Tuberculosis

Tuberculosis cases are increasing in Washington, which has put public health officials on “heightened alert,” according to a recent announcement from the Washington State Department of Health.

Widespread disruptions in health care and missed tuberculosis diagnoses during the COVID-19 pandemic have likely added to the increase – both locally and globally.

“It’s been 20 years since we saw a cluster of TB cases like this,” Tao Sheng Kwan-Gett, MD, the state’s chief science officer, said in the announcement.

“The pandemic has likely contributed to the rise in cases and the outbreak in at least one correctional facility,” he said. “Increased access to TB testing and treatment in the community is going to be key to getting TB under control.”

Case numbers appeared to fall in Washington during the first year of the pandemic, possibly because of less reporting and missed diagnoses. But in 2021, cases rose quickly. The state reported 199 cases, marking a 22% increase from 2020.

So far this year, 70 cases have been reported, including 17 new cases that all have connections with each other and several state prisons.

The state’s Department of Corrections, Department of Health, and the Centers for Disease Control and Prevention are working together on testing and decreasing spread, MaryAnn Curl, MD, the chief medical officer for the Department of Corrections, said in the statement.

Tuberculosis cases are increasing worldwide. For the first time in more than a decade, TB deaths increased to about 1.5 million, according to the World Health Organization’s 2021 Global Tuberculosis Report.

Across the U.S., the number of reported TB cases significantly declined at the beginning of the pandemic in 2020 but increased again in 2021, according to a recent CDC study.

The Kansas Department of Health also reported an outbreak of TB cases in March, according to USA Today.

At the beginning of the pandemic, some people with TB may have been diagnosed with COVID-19 because both are infectious diseases that attack the lungs and have similar symptoms, the Washington Health Department said.

Like COVID-19, tuberculosis can spread through the air when an infected person coughs or sneezes. But unlike COVID-19, TB typically requires that you have prolonged exposure to become infected.

Symptoms of tuberculosis can include chest pain and coughing, with or without blood, as well as fever, night sweats, weight loss, and fatigue.

Tuberculosis is preventable, treatable, and curable, the Washington Health Department said. Those who travel to countries where TB is more common face higher risks for exposure, as well as those who live or work in settings where TB may spread, such as homeless shelters, prisons, jails, and nursing homes.

People can develop inactive TB, also called latent TB, which doesn’t have any symptoms and isn’t contagious. If people with inactive TB don’t get quick diagnosis or treatment, the infection can become active TB and cause symptoms. State health officials estimated that about 200,000 people in Washington have inactive TB.

Tuberculosis treatment can take a minimum of 6 months, and if it’s not followed carefully, symptoms can become more severe, the Health Department said. Incomplete treatment can also contribute to the spread of antibiotic-resistant strains of tuberculosis.

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

Tuberculosis cases are increasing in Washington, which has put public health officials on “heightened alert,” according to a recent announcement from the Washington State Department of Health.

Widespread disruptions in health care and missed tuberculosis diagnoses during the COVID-19 pandemic have likely added to the increase – both locally and globally.

“It’s been 20 years since we saw a cluster of TB cases like this,” Tao Sheng Kwan-Gett, MD, the state’s chief science officer, said in the announcement.

“The pandemic has likely contributed to the rise in cases and the outbreak in at least one correctional facility,” he said. “Increased access to TB testing and treatment in the community is going to be key to getting TB under control.”

Case numbers appeared to fall in Washington during the first year of the pandemic, possibly because of less reporting and missed diagnoses. But in 2021, cases rose quickly. The state reported 199 cases, marking a 22% increase from 2020.

So far this year, 70 cases have been reported, including 17 new cases that all have connections with each other and several state prisons.

The state’s Department of Corrections, Department of Health, and the Centers for Disease Control and Prevention are working together on testing and decreasing spread, MaryAnn Curl, MD, the chief medical officer for the Department of Corrections, said in the statement.

Tuberculosis cases are increasing worldwide. For the first time in more than a decade, TB deaths increased to about 1.5 million, according to the World Health Organization’s 2021 Global Tuberculosis Report.

