Zoonoses

Thanks to decades of successful vector control strategies, vector-borne transmission of Chagas disease has significantly decreased in many regions. Oral ingestion of Trypanosoma cruzi through contaminated food and beverages, however, is increasing. Unlike vector transmission, oral transmission of Chagas disease entails high lethality in pediatric and adult populations.

“The oral transmission of Chagas disease is becoming a much more recognized route, and it is crucial to understand that people can die from this type of transmission,” Norman L. Beatty, MD, assistant professor of infectious diseases and global medicine at the University of Florida College of Medicine in Gainesville, Florida, told this news organization. Dr. Beatty is the lead author of a recent article on the subject.

In regions where the parasite circulates in the environment, people are consuming foods, fruit juices, and possibly wild animal meat that may be contaminated. “As we experience changes in our environment and in the way we consume food, it is crucial to consider how food preparation is carried out in areas where T cruzi transmission occurs in the environment,” said Dr. Beatty. “And as organic farming methods without insecticides become increasingly common, more research is needed in these areas, both in Latin America and in the United States, to understand if oral transmission of T cruzi is occurring.”

In the Amazon basin, foodborne transmission is already the leading cause of acute Chagas disease. It has been described in Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, and Venezuela.

Dr. Beatty’s colleagues recently treated a Brazilian patient at the hospital in Florida. “He came to our hospital very ill, with acute myocarditis after consuming contaminated açaí.” Clarifying that there is widespread awareness about oral transmission in Brazil, he stated, “We are concerned that it may not be recognized in other areas of Latin America.”

Mexico and regions of Central America have little to no information on oral transmission, but it is likely occurring, and cases may be going undetected in the region, said Dr. Beatty.

He investigated the issue in Colombia as part of an international collaboration involving the University of Antioquia, aiming to find ways to mitigate oral transmission and create a model that can be used throughout Latin America and the United States. For the Colombia study, they reviewed all cases reported to the Ministry of Health and Social Protection, and oral transmission turned out to be more common than the research group expected. “Still, I imagine that in certain areas with limited resources…there are many more cases that are not being reported.

“A myth I would like to dispel is that Chagas disease is not being transmitted in the United States,” Dr. Beatty added. He mentioned that at least 30 American states have vectors, and in Florida, it was documented that triatomines invaded homes and bit residents. In addition, 30% of these insects are infected with T cruzi. Research is underway to determine whether Floridians are becoming infected and if they are also at risk of contracting Chagas disease orally, said Dr. Beatty. “In the United States, we know very little about how many people are infected and what the infection routes are. Much more research is needed.”

Roberto Chuit, MD, PhD, a doctor in public health and an external consultant for the Pan American Health Organization (PAHO), agreed that this route of food contamination, which occurs because of vector-borne parasites, was until recently masked or hidden by the predominance of vector presence. Just as it began to gain importance as other transmission routes were controlled, “it now has extremely high importance in the Americas, as does vertical transmission,” he said.

In 2023, more than 50 years after the first description of oral transmission, the PAHO expert meeting proposed to alert health services and the broader community about the severity and potential lethality of oral Chagas disease outbreaks to elicit immediate responses and mitigation measures. The body also proposed conducting studies to provide detailed information on the contamination source and the wild vectors present in oral transmission foci.
 

Unique Clinical Manifestations

The exacerbated signs and symptoms of oral infection (see sidebar) are attributed to the high parasite loads in contaminated food and beverages. A single crushed triatomine along with a food or beverage harboring T cruzi can contain an estimated 600,000 metacyclic trypomastigotes, compared with 3000-4000 per µL when infection occurs by triatomine fecal matter. The robust systemic immune response observed in patients with acute oral Chagas disease is thought to result from more efficient transmission after penetration through the oral, pharyngeal, and gastric mucosae.
 

Seven Things to Know About Orally Transmitted Chagas Disease

1. It presents with exacerbated symptoms and rapid disease progression in immunocompetent individuals. This presentation is not common in vector-borne, congenital, or transfusion-related transmission. It can cause fulminant myocarditis and heart failure, meningoencephalitis, or potentially fatal shock due to parasitemia.

2. Most patients (71%-100%) with acute oral Chagas present with fever.

3. Electrocardiographic abnormalities, specifically ventricular depolarization alterations and pericardial involvement, are observed in most patients.

4. Facial edema, which typically affects the entire face and parts of the lips, is present in 57%-100% of patients with acute oral Chagas disease. In those with acute symptoms from vector transmission, unilateral periorbital swelling (Romaña’s sign) is more common.

5. Other notable systemic symptoms include edema of the lower extremities, myalgia, generalized lymphadenopathy, abdominal discomfort, dyspnea, vomiting, diarrhea, hepatomegaly, splenomegaly, headache, chest pain, cutaneous erythematous rash, jaundice, arthralgia, epistaxis, hematemesis, melena, and palpitations.

6. The incubation period after oral ingestion of products contaminated with Trypanosoma cruzi is approximately 3-22 days, in contrast to 4-15 days for vector-borne transmission and 8-160 days for transfusion and transplant-related transmission.

7. Patients need antiparasitic drugs immediately.
 

Thinking Epidemiologically

Dr. Chuit recalled that suspicion of food contamination should be based on epidemiology, especially in outbreaks affecting several people and in regions where Chagas vectors have been described. Sometimes, however, a single careless tourist consumes contaminated products.

“The difficulty is that many times it is not considered, and if it is not considered, the search for the parasite is not requested,” said Dr. Chuit. He added that it is common for the professional to consider Chagas disease only if viral and bacterial isolation tests are negative. Clinicians sometimes consider Chagas disease because the patient has not responded to regular treatments for other causes, such as antibiotics and hydration.

Epidemiology is important, especially when Chagas disease is diagnosed in groups or a family, because they are usually not isolated cases but outbreaks of 3-40 cases, according to Dr. Chuit. “Under these conditions, it must be quickly considered…that this parasite may be involved.”

One of the difficulties is that the source of these oral transmissions is not recognized most of the time. In general, the sources are usually foods that are more likely to be contaminated by insects or insect feces, such as orange juice or sugarcane. But in fact, any food or beverage left unattended could be contaminated by vectors or possible secretions from infected marsupial odoriferous glands.

An analysis of 32 outbreaks from 1965 to 2022 showed that the main foods involved in oral transmission were homemade fruit juices. But different vector species were identified, and the reservoirs were mainly dogs, rodents, and large American opossums (Didelphis).

The largest oral Chagas outbreak was linked to the consumption of contaminated guava juice in a primary school in Caracas, Venezuela. Nonindustrially produced açaí is a common source of orally acquired Chagas disease in Brazil. In Colombia, Chagas disease has been associated with the consumption of palm wine, sugar cane, and tangerine juice. Other oral transmission routes include consuming meat from wild animals and ingesting blood from infected armadillos, which is related to a traditional medicine practice.
 

Deadly Yet Easily Treatable

In the outbreak of 119 confirmed and suspected cases in Venezuela, 20.3% required hospitalization, and a 5-year-old child died of acute myocarditis. These percentages differ from those reported in vector transmission, which is asymptomatic in the acute phase for 95%-99% of cases or will only develop a mild febrile illness that resolves on its own.

“Not all cases will present as severe, because depending on the inoculum, there may be individuals with subclinical situations. But any food poisoning that occurs in endemic areas, where food is not properly controlled, and these street foods are associated with processes in jungle areas, raises the possibility that T cruzi is involved and should be considered as a differential diagnosis,» noted Dr. Chuit. “The treatment is highly effective, and people recover quickly.”

“The most important thing about oral transmission of Chagas is that someone infected in this way needs antiparasitic drugs immediately. We can cure them if we treat them immediately,” said Dr. Beatty, adding that treatment is sometimes delayed due to lack of access to appropriate antiparasitic drugs. “Here in the United States and in Latin America, it is quite common for healthcare professionals not to understand the differences between vector, vertical, and oral transmission. By not treating these patients, they become ill quickly.”

Dr. Beatty and Dr. Chuit declared no relevant financial conflicts of interest.

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Thanks to decades of successful vector control strategies, vector-borne transmission of Chagas disease has significantly decreased in many regions. Oral ingestion of Trypanosoma cruzi through contaminated food and beverages, however, is increasing. Unlike vector transmission, oral transmission of Chagas disease entails high lethality in pediatric and adult populations.

“The oral transmission of Chagas disease is becoming a much more recognized route, and it is crucial to understand that people can die from this type of transmission,” Norman L. Beatty, MD, assistant professor of infectious diseases and global medicine at the University of Florida College of Medicine in Gainesville, Florida, told this news organization. Dr. Beatty is the lead author of a recent article on the subject.

In regions where the parasite circulates in the environment, people are consuming foods, fruit juices, and possibly wild animal meat that may be contaminated. “As we experience changes in our environment and in the way we consume food, it is crucial to consider how food preparation is carried out in areas where T cruzi transmission occurs in the environment,” said Dr. Beatty. “And as organic farming methods without insecticides become increasingly common, more research is needed in these areas, both in Latin America and in the United States, to understand if oral transmission of T cruzi is occurring.”

In the Amazon basin, foodborne transmission is already the leading cause of acute Chagas disease. It has been described in Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, and Venezuela.

Dr. Beatty’s colleagues recently treated a Brazilian patient at the hospital in Florida. “He came to our hospital very ill, with acute myocarditis after consuming contaminated açaí.” Clarifying that there is widespread awareness about oral transmission in Brazil, he stated, “We are concerned that it may not be recognized in other areas of Latin America.”

Mexico and regions of Central America have little to no information on oral transmission, but it is likely occurring, and cases may be going undetected in the region, said Dr. Beatty.

He investigated the issue in Colombia as part of an international collaboration involving the University of Antioquia, aiming to find ways to mitigate oral transmission and create a model that can be used throughout Latin America and the United States. For the Colombia study, they reviewed all cases reported to the Ministry of Health and Social Protection, and oral transmission turned out to be more common than the research group expected. “Still, I imagine that in certain areas with limited resources…there are many more cases that are not being reported.

“A myth I would like to dispel is that Chagas disease is not being transmitted in the United States,” Dr. Beatty added. He mentioned that at least 30 American states have vectors, and in Florida, it was documented that triatomines invaded homes and bit residents. In addition, 30% of these insects are infected with T cruzi. Research is underway to determine whether Floridians are becoming infected and if they are also at risk of contracting Chagas disease orally, said Dr. Beatty. “In the United States, we know very little about how many people are infected and what the infection routes are. Much more research is needed.”

Roberto Chuit, MD, PhD, a doctor in public health and an external consultant for the Pan American Health Organization (PAHO), agreed that this route of food contamination, which occurs because of vector-borne parasites, was until recently masked or hidden by the predominance of vector presence. Just as it began to gain importance as other transmission routes were controlled, “it now has extremely high importance in the Americas, as does vertical transmission,” he said.

In 2023, more than 50 years after the first description of oral transmission, the PAHO expert meeting proposed to alert health services and the broader community about the severity and potential lethality of oral Chagas disease outbreaks to elicit immediate responses and mitigation measures. The body also proposed conducting studies to provide detailed information on the contamination source and the wild vectors present in oral transmission foci.
 

Unique Clinical Manifestations

The exacerbated signs and symptoms of oral infection (see sidebar) are attributed to the high parasite loads in contaminated food and beverages. A single crushed triatomine along with a food or beverage harboring T cruzi can contain an estimated 600,000 metacyclic trypomastigotes, compared with 3000-4000 per µL when infection occurs by triatomine fecal matter. The robust systemic immune response observed in patients with acute oral Chagas disease is thought to result from more efficient transmission after penetration through the oral, pharyngeal, and gastric mucosae.
 

Seven Things to Know About Orally Transmitted Chagas Disease

1. It presents with exacerbated symptoms and rapid disease progression in immunocompetent individuals. This presentation is not common in vector-borne, congenital, or transfusion-related transmission. It can cause fulminant myocarditis and heart failure, meningoencephalitis, or potentially fatal shock due to parasitemia.

2. Most patients (71%-100%) with acute oral Chagas present with fever.

3. Electrocardiographic abnormalities, specifically ventricular depolarization alterations and pericardial involvement, are observed in most patients.

4. Facial edema, which typically affects the entire face and parts of the lips, is present in 57%-100% of patients with acute oral Chagas disease. In those with acute symptoms from vector transmission, unilateral periorbital swelling (Romaña’s sign) is more common.

5. Other notable systemic symptoms include edema of the lower extremities, myalgia, generalized lymphadenopathy, abdominal discomfort, dyspnea, vomiting, diarrhea, hepatomegaly, splenomegaly, headache, chest pain, cutaneous erythematous rash, jaundice, arthralgia, epistaxis, hematemesis, melena, and palpitations.

6. The incubation period after oral ingestion of products contaminated with Trypanosoma cruzi is approximately 3-22 days, in contrast to 4-15 days for vector-borne transmission and 8-160 days for transfusion and transplant-related transmission.

7. Patients need antiparasitic drugs immediately.
 

Thinking Epidemiologically

Dr. Chuit recalled that suspicion of food contamination should be based on epidemiology, especially in outbreaks affecting several people and in regions where Chagas vectors have been described. Sometimes, however, a single careless tourist consumes contaminated products.

“The difficulty is that many times it is not considered, and if it is not considered, the search for the parasite is not requested,” said Dr. Chuit. He added that it is common for the professional to consider Chagas disease only if viral and bacterial isolation tests are negative. Clinicians sometimes consider Chagas disease because the patient has not responded to regular treatments for other causes, such as antibiotics and hydration.

Epidemiology is important, especially when Chagas disease is diagnosed in groups or a family, because they are usually not isolated cases but outbreaks of 3-40 cases, according to Dr. Chuit. “Under these conditions, it must be quickly considered…that this parasite may be involved.”

One of the difficulties is that the source of these oral transmissions is not recognized most of the time. In general, the sources are usually foods that are more likely to be contaminated by insects or insect feces, such as orange juice or sugarcane. But in fact, any food or beverage left unattended could be contaminated by vectors or possible secretions from infected marsupial odoriferous glands.

An analysis of 32 outbreaks from 1965 to 2022 showed that the main foods involved in oral transmission were homemade fruit juices. But different vector species were identified, and the reservoirs were mainly dogs, rodents, and large American opossums (Didelphis).

The largest oral Chagas outbreak was linked to the consumption of contaminated guava juice in a primary school in Caracas, Venezuela. Nonindustrially produced açaí is a common source of orally acquired Chagas disease in Brazil. In Colombia, Chagas disease has been associated with the consumption of palm wine, sugar cane, and tangerine juice. Other oral transmission routes include consuming meat from wild animals and ingesting blood from infected armadillos, which is related to a traditional medicine practice.
 

Deadly Yet Easily Treatable

In the outbreak of 119 confirmed and suspected cases in Venezuela, 20.3% required hospitalization, and a 5-year-old child died of acute myocarditis. These percentages differ from those reported in vector transmission, which is asymptomatic in the acute phase for 95%-99% of cases or will only develop a mild febrile illness that resolves on its own.

“Not all cases will present as severe, because depending on the inoculum, there may be individuals with subclinical situations. But any food poisoning that occurs in endemic areas, where food is not properly controlled, and these street foods are associated with processes in jungle areas, raises the possibility that T cruzi is involved and should be considered as a differential diagnosis,» noted Dr. Chuit. “The treatment is highly effective, and people recover quickly.”

“The most important thing about oral transmission of Chagas is that someone infected in this way needs antiparasitic drugs immediately. We can cure them if we treat them immediately,” said Dr. Beatty, adding that treatment is sometimes delayed due to lack of access to appropriate antiparasitic drugs. “Here in the United States and in Latin America, it is quite common for healthcare professionals not to understand the differences between vector, vertical, and oral transmission. By not treating these patients, they become ill quickly.”

