caring for aquariums. He said that the filter, filter floss, biofilm, charcoal, and gravel might have exceptionally high concentrations of bacteria. Dr. Smith also recommended gloves when cleaning aquariums and not doing this task if immunocompromised.

Dr. Smith, who was not involved in the CDC study, shared a broader perspective, noting that “the reason why it’s important to federal regulators is that [B. pseudomallei] is a tier 1 select agent. And so, when that was isolated, it sent up all the red flags.” The far more common Mycobacterium marinum, or fish handler’s disease, is not reportable.

Mycobacterium marinum is another pathogen of concern that can be acquired from aquariums. These infections typically occur as nodular lesions on the arms and require months of therapy.

Dr. Smith stressed the importance of physicians eliciting a careful exposure history as the key to diagnosing zoonoses. For most exotic aquarium animals, he noted, “They’re caught in the wild wherever they are. They’re transported to a major hub to transport to the U.S., and a lot of times, we don’t have quarantine for those animals.”

Aquatic zoonoses (infections from water) are important because an estimated 11.5 million U.S. households have pet fish, totaling about 139 million freshwater fish, Dr. Smith said.

Many infections also occur in the course of water sports – or even hiking and getting a cut or abrasion wet from a stream or lake. Aeromonas hydrophila can cause life-threatening infections. Vibrio vulnificus infections from salt-water injuries can cause sepsis and characteristic hemorrhagic bullae – large, discolored blisters filled with body fluid – during the summer. And eating contaminated shellfish has a 50%-60% death rate.

Other exposures to water-loving bacteria happen during fishing or cleaning/preparing fish. For example, Streptococcus iniae has caused cellulitis, arthritis, endocarditis, and meningitis following superficial or puncture injuries, notably from cleaning tilapia.

Other infections from contact with fish include Erysipelothrix rhusiopathiae (primarily skin infections) and gastroenteritis from Plesiomonas shigelloides, Campylobacter spp, and Salmonella spp.

Each of these zoonoses illustrates the importance of a careful exposure history when there’s an atypical presentation or an infection that is not responding promptly to empiric treatment. The aquarium case broadens the differential to include melioidosis, a serious disease from southeast Asia.

Dr. Dawson and Dr. Smith have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A Maryland woman came down with a severe tropical infection called melioidosis from her freshwater home aquarium, says a report in Emerging Infectious Diseases describing a new route of transmission. Melioidosis is caused by the bacteria Burkholderia pseudomallei in soil or water.

Until last year, almost all U.S. cases of melioidosis were from people who lived or traveled to disease-endemic areas. It has been a rare infection in the United States.

But this is not the first case of melioidosis from an unusual source. Earlier in 2021, CDC and state epidemiologists traced an outbreak of melioidosis in Georgia, Kansas, Minnesota, and Texas to B pseudomallei in a bottle of “Better Homes & Gardens Lavender & Chamomile Essential Oil Infused Aromatherapy Room Spray with Gemstones.”

In the aquarium case, the patient was a 56-year-old woman with diabetes and rheumatologic disease. She had been on immunosuppressives (methotrexate, azathioprine, and prednisone) until 1 month before she became symptomatic. She was hospitalized for fever and pneumonia.

Multiple blood cultures obtained on days 1-4 grew B. pseudomallei, but she had no evidence of endocarditis or intravascular seeding. Despite weeks of meropenem (Merrem), she developed evidence of a lung abscess, and trimethoprim/sulfamethoxazole (Bactrim) was added. Ultimately, the patient required a 12-week course of antibiotics.

CDC epidemiologist Patrick Dawson, PhD, first author of the report, told this news organization that although outbreak investigators always ask about pet ownership, they have not explicitly asked about fish. In this case, the patient did not volunteer exposure to the fish.

When state epidemiologists visited the patient’s home, “one of the first things they saw was a few aquariums,” Dr. Dawson said. Seeing the water and knowing “that most freshwater tropical fish in the U.S. are imported from Southeast Asia” led them to culture specifically for B. pseudomallei, which can be difficult for the microbiology lab to identify.

From there, Dr. Dawson explained, “The Maryland Department of Health sent a team to the local pet store” but did not find any of the bacteria there. (The patient had bought her fish 6 months earlier.) The investigators then worked with the national brand “to identify where they had actually sourced the fish from.”

Two retailers supply almost all of U.S. guppies and plants. While investigators could not find an exact matching isolate after so many months had elapsed, they found a positive PCR for B. pseudomallei in a water sample from imported fish in Los Angeles.

Dr. Dawson said tropical fish are imported from southeast Asia and typically come from small family fish farms. The fish import industry has “certain products that they add to the water to hopefully kill any bacteria.” He was unaware whether this included antibiotics but suggested, “we would have seen many more cases [of antibiotic resistance] by now” if it did.

In general advice for the public, Dr. Dawson said, “I would recommend washing hands before and after contact with the aquarium. If you have cuts or wounds on your hands, it’s really important to wear gloves if you have to go clean or maintain the aquarium and you’re putting your hands in the water, just for that extra layer of protection. It’s probably a strong idea to just avoid that altogether if someone’s immunocompromised. And not letting young children under 5 years old clean aquariums.” These are the “simplest things to do to protect yourself.”

Stephen A. Smith, DVM, PhD, a professor in the Aquatic Medicine Program at Virginia-Maryland College of Veterinary Medicine, Blacksburg, also stressed the importance of careful hand hygiene when caring for aquariums. He said that the filter, filter floss, biofilm, charcoal, and gravel might have exceptionally high concentrations of bacteria. Dr. Smith also recommended gloves when cleaning aquariums and not doing this task if immunocompromised.

Dr. Smith, who was not involved in the CDC study, shared a broader perspective, noting that “the reason why it’s important to federal regulators is that [B. pseudomallei] is a tier 1 select agent. And so, when that was isolated, it sent up all the red flags.” The far more common Mycobacterium marinum, or fish handler’s disease, is not reportable.

Mycobacterium marinum is another pathogen of concern that can be acquired from aquariums. These infections typically occur as nodular lesions on the arms and require months of therapy.

Dr. Smith stressed the importance of physicians eliciting a careful exposure history as the key to diagnosing zoonoses. For most exotic aquarium animals, he noted, “They’re caught in the wild wherever they are. They’re transported to a major hub to transport to the U.S., and a lot of times, we don’t have quarantine for those animals.”

Aquatic zoonoses (infections from water) are important because an estimated 11.5 million U.S. households have pet fish, totaling about 139 million freshwater fish, Dr. Smith said.

Many infections also occur in the course of water sports – or even hiking and getting a cut or abrasion wet from a stream or lake. Aeromonas hydrophila can cause life-threatening infections. Vibrio vulnificus infections from salt-water injuries can cause sepsis and characteristic hemorrhagic bullae – large, discolored blisters filled with body fluid – during the summer. And eating contaminated shellfish has a 50%-60% death rate.

Other exposures to water-loving bacteria happen during fishing or cleaning/preparing fish. For example, Streptococcus iniae has caused cellulitis, arthritis, endocarditis, and meningitis following superficial or puncture injuries, notably from cleaning tilapia.

Other infections from contact with fish include Erysipelothrix rhusiopathiae (primarily skin infections) and gastroenteritis from Plesiomonas shigelloides, Campylobacter spp, and Salmonella spp.

Each of these zoonoses illustrates the importance of a careful exposure history when there’s an atypical presentation or an infection that is not responding promptly to empiric treatment. The aquarium case broadens the differential to include melioidosis, a serious disease from southeast Asia.

Dr. Dawson and Dr. Smith have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Years ago, when rheumatologist Leonard Sigal, MD, was undertaking research on Lyme disease and treating patients with the condition at the Robert Wood Johnson Medical School, New Brunswick, N.J., a regular stream of abuse and threats became the usual background noise of his work. He didn’t get used to it, but it never stopped.

Lyme_tick_CDC_photo_web.jpg

“I was accused of incredibly heinous crimes,” Dr. Sigal said in an interview. “I was accused of lying, cheating, of doing things to make money that were against the public interest and against the interest of patients in general.”

It’s an experience many doctors who treat Lyme disease have endured, so much so that some infectious disease doctors aren’t comfortable treating patients with Lyme disease, according to Timothy Flanigan, MD, a professor of infectious disease at Brown University, Providence, R.I.

But it wasn’t until Dr. Sigal left academia in 2003 that he realized the toll all that background abuse had been taking on him.