Across the U.S., the number of reported TB cases significantly declined at the beginning of the pandemic in 2020 but increased again in 2021, according to a recent CDC study.

The Kansas Department of Health also reported an outbreak of TB cases in March, according to USA Today.

At the beginning of the pandemic, some people with TB may have been diagnosed with COVID-19 because both are infectious diseases that attack the lungs and have similar symptoms, the Washington Health Department said.

Like COVID-19, tuberculosis can spread through the air when an infected person coughs or sneezes. But unlike COVID-19, TB typically requires that you have prolonged exposure to become infected.

Symptoms of tuberculosis can include chest pain and coughing, with or without blood, as well as fever, night sweats, weight loss, and fatigue.

Tuberculosis is preventable, treatable, and curable, the Washington Health Department said. Those who travel to countries where TB is more common face higher risks for exposure, as well as those who live or work in settings where TB may spread, such as homeless shelters, prisons, jails, and nursing homes.

People can develop inactive TB, also called latent TB, which doesn’t have any symptoms and isn’t contagious. If people with inactive TB don’t get quick diagnosis or treatment, the infection can become active TB and cause symptoms. State health officials estimated that about 200,000 people in Washington have inactive TB.

Tuberculosis treatment can take a minimum of 6 months, and if it’s not followed carefully, symptoms can become more severe, the Health Department said. Incomplete treatment can also contribute to the spread of antibiotic-resistant strains of tuberculosis.

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

Tuberculosis cases are increasing in Washington, which has put public health officials on “heightened alert,” according to a recent announcement from the Washington State Department of Health.

Widespread disruptions in health care and missed tuberculosis diagnoses during the COVID-19 pandemic have likely added to the increase – both locally and globally.

“It’s been 20 years since we saw a cluster of TB cases like this,” Tao Sheng Kwan-Gett, MD, the state’s chief science officer, said in the announcement.

“The pandemic has likely contributed to the rise in cases and the outbreak in at least one correctional facility,” he said. “Increased access to TB testing and treatment in the community is going to be key to getting TB under control.”

Case numbers appeared to fall in Washington during the first year of the pandemic, possibly because of less reporting and missed diagnoses. But in 2021, cases rose quickly. The state reported 199 cases, marking a 22% increase from 2020.

So far this year, 70 cases have been reported, including 17 new cases that all have connections with each other and several state prisons.

The state’s Department of Corrections, Department of Health, and the Centers for Disease Control and Prevention are working together on testing and decreasing spread, MaryAnn Curl, MD, the chief medical officer for the Department of Corrections, said in the statement.

Tuberculosis cases are increasing worldwide. For the first time in more than a decade, TB deaths increased to about 1.5 million, according to the World Health Organization’s 2021 Global Tuberculosis Report.

Across the U.S., the number of reported TB cases significantly declined at the beginning of the pandemic in 2020 but increased again in 2021, according to a recent CDC study.

The Kansas Department of Health also reported an outbreak of TB cases in March, according to USA Today.

At the beginning of the pandemic, some people with TB may have been diagnosed with COVID-19 because both are infectious diseases that attack the lungs and have similar symptoms, the Washington Health Department said.

Like COVID-19, tuberculosis can spread through the air when an infected person coughs or sneezes. But unlike COVID-19, TB typically requires that you have prolonged exposure to become infected.

Symptoms of tuberculosis can include chest pain and coughing, with or without blood, as well as fever, night sweats, weight loss, and fatigue.

Tuberculosis is preventable, treatable, and curable, the Washington Health Department said. Those who travel to countries where TB is more common face higher risks for exposure, as well as those who live or work in settings where TB may spread, such as homeless shelters, prisons, jails, and nursing homes.

People can develop inactive TB, also called latent TB, which doesn’t have any symptoms and isn’t contagious. If people with inactive TB don’t get quick diagnosis or treatment, the infection can become active TB and cause symptoms. State health officials estimated that about 200,000 people in Washington have inactive TB.

Tuberculosis treatment can take a minimum of 6 months, and if it’s not followed carefully, symptoms can become more severe, the Health Department said. Incomplete treatment can also contribute to the spread of antibiotic-resistant strains of tuberculosis.