Dr. Beatty and Dr. Chuit declared no relevant financial conflicts of interest.

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Thanks to decades of successful vector control strategies, vector-borne transmission of Chagas disease has significantly decreased in many regions. Oral ingestion of Trypanosoma cruzi through contaminated food and beverages, however, is increasing. Unlike vector transmission, oral transmission of Chagas disease entails high lethality in pediatric and adult populations.

“The oral transmission of Chagas disease is becoming a much more recognized route, and it is crucial to understand that people can die from this type of transmission,” Norman L. Beatty, MD, assistant professor of infectious diseases and global medicine at the University of Florida College of Medicine in Gainesville, Florida, told this news organization. Dr. Beatty is the lead author of a recent article on the subject.

In regions where the parasite circulates in the environment, people are consuming foods, fruit juices, and possibly wild animal meat that may be contaminated. “As we experience changes in our environment and in the way we consume food, it is crucial to consider how food preparation is carried out in areas where T cruzi transmission occurs in the environment,” said Dr. Beatty. “And as organic farming methods without insecticides become increasingly common, more research is needed in these areas, both in Latin America and in the United States, to understand if oral transmission of T cruzi is occurring.”

In the Amazon basin, foodborne transmission is already the leading cause of acute Chagas disease. It has been described in Argentina, Bolivia, Brazil, Colombia, Ecuador, French Guiana, and Venezuela.

Dr. Beatty’s colleagues recently treated a Brazilian patient at the hospital in Florida. “He came to our hospital very ill, with acute myocarditis after consuming contaminated açaí.” Clarifying that there is widespread awareness about oral transmission in Brazil, he stated, “We are concerned that it may not be recognized in other areas of Latin America.”

Mexico and regions of Central America have little to no information on oral transmission, but it is likely occurring, and cases may be going undetected in the region, said Dr. Beatty.

He investigated the issue in Colombia as part of an international collaboration involving the University of Antioquia, aiming to find ways to mitigate oral transmission and create a model that can be used throughout Latin America and the United States. For the Colombia study, they reviewed all cases reported to the Ministry of Health and Social Protection, and oral transmission turned out to be more common than the research group expected. “Still, I imagine that in certain areas with limited resources…there are many more cases that are not being reported.

“A myth I would like to dispel is that Chagas disease is not being transmitted in the United States,” Dr. Beatty added. He mentioned that at least 30 American states have vectors, and in Florida, it was documented that triatomines invaded homes and bit residents. In addition, 30% of these insects are infected with T cruzi. Research is underway to determine whether Floridians are becoming infected and if they are also at risk of contracting Chagas disease orally, said Dr. Beatty. “In the United States, we know very little about how many people are infected and what the infection routes are. Much more research is needed.”

Roberto Chuit, MD, PhD, a doctor in public health and an external consultant for the Pan American Health Organization (PAHO), agreed that this route of food contamination, which occurs because of vector-borne parasites, was until recently masked or hidden by the predominance of vector presence. Just as it began to gain importance as other transmission routes were controlled, “it now has extremely high importance in the Americas, as does vertical transmission,” he said.

In 2023, more than 50 years after the first description of oral transmission, the PAHO expert meeting proposed to alert health services and the broader community about the severity and potential lethality of oral Chagas disease outbreaks to elicit immediate responses and mitigation measures. The body also proposed conducting studies to provide detailed information on the contamination source and the wild vectors present in oral transmission foci.
 

Unique Clinical Manifestations

The exacerbated signs and symptoms of oral infection (see sidebar) are attributed to the high parasite loads in contaminated food and beverages. A single crushed triatomine along with a food or beverage harboring T cruzi can contain an estimated 600,000 metacyclic trypomastigotes, compared with 3000-4000 per µL when infection occurs by triatomine fecal matter. The robust systemic immune response observed in patients with acute oral Chagas disease is thought to result from more efficient transmission after penetration through the oral, pharyngeal, and gastric mucosae.
 

Seven Things to Know About Orally Transmitted Chagas Disease

1. It presents with exacerbated symptoms and rapid disease progression in immunocompetent individuals. This presentation is not common in vector-borne, congenital, or transfusion-related transmission. It can cause fulminant myocarditis and heart failure, meningoencephalitis, or potentially fatal shock due to parasitemia.

2. Most patients (71%-100%) with acute oral Chagas present with fever.

3. Electrocardiographic abnormalities, specifically ventricular depolarization alterations and pericardial involvement, are observed in most patients.

4. Facial edema, which typically affects the entire face and parts of the lips, is present in 57%-100% of patients with acute oral Chagas disease. In those with acute symptoms from vector transmission, unilateral periorbital swelling (Romaña’s sign) is more common.

5. Other notable systemic symptoms include edema of the lower extremities, myalgia, generalized lymphadenopathy, abdominal discomfort, dyspnea, vomiting, diarrhea, hepatomegaly, splenomegaly, headache, chest pain, cutaneous erythematous rash, jaundice, arthralgia, epistaxis, hematemesis, melena, and palpitations.

6. The incubation period after oral ingestion of products contaminated with Trypanosoma cruzi is approximately 3-22 days, in contrast to 4-15 days for vector-borne transmission and 8-160 days for transfusion and transplant-related transmission.

7. Patients need antiparasitic drugs immediately.
 

Thinking Epidemiologically

Dr. Chuit recalled that suspicion of food contamination should be based on epidemiology, especially in outbreaks affecting several people and in regions where Chagas vectors have been described. Sometimes, however, a single careless tourist consumes contaminated products.

“The difficulty is that many times it is not considered, and if it is not considered, the search for the parasite is not requested,” said Dr. Chuit. He added that it is common for the professional to consider Chagas disease only if viral and bacterial isolation tests are negative. Clinicians sometimes consider Chagas disease because the patient has not responded to regular treatments for other causes, such as antibiotics and hydration.

Epidemiology is important, especially when Chagas disease is diagnosed in groups or a family, because they are usually not isolated cases but outbreaks of 3-40 cases, according to Dr. Chuit. “Under these conditions, it must be quickly considered…that this parasite may be involved.”

One of the difficulties is that the source of these oral transmissions is not recognized most of the time. In general, the sources are usually foods that are more likely to be contaminated by insects or insect feces, such as orange juice or sugarcane. But in fact, any food or beverage left unattended could be contaminated by vectors or possible secretions from infected marsupial odoriferous glands.

An analysis of 32 outbreaks from 1965 to 2022 showed that the main foods involved in oral transmission were homemade fruit juices. But different vector species were identified, and the reservoirs were mainly dogs, rodents, and large American opossums (Didelphis).

The largest oral Chagas outbreak was linked to the consumption of contaminated guava juice in a primary school in Caracas, Venezuela. Nonindustrially produced açaí is a common source of orally acquired Chagas disease in Brazil. In Colombia, Chagas disease has been associated with the consumption of palm wine, sugar cane, and tangerine juice. Other oral transmission routes include consuming meat from wild animals and ingesting blood from infected armadillos, which is related to a traditional medicine practice.
 

Deadly Yet Easily Treatable

In the outbreak of 119 confirmed and suspected cases in Venezuela, 20.3% required hospitalization, and a 5-year-old child died of acute myocarditis. These percentages differ from those reported in vector transmission, which is asymptomatic in the acute phase for 95%-99% of cases or will only develop a mild febrile illness that resolves on its own.

“Not all cases will present as severe, because depending on the inoculum, there may be individuals with subclinical situations. But any food poisoning that occurs in endemic areas, where food is not properly controlled, and these street foods are associated with processes in jungle areas, raises the possibility that T cruzi is involved and should be considered as a differential diagnosis,» noted Dr. Chuit. “The treatment is highly effective, and people recover quickly.”

“The most important thing about oral transmission of Chagas is that someone infected in this way needs antiparasitic drugs immediately. We can cure them if we treat them immediately,” said Dr. Beatty, adding that treatment is sometimes delayed due to lack of access to appropriate antiparasitic drugs. “Here in the United States and in Latin America, it is quite common for healthcare professionals not to understand the differences between vector, vertical, and oral transmission. By not treating these patients, they become ill quickly.”

Dr. Beatty and Dr. Chuit declared no relevant financial conflicts of interest.

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Non–Lyme disease, tick-borne illnesses — such as spotted fever group rickettsiosis (SFGR), ehrlichiosis, and alpha-gal syndrome (AGS) — are emerging public health threats, but whether prior tick exposures are responsible for long-term complications, such as musculoskeletal symptoms or osteoarthritis, has been unclear.

Many patients attribute their nonspecific long-term symptoms, such as musculoskeletal pain, to previous illnesses from tick bites, note authors of a study published in JAMA Network Open. But the researchers, led by Diana L. Zychowski, MD, MPH, with the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, found that Ehrlichia or Rickettsia seropositivity was not associated with chronic musculoskeletal symptoms, though they write that “further investigation into the pathogenesis of [alpha-gal] syndrome is needed.”
 

Tick-Borne Illness Cases Multiplying

Cases of tick-borne illness (TBD) in the United States have multiplied in recent years. More than 50,000 cases of TBD in the United States were reported in 2019, which doubled the number of cases over the previous 2 decades, the authors note.

Most of the cases are Lyme disease, but others — including SFGR and ehrlichiosis — represent an important public health threat, especially in southeastern states, the authors write. Cases of ehrlichiosis, for example, transmitted by the lone star tick, soared more than 10-fold since 2000.

The goal of this study was to evaluate whether there was an association between prior exposure to TBDs endemic to the southeastern United States and chronic musculoskeletal symptoms and radiographic measures of osteoarthritis.

Researchers analyzed 488 blood samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing population-based study in Johnston County, North Carolina. JoCo OA participants include noninstitutionalized White and Black Johnston County residents 45 years old or older with osteoarthritis.

They measured seroprevalence of Rickettsia- and Ehrlichia-specific immunoglobulin G (IgG) as well as alpha-gal immunoglobulin E (IgE) in patient samples. Only alpha-gal IgE was linked in the study with knee pain, aching, or stiffness. Antibodies to Rickettsia, Ehrlichia, and alpha-gal were not associated with radiographic, symptomatic knee osteoarthritis.

“To our knowledge,” the authors write, “this study was the first population-based seroprevalence study of SFGR, Ehrlichia, and [alpha]-gal.”

The study also found a high prevalence of TBD exposure in the cohort. More than a third (36.5%) had either an alpha-gal IgE level greater than 0.1 IU/mL, a positive test for SFGR IgG antibodies, or a positive test for Ehrlichia IgG antibodies.

Given that not every tick carries an infectious pathogen, the findings show human-tick interactions are common, they write.

“These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions,” the authors conclude.

This study was funded by a Creativity Hub Award from the University of North Carolina Office of the Vice Chancellor for Research. The JoCo OA project is supported in part by grants from the Association of Schools of Public Health/Centers for Disease Control and Prevention (CDC); and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Authors reported grants from the National Institutes of Health, the CDC, and several pharmaceutical companies.

Non–Lyme disease, tick-borne illnesses — such as spotted fever group rickettsiosis (SFGR), ehrlichiosis, and alpha-gal syndrome (AGS) — are emerging public health threats, but whether prior tick exposures are responsible for long-term complications, such as musculoskeletal symptoms or osteoarthritis, has been unclear.

Many patients attribute their nonspecific long-term symptoms, such as musculoskeletal pain, to previous illnesses from tick bites, note authors of a study published in JAMA Network Open. But the researchers, led by Diana L. Zychowski, MD, MPH, with the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, found that Ehrlichia or Rickettsia seropositivity was not associated with chronic musculoskeletal symptoms, though they write that “further investigation into the pathogenesis of [alpha-gal] syndrome is needed.”
 

Tick-Borne Illness Cases Multiplying

Cases of tick-borne illness (TBD) in the United States have multiplied in recent years. More than 50,000 cases of TBD in the United States were reported in 2019, which doubled the number of cases over the previous 2 decades, the authors note.

Most of the cases are Lyme disease, but others — including SFGR and ehrlichiosis — represent an important public health threat, especially in southeastern states, the authors write. Cases of ehrlichiosis, for example, transmitted by the lone star tick, soared more than 10-fold since 2000.

The goal of this study was to evaluate whether there was an association between prior exposure to TBDs endemic to the southeastern United States and chronic musculoskeletal symptoms and radiographic measures of osteoarthritis.

Researchers analyzed 488 blood samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing population-based study in Johnston County, North Carolina. JoCo OA participants include noninstitutionalized White and Black Johnston County residents 45 years old or older with osteoarthritis.

They measured seroprevalence of Rickettsia- and Ehrlichia-specific immunoglobulin G (IgG) as well as alpha-gal immunoglobulin E (IgE) in patient samples. Only alpha-gal IgE was linked in the study with knee pain, aching, or stiffness. Antibodies to Rickettsia, Ehrlichia, and alpha-gal were not associated with radiographic, symptomatic knee osteoarthritis.

“To our knowledge,” the authors write, “this study was the first population-based seroprevalence study of SFGR, Ehrlichia, and [alpha]-gal.”

The study also found a high prevalence of TBD exposure in the cohort. More than a third (36.5%) had either an alpha-gal IgE level greater than 0.1 IU/mL, a positive test for SFGR IgG antibodies, or a positive test for Ehrlichia IgG antibodies.

Given that not every tick carries an infectious pathogen, the findings show human-tick interactions are common, they write.

“These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions,” the authors conclude.

This study was funded by a Creativity Hub Award from the University of North Carolina Office of the Vice Chancellor for Research. The JoCo OA project is supported in part by grants from the Association of Schools of Public Health/Centers for Disease Control and Prevention (CDC); and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Authors reported grants from the National Institutes of Health, the CDC, and several pharmaceutical companies.

Non–Lyme disease, tick-borne illnesses — such as spotted fever group rickettsiosis (SFGR), ehrlichiosis, and alpha-gal syndrome (AGS) — are emerging public health threats, but whether prior tick exposures are responsible for long-term complications, such as musculoskeletal symptoms or osteoarthritis, has been unclear.

Many patients attribute their nonspecific long-term symptoms, such as musculoskeletal pain, to previous illnesses from tick bites, note authors of a study published in JAMA Network Open. But the researchers, led by Diana L. Zychowski, MD, MPH, with the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, found that Ehrlichia or Rickettsia seropositivity was not associated with chronic musculoskeletal symptoms, though they write that “further investigation into the pathogenesis of [alpha-gal] syndrome is needed.”
 

Tick-Borne Illness Cases Multiplying

Cases of tick-borne illness (TBD) in the United States have multiplied in recent years. More than 50,000 cases of TBD in the United States were reported in 2019, which doubled the number of cases over the previous 2 decades, the authors note.

Most of the cases are Lyme disease, but others — including SFGR and ehrlichiosis — represent an important public health threat, especially in southeastern states, the authors write. Cases of ehrlichiosis, for example, transmitted by the lone star tick, soared more than 10-fold since 2000.

The goal of this study was to evaluate whether there was an association between prior exposure to TBDs endemic to the southeastern United States and chronic musculoskeletal symptoms and radiographic measures of osteoarthritis.

Researchers analyzed 488 blood samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing population-based study in Johnston County, North Carolina. JoCo OA participants include noninstitutionalized White and Black Johnston County residents 45 years old or older with osteoarthritis.

They measured seroprevalence of Rickettsia- and Ehrlichia-specific immunoglobulin G (IgG) as well as alpha-gal immunoglobulin E (IgE) in patient samples. Only alpha-gal IgE was linked in the study with knee pain, aching, or stiffness. Antibodies to Rickettsia, Ehrlichia, and alpha-gal were not associated with radiographic, symptomatic knee osteoarthritis.