“It was a breath of fresh air,” he said. “I didn’t have to go into clinic and argue with people. I didn’t have to read articles in the newspaper that made no sense whatsoever. I didn’t have to hear through second and third parties how such and such was saying horrible things about me. I didn’t have to fight anymore. When I was in industry and working on stuff that had nothing to do with Lyme disease, I realized what a relief it was not to have that burden.”

Sigal_Leonard_MA_web.jpg

So the last thing Dr. Sigal expected after all these years was to find himself named in a lawsuit alleging that he was part of a conspiracy to deny patients of what they claimed was appropriate treatment for Lyme disease. Yet, that’s exactly what happened in November 2017, when a group of 24 patients with Lyme disease, led by Texas resident Lisa Torrey, filed a lawsuit against the Infectious Diseases Society of America, eight insurance companies, and 7 of the doctors involved in producing the IDSA guidelines on Lyme disease diagnosis and management. Dr. Sigal himself had not even participated in writing the guidelines. He simply reviewed them, made a few grammatical suggestions, and said they looked good. Over the next 4 years, however, he and his fellow defendants rode an emotional roller coaster of seemingly endless motions, amendments, and other legal developments, waiting to find out whether they would owe millions of dollars for simply summarizing – or just reviewing – the available medical literature on Lyme disease.

“There were times I was on the verge of real anger. I was frustrated. There were times I was frightened, and, occasionally, I would just think of it as being silly. But when I thought of it as being silly, I had to remember I was being sued in Texas, because who knows what’s going to happen,” Dr. Sigal said. “It’s not as though I was being sued in a jurisdiction where anybody knew about Lyme disease. There are examples of physicians who are convicted of doing things they didn’t do because they were sued in the wrong jurisdiction.”

Several individuals who spoke with this news organization on condition of anonymity said that the district court where the suit was filed is notorious for being especially friendly to plaintiffs. But in legal rulings issued on Sept. 1 and Sept. 20, 2021, a federal judge in Texas dismissed all the patient group’s claims. The plaintiffs filed an appeal on Oct. 19. It’s unclear whether that has any reasonable chance of success.

McQuillen_Daniel_P_MA_web.jpg

“One of the things this court case does is validate the fact that our [guidelines] process is a legitimate process and there isn’t outside influence from insurance companies or pharma firms,” Daniel McQuillen, MD, president of IDSA, said in an interview. “We don’t really want anything other than to be vindicated, which we were, 100%.”

But that vindication came with a cost, both emotional and financial. Although IDSA’s insurance covered many of its legal costs, “it’s not a trivial expense,” Dr. McQuillen said. “We’re left with a baseless lawsuit with no facts that went on for 4 years, and our [medical] society basically bore all that expense, which isn’t really particularly fair.”
 

‘Preposterous’ accusations

The lawsuit alleged that the IDSA, the seven named physicians, and the insurance companies had “engaged in a decades-long conspiracy to deny the existence and prevent treatment of chronic Lyme disease.” The patient group claimed that the doctors knew that many patients with Lyme disease do not respond to short-term antibiotic treatment and instead need “long-term antibiotic treatment until the symptoms are resolved,” an assertion not supported by the scientific evidence.

Flanigan_Timothy_RI_web.jpg

What many patients call “chronic Lyme disease” is termed posttreatment Lyme disease syndrome (PTDLS), a constellation of symptoms that include pain, fatigue, and cognitive difficulties that some people experience after a 2- to 4-week course of antibiotics for Lyme disease. It took years of patient advocacy before the Centers for Disease Control and Prevention recognized PTLDS as a condition, but awareness of it has been increasing, said Dr. Flanigan, who was not involved in the lawsuit but treats patients with Lyme disease and PTLDS.

“Long haulers and sequelae of COVID have really opened the eyes of many practitioners that these long-term inflammatory conditions are real and very challenging to treat, and we need to work with patients to help them improve their health,” Dr. Flanigan said. “It’s a sad commentary on our society that the difficulty in treating patients with posttreatment Lyme disease syndrome, or what is commonly referred to by patients as chronic Lyme, ends up in a lawsuit in court.” He said he’s glad the lawsuit was dismissed but added that “there’s a crying need for additional high-quality, evidence-based research to help patients who are suffering from posttreatment Lyme disease syndrome.”

Patients fought for broader recognition of their condition, and some of them organized. They came up with their own ideas of what was causing their symptoms to persist. One that especially took hold was that infection from Borrelia burgdorferi, the bacteria that causes Lyme disease, persists after initial antibiotic treatment, causing so-called chronic Lyme disease. The cause of PTLDS is still under investigation, and the evidence does not support the idea of a persistent bacterial infection. Multiple studies from the National Institutes of Health have shown that long-term use of antibiotics does not benefit patients who continue to experience symptoms after initial treatment. Several studies have shown that severe adverse effects can result from extended intravenous antibiotic treatment, including death.

[embed:render:related:node:233159]

Nevertheless, the plaintiffs in the lawsuit argued that the insurance companies “enlisted the help of doctors who were researching Lyme disease – the IDSA panelists – and paid them large fees to develop arbitrary guidelines for testing Lyme disease,” thereby enabling the insurance companies to deny coverage for long-term antibiotic treatment to patients.

“The assertions were just preposterous,” Dr. McQuillen said.

In addition to the conspiracy charge, the plaintiffs brought additional accusations to the lawsuit over the years, including racketeering and claims that the guidelines contain false representations regarding Lyme disease testing and treatment. The plaintiffs claimed that the guidelines didn’t acknowledge that treatment can fail and included false information about how to test for Lyme disease. In reality, however, the guidelines do acknowledge that not all patients respond to the recommended 2- to 4-week course of antibiotics and that some diagnoses should be made clinically rather than on the basis of testing.

Regardless, guidelines are not stipulations. They’re a summation of the medical and scientific findings on Lyme disease based on careful review of hundreds of studies.

“They make really clear that adherence to the guidelines [is] voluntary. They aren’t a standard of care from which deviation of care is a problem,” Dr. McQuillen said. “You take those guidelines and apply it to the patient in front of you, and you see what fits best for that patient, because not every patient is going to fit into guidelines.”

Further, the authors said that IDSA vets their recommendations for any potential conflicts of interest in accordance with the organization’s guidelines practices.

“The point of the guidelines is to have people on the committee who don’t care what the guidelines are as long as we have good patient care,” Dr. McQuillen said.

Choosing to fight

Malpractice insurance does not cover this kind of lawsuit, because the doctors named in it did not personally treat any of the patients who filed it. Thus, the doctors were at risk of losing thousands, or millions, of dollars in legal fees, even if they ultimately prevail. Several of the physicians’ academic and health care institutions stepped in to cover some fees, and IDSA covered the rest in a joint defense.

“The IDSA provided me a lawyer at no cost to me, and I felt protected by them,” Dr. Sigal said. “They took care of me and made sure I was safe, and I am grateful to them for that.”

Dr. McQuillen said the expenses exceeded what the organization’s umbrella insurance covered. The physicians had invested their time and effort into the guidelines without any financial compensation.

“They’ve basically put a lot of sweat equity into producing guidelines” that follow the organization’s practices and ethics, Dr. McQuillen said. “To leave them out on an island by themselves is just not the right thing to do. We wouldn’t do that for any of our members who did something on behalf of our society.”

IDSA could have chosen to settle the lawsuit, as the insurance companies did.

“None of us on the board felt that was the right thing to do, because we believe in the process, and the science is right, and you shouldn’t be able to try to change that by having a lawsuit that’s baseless,” Dr. McQuillen said.

Several of the doctors named in the suit spoke with this news organization off the record about the exhaustion, frustration, and general suffering the suit has caused them over the past several years, including ongoing harassment that targeted their families and often became quite personal. But none expressed any wish that IDSA had chosen the faster, cheaper, easier route of settling.

“I love the organization for having done this rather than caving and paying,” Dr. Sigal said. “They showed real moral character, real integrity in fighting this suit, because they had done nothing wrong.”

Fighting the suit was about more than standing by the science, though. It’s essential to ensure physicians continue to conduct research and write clinical guidelines, even about ambiguous or controversial topics, said Raymond J. Dattwyler, MD, a professor of microbiology, immunology, and medicine at New York Medical College, Valhalla, who wrote the treatment part of the guidelines and was named in the suit.

[embed:render:related:node:205511]

“I was really surprised that someone would sue for scientific guidelines, because guidelines are common across medicine, and they’re just a roadmap to help practicing physicians understand how to handle evaluation or treatment of any number of particular problems,” Dr. Dattwyler said in an interview. But he wasn’t surprised that IDSA chose to fight the accusations, “because the principle involved is so compelling. It’s really standing up for all medical societies, and it’s very important to have guidelines. For the health and welfare of the American public, you need to have good information readily available to the practicing physicians.”