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

Every day we see stark images of the war in Ukraine – bombed-out buildings, explosions, and bodies lying in the streets. But there’s another, less visible war against the bacteria and viruses that are gathering their forces together. They, too, will infect parts of the population and may spread throughout Europe. Here’s what Ukrainians, and their neighbors, are facing on the infectious disease front.

Andrey Zinchuk, MD, MHS, a pulmonary/critical care physician at Yale and a native of Ukraine who immigrated to the U.S. at the age of 14 with his family, set the background for understanding this crisis. He said that TB and HIV rates in Ukraine have long been especially high, even before the current conflict: “Part of the challenge of the health care system in Ukraine is that it’s difficult to maintain a steady policy because of political instability,” he said. “We’ve had three revolutions in the last 20 years,” not counting the current Russian invasion.

The first was the breakup of the Soviet Union, which led to “an epidemic of people with HIV, hepatitis, and opioid use.” Next was the Orange Revolution in 2004 over fraud during a presidential election. In 2014 came the Maiden Revolution, after the government chose closer ties to Russia rather than Europe. Then-president Viktor Yanukovych fled to Russia.

“That’s when Russia annexed Crimea. There was essentially infiltration in Russian propaganda in the east of the country,” Dr. Zinchuk said. “This helped the Russians manufacture uprisings there to create a separatist state (the Luhansk and Donetsk People’s Republics) which were mostly Russian-speaking parts of the country,” an area known as the Donbas. This resulted in a war in eastern Ukraine that began 2014, with more than 10,000 deaths.

After the 2014 revolution, Dr. Zinchuk said, “There was a tremendous change in the way ... medical care was provided, and tremendous growth and stability in the medical supply for those chronic medical conditions.”

Nevertheless, health care expenditures in Ukraine have been quite low. Even before the current conflict, Dr. Zinchuk noted, annual health care expenditures in Ukraine were about $600 per capita. In comparison, it’s about $4,500 per person in Germany and $12,530 in the United States.

Despite those low per-capita expenditures in Ukraine, access to medicines – such as insulin for diabetes and antibiotics for tuberculosis – was stable before the war. But now, Dr. Zinchuk said, his aunt and uncle have had to flee Kyiv for the countryside and, while safe, they have “no plumbing and have to heat the house by burning firewood.” More significantly, their supply of medicine is unstable.

Asked what infections are of most immediate concern, Sten Vermund, MD, PhD, Dean of the Yale School of Public Health, told this news organization that it was “diarrheal diseases, especially in kids ... The water supply [of Mariupol] is no longer potable, but people are drinking it anyway. And sewage systems are destroyed, and raw sewage is just released into the rivers and streams. So the whole family of diarrheal diseases and war are bedfellows. So are respiratory diseases, whenever we have mass migrations and mixing of ... homeless people and transients.” 

There is one notable piece of good news that may reduce the spread of infectious diseases. Unlike the aftermath of World War II or the ongoing conflicts in the Middle East, Africa, and South Asia, refugees from the war in Ukraine are being taken into individual households throughout Poland, Germany, and other countries and are not being held in large displaced-persons camps. Dr. Vermund added, “The Syrian refugee camps in Lebanon are just tent camps with a million, 2 million people in them ... In theory, what the Poles are doing is a good thing from the point of view of preventing the spread of infection.”

One way of examining infections in war zones is by considering them based on how they are spread.
 

Respiratory infections

Although not as high on the list of concerns as TB or HIV, COVID-19 remains a big problem for infectious disease experts. Last fall, Ukraine ranked just behind the U.S. and Russia in deaths from COVID and in the top 10 in infections. Despite these dismal numbers, only 35% of people had completed the initial vaccination series.

The same conditions that fuel TB and COVID – crowding, especially in poorly ventilated settings – could lead to another measles outbreak. One occurred in Ukraine from 2017-2020, resulting in more than 115,000 cases. Even though the immunization rate for measles has now reached about 80%, the CDC considers Ukraine at high risk for another large outbreak since measles is so highly contagious.