“To our knowledge,” the authors write, “this study was the first population-based seroprevalence study of SFGR, Ehrlichia, and [alpha]-gal.”

The study also found a high prevalence of TBD exposure in the cohort. More than a third (36.5%) had either an alpha-gal IgE level greater than 0.1 IU/mL, a positive test for SFGR IgG antibodies, or a positive test for Ehrlichia IgG antibodies.

Given that not every tick carries an infectious pathogen, the findings show human-tick interactions are common, they write.

“These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions,” the authors conclude.

This study was funded by a Creativity Hub Award from the University of North Carolina Office of the Vice Chancellor for Research. The JoCo OA project is supported in part by grants from the Association of Schools of Public Health/Centers for Disease Control and Prevention (CDC); and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Authors reported grants from the National Institutes of Health, the CDC, and several pharmaceutical companies.

When they started the open biopsy, surgeons didn’t know what they were going to find, but they certainly didn’t expect this.

The stringlike worm was five-sixteenths of an inch long, was alive, and wiggled.

“It stunned everyone in that operating theater,” Sanjaya Senanayake, MBBS, an associate professor of infectious disease at Australian National University, Canberra, and senior author of the case report, said in an interview. “When you operate on a brain, you don’t expect to find anything alive.”

The parasitic worm was about half the width of a dime. Helminths like it can usually be seen with the naked eye but are often found in the intestines after being transmitted by soil and infecting the gastrointestinal tract. But this one made it into a woman’s brain in a first-of-its-kind case reported in the journal Emerging Infectious Diseases).

“We weren’t suspecting a worm at all,” Dr. Senanayake said. “There was something abnormal there. Was it going to be granulomatous lesion? Was it going to be cancer? Who knows, but it needed to be biopsied, and a worm was the last thing at the back of anyone’s mind,” he said.
 

A year of inexplicable symptoms

The 64-year-old woman was diagnosed with pneumonia and had a high white blood cell count, low hemoglobin, high platelets, and a very high C-reactive protein of 102 mg/L.

She hadn’t fully recovered from her illness when the abdominal pain and diarrhea started. And then she had a dry cough and night sweats.

After 3 weeks of discomfort, she was admitted to the hospital. She had a history of diabetes, hypothyroidism, and depression, and doctors began looking for answers to her acute illness.

They tested for autoimmune diseases and parasitic infections and prescribed prednisolone to help ease symptoms.

But 3 weeks later, her fever and cough persisted, and she was readmitted to the hospital. Doctors ordered more tests, and her eosinophils were still high, plus there were lesions on her liver, spleen, and lungs.

But tests were negative for bacterial, fungal, and mycobacterial cultures. Her stools showed no evidence of parasites.

She was prescribed mycophenolate and then ivermectin in case her tests for roundworm were a false negative. Doctors suspected Strongyloides, but lesions remained on her spleen even as the liver and lung lesions improved.

Reducing the prednisolone dose affected respiratory symptoms, so by January 2022, a year after initial symptoms began, the medical team added the monoclonal antibody mepolizumab. But her symptoms worsened, and she developed forgetfulness and more depression.

After a brain MRI revealed a right frontal lobe lesion, the team recommended an open biopsy and discovered the worm. The specimen was Ophidascaris robertsi, the intestinal roundworm typically of the carpet python. Never before seen in a human, the only other animals in its life cycle are small marsupials or mammals consumed by pythons.
 

A snake’s bug

Although this is the first case of an Ophidascaris infection in a human, other cases could occur, warn the doctors in their case report.

The best guess for how the patient contracted the infection was by inadvertently consuming larval eggs on wild vegetation that she collected near her home to eat. She lived near a lake known to be home to carpet pythons, so the eggs could have been on the plants she collected or on her hands or kitchen equipment.

“If you’re foraging or using native grasses or plants in recipes, it would be a good idea to cook those instead of having a salad,” Dr. Senanayake said. “That would make the chance of getting something really rare even less likely.”

It’s unclear how or why the worm, which usually stays in the gut, made its way into the patient’s brain, but her long course of immunosuppressing drugs may have played a role, the team points out. “If the normal immune barriers are reduced, then it’s easier for the parasite to move around between organ systems,” Dr. Senanayake said.

Doctors also wondered if she may have been getting re-infected when she went home between hospital admissions. After removing the worm, she received 4 weeks of treatment with albendazole to eliminate any other possible larvae in other organs, especially since Ophidascaris larvae have been known to survive for long periods – more than 4 years in laboratory rats. “The hope is that she’s been cured of this parasitic infection,” Dr. Senanayake said.

As people around the world contend with the global COVID pandemic, they might not realize that new infections are arising around the world every year, he explained.
 

Novel parasitic infections

“The reality is that 30 new infections appeared in the last 30 years, and three-quarters of them are zoonotic, animal infections spilling over into the human world,” Dr. Senanayake said.

Though some of that number is the result of improved surveillance and diagnostics, a real increase has been occurring as human settlements continue expanding.

“This is just a reflection of how burgeoning human populations are encroaching upon animal habitats, and we’re getting more interactions between humans and wild animals, domestic animals and wild animals, and humans and natural flora, which is increasing the risk of this type of infection being recognized,” he explained.

The Ophidascaris worm found in this instance is in other snake species in different continents around the world, too. “Awareness of this case will hopefully lead to the diagnosis and treatment of other cases,” Dr. Senanayake added.

Though it’s certainly surprising to find this particular parasite in a human, finding a zoonotic organism in a person isn’t that strange, according to Janet Foley, DVM, PhD, a professor of veterinary medicine at the University of California, Davis. This is especially true if the usual host is closely related to humans, like primates, or spends a lot of time around them, like rats.

“There are still a lot of parasites and diseases out there in wildlife that haven’t been discovered, and we don’t know the risk,” said Dr. Foley. “But still, the risk would have to be low, generally, or we would see more human cases.”

In the United States, the roundworm common in raccoon feces is Baylisascaris procyonis and can be dangerous for people. “There have been deaths in people exposed to these worms, which do seem to prefer to travel to a human brain,” Dr. Foley said.

A 2016 Centers for Disease Control and Prevention report described seven U.S. cases identified between May 2013 and December 2015, including six that caused central nervous system disease. Another case report in 2018 involved a toddler who had eaten dirt and animal feces in his backyard.

And this past June, an Emerging Infectious Diseases case report described a B. procyonis infection in a 7-year-old with autism spectrum disorder and a history of pica. He had put material in his mouth from the ground near a tree where epidemiologists later found raccoon feces.

Still, Dr. Senanayake cautions against people jumping to conclusions about parasitic infections when they experience symptoms that aren’t otherwise immediately explainable.

The typical person who develops forgetfulness, depression, and a fever probably doesn’t have a worm in their brain or need an immediate MRI, he pointed out. “There may be other cases out there, but common things happen commonly, and this is likely to be rare,” Dr. Senanayake said.

This case demonstrates the challenge in picking a course of treatment when the differential diagnoses for hypereosinophilic syndromes is so broad.
 

Tricky hypereosinophilic syndromes

One of those differentials for the syndromes is parasitic infections, for which treatment would be antiparasitic agents, but another differential is an autoimmune condition that would call for immunosuppression.

“Obviously, as with this case, you don’t want to give someone immunosuppressive treatment if they’ve got a parasite, so you want to look really hard for a parasite before you start them on immunosuppressive treatment for an immunological condition,” Dr. Senanayake said.

But all the blood tests for different antibodies came back negative for parasites, “and this parasite was simply difficult to find until they pulled it from her brain,” he said.

Infectious disease physicians are always looking for the unusual and exotic, Dr. Senanayake explained. But it’s important to exclude the common, easy things first, he added. It’s after exhausting all the likely culprits that “you have to start really thinking laterally and putting resources into unusual tests.”

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

When they started the open biopsy, surgeons didn’t know what they were going to find, but they certainly didn’t expect this.

The stringlike worm was five-sixteenths of an inch long, was alive, and wiggled.

“It stunned everyone in that operating theater,” Sanjaya Senanayake, MBBS, an associate professor of infectious disease at Australian National University, Canberra, and senior author of the case report, said in an interview. “When you operate on a brain, you don’t expect to find anything alive.”

The parasitic worm was about half the width of a dime. Helminths like it can usually be seen with the naked eye but are often found in the intestines after being transmitted by soil and infecting the gastrointestinal tract. But this one made it into a woman’s brain in a first-of-its-kind case reported in the journal Emerging Infectious Diseases).

“We weren’t suspecting a worm at all,” Dr. Senanayake said. “There was something abnormal there. Was it going to be granulomatous lesion? Was it going to be cancer? Who knows, but it needed to be biopsied, and a worm was the last thing at the back of anyone’s mind,” he said.
 

A year of inexplicable symptoms

The 64-year-old woman was diagnosed with pneumonia and had a high white blood cell count, low hemoglobin, high platelets, and a very high C-reactive protein of 102 mg/L.

She hadn’t fully recovered from her illness when the abdominal pain and diarrhea started. And then she had a dry cough and night sweats.

After 3 weeks of discomfort, she was admitted to the hospital. She had a history of diabetes, hypothyroidism, and depression, and doctors began looking for answers to her acute illness.

They tested for autoimmune diseases and parasitic infections and prescribed prednisolone to help ease symptoms.

But 3 weeks later, her fever and cough persisted, and she was readmitted to the hospital. Doctors ordered more tests, and her eosinophils were still high, plus there were lesions on her liver, spleen, and lungs.

But tests were negative for bacterial, fungal, and mycobacterial cultures. Her stools showed no evidence of parasites.

She was prescribed mycophenolate and then ivermectin in case her tests for roundworm were a false negative. Doctors suspected Strongyloides, but lesions remained on her spleen even as the liver and lung lesions improved.

Reducing the prednisolone dose affected respiratory symptoms, so by January 2022, a year after initial symptoms began, the medical team added the monoclonal antibody mepolizumab. But her symptoms worsened, and she developed forgetfulness and more depression.

After a brain MRI revealed a right frontal lobe lesion, the team recommended an open biopsy and discovered the worm. The specimen was Ophidascaris robertsi, the intestinal roundworm typically of the carpet python. Never before seen in a human, the only other animals in its life cycle are small marsupials or mammals consumed by pythons.
 

A snake’s bug

Although this is the first case of an Ophidascaris infection in a human, other cases could occur, warn the doctors in their case report.

The best guess for how the patient contracted the infection was by inadvertently consuming larval eggs on wild vegetation that she collected near her home to eat. She lived near a lake known to be home to carpet pythons, so the eggs could have been on the plants she collected or on her hands or kitchen equipment.

“If you’re foraging or using native grasses or plants in recipes, it would be a good idea to cook those instead of having a salad,” Dr. Senanayake said. “That would make the chance of getting something really rare even less likely.”

It’s unclear how or why the worm, which usually stays in the gut, made its way into the patient’s brain, but her long course of immunosuppressing drugs may have played a role, the team points out. “If the normal immune barriers are reduced, then it’s easier for the parasite to move around between organ systems,” Dr. Senanayake said.

Doctors also wondered if she may have been getting re-infected when she went home between hospital admissions. After removing the worm, she received 4 weeks of treatment with albendazole to eliminate any other possible larvae in other organs, especially since Ophidascaris larvae have been known to survive for long periods – more than 4 years in laboratory rats. “The hope is that she’s been cured of this parasitic infection,” Dr. Senanayake said.

As people around the world contend with the global COVID pandemic, they might not realize that new infections are arising around the world every year, he explained.
 

Novel parasitic infections

“The reality is that 30 new infections appeared in the last 30 years, and three-quarters of them are zoonotic, animal infections spilling over into the human world,” Dr. Senanayake said.

Though some of that number is the result of improved surveillance and diagnostics, a real increase has been occurring as human settlements continue expanding.

“This is just a reflection of how burgeoning human populations are encroaching upon animal habitats, and we’re getting more interactions between humans and wild animals, domestic animals and wild animals, and humans and natural flora, which is increasing the risk of this type of infection being recognized,” he explained.

The Ophidascaris worm found in this instance is in other snake species in different continents around the world, too. “Awareness of this case will hopefully lead to the diagnosis and treatment of other cases,” Dr. Senanayake added.

Though it’s certainly surprising to find this particular parasite in a human, finding a zoonotic organism in a person isn’t that strange, according to Janet Foley, DVM, PhD, a professor of veterinary medicine at the University of California, Davis. This is especially true if the usual host is closely related to humans, like primates, or spends a lot of time around them, like rats.

“There are still a lot of parasites and diseases out there in wildlife that haven’t been discovered, and we don’t know the risk,” said Dr. Foley. “But still, the risk would have to be low, generally, or we would see more human cases.”

In the United States, the roundworm common in raccoon feces is Baylisascaris procyonis and can be dangerous for people. “There have been deaths in people exposed to these worms, which do seem to prefer to travel to a human brain,” Dr. Foley said.

A 2016 Centers for Disease Control and Prevention report described seven U.S. cases identified between May 2013 and December 2015, including six that caused central nervous system disease. Another case report in 2018 involved a toddler who had eaten dirt and animal feces in his backyard.

And this past June, an Emerging Infectious Diseases case report described a B. procyonis infection in a 7-year-old with autism spectrum disorder and a history of pica. He had put material in his mouth from the ground near a tree where epidemiologists later found raccoon feces.

Still, Dr. Senanayake cautions against people jumping to conclusions about parasitic infections when they experience symptoms that aren’t otherwise immediately explainable.

The typical person who develops forgetfulness, depression, and a fever probably doesn’t have a worm in their brain or need an immediate MRI, he pointed out. “There may be other cases out there, but common things happen commonly, and this is likely to be rare,” Dr. Senanayake said.

This case demonstrates the challenge in picking a course of treatment when the differential diagnoses for hypereosinophilic syndromes is so broad.
 

Tricky hypereosinophilic syndromes

One of those differentials for the syndromes is parasitic infections, for which treatment would be antiparasitic agents, but another differential is an autoimmune condition that would call for immunosuppression.

“Obviously, as with this case, you don’t want to give someone immunosuppressive treatment if they’ve got a parasite, so you want to look really hard for a parasite before you start them on immunosuppressive treatment for an immunological condition,” Dr. Senanayake said.

But all the blood tests for different antibodies came back negative for parasites, “and this parasite was simply difficult to find until they pulled it from her brain,” he said.

Infectious disease physicians are always looking for the unusual and exotic, Dr. Senanayake explained. But it’s important to exclude the common, easy things first, he added. It’s after exhausting all the likely culprits that “you have to start really thinking laterally and putting resources into unusual tests.”

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

When they started the open biopsy, surgeons didn’t know what they were going to find, but they certainly didn’t expect this.

The stringlike worm was five-sixteenths of an inch long, was alive, and wiggled.

“It stunned everyone in that operating theater,” Sanjaya Senanayake, MBBS, an associate professor of infectious disease at Australian National University, Canberra, and senior author of the case report, said in an interview. “When you operate on a brain, you don’t expect to find anything alive.”

The parasitic worm was about half the width of a dime. Helminths like it can usually be seen with the naked eye but are often found in the intestines after being transmitted by soil and infecting the gastrointestinal tract. But this one made it into a woman’s brain in a first-of-its-kind case reported in the journal Emerging Infectious Diseases).

“We weren’t suspecting a worm at all,” Dr. Senanayake said. “There was something abnormal there. Was it going to be granulomatous lesion? Was it going to be cancer? Who knows, but it needed to be biopsied, and a worm was the last thing at the back of anyone’s mind,” he said.
 