If the patient group had won in a settlement, it could potentially have led to less rigorous guidelines from other medical organizations, which would have had an adverse effect on public health, Dr. Dattwyler said. Such a chilling effect could reverberate far beyond the management of Lyme disease.

“One of the problems with our legal system is anybody can sue anybody, but it costs so much to defend yourself,” Dr. Dattwyler said. “This lawsuit costs millions, so that’s chilling. That’s going to inhibit guidelines, and it’s not only guidelines for infectious disease but it’s guidelines for cancer, guidelines for allergic diseases, guidelines for any number of things.”

To an extent, the threats and harassment that patient groups have directed toward different doctors have already had a chilling effect.

“For the people who gave of their time in good faith to generate these guidelines to get harassed everywhere, all the time, sometimes at home, sometimes at their place of work, it’s just unfair,” Dr. McQuillen said. “It also might discourage people from working in research to try to figure out better diagnostics or get a vaccine that actually works. Even if you really find it incredibly interesting, if laying over you is the threat that someone is going to sue you baselessly, and you’re going to have to put the time and effort into defending that, not to mention the money, I can’t see how that would be considered a positive that would encourage you to do it. In some ways, attacking people that are trying to help may drive them away from trying to help.

“At the same time, professional disagreements among practitioners – including a small minority who do treat patients with lengthy courses of antibiotics – can ultimately harm patient care, Dr. Flanigan said.

“There’s a lot of energy being expended fighting among different care providers, and often the individual needs of the patients seem to be not addressed,” Dr. Flanigan said. “The discord between different approaches often seems more important than spending time with the individual patient and trying to find a tailored approach to treatment which can benefit the patient best.”

At the same time, Dr. Sigal said he believes most of the clinicians who use non–evidence-based treatments for their patients do so because they genuinely believe it’s the right thing to do.

“I think they’re motivated by the same concerns that I have, and that is, I need to do what’s best for my patient,” Dr. Sigal said. Ultimately, the evidence should lead the way. “The only arbiter we possibly have in deciding these things is the medical scientific literature,” he added, “and if you can’t subscribe to that, then this way lies madness.”

A version of this article first appeared on Medscape.com.

Years ago, when rheumatologist Leonard Sigal, MD, was undertaking research on Lyme disease and treating patients with the condition at the Robert Wood Johnson Medical School, New Brunswick, N.J., a regular stream of abuse and threats became the usual background noise of his work. He didn’t get used to it, but it never stopped.

Lyme_tick_CDC_photo_web.jpg

“I was accused of incredibly heinous crimes,” Dr. Sigal said in an interview. “I was accused of lying, cheating, of doing things to make money that were against the public interest and against the interest of patients in general.”

It’s an experience many doctors who treat Lyme disease have endured, so much so that some infectious disease doctors aren’t comfortable treating patients with Lyme disease, according to Timothy Flanigan, MD, a professor of infectious disease at Brown University, Providence, R.I.

But it wasn’t until Dr. Sigal left academia in 2003 that he realized the toll all that background abuse had been taking on him.

“It was a breath of fresh air,” he said. “I didn’t have to go into clinic and argue with people. I didn’t have to read articles in the newspaper that made no sense whatsoever. I didn’t have to hear through second and third parties how such and such was saying horrible things about me. I didn’t have to fight anymore. When I was in industry and working on stuff that had nothing to do with Lyme disease, I realized what a relief it was not to have that burden.”

Sigal_Leonard_MA_web.jpg

So the last thing Dr. Sigal expected after all these years was to find himself named in a lawsuit alleging that he was part of a conspiracy to deny patients of what they claimed was appropriate treatment for Lyme disease. Yet, that’s exactly what happened in November 2017, when a group of 24 patients with Lyme disease, led by Texas resident Lisa Torrey, filed a lawsuit against the Infectious Diseases Society of America, eight insurance companies, and 7 of the doctors involved in producing the IDSA guidelines on Lyme disease diagnosis and management. Dr. Sigal himself had not even participated in writing the guidelines. He simply reviewed them, made a few grammatical suggestions, and said they looked good. Over the next 4 years, however, he and his fellow defendants rode an emotional roller coaster of seemingly endless motions, amendments, and other legal developments, waiting to find out whether they would owe millions of dollars for simply summarizing – or just reviewing – the available medical literature on Lyme disease.

“There were times I was on the verge of real anger. I was frustrated. There were times I was frightened, and, occasionally, I would just think of it as being silly. But when I thought of it as being silly, I had to remember I was being sued in Texas, because who knows what’s going to happen,” Dr. Sigal said. “It’s not as though I was being sued in a jurisdiction where anybody knew about Lyme disease. There are examples of physicians who are convicted of doing things they didn’t do because they were sued in the wrong jurisdiction.”

Several individuals who spoke with this news organization on condition of anonymity said that the district court where the suit was filed is notorious for being especially friendly to plaintiffs. But in legal rulings issued on Sept. 1 and Sept. 20, 2021, a federal judge in Texas dismissed all the patient group’s claims. The plaintiffs filed an appeal on Oct. 19. It’s unclear whether that has any reasonable chance of success.

McQuillen_Daniel_P_MA_web.jpg

“One of the things this court case does is validate the fact that our [guidelines] process is a legitimate process and there isn’t outside influence from insurance companies or pharma firms,” Daniel McQuillen, MD, president of IDSA, said in an interview. “We don’t really want anything other than to be vindicated, which we were, 100%.”

But that vindication came with a cost, both emotional and financial. Although IDSA’s insurance covered many of its legal costs, “it’s not a trivial expense,” Dr. McQuillen said. “We’re left with a baseless lawsuit with no facts that went on for 4 years, and our [medical] society basically bore all that expense, which isn’t really particularly fair.”
 

‘Preposterous’ accusations

The lawsuit alleged that the IDSA, the seven named physicians, and the insurance companies had “engaged in a decades-long conspiracy to deny the existence and prevent treatment of chronic Lyme disease.” The patient group claimed that the doctors knew that many patients with Lyme disease do not respond to short-term antibiotic treatment and instead need “long-term antibiotic treatment until the symptoms are resolved,” an assertion not supported by the scientific evidence.

Flanigan_Timothy_RI_web.jpg

What many patients call “chronic Lyme disease” is termed posttreatment Lyme disease syndrome (PTDLS), a constellation of symptoms that include pain, fatigue, and cognitive difficulties that some people experience after a 2- to 4-week course of antibiotics for Lyme disease. It took years of patient advocacy before the Centers for Disease Control and Prevention recognized PTLDS as a condition, but awareness of it has been increasing, said Dr. Flanigan, who was not involved in the lawsuit but treats patients with Lyme disease and PTLDS.

“Long haulers and sequelae of COVID have really opened the eyes of many practitioners that these long-term inflammatory conditions are real and very challenging to treat, and we need to work with patients to help them improve their health,” Dr. Flanigan said. “It’s a sad commentary on our society that the difficulty in treating patients with posttreatment Lyme disease syndrome, or what is commonly referred to by patients as chronic Lyme, ends up in a lawsuit in court.” He said he’s glad the lawsuit was dismissed but added that “there’s a crying need for additional high-quality, evidence-based research to help patients who are suffering from posttreatment Lyme disease syndrome.”

Patients fought for broader recognition of their condition, and some of them organized. They came up with their own ideas of what was causing their symptoms to persist. One that especially took hold was that infection from Borrelia burgdorferi, the bacteria that causes Lyme disease, persists after initial antibiotic treatment, causing so-called chronic Lyme disease. The cause of PTLDS is still under investigation, and the evidence does not support the idea of a persistent bacterial infection. Multiple studies from the National Institutes of Health have shown that long-term use of antibiotics does not benefit patients who continue to experience symptoms after initial treatment. Several studies have shown that severe adverse effects can result from extended intravenous antibiotic treatment, including death.

[embed:render:related:node:233159]

Nevertheless, the plaintiffs in the lawsuit argued that the insurance companies “enlisted the help of doctors who were researching Lyme disease – the IDSA panelists – and paid them large fees to develop arbitrary guidelines for testing Lyme disease,” thereby enabling the insurance companies to deny coverage for long-term antibiotic treatment to patients.

“The assertions were just preposterous,” Dr. McQuillen said.

In addition to the conspiracy charge, the plaintiffs brought additional accusations to the lawsuit over the years, including racketeering and claims that the guidelines contain false representations regarding Lyme disease testing and treatment. The plaintiffs claimed that the guidelines didn’t acknowledge that treatment can fail and included false information about how to test for Lyme disease. In reality, however, the guidelines do acknowledge that not all patients respond to the recommended 2- to 4-week course of antibiotics and that some diagnoses should be made clinically rather than on the basis of testing.