According to the European Centre for Disease Prevention and Control (ECDC), Ukraine reported the second-highest number of TB cases in Europe (28,539). It is also one of the top 10 countries globally with the highest burden of multidrug-resistant tuberculosis (MDR-TB) – 27%. Equally disturbing is its ranking as having the second-highest rate of HIV/TB co-infection (26%) even before the war. Experts say war is a perfect breeding ground for TB, since starvation and overcrowding in poorly ventilated spaces encourages its spread.

Before the war, COVID had already caused severe disruptions in TB diagnosis and treatment access in Ukraine, and the World Health Organization suggested that the pandemic has set back efforts to end TB by more than a decade. 

Drug-resistant TB has been one of the biggest worries. In their report on TB in Ukraine, British tuberculosis experts Tom Wingfield, MBChB, PhD, from the Liverpool School of Tropical Medicine, and Jessica Potter MBBCh, PhD, from Queen Mary University of London, pointed out that “drug resistance thrives on fractured health systems and sporadic medicine supply.”

Frederick Altice, MD, a Yale epidemiologist and addiction specialist, noted, “[if] medication for tuberculosis is discontinued, that not only causes potential recurrence of disease but multidrug-resistant TB disease,” and patients could become infectious again.

Dr. Wingfield expressed concern that people will not seek care because they see it as unaffordable, although he told this news organization that he’s impressed at the Polish government’s efforts to ensure care. Especially with the triad of HIV, TB, and opioid use, Dr. Wingfield and Dr. Potter emphasized that these problems reflect the social determinants of health – “the experiences and conditions in which people live.” These medical conditions are all quite treatable with support, and once treated they pose no risk to others.
 

HIV and opioid use

Before the war, an estimated 260,000 people were living with HIV in Ukraine. Their rate of new HIV diagnoses in 2017 was second highest in the world – 37 out of every 100,000, exceeded only by Russia, with 71 out of 100,000.

Dr. Vermund told this news organization that “when Crimea was seized by the Russians in 2014, there was an immediate crisis among injection drug users who were in drug treatment programs, because it’s illegal in Russia to use buprenorphine or methadone ... So immediately, those programs were shut down, and all the drug users who were holding jobs, supporting their families, were withdrawing from their addictions and searching for a replacement, which was illegal heroin.”

Dr. Altice added that of 800 patients in the region who had to go cold turkey, “ten percent were dead within 6 months. Dependent on unreliable street drugs, some overdosed or committed suicide because they could not get treatment. They went through terrible withdrawal and stress.”

And as they relapsed, the HIV rate soared. “Fifty percent of the methadone patients have got HIV,” Dr. Altice said, “and if they stop taking the methadone, they’re going to stop taking their HIV medications as well. Their lives will become chaotic and very destabilized.”

This experience may soon repeat itself. There were two methadone factories in Ukraine – in Odessa and Kharkiv – that are now shut down by the war. Although there are efforts to import methadone and many other drugs, supply chain issues are “devastating,” Dr. Altice said. “If their medication for tuberculosis is discontinued, that not only causes potential recurrence of disease but multidrug-resistant TB disease,” and they could become infectious again. “[With a] lack of medication, lack of sterile syringes, people will be sharing syringes; they’ll be desperate. So as the desperation level goes up, the risk environment goes up, so that people have decreased opportunities to protect themselves,” and there will be an explosion in HIV.

Dr. Altice observed that with the immigration to Poland and the west, many Ukrainian refugees “are relying on the kindness of strangers.” They are likely to be “fearful to disclose either their HIV or their TB treatment status,” being afraid of being regarded as modern-day lepers, even though they are likely not infectious. Both Dr. Altice and Dr. Potter emphasized the need for the governments of Poland and other receiving countries to provide the refugees with “reassurance that their health information will not be shared with others.” Dr. Altice emphasized that “this is one of the things that I would say that these other countries have to get right.”

Dr. Potter echoed that, noting that extraordinary care needs to be taken so that shared information is not used for deportation.