A year of inexplicable symptoms

The 64-year-old woman was diagnosed with pneumonia and had a high white blood cell count, low hemoglobin, high platelets, and a very high C-reactive protein of 102 mg/L.

She hadn’t fully recovered from her illness when the abdominal pain and diarrhea started. And then she had a dry cough and night sweats.

After 3 weeks of discomfort, she was admitted to the hospital. She had a history of diabetes, hypothyroidism, and depression, and doctors began looking for answers to her acute illness.

They tested for autoimmune diseases and parasitic infections and prescribed prednisolone to help ease symptoms.

But 3 weeks later, her fever and cough persisted, and she was readmitted to the hospital. Doctors ordered more tests, and her eosinophils were still high, plus there were lesions on her liver, spleen, and lungs.

But tests were negative for bacterial, fungal, and mycobacterial cultures. Her stools showed no evidence of parasites.

She was prescribed mycophenolate and then ivermectin in case her tests for roundworm were a false negative. Doctors suspected Strongyloides, but lesions remained on her spleen even as the liver and lung lesions improved.

Reducing the prednisolone dose affected respiratory symptoms, so by January 2022, a year after initial symptoms began, the medical team added the monoclonal antibody mepolizumab. But her symptoms worsened, and she developed forgetfulness and more depression.

After a brain MRI revealed a right frontal lobe lesion, the team recommended an open biopsy and discovered the worm. The specimen was Ophidascaris robertsi, the intestinal roundworm typically of the carpet python. Never before seen in a human, the only other animals in its life cycle are small marsupials or mammals consumed by pythons.
 

A snake’s bug

Although this is the first case of an Ophidascaris infection in a human, other cases could occur, warn the doctors in their case report.

The best guess for how the patient contracted the infection was by inadvertently consuming larval eggs on wild vegetation that she collected near her home to eat. She lived near a lake known to be home to carpet pythons, so the eggs could have been on the plants she collected or on her hands or kitchen equipment.

“If you’re foraging or using native grasses or plants in recipes, it would be a good idea to cook those instead of having a salad,” Dr. Senanayake said. “That would make the chance of getting something really rare even less likely.”

It’s unclear how or why the worm, which usually stays in the gut, made its way into the patient’s brain, but her long course of immunosuppressing drugs may have played a role, the team points out. “If the normal immune barriers are reduced, then it’s easier for the parasite to move around between organ systems,” Dr. Senanayake said.

Doctors also wondered if she may have been getting re-infected when she went home between hospital admissions. After removing the worm, she received 4 weeks of treatment with albendazole to eliminate any other possible larvae in other organs, especially since Ophidascaris larvae have been known to survive for long periods – more than 4 years in laboratory rats. “The hope is that she’s been cured of this parasitic infection,” Dr. Senanayake said.

As people around the world contend with the global COVID pandemic, they might not realize that new infections are arising around the world every year, he explained.
 

Novel parasitic infections

“The reality is that 30 new infections appeared in the last 30 years, and three-quarters of them are zoonotic, animal infections spilling over into the human world,” Dr. Senanayake said.

Though some of that number is the result of improved surveillance and diagnostics, a real increase has been occurring as human settlements continue expanding.

“This is just a reflection of how burgeoning human populations are encroaching upon animal habitats, and we’re getting more interactions between humans and wild animals, domestic animals and wild animals, and humans and natural flora, which is increasing the risk of this type of infection being recognized,” he explained.

The Ophidascaris worm found in this instance is in other snake species in different continents around the world, too. “Awareness of this case will hopefully lead to the diagnosis and treatment of other cases,” Dr. Senanayake added.

Though it’s certainly surprising to find this particular parasite in a human, finding a zoonotic organism in a person isn’t that strange, according to Janet Foley, DVM, PhD, a professor of veterinary medicine at the University of California, Davis. This is especially true if the usual host is closely related to humans, like primates, or spends a lot of time around them, like rats.

“There are still a lot of parasites and diseases out there in wildlife that haven’t been discovered, and we don’t know the risk,” said Dr. Foley. “But still, the risk would have to be low, generally, or we would see more human cases.”

In the United States, the roundworm common in raccoon feces is Baylisascaris procyonis and can be dangerous for people. “There have been deaths in people exposed to these worms, which do seem to prefer to travel to a human brain,” Dr. Foley said.

A 2016 Centers for Disease Control and Prevention report described seven U.S. cases identified between May 2013 and December 2015, including six that caused central nervous system disease. Another case report in 2018 involved a toddler who had eaten dirt and animal feces in his backyard.

And this past June, an Emerging Infectious Diseases case report described a B. procyonis infection in a 7-year-old with autism spectrum disorder and a history of pica. He had put material in his mouth from the ground near a tree where epidemiologists later found raccoon feces.

Still, Dr. Senanayake cautions against people jumping to conclusions about parasitic infections when they experience symptoms that aren’t otherwise immediately explainable.

The typical person who develops forgetfulness, depression, and a fever probably doesn’t have a worm in their brain or need an immediate MRI, he pointed out. “There may be other cases out there, but common things happen commonly, and this is likely to be rare,” Dr. Senanayake said.

This case demonstrates the challenge in picking a course of treatment when the differential diagnoses for hypereosinophilic syndromes is so broad.
 

Tricky hypereosinophilic syndromes

One of those differentials for the syndromes is parasitic infections, for which treatment would be antiparasitic agents, but another differential is an autoimmune condition that would call for immunosuppression.

“Obviously, as with this case, you don’t want to give someone immunosuppressive treatment if they’ve got a parasite, so you want to look really hard for a parasite before you start them on immunosuppressive treatment for an immunological condition,” Dr. Senanayake said.

But all the blood tests for different antibodies came back negative for parasites, “and this parasite was simply difficult to find until they pulled it from her brain,” he said.

Infectious disease physicians are always looking for the unusual and exotic, Dr. Senanayake explained. But it’s important to exclude the common, easy things first, he added. It’s after exhausting all the likely culprits that “you have to start really thinking laterally and putting resources into unusual tests.”

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

Several signs are pointing to an impending surge in the number of human cases of West Nile virus in several regions of the United States.

West Nile virus is spread by infected mosquitoes and currently there is no cure or virus-specific treatment. In rare cases, it can be deadly. It can infect humans, birds, horses, and other mammals.

West Nile Virus is the leading cause of mosquito-borne disease in the continental United States. As of Aug. 8, 126 human cases had been identified across 22 states, according to the Centers for Disease Control and Prevention.

“Particularly here in California, it’s peak risk right now,” said Vicki Kramer, PhD, chief of vector-borne diseases in the California Department of Public Health. She said scientists there are seeing higher mosquito and infected mosquito numbers.
 

“Peak risk right now”

Dead birds are tested for the virus and by Aug. 4, 181 of the 913 birds tested in California have been positive, three times the total testing positive by this time in 2022.

“Last year at this time, we had 60 positive dead birds out of 817 tested,” Dr. Kramer said.

Severe flooding and high heat can contribute to the rise in mosquito populations and many parts of the country have seen plenty of both.

One of the ways scientists track infected mosquito patterns in California is by using flocks of strategically placed sentinel chickens.

“Chickens are a mosquito magnet,” Dr. Kramer said.

Chickens don’t get sick with the virus, but they do build antibodies to it. Surveillance teams check their blood every other week to track the virus.

Daniel Pastula, MD, MHS, chief of neuroinfectious diseases and global neurology at the University of Colorado School of Medicine and the Colorado School of Public Health, said the state is watching troubling signs as well.

“The concern this year,” Dr. Pastula said, “particularly along the Front Range in Colorado, is we’ve found many more mosquitoes [that are] positive for West Nile earlier in the season compared with other years.

“We’re bracing for higher-than-baseline human cases,” he said.

Asked about this year’s first human case, reported in Toronto, a region with a long winter and low incidence of the virus, he said that provides a further example that people need to be prepared even in climates not known to be mosquito-dense.

He added, however, that climate is only one factor in the severity of the season. Others include birds’ immunity and migratory patterns.

Dr. Pastula said that fluctuations in temperature and rainfall are rising with climate change and are disrupting normal baseline levels of West Nile.

“That shows we need to be prepared for West Nile virus and other mosquito-borne diseases in any place in North America or really the world. We recently saw malaria cases in the southern United States. It just shows you how dangerous mosquitoes can be.”
 

Avoid mosquito bites

Dr. Pastula and Dr. Kramer list the precautions people can take to protect themselves from West Nile virus:

• Limit outdoor exposure particularly at dusk and dawn.
• Wear protective clothing.
• Use .
• Repair window screens so mosquitoes cannot fly through.
• Dump and drain standing water on your property and maintain swimming pools.

Dr. Pastula noted that summer is the time human cases start to mount – typically from July and August to the first hard freeze.

“We have been warning people here up and down the Front Range of Colorado to take prevention very seriously,” Dr. Pastula said.

He pointed out that 80% who are infected with West Nile will have no symptoms.

About 20% will have flu-like illness – high fever, body and joint aches, rash, diarrhea, or headaches. Symptoms may last for weeks. About 1% of the time, he said, people can get neuroinvasive West Nile.

Dr. Pastula explained that the virus can infect the covering of the brain and spinal cord causing meningitis with very high fever, severe headaches, stiff neck, and sensitivity to light.

So far this year, there have been 89 neuroinvasive cases reported nationally, according to the CDC.

With West Nile encephalitis, the virus “can infect the brain itself causing altered mental status, movement disorders, or weakness,” Dr. Pastula said.

Sometimes it can infect the gray matter of the spinal cord causing a West Nile virus poliomyelitis, which brings polio-like symptoms.

“The West Nile encephalitis and poliomyelitis can cause permanent deficits or even death,” he said. “It’s uncommon but it’s not trivial.”

Several vaccine candidates are in development, Dr. Pastula said, but none has reached clinical trials. Part of the reason for that, he said, is that scientists must be able to predict the timing of an outbreak.

“We’re not really great at predicting outbreaks,” he said.

Although the risk for neuroinvasive disease is small, it can be higher in certain groups, he said – those who are over age 60 years or are immunocompromised; those who have diabetes, cancer, or kidney disease; or those who have undergone organ transplants.

Those infected should see a health care professional and may be able to get relief with the usual medications for flu-like illness.

Some with severe infection may need to go to the hospital, Dr. Pastula said.
 

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

Several signs are pointing to an impending surge in the number of human cases of West Nile virus in several regions of the United States.

West Nile virus is spread by infected mosquitoes and currently there is no cure or virus-specific treatment. In rare cases, it can be deadly. It can infect humans, birds, horses, and other mammals.

West Nile Virus is the leading cause of mosquito-borne disease in the continental United States. As of Aug. 8, 126 human cases had been identified across 22 states, according to the Centers for Disease Control and Prevention.

“Particularly here in California, it’s peak risk right now,” said Vicki Kramer, PhD, chief of vector-borne diseases in the California Department of Public Health. She said scientists there are seeing higher mosquito and infected mosquito numbers.
 

“Peak risk right now”

Dead birds are tested for the virus and by Aug. 4, 181 of the 913 birds tested in California have been positive, three times the total testing positive by this time in 2022.

“Last year at this time, we had 60 positive dead birds out of 817 tested,” Dr. Kramer said.

Severe flooding and high heat can contribute to the rise in mosquito populations and many parts of the country have seen plenty of both.

One of the ways scientists track infected mosquito patterns in California is by using flocks of strategically placed sentinel chickens.

“Chickens are a mosquito magnet,” Dr. Kramer said.

Chickens don’t get sick with the virus, but they do build antibodies to it. Surveillance teams check their blood every other week to track the virus.

Daniel Pastula, MD, MHS, chief of neuroinfectious diseases and global neurology at the University of Colorado School of Medicine and the Colorado School of Public Health, said the state is watching troubling signs as well.

“The concern this year,” Dr. Pastula said, “particularly along the Front Range in Colorado, is we’ve found many more mosquitoes [that are] positive for West Nile earlier in the season compared with other years.

“We’re bracing for higher-than-baseline human cases,” he said.

Asked about this year’s first human case, reported in Toronto, a region with a long winter and low incidence of the virus, he said that provides a further example that people need to be prepared even in climates not known to be mosquito-dense.

He added, however, that climate is only one factor in the severity of the season. Others include birds’ immunity and migratory patterns.

Dr. Pastula said that fluctuations in temperature and rainfall are rising with climate change and are disrupting normal baseline levels of West Nile.

“That shows we need to be prepared for West Nile virus and other mosquito-borne diseases in any place in North America or really the world. We recently saw malaria cases in the southern United States. It just shows you how dangerous mosquitoes can be.”
 

Avoid mosquito bites

Dr. Pastula and Dr. Kramer list the precautions people can take to protect themselves from West Nile virus:

• Limit outdoor exposure particularly at dusk and dawn.
• Wear protective clothing.
• Use .
• Repair window screens so mosquitoes cannot fly through.
• Dump and drain standing water on your property and maintain swimming pools.

Dr. Pastula noted that summer is the time human cases start to mount – typically from July and August to the first hard freeze.

“We have been warning people here up and down the Front Range of Colorado to take prevention very seriously,” Dr. Pastula said.

He pointed out that 80% who are infected with West Nile will have no symptoms.

About 20% will have flu-like illness – high fever, body and joint aches, rash, diarrhea, or headaches. Symptoms may last for weeks. About 1% of the time, he said, people can get neuroinvasive West Nile.

Dr. Pastula explained that the virus can infect the covering of the brain and spinal cord causing meningitis with very high fever, severe headaches, stiff neck, and sensitivity to light.

So far this year, there have been 89 neuroinvasive cases reported nationally, according to the CDC.

With West Nile encephalitis, the virus “can infect the brain itself causing altered mental status, movement disorders, or weakness,” Dr. Pastula said.

Sometimes it can infect the gray matter of the spinal cord causing a West Nile virus poliomyelitis, which brings polio-like symptoms.

“The West Nile encephalitis and poliomyelitis can cause permanent deficits or even death,” he said. “It’s uncommon but it’s not trivial.”

Several vaccine candidates are in development, Dr. Pastula said, but none has reached clinical trials. Part of the reason for that, he said, is that scientists must be able to predict the timing of an outbreak.

“We’re not really great at predicting outbreaks,” he said.

Although the risk for neuroinvasive disease is small, it can be higher in certain groups, he said – those who are over age 60 years or are immunocompromised; those who have diabetes, cancer, or kidney disease; or those who have undergone organ transplants.

Those infected should see a health care professional and may be able to get relief with the usual medications for flu-like illness.

Some with severe infection may need to go to the hospital, Dr. Pastula said.
 

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

Several signs are pointing to an impending surge in the number of human cases of West Nile virus in several regions of the United States.

West Nile virus is spread by infected mosquitoes and currently there is no cure or virus-specific treatment. In rare cases, it can be deadly. It can infect humans, birds, horses, and other mammals.

West Nile Virus is the leading cause of mosquito-borne disease in the continental United States. As of Aug. 8, 126 human cases had been identified across 22 states, according to the Centers for Disease Control and Prevention.

“Particularly here in California, it’s peak risk right now,” said Vicki Kramer, PhD, chief of vector-borne diseases in the California Department of Public Health. She said scientists there are seeing higher mosquito and infected mosquito numbers.
 

“Peak risk right now”

Dead birds are tested for the virus and by Aug. 4, 181 of the 913 birds tested in California have been positive, three times the total testing positive by this time in 2022.

“Last year at this time, we had 60 positive dead birds out of 817 tested,” Dr. Kramer said.

Severe flooding and high heat can contribute to the rise in mosquito populations and many parts of the country have seen plenty of both.