Regardless, guidelines are not stipulations. They’re a summation of the medical and scientific findings on Lyme disease based on careful review of hundreds of studies.

“They make really clear that adherence to the guidelines [is] voluntary. They aren’t a standard of care from which deviation of care is a problem,” Dr. McQuillen said. “You take those guidelines and apply it to the patient in front of you, and you see what fits best for that patient, because not every patient is going to fit into guidelines.”

Further, the authors said that IDSA vets their recommendations for any potential conflicts of interest in accordance with the organization’s guidelines practices.

“The point of the guidelines is to have people on the committee who don’t care what the guidelines are as long as we have good patient care,” Dr. McQuillen said.

Choosing to fight

Malpractice insurance does not cover this kind of lawsuit, because the doctors named in it did not personally treat any of the patients who filed it. Thus, the doctors were at risk of losing thousands, or millions, of dollars in legal fees, even if they ultimately prevail. Several of the physicians’ academic and health care institutions stepped in to cover some fees, and IDSA covered the rest in a joint defense.

“The IDSA provided me a lawyer at no cost to me, and I felt protected by them,” Dr. Sigal said. “They took care of me and made sure I was safe, and I am grateful to them for that.”

Dr. McQuillen said the expenses exceeded what the organization’s umbrella insurance covered. The physicians had invested their time and effort into the guidelines without any financial compensation.

“They’ve basically put a lot of sweat equity into producing guidelines” that follow the organization’s practices and ethics, Dr. McQuillen said. “To leave them out on an island by themselves is just not the right thing to do. We wouldn’t do that for any of our members who did something on behalf of our society.”

IDSA could have chosen to settle the lawsuit, as the insurance companies did.

“None of us on the board felt that was the right thing to do, because we believe in the process, and the science is right, and you shouldn’t be able to try to change that by having a lawsuit that’s baseless,” Dr. McQuillen said.

Several of the doctors named in the suit spoke with this news organization off the record about the exhaustion, frustration, and general suffering the suit has caused them over the past several years, including ongoing harassment that targeted their families and often became quite personal. But none expressed any wish that IDSA had chosen the faster, cheaper, easier route of settling.

“I love the organization for having done this rather than caving and paying,” Dr. Sigal said. “They showed real moral character, real integrity in fighting this suit, because they had done nothing wrong.”

Fighting the suit was about more than standing by the science, though. It’s essential to ensure physicians continue to conduct research and write clinical guidelines, even about ambiguous or controversial topics, said Raymond J. Dattwyler, MD, a professor of microbiology, immunology, and medicine at New York Medical College, Valhalla, who wrote the treatment part of the guidelines and was named in the suit.

[embed:render:related:node:205511]

“I was really surprised that someone would sue for scientific guidelines, because guidelines are common across medicine, and they’re just a roadmap to help practicing physicians understand how to handle evaluation or treatment of any number of particular problems,” Dr. Dattwyler said in an interview. But he wasn’t surprised that IDSA chose to fight the accusations, “because the principle involved is so compelling. It’s really standing up for all medical societies, and it’s very important to have guidelines. For the health and welfare of the American public, you need to have good information readily available to the practicing physicians.”

If the patient group had won in a settlement, it could potentially have led to less rigorous guidelines from other medical organizations, which would have had an adverse effect on public health, Dr. Dattwyler said. Such a chilling effect could reverberate far beyond the management of Lyme disease.

“One of the problems with our legal system is anybody can sue anybody, but it costs so much to defend yourself,” Dr. Dattwyler said. “This lawsuit costs millions, so that’s chilling. That’s going to inhibit guidelines, and it’s not only guidelines for infectious disease but it’s guidelines for cancer, guidelines for allergic diseases, guidelines for any number of things.”

To an extent, the threats and harassment that patient groups have directed toward different doctors have already had a chilling effect.

“For the people who gave of their time in good faith to generate these guidelines to get harassed everywhere, all the time, sometimes at home, sometimes at their place of work, it’s just unfair,” Dr. McQuillen said. “It also might discourage people from working in research to try to figure out better diagnostics or get a vaccine that actually works. Even if you really find it incredibly interesting, if laying over you is the threat that someone is going to sue you baselessly, and you’re going to have to put the time and effort into defending that, not to mention the money, I can’t see how that would be considered a positive that would encourage you to do it. In some ways, attacking people that are trying to help may drive them away from trying to help.

“At the same time, professional disagreements among practitioners – including a small minority who do treat patients with lengthy courses of antibiotics – can ultimately harm patient care, Dr. Flanigan said.

“There’s a lot of energy being expended fighting among different care providers, and often the individual needs of the patients seem to be not addressed,” Dr. Flanigan said. “The discord between different approaches often seems more important than spending time with the individual patient and trying to find a tailored approach to treatment which can benefit the patient best.”

At the same time, Dr. Sigal said he believes most of the clinicians who use non–evidence-based treatments for their patients do so because they genuinely believe it’s the right thing to do.

“I think they’re motivated by the same concerns that I have, and that is, I need to do what’s best for my patient,” Dr. Sigal said. Ultimately, the evidence should lead the way. “The only arbiter we possibly have in deciding these things is the medical scientific literature,” he added, “and if you can’t subscribe to that, then this way lies madness.”

A version of this article first appeared on Medscape.com.

Years ago, when rheumatologist Leonard Sigal, MD, was undertaking research on Lyme disease and treating patients with the condition at the Robert Wood Johnson Medical School, New Brunswick, N.J., a regular stream of abuse and threats became the usual background noise of his work. He didn’t get used to it, but it never stopped.

Lyme_tick_CDC_photo_web.jpg

“I was accused of incredibly heinous crimes,” Dr. Sigal said in an interview. “I was accused of lying, cheating, of doing things to make money that were against the public interest and against the interest of patients in general.”

It’s an experience many doctors who treat Lyme disease have endured, so much so that some infectious disease doctors aren’t comfortable treating patients with Lyme disease, according to Timothy Flanigan, MD, a professor of infectious disease at Brown University, Providence, R.I.

But it wasn’t until Dr. Sigal left academia in 2003 that he realized the toll all that background abuse had been taking on him.

“It was a breath of fresh air,” he said. “I didn’t have to go into clinic and argue with people. I didn’t have to read articles in the newspaper that made no sense whatsoever. I didn’t have to hear through second and third parties how such and such was saying horrible things about me. I didn’t have to fight anymore. When I was in industry and working on stuff that had nothing to do with Lyme disease, I realized what a relief it was not to have that burden.”

Sigal_Leonard_MA_web.jpg

So the last thing Dr. Sigal expected after all these years was to find himself named in a lawsuit alleging that he was part of a conspiracy to deny patients of what they claimed was appropriate treatment for Lyme disease. Yet, that’s exactly what happened in November 2017, when a group of 24 patients with Lyme disease, led by Texas resident Lisa Torrey, filed a lawsuit against the Infectious Diseases Society of America, eight insurance companies, and 7 of the doctors involved in producing the IDSA guidelines on Lyme disease diagnosis and management. Dr. Sigal himself had not even participated in writing the guidelines. He simply reviewed them, made a few grammatical suggestions, and said they looked good. Over the next 4 years, however, he and his fellow defendants rode an emotional roller coaster of seemingly endless motions, amendments, and other legal developments, waiting to find out whether they would owe millions of dollars for simply summarizing – or just reviewing – the available medical literature on Lyme disease.

“There were times I was on the verge of real anger. I was frustrated. There were times I was frightened, and, occasionally, I would just think of it as being silly. But when I thought of it as being silly, I had to remember I was being sued in Texas, because who knows what’s going to happen,” Dr. Sigal said. “It’s not as though I was being sued in a jurisdiction where anybody knew about Lyme disease. There are examples of physicians who are convicted of doing things they didn’t do because they were sued in the wrong jurisdiction.”

Several individuals who spoke with this news organization on condition of anonymity said that the district court where the suit was filed is notorious for being especially friendly to plaintiffs. But in legal rulings issued on Sept. 1 and Sept. 20, 2021, a federal judge in Texas dismissed all the patient group’s claims. The plaintiffs filed an appeal on Oct. 19. It’s unclear whether that has any reasonable chance of success.

McQuillen_Daniel_P_MA_web.jpg

“One of the things this court case does is validate the fact that our [guidelines] process is a legitimate process and there isn’t outside influence from insurance companies or pharma firms,” Daniel McQuillen, MD, president of IDSA, said in an interview. “We don’t really want anything other than to be vindicated, which we were, 100%.”