One of the ways scientists track infected mosquito patterns in California is by using flocks of strategically placed sentinel chickens.

“Chickens are a mosquito magnet,” Dr. Kramer said.

Chickens don’t get sick with the virus, but they do build antibodies to it. Surveillance teams check their blood every other week to track the virus.

Daniel Pastula, MD, MHS, chief of neuroinfectious diseases and global neurology at the University of Colorado School of Medicine and the Colorado School of Public Health, said the state is watching troubling signs as well.

“The concern this year,” Dr. Pastula said, “particularly along the Front Range in Colorado, is we’ve found many more mosquitoes [that are] positive for West Nile earlier in the season compared with other years.

“We’re bracing for higher-than-baseline human cases,” he said.

Asked about this year’s first human case, reported in Toronto, a region with a long winter and low incidence of the virus, he said that provides a further example that people need to be prepared even in climates not known to be mosquito-dense.

He added, however, that climate is only one factor in the severity of the season. Others include birds’ immunity and migratory patterns.

Dr. Pastula said that fluctuations in temperature and rainfall are rising with climate change and are disrupting normal baseline levels of West Nile.

“That shows we need to be prepared for West Nile virus and other mosquito-borne diseases in any place in North America or really the world. We recently saw malaria cases in the southern United States. It just shows you how dangerous mosquitoes can be.”
 

Avoid mosquito bites

Dr. Pastula and Dr. Kramer list the precautions people can take to protect themselves from West Nile virus:

• Limit outdoor exposure particularly at dusk and dawn.
• Wear protective clothing.
• Use .
• Repair window screens so mosquitoes cannot fly through.
• Dump and drain standing water on your property and maintain swimming pools.

Dr. Pastula noted that summer is the time human cases start to mount – typically from July and August to the first hard freeze.

“We have been warning people here up and down the Front Range of Colorado to take prevention very seriously,” Dr. Pastula said.

He pointed out that 80% who are infected with West Nile will have no symptoms.

About 20% will have flu-like illness – high fever, body and joint aches, rash, diarrhea, or headaches. Symptoms may last for weeks. About 1% of the time, he said, people can get neuroinvasive West Nile.

Dr. Pastula explained that the virus can infect the covering of the brain and spinal cord causing meningitis with very high fever, severe headaches, stiff neck, and sensitivity to light.

So far this year, there have been 89 neuroinvasive cases reported nationally, according to the CDC.

With West Nile encephalitis, the virus “can infect the brain itself causing altered mental status, movement disorders, or weakness,” Dr. Pastula said.

Sometimes it can infect the gray matter of the spinal cord causing a West Nile virus poliomyelitis, which brings polio-like symptoms.

“The West Nile encephalitis and poliomyelitis can cause permanent deficits or even death,” he said. “It’s uncommon but it’s not trivial.”

Several vaccine candidates are in development, Dr. Pastula said, but none has reached clinical trials. Part of the reason for that, he said, is that scientists must be able to predict the timing of an outbreak.

“We’re not really great at predicting outbreaks,” he said.

Although the risk for neuroinvasive disease is small, it can be higher in certain groups, he said – those who are over age 60 years or are immunocompromised; those who have diabetes, cancer, or kidney disease; or those who have undergone organ transplants.

Those infected should see a health care professional and may be able to get relief with the usual medications for flu-like illness.

Some with severe infection may need to go to the hospital, Dr. Pastula said.
 

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

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Nath_Avindra_MD_web.jpg

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Henrich_Timothy_J_CALIF_web.jpg

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Fallon_Brian_NY_web.jpg

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Putrino_David_NY_web.jpg

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Nath_Avindra_MD_web.jpg

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Henrich_Timothy_J_CALIF_web.jpg

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Fallon_Brian_NY_web.jpg

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Putrino_David_NY_web.jpg

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Nath_Avindra_MD_web.jpg

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Henrich_Timothy_J_CALIF_web.jpg

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

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Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

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It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Several recent developments in Lyme disease treatment and diagnosis may pave the way forward for combating disease that persists following missed or delayed diagnoses or remains following standard treatment. These include combination therapy to address “persister” bacteria and diagnostic tests that test directly for the pathogen and/or indirectly test for host response, according to experts who presented at a 2-day National Academies of Science, Engineering and Medicine workshop on infection-associated chronic illnesses.

Research has shown that 60% of people who are infected and not treated during the early or early disseminated stages of Lyme disease go on to develop late Lyme arthritis, said John Aucott, MD, director of the Johns Hopkins Lyme Disease Clinical Research Center in Baltimore. And in the real world, there’s an additional category of patients: Those who are misdiagnosed and develop infection-related persistent symptoms – such as fatigue, brain fog/cognitive dysfunction, and musculoskeletal problems – that don’t match the “textbook schematic” involving late Lyme arthritis and late neurologic disease.

Aucott_John_MD_web.jpg

Moreover, of patients who are treated with protocols recommended by the Infectious Diseases Society of America (IDSA), about 15% go on to develop persistent symptoms at 6 months – again, symptoms that don’t match textbook manifestations and do match symptoms of other infection-associated chronic illnesses. As a “research construct,” this has been coined posttreatment Lyme disease (PTLD), he said at the workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

(On a practical level, it is hard to know clinically who has early disseminated disease unless they have multiple erythema migrans rashes or neurologic or cardiac involvement, he said after the meeting.)

All this points to the need for tests that are sensitive and specific for diagnosis at all stages of infection and disease, he said in a talk on diagnostics. Currently available tests – those that fit into the widely used two-tiered enzyme-linked immunosorbent assay, Western Blot serology testing – have significant limitations in sensitivity and specificity, including for acute infection when the body has not generated enough antibodies, yet treatment is most likely to succeed.
 

Move toward combination therapy research

Lyme disease is most commonly treated with doxycycline, and that’s problematic because the antibiotic is a microstatic whose efficacy relies on immune clearance of static bacteria, said Monica E. Embers, PhD, director of vector-borne disease at the Tulane National Primate Research Center and associate professor of immunology at Tulane University, New Orleans.

Embers_Monica_LA_web.jpg

“But we know that Borrelia burgdorferi has the capability to evade the host immune response in almost every way possible. Persistence is the norm in an immunocompetent host ... [and] dormant bacteria/persisters are more tolerant of microstatic antibiotics,” she said.

Other considerations for antibiotic efficacy include the fact that B. burgdorferi survives for many months inside ticks without nutrient replenishment or replication, “so dormancy is part of their life cycle,” she said. Moreover, the bacteria can be found deep in connective tissues and joints.

The efficacy of accepted regimens of antibiotic treatment has been “a very contentious issue,” she said, noting that guidelines from the International Lyme and Associated Diseases Society “leave open the possibility for antibiotic retreatment when a chronic infection is judged to be a possible cause [of ongoing symptoms].”

The development of persister B. burgdorferi in the presence of antibiotics has been well studied in vitro, which has limitations, Dr. Embers said. But her group specializes in animal models and has shown persistence of antimicrobial-tolerant B. burgdorferi in tick-inoculated rhesus macaques 8-9 months after treatment with oral doxycycline.

“We [also] saw persistence of mild-moderate inflammation in the brain, peripheral nerves, spinal cord, joints and skeletal muscle, and in the heart,” Dr. Embers said, who coauthored a 2022 review of B. burgdorferi antimicrobial-tolerant persistence in Lyme disease and PTLD.

Her work has also shown that ceftriaxone, which is recommended by IDSA for patients with clinically evident neurological and/or cardiac involvement, does not clear infection in mice. “In general, single drugs have not been capable of clearing the infection, yet combinations show promise,” she said.

Dr. Embers has combed large drug libraries looking for combinations of antibiotics that employ different mechanisms of action in hopes of eliminating persister spirochetes. Certain combinations have shown promise in mice and have been tested in her rhesus macaque model; data analyses are underway.

Other research teams, such as that of Ying Zhang, MD, PhD, at Johns Hopkins, have similarly been screening combinations of antibiotics and other compounds, identifying candidates for further testing.

During a question and answer period, Dr. Embers said her team is also investigating the pathophysiology and long-term effects of tick-borne coinfections, including Bartonella, and is pursuing a hypothesis that infection with Borrelia allows Bartonella to cause more extensive disease and persist longer. “I think Lyme is at the core because of its ability to evade and suppress the immune response so effectively.”
 

Diagnostic possibilities, biomarkers for PTLD

Direct diagnostic tests for microbial nucleic acid and proteins “are promising alternatives for indirect serologic tests,” Dr. Aucott said. For instance, in addition to polymerase chain reaction tests, which “are making advances,” it may be possible to target the B. burgdorferi peptidoglycan for antigen detection.

Researchers have shown that peptidoglycan, a component of the B. burgdorferi cell envelope, is a persistent antigen in the synovial fluid of patients with Lyme arthritis who have been treated with oral and intravenous antibiotics, and that it likely contributes to inflammation.

“Maybe the infection is gone but parts of the bacteria are still there that are driving inflammation,” said Dr. Aucott, also associate professor of medicine at John Hopkins.

Researchers have also been looking at the host response to B. burgdorferi – including cytokines, chemokines, and autoantibiodies – to identify biomarkers for PTLD and to identify patients during posttreatment follow-up who are at increased risk of developing PTLD, with the hope of someday intervening. Persistently high levels of interleukin-23, CCL19, and interferon-alpha have each been associated in different studies with persistent symptoms after treatment, Dr. Aucott said.

In addition, metabolomics research is showing that patients with PTLD have metabolic fingerprints that are different from those who return to good health after treatment, and it may be possible to identify an epigenetic signature for Lyme disease. A project sponsored by the Defense Advanced Research Projects Agency called ECHO (Epigenetic Characterization and Observation) aims to identify epigenetic signatures of exposures to various threats, including B. burgdorferi.

“At the very proximal end of [indirectly testing for host response], there are modifications of the DNA that can occur in response to infectious insults ... and that changed DNA changes RNA expression and protein synthesis,” Dr. Aucott explained. DARPA’s project is “exciting because their goal [at DARPA] is to have a diagnostic test quickly as a result of this epigenetics work.”

Imaging research is also fast offering diagnostic opportunities, Dr. Aucott said. Levels of microglial activation on brain PET imaging have been found to correlate with PTLD, and a study at Johns Hopkins of multimodal neuroimaging with functional MRI and diffusion tensor imaging has shown distinct changes to white matter activation within the frontal lobe of patients with PTLD, compared with controls.

The NASEM workshop did not collect or require disclosures of its participants.

Several recent developments in Lyme disease treatment and diagnosis may pave the way forward for combating disease that persists following missed or delayed diagnoses or remains following standard treatment. These include combination therapy to address “persister” bacteria and diagnostic tests that test directly for the pathogen and/or indirectly test for host response, according to experts who presented at a 2-day National Academies of Science, Engineering and Medicine workshop on infection-associated chronic illnesses.

Research has shown that 60% of people who are infected and not treated during the early or early disseminated stages of Lyme disease go on to develop late Lyme arthritis, said John Aucott, MD, director of the Johns Hopkins Lyme Disease Clinical Research Center in Baltimore. And in the real world, there’s an additional category of patients: Those who are misdiagnosed and develop infection-related persistent symptoms – such as fatigue, brain fog/cognitive dysfunction, and musculoskeletal problems – that don’t match the “textbook schematic” involving late Lyme arthritis and late neurologic disease.

Aucott_John_MD_web.jpg

Moreover, of patients who are treated with protocols recommended by the Infectious Diseases Society of America (IDSA), about 15% go on to develop persistent symptoms at 6 months – again, symptoms that don’t match textbook manifestations and do match symptoms of other infection-associated chronic illnesses. As a “research construct,” this has been coined posttreatment Lyme disease (PTLD), he said at the workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

(On a practical level, it is hard to know clinically who has early disseminated disease unless they have multiple erythema migrans rashes or neurologic or cardiac involvement, he said after the meeting.)

All this points to the need for tests that are sensitive and specific for diagnosis at all stages of infection and disease, he said in a talk on diagnostics. Currently available tests – those that fit into the widely used two-tiered enzyme-linked immunosorbent assay, Western Blot serology testing – have significant limitations in sensitivity and specificity, including for acute infection when the body has not generated enough antibodies, yet treatment is most likely to succeed.
 

Move toward combination therapy research

Lyme disease is most commonly treated with doxycycline, and that’s problematic because the antibiotic is a microstatic whose efficacy relies on immune clearance of static bacteria, said Monica E. Embers, PhD, director of vector-borne disease at the Tulane National Primate Research Center and associate professor of immunology at Tulane University, New Orleans.

Embers_Monica_LA_web.jpg

“But we know that Borrelia burgdorferi has the capability to evade the host immune response in almost every way possible. Persistence is the norm in an immunocompetent host ... [and] dormant bacteria/persisters are more tolerant of microstatic antibiotics,” she said.

Other considerations for antibiotic efficacy include the fact that B. burgdorferi survives for many months inside ticks without nutrient replenishment or replication, “so dormancy is part of their life cycle,” she said. Moreover, the bacteria can be found deep in connective tissues and joints.

The efficacy of accepted regimens of antibiotic treatment has been “a very contentious issue,” she said, noting that guidelines from the International Lyme and Associated Diseases Society “leave open the possibility for antibiotic retreatment when a chronic infection is judged to be a possible cause [of ongoing symptoms].”

The development of persister B. burgdorferi in the presence of antibiotics has been well studied in vitro, which has limitations, Dr. Embers said. But her group specializes in animal models and has shown persistence of antimicrobial-tolerant B. burgdorferi in tick-inoculated rhesus macaques 8-9 months after treatment with oral doxycycline.

“We [also] saw persistence of mild-moderate inflammation in the brain, peripheral nerves, spinal cord, joints and skeletal muscle, and in the heart,” Dr. Embers said, who coauthored a 2022 review of B. burgdorferi antimicrobial-tolerant persistence in Lyme disease and PTLD.

Her work has also shown that ceftriaxone, which is recommended by IDSA for patients with clinically evident neurological and/or cardiac involvement, does not clear infection in mice. “In general, single drugs have not been capable of clearing the infection, yet combinations show promise,” she said.

Dr. Embers has combed large drug libraries looking for combinations of antibiotics that employ different mechanisms of action in hopes of eliminating persister spirochetes. Certain combinations have shown promise in mice and have been tested in her rhesus macaque model; data analyses are underway.

Other research teams, such as that of Ying Zhang, MD, PhD, at Johns Hopkins, have similarly been screening combinations of antibiotics and other compounds, identifying candidates for further testing.

During a question and answer period, Dr. Embers said her team is also investigating the pathophysiology and long-term effects of tick-borne coinfections, including Bartonella, and is pursuing a hypothesis that infection with Borrelia allows Bartonella to cause more extensive disease and persist longer. “I think Lyme is at the core because of its ability to evade and suppress the immune response so effectively.”
 

Diagnostic possibilities, biomarkers for PTLD

Direct diagnostic tests for microbial nucleic acid and proteins “are promising alternatives for indirect serologic tests,” Dr. Aucott said. For instance, in addition to polymerase chain reaction tests, which “are making advances,” it may be possible to target the B. burgdorferi peptidoglycan for antigen detection.

Researchers have shown that peptidoglycan, a component of the B. burgdorferi cell envelope, is a persistent antigen in the synovial fluid of patients with Lyme arthritis who have been treated with oral and intravenous antibiotics, and that it likely contributes to inflammation.

“Maybe the infection is gone but parts of the bacteria are still there that are driving inflammation,” said Dr. Aucott, also associate professor of medicine at John Hopkins.

Researchers have also been looking at the host response to B. burgdorferi – including cytokines, chemokines, and autoantibiodies – to identify biomarkers for PTLD and to identify patients during posttreatment follow-up who are at increased risk of developing PTLD, with the hope of someday intervening. Persistently high levels of interleukin-23, CCL19, and interferon-alpha have each been associated in different studies with persistent symptoms after treatment, Dr. Aucott said.

In addition, metabolomics research is showing that patients with PTLD have metabolic fingerprints that are different from those who return to good health after treatment, and it may be possible to identify an epigenetic signature for Lyme disease. A project sponsored by the Defense Advanced Research Projects Agency called ECHO (Epigenetic Characterization and Observation) aims to identify epigenetic signatures of exposures to various threats, including B. burgdorferi.

“At the very proximal end of [indirectly testing for host response], there are modifications of the DNA that can occur in response to infectious insults ... and that changed DNA changes RNA expression and protein synthesis,” Dr. Aucott explained. DARPA’s project is “exciting because their goal [at DARPA] is to have a diagnostic test quickly as a result of this epigenetics work.”

Imaging research is also fast offering diagnostic opportunities, Dr. Aucott said. Levels of microglial activation on brain PET imaging have been found to correlate with PTLD, and a study at Johns Hopkins of multimodal neuroimaging with functional MRI and diffusion tensor imaging has shown distinct changes to white matter activation within the frontal lobe of patients with PTLD, compared with controls.

The NASEM workshop did not collect or require disclosures of its participants.

Several recent developments in Lyme disease treatment and diagnosis may pave the way forward for combating disease that persists following missed or delayed diagnoses or remains following standard treatment. These include combination therapy to address “persister” bacteria and diagnostic tests that test directly for the pathogen and/or indirectly test for host response, according to experts who presented at a 2-day National Academies of Science, Engineering and Medicine workshop on infection-associated chronic illnesses.

Research has shown that 60% of people who are infected and not treated during the early or early disseminated stages of Lyme disease go on to develop late Lyme arthritis, said John Aucott, MD, director of the Johns Hopkins Lyme Disease Clinical Research Center in Baltimore. And in the real world, there’s an additional category of patients: Those who are misdiagnosed and develop infection-related persistent symptoms – such as fatigue, brain fog/cognitive dysfunction, and musculoskeletal problems – that don’t match the “textbook schematic” involving late Lyme arthritis and late neurologic disease.

Aucott_John_MD_web.jpg

Moreover, of patients who are treated with protocols recommended by the Infectious Diseases Society of America (IDSA), about 15% go on to develop persistent symptoms at 6 months – again, symptoms that don’t match textbook manifestations and do match symptoms of other infection-associated chronic illnesses. As a “research construct,” this has been coined posttreatment Lyme disease (PTLD), he said at the workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

(On a practical level, it is hard to know clinically who has early disseminated disease unless they have multiple erythema migrans rashes or neurologic or cardiac involvement, he said after the meeting.)

All this points to the need for tests that are sensitive and specific for diagnosis at all stages of infection and disease, he said in a talk on diagnostics. Currently available tests – those that fit into the widely used two-tiered enzyme-linked immunosorbent assay, Western Blot serology testing – have significant limitations in sensitivity and specificity, including for acute infection when the body has not generated enough antibodies, yet treatment is most likely to succeed.
 

Move toward combination therapy research

Lyme disease is most commonly treated with doxycycline, and that’s problematic because the antibiotic is a microstatic whose efficacy relies on immune clearance of static bacteria, said Monica E. Embers, PhD, director of vector-borne disease at the Tulane National Primate Research Center and associate professor of immunology at Tulane University, New Orleans.

Embers_Monica_LA_web.jpg

“But we know that Borrelia burgdorferi has the capability to evade the host immune response in almost every way possible. Persistence is the norm in an immunocompetent host ... [and] dormant bacteria/persisters are more tolerant of microstatic antibiotics,” she said.

Other considerations for antibiotic efficacy include the fact that B. burgdorferi survives for many months inside ticks without nutrient replenishment or replication, “so dormancy is part of their life cycle,” she said. Moreover, the bacteria can be found deep in connective tissues and joints.

The efficacy of accepted regimens of antibiotic treatment has been “a very contentious issue,” she said, noting that guidelines from the International Lyme and Associated Diseases Society “leave open the possibility for antibiotic retreatment when a chronic infection is judged to be a possible cause [of ongoing symptoms].”

The development of persister B. burgdorferi in the presence of antibiotics has been well studied in vitro, which has limitations, Dr. Embers said. But her group specializes in animal models and has shown persistence of antimicrobial-tolerant B. burgdorferi in tick-inoculated rhesus macaques 8-9 months after treatment with oral doxycycline.

“We [also] saw persistence of mild-moderate inflammation in the brain, peripheral nerves, spinal cord, joints and skeletal muscle, and in the heart,” Dr. Embers said, who coauthored a 2022 review of B. burgdorferi antimicrobial-tolerant persistence in Lyme disease and PTLD.

Her work has also shown that ceftriaxone, which is recommended by IDSA for patients with clinically evident neurological and/or cardiac involvement, does not clear infection in mice. “In general, single drugs have not been capable of clearing the infection, yet combinations show promise,” she said.

Dr. Embers has combed large drug libraries looking for combinations of antibiotics that employ different mechanisms of action in hopes of eliminating persister spirochetes. Certain combinations have shown promise in mice and have been tested in her rhesus macaque model; data analyses are underway.

Other research teams, such as that of Ying Zhang, MD, PhD, at Johns Hopkins, have similarly been screening combinations of antibiotics and other compounds, identifying candidates for further testing.

During a question and answer period, Dr. Embers said her team is also investigating the pathophysiology and long-term effects of tick-borne coinfections, including Bartonella, and is pursuing a hypothesis that infection with Borrelia allows Bartonella to cause more extensive disease and persist longer. “I think Lyme is at the core because of its ability to evade and suppress the immune response so effectively.”
 

Diagnostic possibilities, biomarkers for PTLD

Direct diagnostic tests for microbial nucleic acid and proteins “are promising alternatives for indirect serologic tests,” Dr. Aucott said. For instance, in addition to polymerase chain reaction tests, which “are making advances,” it may be possible to target the B. burgdorferi peptidoglycan for antigen detection.

Researchers have shown that peptidoglycan, a component of the B. burgdorferi cell envelope, is a persistent antigen in the synovial fluid of patients with Lyme arthritis who have been treated with oral and intravenous antibiotics, and that it likely contributes to inflammation.

“Maybe the infection is gone but parts of the bacteria are still there that are driving inflammation,” said Dr. Aucott, also associate professor of medicine at John Hopkins.

Researchers have also been looking at the host response to B. burgdorferi – including cytokines, chemokines, and autoantibiodies – to identify biomarkers for PTLD and to identify patients during posttreatment follow-up who are at increased risk of developing PTLD, with the hope of someday intervening. Persistently high levels of interleukin-23, CCL19, and interferon-alpha have each been associated in different studies with persistent symptoms after treatment, Dr. Aucott said.

In addition, metabolomics research is showing that patients with PTLD have metabolic fingerprints that are different from those who return to good health after treatment, and it may be possible to identify an epigenetic signature for Lyme disease. A project sponsored by the Defense Advanced Research Projects Agency called ECHO (Epigenetic Characterization and Observation) aims to identify epigenetic signatures of exposures to various threats, including B. burgdorferi.

“At the very proximal end of [indirectly testing for host response], there are modifications of the DNA that can occur in response to infectious insults ... and that changed DNA changes RNA expression and protein synthesis,” Dr. Aucott explained. DARPA’s project is “exciting because their goal [at DARPA] is to have a diagnostic test quickly as a result of this epigenetics work.”

Imaging research is also fast offering diagnostic opportunities, Dr. Aucott said. Levels of microglial activation on brain PET imaging have been found to correlate with PTLD, and a study at Johns Hopkins of multimodal neuroimaging with functional MRI and diffusion tensor imaging has shown distinct changes to white matter activation within the frontal lobe of patients with PTLD, compared with controls.

The NASEM workshop did not collect or require disclosures of its participants.

An estimated 3 in every 10 white-tailed deer in the United States have had COVID-19, and new research suggests deer populations could be a source of virus mutations that may be passed to humans.

According to the U.S. Department of Agriculture, which led the research project, humans transmitted the virus to deer at least 100 times. The virus then spread widely among free-ranging deer populations, and there were three possible cases of the deer transmitting the virus to humans.

The data comes from tests done between November 2021 and April 2022 on more than 12,000 deer found across half of the United States. Sequencing of the virus found in the deer showed that deer had been exposed to all of the prominent variants, including Alpha, Gamma, Delta, and Omicron.

Some of the findings about transmission were published in the journal Nature Communications, in which researchers noted that in addition to being identified in deer, the virus has been found in wild and domestic animals, including mink, rats, otters, ferrets, hamsters, gorillas, cats, dogs, lions, and tigers. Animal-to-human transmission has been documented or suspected in mink and domestic cats, in addition to white-tailed deer.

The findings are important because the animal populations can become “reservoirs ... in which the virus circulates covertly, persisting in the population and can be transmitted to other animals or humans potentially causing disease outbreaks,” according to the paper, which was a collaboration among scientists from the U.S. Department of Agriculture, CDC, and the University of Missouri–Columbia.

In the three cases of possible deer-to-human transmission, researchers said that mutated versions of the virus previously found only in deer had been found in COVID test samples taken from one person in North Carolina and two people in Massachusetts. Those deer-specific mutated versions of the virus have not been found in any other human samples, lending evidence that the mutations occurred within deer.

“Deer regularly interact with humans and are commonly found in human environments – near our homes, pets, wastewater, and trash,” researcher and University of Missouri–Columbia professor Xiu-Feng “Henry” Wan, PhD, said in a statement. “The potential for SARS-CoV-2, or any zoonotic disease, to persist and evolve in wildlife populations can pose unique public health risks.”

In the Nature Communications paper, the researchers suggested that deer may be exposed to the virus from human food waste, masks, or other waste products. The authors concluded that further study is needed to determine how virus transmission occurs between deer and humans.

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

An estimated 3 in every 10 white-tailed deer in the United States have had COVID-19, and new research suggests deer populations could be a source of virus mutations that may be passed to humans.

According to the U.S. Department of Agriculture, which led the research project, humans transmitted the virus to deer at least 100 times. The virus then spread widely among free-ranging deer populations, and there were three possible cases of the deer transmitting the virus to humans.

The data comes from tests done between November 2021 and April 2022 on more than 12,000 deer found across half of the United States. Sequencing of the virus found in the deer showed that deer had been exposed to all of the prominent variants, including Alpha, Gamma, Delta, and Omicron.

Some of the findings about transmission were published in the journal Nature Communications, in which researchers noted that in addition to being identified in deer, the virus has been found in wild and domestic animals, including mink, rats, otters, ferrets, hamsters, gorillas, cats, dogs, lions, and tigers. Animal-to-human transmission has been documented or suspected in mink and domestic cats, in addition to white-tailed deer.

The findings are important because the animal populations can become “reservoirs ... in which the virus circulates covertly, persisting in the population and can be transmitted to other animals or humans potentially causing disease outbreaks,” according to the paper, which was a collaboration among scientists from the U.S. Department of Agriculture, CDC, and the University of Missouri–Columbia.

In the three cases of possible deer-to-human transmission, researchers said that mutated versions of the virus previously found only in deer had been found in COVID test samples taken from one person in North Carolina and two people in Massachusetts. Those deer-specific mutated versions of the virus have not been found in any other human samples, lending evidence that the mutations occurred within deer.

“Deer regularly interact with humans and are commonly found in human environments – near our homes, pets, wastewater, and trash,” researcher and University of Missouri–Columbia professor Xiu-Feng “Henry” Wan, PhD, said in a statement. “The potential for SARS-CoV-2, or any zoonotic disease, to persist and evolve in wildlife populations can pose unique public health risks.”

In the Nature Communications paper, the researchers suggested that deer may be exposed to the virus from human food waste, masks, or other waste products. The authors concluded that further study is needed to determine how virus transmission occurs between deer and humans.

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

An estimated 3 in every 10 white-tailed deer in the United States have had COVID-19, and new research suggests deer populations could be a source of virus mutations that may be passed to humans.

According to the U.S. Department of Agriculture, which led the research project, humans transmitted the virus to deer at least 100 times. The virus then spread widely among free-ranging deer populations, and there were three possible cases of the deer transmitting the virus to humans.

The data comes from tests done between November 2021 and April 2022 on more than 12,000 deer found across half of the United States. Sequencing of the virus found in the deer showed that deer had been exposed to all of the prominent variants, including Alpha, Gamma, Delta, and Omicron.

Some of the findings about transmission were published in the journal Nature Communications, in which researchers noted that in addition to being identified in deer, the virus has been found in wild and domestic animals, including mink, rats, otters, ferrets, hamsters, gorillas, cats, dogs, lions, and tigers. Animal-to-human transmission has been documented or suspected in mink and domestic cats, in addition to white-tailed deer.

The findings are important because the animal populations can become “reservoirs ... in which the virus circulates covertly, persisting in the population and can be transmitted to other animals or humans potentially causing disease outbreaks,” according to the paper, which was a collaboration among scientists from the U.S. Department of Agriculture, CDC, and the University of Missouri–Columbia.

In the three cases of possible deer-to-human transmission, researchers said that mutated versions of the virus previously found only in deer had been found in COVID test samples taken from one person in North Carolina and two people in Massachusetts. Those deer-specific mutated versions of the virus have not been found in any other human samples, lending evidence that the mutations occurred within deer.

“Deer regularly interact with humans and are commonly found in human environments – near our homes, pets, wastewater, and trash,” researcher and University of Missouri–Columbia professor Xiu-Feng “Henry” Wan, PhD, said in a statement. “The potential for SARS-CoV-2, or any zoonotic disease, to persist and evolve in wildlife populations can pose unique public health risks.”

In the Nature Communications paper, the researchers suggested that deer may be exposed to the virus from human food waste, masks, or other waste products. The authors concluded that further study is needed to determine how virus transmission occurs between deer and humans.

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

It turns out that some people really are tick magnets.

Researchers have discovered that ticks can defy gravity in their quest to latch onto people and animals. The key is static electricity, just like when someone rubs a balloon and things stick to it.

The study was published in the journal Current Biology. In the first phase of the research, scientists exposed ticks to furry rabbit feet and to acrylic surfaces that each had electrostatic charges.

“Ticks were readily attracted across air gaps of up to several millimeters or centimeters onto these statically charged surfaces,” the authors wrote. “This establishes that electrostatic attraction of ticks onto hosts can take place over large air gaps of many body lengths of a tick.”

In a second part of the study, the researchers created computer models simulating the electrostatic charges that exist in environments where both ticks and mammals are found. In one simulation, the researchers observed that the body parts of a cow with the most electric charge were the nose, tail, and legs, which are the body parts most likely to be encountered by a tick. They also found that the vegetation near the animal had a strong electric field that is just a few millimeters wide.

In a final phase of the study, the researchers conducted laboratory experiments in which they re-created the electric field conditions from the computer model and successfully lifted some ticks across an air gap, although some ticks did not make the full leap if they were observed to be resisting.

The authors noted that their findings could be applied to developing new tick prevention strategies, such as designing clothing that resists electrostatic charges or spraying livestock.

The study authors reported that they had no conflicts of interest.

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

It turns out that some people really are tick magnets.

Researchers have discovered that ticks can defy gravity in their quest to latch onto people and animals. The key is static electricity, just like when someone rubs a balloon and things stick to it.

The study was published in the journal Current Biology. In the first phase of the research, scientists exposed ticks to furry rabbit feet and to acrylic surfaces that each had electrostatic charges.