But that vindication came with a cost, both emotional and financial. Although IDSA’s insurance covered many of its legal costs, “it’s not a trivial expense,” Dr. McQuillen said. “We’re left with a baseless lawsuit with no facts that went on for 4 years, and our [medical] society basically bore all that expense, which isn’t really particularly fair.”
 

‘Preposterous’ accusations

The lawsuit alleged that the IDSA, the seven named physicians, and the insurance companies had “engaged in a decades-long conspiracy to deny the existence and prevent treatment of chronic Lyme disease.” The patient group claimed that the doctors knew that many patients with Lyme disease do not respond to short-term antibiotic treatment and instead need “long-term antibiotic treatment until the symptoms are resolved,” an assertion not supported by the scientific evidence.

Flanigan_Timothy_RI_web.jpg

What many patients call “chronic Lyme disease” is termed posttreatment Lyme disease syndrome (PTDLS), a constellation of symptoms that include pain, fatigue, and cognitive difficulties that some people experience after a 2- to 4-week course of antibiotics for Lyme disease. It took years of patient advocacy before the Centers for Disease Control and Prevention recognized PTLDS as a condition, but awareness of it has been increasing, said Dr. Flanigan, who was not involved in the lawsuit but treats patients with Lyme disease and PTLDS.

“Long haulers and sequelae of COVID have really opened the eyes of many practitioners that these long-term inflammatory conditions are real and very challenging to treat, and we need to work with patients to help them improve their health,” Dr. Flanigan said. “It’s a sad commentary on our society that the difficulty in treating patients with posttreatment Lyme disease syndrome, or what is commonly referred to by patients as chronic Lyme, ends up in a lawsuit in court.” He said he’s glad the lawsuit was dismissed but added that “there’s a crying need for additional high-quality, evidence-based research to help patients who are suffering from posttreatment Lyme disease syndrome.”

Patients fought for broader recognition of their condition, and some of them organized. They came up with their own ideas of what was causing their symptoms to persist. One that especially took hold was that infection from Borrelia burgdorferi, the bacteria that causes Lyme disease, persists after initial antibiotic treatment, causing so-called chronic Lyme disease. The cause of PTLDS is still under investigation, and the evidence does not support the idea of a persistent bacterial infection. Multiple studies from the National Institutes of Health have shown that long-term use of antibiotics does not benefit patients who continue to experience symptoms after initial treatment. Several studies have shown that severe adverse effects can result from extended intravenous antibiotic treatment, including death.

[embed:render:related:node:233159]

Nevertheless, the plaintiffs in the lawsuit argued that the insurance companies “enlisted the help of doctors who were researching Lyme disease – the IDSA panelists – and paid them large fees to develop arbitrary guidelines for testing Lyme disease,” thereby enabling the insurance companies to deny coverage for long-term antibiotic treatment to patients.

“The assertions were just preposterous,” Dr. McQuillen said.

In addition to the conspiracy charge, the plaintiffs brought additional accusations to the lawsuit over the years, including racketeering and claims that the guidelines contain false representations regarding Lyme disease testing and treatment. The plaintiffs claimed that the guidelines didn’t acknowledge that treatment can fail and included false information about how to test for Lyme disease. In reality, however, the guidelines do acknowledge that not all patients respond to the recommended 2- to 4-week course of antibiotics and that some diagnoses should be made clinically rather than on the basis of testing.

Regardless, guidelines are not stipulations. They’re a summation of the medical and scientific findings on Lyme disease based on careful review of hundreds of studies.

“They make really clear that adherence to the guidelines [is] voluntary. They aren’t a standard of care from which deviation of care is a problem,” Dr. McQuillen said. “You take those guidelines and apply it to the patient in front of you, and you see what fits best for that patient, because not every patient is going to fit into guidelines.”

Further, the authors said that IDSA vets their recommendations for any potential conflicts of interest in accordance with the organization’s guidelines practices.

“The point of the guidelines is to have people on the committee who don’t care what the guidelines are as long as we have good patient care,” Dr. McQuillen said.

Choosing to fight

Malpractice insurance does not cover this kind of lawsuit, because the doctors named in it did not personally treat any of the patients who filed it. Thus, the doctors were at risk of losing thousands, or millions, of dollars in legal fees, even if they ultimately prevail. Several of the physicians’ academic and health care institutions stepped in to cover some fees, and IDSA covered the rest in a joint defense.

“The IDSA provided me a lawyer at no cost to me, and I felt protected by them,” Dr. Sigal said. “They took care of me and made sure I was safe, and I am grateful to them for that.”

Dr. McQuillen said the expenses exceeded what the organization’s umbrella insurance covered. The physicians had invested their time and effort into the guidelines without any financial compensation.

“They’ve basically put a lot of sweat equity into producing guidelines” that follow the organization’s practices and ethics, Dr. McQuillen said. “To leave them out on an island by themselves is just not the right thing to do. We wouldn’t do that for any of our members who did something on behalf of our society.”

IDSA could have chosen to settle the lawsuit, as the insurance companies did.

“None of us on the board felt that was the right thing to do, because we believe in the process, and the science is right, and you shouldn’t be able to try to change that by having a lawsuit that’s baseless,” Dr. McQuillen said.

Several of the doctors named in the suit spoke with this news organization off the record about the exhaustion, frustration, and general suffering the suit has caused them over the past several years, including ongoing harassment that targeted their families and often became quite personal. But none expressed any wish that IDSA had chosen the faster, cheaper, easier route of settling.

“I love the organization for having done this rather than caving and paying,” Dr. Sigal said. “They showed real moral character, real integrity in fighting this suit, because they had done nothing wrong.”

Fighting the suit was about more than standing by the science, though. It’s essential to ensure physicians continue to conduct research and write clinical guidelines, even about ambiguous or controversial topics, said Raymond J. Dattwyler, MD, a professor of microbiology, immunology, and medicine at New York Medical College, Valhalla, who wrote the treatment part of the guidelines and was named in the suit.

[embed:render:related:node:205511]

“I was really surprised that someone would sue for scientific guidelines, because guidelines are common across medicine, and they’re just a roadmap to help practicing physicians understand how to handle evaluation or treatment of any number of particular problems,” Dr. Dattwyler said in an interview. But he wasn’t surprised that IDSA chose to fight the accusations, “because the principle involved is so compelling. It’s really standing up for all medical societies, and it’s very important to have guidelines. For the health and welfare of the American public, you need to have good information readily available to the practicing physicians.”

If the patient group had won in a settlement, it could potentially have led to less rigorous guidelines from other medical organizations, which would have had an adverse effect on public health, Dr. Dattwyler said. Such a chilling effect could reverberate far beyond the management of Lyme disease.

“One of the problems with our legal system is anybody can sue anybody, but it costs so much to defend yourself,” Dr. Dattwyler said. “This lawsuit costs millions, so that’s chilling. That’s going to inhibit guidelines, and it’s not only guidelines for infectious disease but it’s guidelines for cancer, guidelines for allergic diseases, guidelines for any number of things.”

To an extent, the threats and harassment that patient groups have directed toward different doctors have already had a chilling effect.

“For the people who gave of their time in good faith to generate these guidelines to get harassed everywhere, all the time, sometimes at home, sometimes at their place of work, it’s just unfair,” Dr. McQuillen said. “It also might discourage people from working in research to try to figure out better diagnostics or get a vaccine that actually works. Even if you really find it incredibly interesting, if laying over you is the threat that someone is going to sue you baselessly, and you’re going to have to put the time and effort into defending that, not to mention the money, I can’t see how that would be considered a positive that would encourage you to do it. In some ways, attacking people that are trying to help may drive them away from trying to help.

“At the same time, professional disagreements among practitioners – including a small minority who do treat patients with lengthy courses of antibiotics – can ultimately harm patient care, Dr. Flanigan said.

“There’s a lot of energy being expended fighting among different care providers, and often the individual needs of the patients seem to be not addressed,” Dr. Flanigan said. “The discord between different approaches often seems more important than spending time with the individual patient and trying to find a tailored approach to treatment which can benefit the patient best.”

At the same time, Dr. Sigal said he believes most of the clinicians who use non–evidence-based treatments for their patients do so because they genuinely believe it’s the right thing to do.

“I think they’re motivated by the same concerns that I have, and that is, I need to do what’s best for my patient,” Dr. Sigal said. Ultimately, the evidence should lead the way. “The only arbiter we possibly have in deciding these things is the medical scientific literature,” he added, “and if you can’t subscribe to that, then this way lies madness.”

A version of this article first appeared on Medscape.com.

A new study from Africa shows a remarkable 70% reduction in malaria if two treatments — a vaccine and an antimalarial medication — are combined instead of giving them individually.

Malaria is endemic in the tropics. The World Health Organization (WHO) reports that in 2019, there were 229 million cases and 409,000 deaths from this parasitic infection. Most of the burden (94%) occurs in Africa, and children younger than age 5 account for 67% of the deaths.

In the Sahel region of Africa, a broad, sub-Saharan band that stretches across the continent, high malaria transmission is seasonal. Children in some countries there are treated with monthly courses of sulfadoxine-pyrimethamine and amodiaquine chemoprophylaxis during the four higher-risk months. Such seasonal malaria chemoprophylaxis (SMC) has been shown to reduce infections by up to 88% and costs an average of $3.43 per child per year.

This double-blind, randomized controlled trial enrolled young children (5-17 months old) in Burkina Faso and Mali, where SMC is the current treatment regimen. Nearly 6,000 children received either chemoprophylaxis, the RTS,S/AS01E malaria vaccine (RTS,S), or both treatments. The study, led by investigators at the London School of Hygiene and Tropical Medicine (LSHTM), was reported in the New England Journal of Medicine.

Co-lead investigator Daniel Chandramohan, MBBS, PhD, MSc, professor of public health at LSHTM, said in an interview that SMC administration is quite labor-intensive and that “we thought we can replace these four cycles of seasonal cure prevention with one seasonal vaccination like the flu vaccine ... and that there might be some additive benefit.”

Instead, the study found the combination reduces the incidence of malaria by 62% against clinical malaria infection, 70% against severe malaria, and 73% against death from malaria compared with SMC alone. “Not in our wildest dreams would I have hypothesized that this is a possibility,” Dr. Chandramohan said. He continued that this was unlikely a “freak result” because the findings are “consistent between both countries. Two, it is consistent across the years. Three, all the malaria outcomes ... are consistently showing the protective effect at the same level.”

To maintain the blinded study design, children received injections of rabies vaccine and hepatitis A vaccine instead of a placebo for RTS,S. Both were chosen to provide additional benefits by protecting children against those infections.

With so many children followed over years, accuracy in providing the correct treatment for each study arm can be difficult. Each child was given a QR code and picture identification to facilitate drug distribution each year in this study.

Miriam K. Laufer, MD, professor and associate director for malaria research at the University of Maryland, Baltimore, who was not involved in the study, said in an interview, “This is a spectacular result, you know, decreasing disease by 60%-70% using interventions that we already have.”

RTS,S is not a new vaccine; it was developed in 2001 by GlaxoSmithKline with Path’s Malaria Vaccine Initiative, then manufactured by GSK. The Gates Foundation has supported production. Dr. Chandramohan said GSK has transferred the technology to Bharat, in India, and that it will take 2-3 years to ramp up production. Until then, enough vaccine is available to supply Kenya, Malawi, and Ghana, where the pilot studies are being done.

Dr. Laufer stressed that the “group that got RTS,S did as well as the group that received SMC.” She noted that the use of SMC is limited to specific areas of the Sahel sub-region of Africa, with a brief transmission period. In other areas of Africa where malaria has a longer transmission period, SMC isn’t as effective. “RTS,S vaccine could really have an impact” there, she added.

Asked if RTS,S might be substituted for SMC to reduce the likelihood of resistance emerging, Dr. Laufer said, “Giving RTS,S vaccine is as good as using repeated treatment of malaria drugs during the malaria season. And that’s important for two reasons. One is that the advantage of a vaccine is that you’re not producing pressure of drugs that would enable drug resistance to emerge and spread. So maybe your vaccine efficacy could last longer than drug efficacy. We don’t know the answer to that.”

Hypothesizing about the unexpectedly good trial results, Dr. Laufer explained, “We know that RTS,S decreases the number of parasites that make it into the blood when a child is bitten by an infected mosquito. When drugs like sulfadoxine-pyrimethamine and amodiaquine that have moderate efficacy only have to kill off a small number of parasites, they can work better. Maybe that explains why the combination of RTS,S and SMC created such a positive outcome.”

Dr. Laufer echoed Chandramohan, saying, “Results were much more dramatic than anybody – certainly than I anticipated.” Both physicians anticipate that WHO will give full approval for this combination this fall.

Dr. Chandramohan and Dr. Laufer have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study from Africa shows a remarkable 70% reduction in malaria if two treatments — a vaccine and an antimalarial medication — are combined instead of giving them individually.

Malaria is endemic in the tropics. The World Health Organization (WHO) reports that in 2019, there were 229 million cases and 409,000 deaths from this parasitic infection. Most of the burden (94%) occurs in Africa, and children younger than age 5 account for 67% of the deaths.

In the Sahel region of Africa, a broad, sub-Saharan band that stretches across the continent, high malaria transmission is seasonal. Children in some countries there are treated with monthly courses of sulfadoxine-pyrimethamine and amodiaquine chemoprophylaxis during the four higher-risk months. Such seasonal malaria chemoprophylaxis (SMC) has been shown to reduce infections by up to 88% and costs an average of $3.43 per child per year.

This double-blind, randomized controlled trial enrolled young children (5-17 months old) in Burkina Faso and Mali, where SMC is the current treatment regimen. Nearly 6,000 children received either chemoprophylaxis, the RTS,S/AS01E malaria vaccine (RTS,S), or both treatments. The study, led by investigators at the London School of Hygiene and Tropical Medicine (LSHTM), was reported in the New England Journal of Medicine.

Co-lead investigator Daniel Chandramohan, MBBS, PhD, MSc, professor of public health at LSHTM, said in an interview that SMC administration is quite labor-intensive and that “we thought we can replace these four cycles of seasonal cure prevention with one seasonal vaccination like the flu vaccine ... and that there might be some additive benefit.”

Instead, the study found the combination reduces the incidence of malaria by 62% against clinical malaria infection, 70% against severe malaria, and 73% against death from malaria compared with SMC alone. “Not in our wildest dreams would I have hypothesized that this is a possibility,” Dr. Chandramohan said. He continued that this was unlikely a “freak result” because the findings are “consistent between both countries. Two, it is consistent across the years. Three, all the malaria outcomes ... are consistently showing the protective effect at the same level.”

To maintain the blinded study design, children received injections of rabies vaccine and hepatitis A vaccine instead of a placebo for RTS,S. Both were chosen to provide additional benefits by protecting children against those infections.

With so many children followed over years, accuracy in providing the correct treatment for each study arm can be difficult. Each child was given a QR code and picture identification to facilitate drug distribution each year in this study.

Miriam K. Laufer, MD, professor and associate director for malaria research at the University of Maryland, Baltimore, who was not involved in the study, said in an interview, “This is a spectacular result, you know, decreasing disease by 60%-70% using interventions that we already have.”

RTS,S is not a new vaccine; it was developed in 2001 by GlaxoSmithKline with Path’s Malaria Vaccine Initiative, then manufactured by GSK. The Gates Foundation has supported production. Dr. Chandramohan said GSK has transferred the technology to Bharat, in India, and that it will take 2-3 years to ramp up production. Until then, enough vaccine is available to supply Kenya, Malawi, and Ghana, where the pilot studies are being done.

Dr. Laufer stressed that the “group that got RTS,S did as well as the group that received SMC.” She noted that the use of SMC is limited to specific areas of the Sahel sub-region of Africa, with a brief transmission period. In other areas of Africa where malaria has a longer transmission period, SMC isn’t as effective. “RTS,S vaccine could really have an impact” there, she added.

Asked if RTS,S might be substituted for SMC to reduce the likelihood of resistance emerging, Dr. Laufer said, “Giving RTS,S vaccine is as good as using repeated treatment of malaria drugs during the malaria season. And that’s important for two reasons. One is that the advantage of a vaccine is that you’re not producing pressure of drugs that would enable drug resistance to emerge and spread. So maybe your vaccine efficacy could last longer than drug efficacy. We don’t know the answer to that.”

Hypothesizing about the unexpectedly good trial results, Dr. Laufer explained, “We know that RTS,S decreases the number of parasites that make it into the blood when a child is bitten by an infected mosquito. When drugs like sulfadoxine-pyrimethamine and amodiaquine that have moderate efficacy only have to kill off a small number of parasites, they can work better. Maybe that explains why the combination of RTS,S and SMC created such a positive outcome.”