“Ticks were readily attracted across air gaps of up to several millimeters or centimeters onto these statically charged surfaces,” the authors wrote. “This establishes that electrostatic attraction of ticks onto hosts can take place over large air gaps of many body lengths of a tick.”

In a second part of the study, the researchers created computer models simulating the electrostatic charges that exist in environments where both ticks and mammals are found. In one simulation, the researchers observed that the body parts of a cow with the most electric charge were the nose, tail, and legs, which are the body parts most likely to be encountered by a tick. They also found that the vegetation near the animal had a strong electric field that is just a few millimeters wide.

In a final phase of the study, the researchers conducted laboratory experiments in which they re-created the electric field conditions from the computer model and successfully lifted some ticks across an air gap, although some ticks did not make the full leap if they were observed to be resisting.

The authors noted that their findings could be applied to developing new tick prevention strategies, such as designing clothing that resists electrostatic charges or spraying livestock.

The study authors reported that they had no conflicts of interest.

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

It turns out that some people really are tick magnets.

Researchers have discovered that ticks can defy gravity in their quest to latch onto people and animals. The key is static electricity, just like when someone rubs a balloon and things stick to it.

The study was published in the journal Current Biology. In the first phase of the research, scientists exposed ticks to furry rabbit feet and to acrylic surfaces that each had electrostatic charges.

“Ticks were readily attracted across air gaps of up to several millimeters or centimeters onto these statically charged surfaces,” the authors wrote. “This establishes that electrostatic attraction of ticks onto hosts can take place over large air gaps of many body lengths of a tick.”

In a second part of the study, the researchers created computer models simulating the electrostatic charges that exist in environments where both ticks and mammals are found. In one simulation, the researchers observed that the body parts of a cow with the most electric charge were the nose, tail, and legs, which are the body parts most likely to be encountered by a tick. They also found that the vegetation near the animal had a strong electric field that is just a few millimeters wide.

In a final phase of the study, the researchers conducted laboratory experiments in which they re-created the electric field conditions from the computer model and successfully lifted some ticks across an air gap, although some ticks did not make the full leap if they were observed to be resisting.

The authors noted that their findings could be applied to developing new tick prevention strategies, such as designing clothing that resists electrostatic charges or spraying livestock.

The study authors reported that they had no conflicts of interest.

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

Researchers using a modeling study of rabies in the United States have quantified the risk of death and exposure and estimated a threshold to help health care providers decide when postexposure prophylaxis (PEP) is appropriate.

raccoon_web.jpg

The model, reported in JAMA Network Open, could help clinicians, particularly those in primary care settings, to more rationally prescribe PEP to people concerned about a potential exposure to the rabies virus (RABV). In the United States, rabies PEP often is given without a comprehensive assessment that considers regional factors as well as species, nature of an attack, and the health and vaccination status of the animal.

Providers err on the side of caution, as rabies infection has a fatality rate near 100%. When exposures are low-risk, however, patients can rack up substantial out-of-pocket expenses or experience unnecessary adverse effects from the series of shots. Those can include injection site reactions, hypersensitivity reactions, and neurological complications.

The authors write that an estimated 55,000 people per year in the United States were treated for potential exposure to RABV in 2017 and 2018, at an estimated cost of more than $3,800 per person treated.
 

Researchers calculate risk threshold

The researchers, led by Kelly Charniga, PhD, MPH, an infectious disease epidemiologist with the U.S. Centers for Disease Control and Prevention in Atlanta, calculated positivity rates using more than 900,000 animal samples tested for RABV between 2011 and 2020. Other parameters were estimated from surveillance data and the literature and probabilities were estimated using Bayes’ rule.

A convenience sample of state public health officials in all states (excluding Hawaii) plus Washington and Puerto Rico was used to help determine a risk threshold for recommending PEP. Respondents were asked whether they would recommend PEP given 24 standardized exposure scenarios while accounting for local rabies epidemiology.

Their model establishes a risk threshold of 0.0004 for PEP administration, which represents the probability that an animal would test positive for RABV given that a person was exposed, and the probability that a person would die from rabies after exposure to a suspect rabid animal and no PEP. PEP should not be recommended with any value lower than that cutoff.

Alfred DeMaria, DPH, a consultant to the Massachusetts Department of Public Health in Boston, who was not involved with the study, said the work will be particularly helpful for primary care physicians, giving them confidence to not recommend PEP when infection is statistically highly unlikely and thereby to reduce unnecessary and costly measures.

“Concern about rabies is often based on a very unlikely scenario,” Dr. DeMaria said. He gave the example of people coming into primary care worried that they might have been exposed after comforting their dog who had been bitten in a fight with a wild animal.

“Has that ever happened in the history of the human species? Not that we know of,” he said.

Many people also think dogs and other domestic animals are a likely source of rabies, which is not the case in the United States, Dr. DeMaria said.

“In most cases, it is exposure to a raccoon, a skunk, or a bat,” he said. “Most calls are for potential bat exposure, especially in the summer when young bats are flying around and are not very savvy about avoiding humans.”

The authors note the difference between the animals likely to bite and the species that carry RABV: “The most common mammals involved in bite events in the U.S. are dogs, cats, and small rodents. These species, when healthy and provoked into biting, represent some of the lowest risk exposures evaluated in this model.”

The canine rabies variant virus was eliminated in the United States in 2004.

The study authors note that their model should not be used in other countries because “most rabies deaths globally are caused by domestic dogs.”

Health department consultation can reduce inappropriate treatment

Dr. DeMaria said the paper may also convince physicians to consult with their health department for a final recommendation.

The authors note that a 2020 study in Cook County, Ill., found patients who received PEP were about 90% less likely to receive inappropriate treatment if their clinician had consulted with a health department.

“Anything that puts the risk in a context, like this paper does, is helpful,” he said.

Most physicians in the United States will never see a patient with rabies, the authors write, but animal bites are common – resulting in hundreds of thousands of primary care and emergency department visits each year when physicians must decide whether to administer PEP.

The study authors and Dr. DeMaria report no relevant financial relationships.

Researchers using a modeling study of rabies in the United States have quantified the risk of death and exposure and estimated a threshold to help health care providers decide when postexposure prophylaxis (PEP) is appropriate.

raccoon_web.jpg

The model, reported in JAMA Network Open, could help clinicians, particularly those in primary care settings, to more rationally prescribe PEP to people concerned about a potential exposure to the rabies virus (RABV). In the United States, rabies PEP often is given without a comprehensive assessment that considers regional factors as well as species, nature of an attack, and the health and vaccination status of the animal.

Providers err on the side of caution, as rabies infection has a fatality rate near 100%. When exposures are low-risk, however, patients can rack up substantial out-of-pocket expenses or experience unnecessary adverse effects from the series of shots. Those can include injection site reactions, hypersensitivity reactions, and neurological complications.

The authors write that an estimated 55,000 people per year in the United States were treated for potential exposure to RABV in 2017 and 2018, at an estimated cost of more than $3,800 per person treated.
 

Researchers calculate risk threshold

The researchers, led by Kelly Charniga, PhD, MPH, an infectious disease epidemiologist with the U.S. Centers for Disease Control and Prevention in Atlanta, calculated positivity rates using more than 900,000 animal samples tested for RABV between 2011 and 2020. Other parameters were estimated from surveillance data and the literature and probabilities were estimated using Bayes’ rule.

A convenience sample of state public health officials in all states (excluding Hawaii) plus Washington and Puerto Rico was used to help determine a risk threshold for recommending PEP. Respondents were asked whether they would recommend PEP given 24 standardized exposure scenarios while accounting for local rabies epidemiology.

Their model establishes a risk threshold of 0.0004 for PEP administration, which represents the probability that an animal would test positive for RABV given that a person was exposed, and the probability that a person would die from rabies after exposure to a suspect rabid animal and no PEP. PEP should not be recommended with any value lower than that cutoff.

Alfred DeMaria, DPH, a consultant to the Massachusetts Department of Public Health in Boston, who was not involved with the study, said the work will be particularly helpful for primary care physicians, giving them confidence to not recommend PEP when infection is statistically highly unlikely and thereby to reduce unnecessary and costly measures.

“Concern about rabies is often based on a very unlikely scenario,” Dr. DeMaria said. He gave the example of people coming into primary care worried that they might have been exposed after comforting their dog who had been bitten in a fight with a wild animal.

“Has that ever happened in the history of the human species? Not that we know of,” he said.

Many people also think dogs and other domestic animals are a likely source of rabies, which is not the case in the United States, Dr. DeMaria said.

“In most cases, it is exposure to a raccoon, a skunk, or a bat,” he said. “Most calls are for potential bat exposure, especially in the summer when young bats are flying around and are not very savvy about avoiding humans.”

The authors note the difference between the animals likely to bite and the species that carry RABV: “The most common mammals involved in bite events in the U.S. are dogs, cats, and small rodents. These species, when healthy and provoked into biting, represent some of the lowest risk exposures evaluated in this model.”

The canine rabies variant virus was eliminated in the United States in 2004.

The study authors note that their model should not be used in other countries because “most rabies deaths globally are caused by domestic dogs.”

Health department consultation can reduce inappropriate treatment

Dr. DeMaria said the paper may also convince physicians to consult with their health department for a final recommendation.

The authors note that a 2020 study in Cook County, Ill., found patients who received PEP were about 90% less likely to receive inappropriate treatment if their clinician had consulted with a health department.

“Anything that puts the risk in a context, like this paper does, is helpful,” he said.

Most physicians in the United States will never see a patient with rabies, the authors write, but animal bites are common – resulting in hundreds of thousands of primary care and emergency department visits each year when physicians must decide whether to administer PEP.

The study authors and Dr. DeMaria report no relevant financial relationships.

Researchers using a modeling study of rabies in the United States have quantified the risk of death and exposure and estimated a threshold to help health care providers decide when postexposure prophylaxis (PEP) is appropriate.

raccoon_web.jpg

The model, reported in JAMA Network Open, could help clinicians, particularly those in primary care settings, to more rationally prescribe PEP to people concerned about a potential exposure to the rabies virus (RABV). In the United States, rabies PEP often is given without a comprehensive assessment that considers regional factors as well as species, nature of an attack, and the health and vaccination status of the animal.

Providers err on the side of caution, as rabies infection has a fatality rate near 100%. When exposures are low-risk, however, patients can rack up substantial out-of-pocket expenses or experience unnecessary adverse effects from the series of shots. Those can include injection site reactions, hypersensitivity reactions, and neurological complications.

The authors write that an estimated 55,000 people per year in the United States were treated for potential exposure to RABV in 2017 and 2018, at an estimated cost of more than $3,800 per person treated.
 

Researchers calculate risk threshold

The researchers, led by Kelly Charniga, PhD, MPH, an infectious disease epidemiologist with the U.S. Centers for Disease Control and Prevention in Atlanta, calculated positivity rates using more than 900,000 animal samples tested for RABV between 2011 and 2020. Other parameters were estimated from surveillance data and the literature and probabilities were estimated using Bayes’ rule.

A convenience sample of state public health officials in all states (excluding Hawaii) plus Washington and Puerto Rico was used to help determine a risk threshold for recommending PEP. Respondents were asked whether they would recommend PEP given 24 standardized exposure scenarios while accounting for local rabies epidemiology.

Their model establishes a risk threshold of 0.0004 for PEP administration, which represents the probability that an animal would test positive for RABV given that a person was exposed, and the probability that a person would die from rabies after exposure to a suspect rabid animal and no PEP. PEP should not be recommended with any value lower than that cutoff.

Alfred DeMaria, DPH, a consultant to the Massachusetts Department of Public Health in Boston, who was not involved with the study, said the work will be particularly helpful for primary care physicians, giving them confidence to not recommend PEP when infection is statistically highly unlikely and thereby to reduce unnecessary and costly measures.

“Concern about rabies is often based on a very unlikely scenario,” Dr. DeMaria said. He gave the example of people coming into primary care worried that they might have been exposed after comforting their dog who had been bitten in a fight with a wild animal.

“Has that ever happened in the history of the human species? Not that we know of,” he said.

Many people also think dogs and other domestic animals are a likely source of rabies, which is not the case in the United States, Dr. DeMaria said.

“In most cases, it is exposure to a raccoon, a skunk, or a bat,” he said. “Most calls are for potential bat exposure, especially in the summer when young bats are flying around and are not very savvy about avoiding humans.”

The authors note the difference between the animals likely to bite and the species that carry RABV: “The most common mammals involved in bite events in the U.S. are dogs, cats, and small rodents. These species, when healthy and provoked into biting, represent some of the lowest risk exposures evaluated in this model.”

The canine rabies variant virus was eliminated in the United States in 2004.

The study authors note that their model should not be used in other countries because “most rabies deaths globally are caused by domestic dogs.”

Health department consultation can reduce inappropriate treatment

Dr. DeMaria said the paper may also convince physicians to consult with their health department for a final recommendation.

The authors note that a 2020 study in Cook County, Ill., found patients who received PEP were about 90% less likely to receive inappropriate treatment if their clinician had consulted with a health department.

“Anything that puts the risk in a context, like this paper does, is helpful,” he said.

Most physicians in the United States will never see a patient with rabies, the authors write, but animal bites are common – resulting in hundreds of thousands of primary care and emergency department visits each year when physicians must decide whether to administer PEP.

The study authors and Dr. DeMaria report no relevant financial relationships.

When most families hear the word rabies, they envision a dog foaming at the mouth and think about receiving multiple painful, often intra-abdominal injections. However, the epidemiology of rabies has changed in the United States. Postexposure prophylaxis (PEP) may not always be indicated and for certain persons preexposure prophylaxis (PrEP) is available and recommended.

Rabies is a Lyssavirus that is transmitted through saliva most often from the bite or scratch of an infected animal. Sometimes it’s via direct contact with mucous membranes. Although rare, cases have been described in which an undiagnosed donor passed the virus via transplant to recipients and four cases of aerosolized transmission were documented in two spelunkers and two laboratory technicians working with the virus. Worldwide it’s estimated that rabies causes 59,000 deaths annually.

163098_Fig 1_web.jpg

Most cases (98%) are secondary to canine rabies. Prior to 1960, dogs were the major reservoir in the United States; however, after introduction of leash laws and animal vaccination in 1947, there was a drastic decline in cases caused by the canine rabies virus variant (CRVV). By 2004, CRVV was eliminated in the United States.

However, the proportion of strains associated with wildlife including raccoons, skunks, foxes, bats, coyotes, and mongoose now account for most of the cases in humans. Wildlife rabies is found in all states except Hawaii. Between 1960 and 2018, 89 cases were acquired in the United States and 62 (70%) were from bat exposure. Dog bites acquired during international travel were the cause of 36 cases.

Once signs and symptoms of disease develop there is no treatment. Regardless of the species variant, rabies virus infection is fatal in over 99% of cases. However, disease can be prevented with prompt initiation of PEP, which includes administration of rabies immune globulin (RIG) and rabies vaccine. Let’s look at a few different scenarios.

1. A delivery person is bitten by your neighbor’s dog while making a delivery. He was told to get rabies vaccine. What should we advise?

Canine rabies has been eliminated in the United States. However, unvaccinated canines can acquire rabies from wildlife. In this situation, you can determine the immunization status of the dog. Contact your local/state health department to assist with enforcement and management. Bites by cats and ferrets should be managed similarly.

Healthy dog:

1. Observe for 10 days.

2. PEP is not indicated unless the animal develops signs/symptoms of rabies. Then euthanize and begin PEP.

Dog appears rabid or suspected to be rabid:

1. Begin PEP.

2. Animal should be euthanized. If immunofluorescent test is negative discontinue PEP.

Dog unavailable:

Contact local/state health department. They are more familiar with rabies surveillance data.