Dr. Laufer echoed Chandramohan, saying, “Results were much more dramatic than anybody – certainly than I anticipated.” Both physicians anticipate that WHO will give full approval for this combination this fall.

Dr. Chandramohan and Dr. Laufer have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A new study from Africa shows a remarkable 70% reduction in malaria if two treatments — a vaccine and an antimalarial medication — are combined instead of giving them individually.

Malaria is endemic in the tropics. The World Health Organization (WHO) reports that in 2019, there were 229 million cases and 409,000 deaths from this parasitic infection. Most of the burden (94%) occurs in Africa, and children younger than age 5 account for 67% of the deaths.

In the Sahel region of Africa, a broad, sub-Saharan band that stretches across the continent, high malaria transmission is seasonal. Children in some countries there are treated with monthly courses of sulfadoxine-pyrimethamine and amodiaquine chemoprophylaxis during the four higher-risk months. Such seasonal malaria chemoprophylaxis (SMC) has been shown to reduce infections by up to 88% and costs an average of $3.43 per child per year.

This double-blind, randomized controlled trial enrolled young children (5-17 months old) in Burkina Faso and Mali, where SMC is the current treatment regimen. Nearly 6,000 children received either chemoprophylaxis, the RTS,S/AS01E malaria vaccine (RTS,S), or both treatments. The study, led by investigators at the London School of Hygiene and Tropical Medicine (LSHTM), was reported in the New England Journal of Medicine.

Co-lead investigator Daniel Chandramohan, MBBS, PhD, MSc, professor of public health at LSHTM, said in an interview that SMC administration is quite labor-intensive and that “we thought we can replace these four cycles of seasonal cure prevention with one seasonal vaccination like the flu vaccine ... and that there might be some additive benefit.”

Instead, the study found the combination reduces the incidence of malaria by 62% against clinical malaria infection, 70% against severe malaria, and 73% against death from malaria compared with SMC alone. “Not in our wildest dreams would I have hypothesized that this is a possibility,” Dr. Chandramohan said. He continued that this was unlikely a “freak result” because the findings are “consistent between both countries. Two, it is consistent across the years. Three, all the malaria outcomes ... are consistently showing the protective effect at the same level.”

To maintain the blinded study design, children received injections of rabies vaccine and hepatitis A vaccine instead of a placebo for RTS,S. Both were chosen to provide additional benefits by protecting children against those infections.

With so many children followed over years, accuracy in providing the correct treatment for each study arm can be difficult. Each child was given a QR code and picture identification to facilitate drug distribution each year in this study.

Miriam K. Laufer, MD, professor and associate director for malaria research at the University of Maryland, Baltimore, who was not involved in the study, said in an interview, “This is a spectacular result, you know, decreasing disease by 60%-70% using interventions that we already have.”

RTS,S is not a new vaccine; it was developed in 2001 by GlaxoSmithKline with Path’s Malaria Vaccine Initiative, then manufactured by GSK. The Gates Foundation has supported production. Dr. Chandramohan said GSK has transferred the technology to Bharat, in India, and that it will take 2-3 years to ramp up production. Until then, enough vaccine is available to supply Kenya, Malawi, and Ghana, where the pilot studies are being done.

Dr. Laufer stressed that the “group that got RTS,S did as well as the group that received SMC.” She noted that the use of SMC is limited to specific areas of the Sahel sub-region of Africa, with a brief transmission period. In other areas of Africa where malaria has a longer transmission period, SMC isn’t as effective. “RTS,S vaccine could really have an impact” there, she added.

Asked if RTS,S might be substituted for SMC to reduce the likelihood of resistance emerging, Dr. Laufer said, “Giving RTS,S vaccine is as good as using repeated treatment of malaria drugs during the malaria season. And that’s important for two reasons. One is that the advantage of a vaccine is that you’re not producing pressure of drugs that would enable drug resistance to emerge and spread. So maybe your vaccine efficacy could last longer than drug efficacy. We don’t know the answer to that.”

Hypothesizing about the unexpectedly good trial results, Dr. Laufer explained, “We know that RTS,S decreases the number of parasites that make it into the blood when a child is bitten by an infected mosquito. When drugs like sulfadoxine-pyrimethamine and amodiaquine that have moderate efficacy only have to kill off a small number of parasites, they can work better. Maybe that explains why the combination of RTS,S and SMC created such a positive outcome.”

Dr. Laufer echoed Chandramohan, saying, “Results were much more dramatic than anybody – certainly than I anticipated.” Both physicians anticipate that WHO will give full approval for this combination this fall.

Dr. Chandramohan and Dr. Laufer have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In its final report on the E-2020 initiative, the World Health Organization touted its progress on its goal of eliminating malaria throughout the world. But critics are charging that progress has stalled.

The E-2020 initiative supported the efforts of 21 countries in eliminating malaria. In a remarkable achievement, especially during the COVID-19 pandemic, eight E-2020 member countries reported zero cases of malaria in 2020. The WHO’s next target is the elimination of malaria in 20 of those countries by 2025.

While applauding these successes, in an interview with this news organization, Sir Nicholas J. White, FRS, professor of tropical medicine, Mahidol University, Salaya, Thailand, and Oxford (England) University, also put those successes in perspective. For one thing, the original 2020 goal was the elimination of malaria in 10 countries. Prof. White acknowledged that there had been very “substantial reductions in global morbidity and mortality” from 2000 to 2015, but he pointed out that those advances have not been sustained.

Prof. White added, “There has never been a really good, detailed inquiry as to why progress has stalled” in the high-burden countries.

Prof. White also provided important historical context, explaining that “100 years ago, malaria was pretty much a global disease. There were few places in the world which did not have malaria. You had malaria up to the Arctic Circle. You had malaria in the United States, particularly in the Tennessee Valley in the southeastern part of the United States. The Centers for Disease Control was formed specifically to counter malaria and malaria interfering with the building of the Erie and Ottawa canals.”

Kim Lindblade, PhD, malaria elimination team lead of the WHO’s Global Malaria Program, addressed those concerns with this news organization. “It’s not completely clear why [progress] has stalled,” she said. “There are lots of potential reasons for it, including stagnating funding.”

Dr. Lindblade added that high-burden countries are “facing big challenges. [Since 2015] there’s this stagnation. We’re fighting against population growth, and countries need to get back on track to continue to decrease their malaria burden. So that’s the big focus right now, to reorganize efforts to help countries achieve the goals of the World Health Assembly.”

Asked how these countries might approach the problem differently, Dr. Lindblade said that in the recent past, there was “almost a one-size-fits-all strategy. Now we’re looking much more carefully at conditions at the district level or provincial level and saying, What is it that this particular district or province needs? … It’s becoming much more tailored to the environment and to the specific epidemiological situation. … and I think that’s gotten a lot of people very excited.”

Because of travel restrictions and lockdowns because of COVID-19, the number of imported cases of malaria has declined. That’s the good news. But the pandemic has made elimination more difficult in other ways. For example, the delivery of insecticide-treated bed nets has been delayed in some areas, as has targeted indoor spraying. People in many areas have put off seeking medical care. Diagnostic capabilities have been reduced because of health care personnel having been diverted to address the COVID-19 crisis.

Still, some of the successes in eliminating malaria have been striking. Iran, for example, reduced its cases from about 98,000 in 1991 to 12,000 just 10 years later. Since then, Iran has established rapid response teams equipped with insecticide-impregnated nets, rapid diagnostic tests, and antimalarials. A network of more than 3,700 community health volunteers has been trained and deployed throughout the country.

A key element of Iran’s success – and that of some of the other countries – is the political will to tackle malaria. This translates to funding. Notably, the most successful countries provide free primary health care to everyone, regardless of their legal or residency status. Volunteer migrant workers are trained to diagnose malaria and to educate fellow migrants about the disease and prevention strategies.

Malaysia and China are examples of two countries at risk of importing malaria through their many people who work abroad in malaria-endemic regions. They have had to increase their surveillance.

Although Malaysia has eliminated most malaria species – those transmitted through people – they still have problems with the malaria parasite hosted by monkeys.

The WHO report stresses the lessons learned through their E-2020 program. Two key criteria are political commitment and associated funding. Next are surveillance and efforts to reach everyone, even in geographically remote or marginalized communities. Close surveillance also enables strategies to be modified to local needs.

Countries need to cooperate, especially along border areas and in regard to communications. The WHO stressed the need for countries to have an integrated response in their approach to malaria, including accurate surveillance, diagnostic testing, treatment, and robust education in preventive measures.

Although these successes were not as evident in some high-burden countries, Prof. White applauded their perseverance, noting, “It’s quite difficult to sustain the political momentum. … That endgame to keep the motivation, keep the support, to getting rid of something is hard.”