2. Patient relocating to Malaysia for 3-4 years. Rabies PrEP was recommended but the family wants your opinion before receiving the vaccine. What would you advise?

Canine rabies is felt to be the primary cause of rabies outside of the United States. Canines are not routinely vaccinated in many foreign destinations, and the availability of RIG and rabies vaccine is not guaranteed in developing countries. As noted above, dog bites during international travel accounted for 28% of U.S. cases between 1960 and 2018.

Word_Bonnie_M_TEX_2021_web.jpg

In May 2022 recommendations for a modified two-dose PrEP schedule was published that identifies five risk groups and includes specific timing for checking rabies titers. The third rabies dose can now be administered up until year 3 (Morb Mortal Wkly Rep. 2022 May 6;71[18]:619-27). For individuals relocating to countries where CRVV is present, I prefer the traditional three-dose PrEP schedule administered between 21 and 28 days. However, we now have options. If exposure occurs any time after completion of a three-dose PrEP series or within 3 years after completion of a two-dose PrEP series, RIG would not be required. All patients would receive two doses of rabies vaccine (days 0, 3). If exposure occurs after 3 years in a person who received two doses of PrEP who did not have documentation of a protective rabies titer (> 5 IU/mL), treatment will include RIG plus four doses of vaccine (days 0, 3, 7, 14).

For this relocating patient, supporting PrEP would be strongly recommended.

3. A mother tells you she sees bats flying around her home at night and a few have even gotten into the home. This morning she saw one in her child’s room. He was still sleeping. Is there anything she needs to do?

Bats have become the predominant source of rabies in the United States. In addition to the cases noted above, three fatal cases occurred between Sept. 28 and Nov. 10, 2021, after bat exposures in August 2021 (MMWR Morb Mortal Wkly Rep. 2022 Jan 7;71:31-2). All had recognized contact with a bat 3-7 weeks prior to onset of symptoms and died 2-3 weeks after symptom onset. One declined PEP and the other two did not realize the risk for rabies from their exposure or did not notice a scratch or bite. Bites from bats may be small and unnoticed. Exposure to a bat in a closed room while sleeping is considered an exposure. Hawaii is the only state not reporting rabid bats.

PEP is recommended for her child. She should identify potential areas bats may enter the home and seal them in addition to removal of any bat roosts.

4. A parent realizes a house guest has been feeding raccoons in the backyard. What’s your response?

While bat rabies is the predominant variant associated with disease in the United States, as illustrated in Figure 1, other species of wildlife including raccoons are a major source of rabies. The geographic spread of the raccoon variant of rabies has been limited by oral vaccination via bait. In the situation noted here, the raccoons have returned because food was being offered thus increasing the families chance of a potential rabies exposure. Wildlife including skunks, raccoons, coyotes, foxes, and mongooses are always considered rabid until proven negative by laboratory testing.

163098_Fig 2_web.jpg

You recommend to stop feeding wildlife and never to approach them. Have them contact the local rabies control unit and/or state wildlife services to assist with removal of the raccoons. Depending on the locale, pest control may be required at the owners expense. Inform the family to seek PEP if anyone is bitten or scratched by the raccoons.

As per the Centers for Disease Control and Prevention, about 55,000 residents receive PEP annually with health-associated expenditures including diagnostics, prevention, and control estimated between $245 and $510 million annually. Rabies is one of the most fatal diseases that can be prevented by avoiding contact with wild animals, maintenance of high immunization rates in pets, and keeping people informed of potential sources including bats. One can’t determine if an animal has rabies by looking at it. Rabies remains an urgent disease that we have to remember to address with our patients and their families. For additional information go to www.CDC.gov/rabies.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She has no relevant financial disclosures.

When most families hear the word rabies, they envision a dog foaming at the mouth and think about receiving multiple painful, often intra-abdominal injections. However, the epidemiology of rabies has changed in the United States. Postexposure prophylaxis (PEP) may not always be indicated and for certain persons preexposure prophylaxis (PrEP) is available and recommended.

Rabies is a Lyssavirus that is transmitted through saliva most often from the bite or scratch of an infected animal. Sometimes it’s via direct contact with mucous membranes. Although rare, cases have been described in which an undiagnosed donor passed the virus via transplant to recipients and four cases of aerosolized transmission were documented in two spelunkers and two laboratory technicians working with the virus. Worldwide it’s estimated that rabies causes 59,000 deaths annually.

163098_Fig 1_web.jpg

Most cases (98%) are secondary to canine rabies. Prior to 1960, dogs were the major reservoir in the United States; however, after introduction of leash laws and animal vaccination in 1947, there was a drastic decline in cases caused by the canine rabies virus variant (CRVV). By 2004, CRVV was eliminated in the United States.

However, the proportion of strains associated with wildlife including raccoons, skunks, foxes, bats, coyotes, and mongoose now account for most of the cases in humans. Wildlife rabies is found in all states except Hawaii. Between 1960 and 2018, 89 cases were acquired in the United States and 62 (70%) were from bat exposure. Dog bites acquired during international travel were the cause of 36 cases.

Once signs and symptoms of disease develop there is no treatment. Regardless of the species variant, rabies virus infection is fatal in over 99% of cases. However, disease can be prevented with prompt initiation of PEP, which includes administration of rabies immune globulin (RIG) and rabies vaccine. Let’s look at a few different scenarios.

1. A delivery person is bitten by your neighbor’s dog while making a delivery. He was told to get rabies vaccine. What should we advise?

Canine rabies has been eliminated in the United States. However, unvaccinated canines can acquire rabies from wildlife. In this situation, you can determine the immunization status of the dog. Contact your local/state health department to assist with enforcement and management. Bites by cats and ferrets should be managed similarly.

Healthy dog:

1. Observe for 10 days.

2. PEP is not indicated unless the animal develops signs/symptoms of rabies. Then euthanize and begin PEP.

Dog appears rabid or suspected to be rabid:

1. Begin PEP.

2. Animal should be euthanized. If immunofluorescent test is negative discontinue PEP.

Dog unavailable:

Contact local/state health department. They are more familiar with rabies surveillance data.

2. Patient relocating to Malaysia for 3-4 years. Rabies PrEP was recommended but the family wants your opinion before receiving the vaccine. What would you advise?

Canine rabies is felt to be the primary cause of rabies outside of the United States. Canines are not routinely vaccinated in many foreign destinations, and the availability of RIG and rabies vaccine is not guaranteed in developing countries. As noted above, dog bites during international travel accounted for 28% of U.S. cases between 1960 and 2018.

Word_Bonnie_M_TEX_2021_web.jpg

In May 2022 recommendations for a modified two-dose PrEP schedule was published that identifies five risk groups and includes specific timing for checking rabies titers. The third rabies dose can now be administered up until year 3 (Morb Mortal Wkly Rep. 2022 May 6;71[18]:619-27). For individuals relocating to countries where CRVV is present, I prefer the traditional three-dose PrEP schedule administered between 21 and 28 days. However, we now have options. If exposure occurs any time after completion of a three-dose PrEP series or within 3 years after completion of a two-dose PrEP series, RIG would not be required. All patients would receive two doses of rabies vaccine (days 0, 3). If exposure occurs after 3 years in a person who received two doses of PrEP who did not have documentation of a protective rabies titer (> 5 IU/mL), treatment will include RIG plus four doses of vaccine (days 0, 3, 7, 14).

For this relocating patient, supporting PrEP would be strongly recommended.

3. A mother tells you she sees bats flying around her home at night and a few have even gotten into the home. This morning she saw one in her child’s room. He was still sleeping. Is there anything she needs to do?

Bats have become the predominant source of rabies in the United States. In addition to the cases noted above, three fatal cases occurred between Sept. 28 and Nov. 10, 2021, after bat exposures in August 2021 (MMWR Morb Mortal Wkly Rep. 2022 Jan 7;71:31-2). All had recognized contact with a bat 3-7 weeks prior to onset of symptoms and died 2-3 weeks after symptom onset. One declined PEP and the other two did not realize the risk for rabies from their exposure or did not notice a scratch or bite. Bites from bats may be small and unnoticed. Exposure to a bat in a closed room while sleeping is considered an exposure. Hawaii is the only state not reporting rabid bats.

PEP is recommended for her child. She should identify potential areas bats may enter the home and seal them in addition to removal of any bat roosts.

4. A parent realizes a house guest has been feeding raccoons in the backyard. What’s your response?

While bat rabies is the predominant variant associated with disease in the United States, as illustrated in Figure 1, other species of wildlife including raccoons are a major source of rabies. The geographic spread of the raccoon variant of rabies has been limited by oral vaccination via bait. In the situation noted here, the raccoons have returned because food was being offered thus increasing the families chance of a potential rabies exposure. Wildlife including skunks, raccoons, coyotes, foxes, and mongooses are always considered rabid until proven negative by laboratory testing.

163098_Fig 2_web.jpg

You recommend to stop feeding wildlife and never to approach them. Have them contact the local rabies control unit and/or state wildlife services to assist with removal of the raccoons. Depending on the locale, pest control may be required at the owners expense. Inform the family to seek PEP if anyone is bitten or scratched by the raccoons.

As per the Centers for Disease Control and Prevention, about 55,000 residents receive PEP annually with health-associated expenditures including diagnostics, prevention, and control estimated between $245 and $510 million annually. Rabies is one of the most fatal diseases that can be prevented by avoiding contact with wild animals, maintenance of high immunization rates in pets, and keeping people informed of potential sources including bats. One can’t determine if an animal has rabies by looking at it. Rabies remains an urgent disease that we have to remember to address with our patients and their families. For additional information go to www.CDC.gov/rabies.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She has no relevant financial disclosures.

When most families hear the word rabies, they envision a dog foaming at the mouth and think about receiving multiple painful, often intra-abdominal injections. However, the epidemiology of rabies has changed in the United States. Postexposure prophylaxis (PEP) may not always be indicated and for certain persons preexposure prophylaxis (PrEP) is available and recommended.

Rabies is a Lyssavirus that is transmitted through saliva most often from the bite or scratch of an infected animal. Sometimes it’s via direct contact with mucous membranes. Although rare, cases have been described in which an undiagnosed donor passed the virus via transplant to recipients and four cases of aerosolized transmission were documented in two spelunkers and two laboratory technicians working with the virus. Worldwide it’s estimated that rabies causes 59,000 deaths annually.

163098_Fig 1_web.jpg

Most cases (98%) are secondary to canine rabies. Prior to 1960, dogs were the major reservoir in the United States; however, after introduction of leash laws and animal vaccination in 1947, there was a drastic decline in cases caused by the canine rabies virus variant (CRVV). By 2004, CRVV was eliminated in the United States.

However, the proportion of strains associated with wildlife including raccoons, skunks, foxes, bats, coyotes, and mongoose now account for most of the cases in humans. Wildlife rabies is found in all states except Hawaii. Between 1960 and 2018, 89 cases were acquired in the United States and 62 (70%) were from bat exposure. Dog bites acquired during international travel were the cause of 36 cases.

Once signs and symptoms of disease develop there is no treatment. Regardless of the species variant, rabies virus infection is fatal in over 99% of cases. However, disease can be prevented with prompt initiation of PEP, which includes administration of rabies immune globulin (RIG) and rabies vaccine. Let’s look at a few different scenarios.

1. A delivery person is bitten by your neighbor’s dog while making a delivery. He was told to get rabies vaccine. What should we advise?

Canine rabies has been eliminated in the United States. However, unvaccinated canines can acquire rabies from wildlife. In this situation, you can determine the immunization status of the dog. Contact your local/state health department to assist with enforcement and management. Bites by cats and ferrets should be managed similarly.

Healthy dog:

1. Observe for 10 days.

2. PEP is not indicated unless the animal develops signs/symptoms of rabies. Then euthanize and begin PEP.

Dog appears rabid or suspected to be rabid:

1. Begin PEP.

2. Animal should be euthanized. If immunofluorescent test is negative discontinue PEP.

Dog unavailable:

Contact local/state health department. They are more familiar with rabies surveillance data.

2. Patient relocating to Malaysia for 3-4 years. Rabies PrEP was recommended but the family wants your opinion before receiving the vaccine. What would you advise?

Canine rabies is felt to be the primary cause of rabies outside of the United States. Canines are not routinely vaccinated in many foreign destinations, and the availability of RIG and rabies vaccine is not guaranteed in developing countries. As noted above, dog bites during international travel accounted for 28% of U.S. cases between 1960 and 2018.

Word_Bonnie_M_TEX_2021_web.jpg

In May 2022 recommendations for a modified two-dose PrEP schedule was published that identifies five risk groups and includes specific timing for checking rabies titers. The third rabies dose can now be administered up until year 3 (Morb Mortal Wkly Rep. 2022 May 6;71[18]:619-27). For individuals relocating to countries where CRVV is present, I prefer the traditional three-dose PrEP schedule administered between 21 and 28 days. However, we now have options. If exposure occurs any time after completion of a three-dose PrEP series or within 3 years after completion of a two-dose PrEP series, RIG would not be required. All patients would receive two doses of rabies vaccine (days 0, 3). If exposure occurs after 3 years in a person who received two doses of PrEP who did not have documentation of a protective rabies titer (> 5 IU/mL), treatment will include RIG plus four doses of vaccine (days 0, 3, 7, 14).

For this relocating patient, supporting PrEP would be strongly recommended.

3. A mother tells you she sees bats flying around her home at night and a few have even gotten into the home. This morning she saw one in her child’s room. He was still sleeping. Is there anything she needs to do?

Bats have become the predominant source of rabies in the United States. In addition to the cases noted above, three fatal cases occurred between Sept. 28 and Nov. 10, 2021, after bat exposures in August 2021 (MMWR Morb Mortal Wkly Rep. 2022 Jan 7;71:31-2). All had recognized contact with a bat 3-7 weeks prior to onset of symptoms and died 2-3 weeks after symptom onset. One declined PEP and the other two did not realize the risk for rabies from their exposure or did not notice a scratch or bite. Bites from bats may be small and unnoticed. Exposure to a bat in a closed room while sleeping is considered an exposure. Hawaii is the only state not reporting rabid bats.

PEP is recommended for her child. She should identify potential areas bats may enter the home and seal them in addition to removal of any bat roosts.

4. A parent realizes a house guest has been feeding raccoons in the backyard. What’s your response?

While bat rabies is the predominant variant associated with disease in the United States, as illustrated in Figure 1, other species of wildlife including raccoons are a major source of rabies. The geographic spread of the raccoon variant of rabies has been limited by oral vaccination via bait. In the situation noted here, the raccoons have returned because food was being offered thus increasing the families chance of a potential rabies exposure. Wildlife including skunks, raccoons, coyotes, foxes, and mongooses are always considered rabid until proven negative by laboratory testing.

163098_Fig 2_web.jpg

You recommend to stop feeding wildlife and never to approach them. Have them contact the local rabies control unit and/or state wildlife services to assist with removal of the raccoons. Depending on the locale, pest control may be required at the owners expense. Inform the family to seek PEP if anyone is bitten or scratched by the raccoons.

As per the Centers for Disease Control and Prevention, about 55,000 residents receive PEP annually with health-associated expenditures including diagnostics, prevention, and control estimated between $245 and $510 million annually. Rabies is one of the most fatal diseases that can be prevented by avoiding contact with wild animals, maintenance of high immunization rates in pets, and keeping people informed of potential sources including bats. One can’t determine if an animal has rabies by looking at it. Rabies remains an urgent disease that we have to remember to address with our patients and their families. For additional information go to www.CDC.gov/rabies.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She has no relevant financial disclosures.