Prof. White and Dr. Lindberg have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In its final report on the E-2020 initiative, the World Health Organization touted its progress on its goal of eliminating malaria throughout the world. But critics are charging that progress has stalled.

The E-2020 initiative supported the efforts of 21 countries in eliminating malaria. In a remarkable achievement, especially during the COVID-19 pandemic, eight E-2020 member countries reported zero cases of malaria in 2020. The WHO’s next target is the elimination of malaria in 20 of those countries by 2025.

While applauding these successes, in an interview with this news organization, Sir Nicholas J. White, FRS, professor of tropical medicine, Mahidol University, Salaya, Thailand, and Oxford (England) University, also put those successes in perspective. For one thing, the original 2020 goal was the elimination of malaria in 10 countries. Prof. White acknowledged that there had been very “substantial reductions in global morbidity and mortality” from 2000 to 2015, but he pointed out that those advances have not been sustained.

Prof. White added, “There has never been a really good, detailed inquiry as to why progress has stalled” in the high-burden countries.

Prof. White also provided important historical context, explaining that “100 years ago, malaria was pretty much a global disease. There were few places in the world which did not have malaria. You had malaria up to the Arctic Circle. You had malaria in the United States, particularly in the Tennessee Valley in the southeastern part of the United States. The Centers for Disease Control was formed specifically to counter malaria and malaria interfering with the building of the Erie and Ottawa canals.”

Kim Lindblade, PhD, malaria elimination team lead of the WHO’s Global Malaria Program, addressed those concerns with this news organization. “It’s not completely clear why [progress] has stalled,” she said. “There are lots of potential reasons for it, including stagnating funding.”

Dr. Lindblade added that high-burden countries are “facing big challenges. [Since 2015] there’s this stagnation. We’re fighting against population growth, and countries need to get back on track to continue to decrease their malaria burden. So that’s the big focus right now, to reorganize efforts to help countries achieve the goals of the World Health Assembly.”

Asked how these countries might approach the problem differently, Dr. Lindblade said that in the recent past, there was “almost a one-size-fits-all strategy. Now we’re looking much more carefully at conditions at the district level or provincial level and saying, What is it that this particular district or province needs? … It’s becoming much more tailored to the environment and to the specific epidemiological situation. … and I think that’s gotten a lot of people very excited.”

Because of travel restrictions and lockdowns because of COVID-19, the number of imported cases of malaria has declined. That’s the good news. But the pandemic has made elimination more difficult in other ways. For example, the delivery of insecticide-treated bed nets has been delayed in some areas, as has targeted indoor spraying. People in many areas have put off seeking medical care. Diagnostic capabilities have been reduced because of health care personnel having been diverted to address the COVID-19 crisis.

Still, some of the successes in eliminating malaria have been striking. Iran, for example, reduced its cases from about 98,000 in 1991 to 12,000 just 10 years later. Since then, Iran has established rapid response teams equipped with insecticide-impregnated nets, rapid diagnostic tests, and antimalarials. A network of more than 3,700 community health volunteers has been trained and deployed throughout the country.

A key element of Iran’s success – and that of some of the other countries – is the political will to tackle malaria. This translates to funding. Notably, the most successful countries provide free primary health care to everyone, regardless of their legal or residency status. Volunteer migrant workers are trained to diagnose malaria and to educate fellow migrants about the disease and prevention strategies.

Malaysia and China are examples of two countries at risk of importing malaria through their many people who work abroad in malaria-endemic regions. They have had to increase their surveillance.

Although Malaysia has eliminated most malaria species – those transmitted through people – they still have problems with the malaria parasite hosted by monkeys.

The WHO report stresses the lessons learned through their E-2020 program. Two key criteria are political commitment and associated funding. Next are surveillance and efforts to reach everyone, even in geographically remote or marginalized communities. Close surveillance also enables strategies to be modified to local needs.

Countries need to cooperate, especially along border areas and in regard to communications. The WHO stressed the need for countries to have an integrated response in their approach to malaria, including accurate surveillance, diagnostic testing, treatment, and robust education in preventive measures.

Although these successes were not as evident in some high-burden countries, Prof. White applauded their perseverance, noting, “It’s quite difficult to sustain the political momentum. … That endgame to keep the motivation, keep the support, to getting rid of something is hard.”

Prof. White and Dr. Lindberg have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In its final report on the E-2020 initiative, the World Health Organization touted its progress on its goal of eliminating malaria throughout the world. But critics are charging that progress has stalled.

The E-2020 initiative supported the efforts of 21 countries in eliminating malaria. In a remarkable achievement, especially during the COVID-19 pandemic, eight E-2020 member countries reported zero cases of malaria in 2020. The WHO’s next target is the elimination of malaria in 20 of those countries by 2025.

While applauding these successes, in an interview with this news organization, Sir Nicholas J. White, FRS, professor of tropical medicine, Mahidol University, Salaya, Thailand, and Oxford (England) University, also put those successes in perspective. For one thing, the original 2020 goal was the elimination of malaria in 10 countries. Prof. White acknowledged that there had been very “substantial reductions in global morbidity and mortality” from 2000 to 2015, but he pointed out that those advances have not been sustained.

Prof. White added, “There has never been a really good, detailed inquiry as to why progress has stalled” in the high-burden countries.

Prof. White also provided important historical context, explaining that “100 years ago, malaria was pretty much a global disease. There were few places in the world which did not have malaria. You had malaria up to the Arctic Circle. You had malaria in the United States, particularly in the Tennessee Valley in the southeastern part of the United States. The Centers for Disease Control was formed specifically to counter malaria and malaria interfering with the building of the Erie and Ottawa canals.”

Kim Lindblade, PhD, malaria elimination team lead of the WHO’s Global Malaria Program, addressed those concerns with this news organization. “It’s not completely clear why [progress] has stalled,” she said. “There are lots of potential reasons for it, including stagnating funding.”

Dr. Lindblade added that high-burden countries are “facing big challenges. [Since 2015] there’s this stagnation. We’re fighting against population growth, and countries need to get back on track to continue to decrease their malaria burden. So that’s the big focus right now, to reorganize efforts to help countries achieve the goals of the World Health Assembly.”

Asked how these countries might approach the problem differently, Dr. Lindblade said that in the recent past, there was “almost a one-size-fits-all strategy. Now we’re looking much more carefully at conditions at the district level or provincial level and saying, What is it that this particular district or province needs? … It’s becoming much more tailored to the environment and to the specific epidemiological situation. … and I think that’s gotten a lot of people very excited.”

Because of travel restrictions and lockdowns because of COVID-19, the number of imported cases of malaria has declined. That’s the good news. But the pandemic has made elimination more difficult in other ways. For example, the delivery of insecticide-treated bed nets has been delayed in some areas, as has targeted indoor spraying. People in many areas have put off seeking medical care. Diagnostic capabilities have been reduced because of health care personnel having been diverted to address the COVID-19 crisis.

Still, some of the successes in eliminating malaria have been striking. Iran, for example, reduced its cases from about 98,000 in 1991 to 12,000 just 10 years later. Since then, Iran has established rapid response teams equipped with insecticide-impregnated nets, rapid diagnostic tests, and antimalarials. A network of more than 3,700 community health volunteers has been trained and deployed throughout the country.

A key element of Iran’s success – and that of some of the other countries – is the political will to tackle malaria. This translates to funding. Notably, the most successful countries provide free primary health care to everyone, regardless of their legal or residency status. Volunteer migrant workers are trained to diagnose malaria and to educate fellow migrants about the disease and prevention strategies.

Malaysia and China are examples of two countries at risk of importing malaria through their many people who work abroad in malaria-endemic regions. They have had to increase their surveillance.

Although Malaysia has eliminated most malaria species – those transmitted through people – they still have problems with the malaria parasite hosted by monkeys.

The WHO report stresses the lessons learned through their E-2020 program. Two key criteria are political commitment and associated funding. Next are surveillance and efforts to reach everyone, even in geographically remote or marginalized communities. Close surveillance also enables strategies to be modified to local needs.

Countries need to cooperate, especially along border areas and in regard to communications. The WHO stressed the need for countries to have an integrated response in their approach to malaria, including accurate surveillance, diagnostic testing, treatment, and robust education in preventive measures.

Although these successes were not as evident in some high-burden countries, Prof. White applauded their perseverance, noting, “It’s quite difficult to sustain the political momentum. … That endgame to keep the motivation, keep the support, to getting rid of something is hard.”

Prof. White and Dr. Lindberg have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.