When refugees are housed with rural hosts, transportation problems sometimes arise, creating major barriers to accessing care and treatment. In particular, refugees with TB, HIV, and addiction who are placed in small, remote locations may have difficulty securing transportation to sites where treatments for their complex illnesses are available, including specialists and medications.

Ukrainian-born microbiologist Olena Rzhepishevska, PhD, of Umeå University in Sweden, said in an interview that a network of European TB researchers have developed a database on TBNet where patients with TB can be specifically placed with understanding and helpful hosts outside of Ukraine. They can receive housing and medication through this network.

So far, 4 million Ukrainians have fled the country and millions more have been displaced internally. Dr. Altice noted that there is an “increased vulnerability beyond the vulnerability that they already [have] just by being a refugee” that we generally don’t recognize. Additionally, Poland and Hungary are not very progressive about methadone therapy nor are those nations well-equipped to provide it.

Dr. Altice explained that even within Ukraine, those who want to move to better their chance of getting their methadone are then at risk of being conscripted. He spoke of the grave calculations men must make, choosing to become internally displaced and risk conscription or losing life-saving methadone or medicines for HIV or TB.

One other unfortunate consequence of war might be a spike in rape, sexual abuse, prostitution, unwanted pregnancies, HIV, and sexually transmitted infections.

There were an estimated 80,100 female sex workers in Ukraine in 2016, with 5.2% HIV positive. In times of war, with no home or income, some women turn to prostitution to survive. Others are victims of sex trafficking, both within Ukraine and as refugees. The Russian invasion increased the risks of a surge in HIV infections, unwanted pregnancies, and abortions. Women who find themselves pregnant due to rape (a common tool of war) or sex trafficking may also struggle to access safe abortions. Poland, for example, has severe restrictions on abortion, and Ukrainian women may turn to unsafe, back-alley abortions, with their resulting high risk of infection.
 

Waterborne infections

Another concern involves waterborne infections. In addition to the common diarrheal diseases such as E coli, which can be expected from poor sanitation, polio is a significant concern. In the fall of 2021, Ukraine had an outbreak of vaccine-derived polio, with two cases of paralysis and 20 additional cases. As polio only paralyzes 1 person in 200 of those infected, many other cases were likely undetected. A vaccination campaign was just beginning when the war began.

Wound infections and antimicrobial resistance

The ECDC also reports high rates of antimicrobial resistance (AMR) in Ukraine, particularly involving common gram-negative bacteria, including Escherichia coli (53% resistance to third-generation cephalosporins), Klebsiella pneumoniae (54% resistance to carbapenems), and Acinetobacter spp. (77% resistance to carbapenems). Because of this, they recommend refugees requiring hospital admission be isolated on admission and screened for AMR. These AMR often complicate traumatic injuries of war.

Prevention

Many of these potential problems stemming from the war in Ukraine and the displacement of millions of its citizens can be avoided.

Attempts are being made to immunize refugees. WHO has made working with countries receiving refugees a priority, particularly by vaccinating children against measles, rubella, and COVID. The European Union has also purchased vaccines for polio and tuberculosis.

But Russia has waged an active anti-vaccine campaign against COVID in Ukraine, while at the same time advocating for vaccines in Russia. According to UNICEF, other countries with relatively low vaccination rates and high vaccine skepticism – Moldova, Romania, and Bulgaria – are at higher risk of polio and measles than those with high vaccination levels.

The continuing war in Ukraine has exacerbated the medical challenges the citizens of Ukraine face at home and as refugees fleeing to neighboring countries. Improving communication among agencies and governments and building trust with the refugees could go a long way toward limiting the spread of preventable infectious diseases as a result of the war.

Continuing to try to keep supply chains open within Ukraine and ensuring adequate supplies of medications and vaccines to refugees will also be essential. But, of course, the better solution is to end the war.

Dr. Altice, Dr. Potter, Dr. Wingfield, Dr. Vermund, and Dr. Zinchuk all report no relevant financial relationships.

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

Every day we see stark images of the war in Ukraine – bombed-out buildings, explosions, and bodies lying in the streets. But there’s another, less visible war against the bacteria and viruses that are gathering their forces together. They, too, will infect parts of the population and may spread throughout Europe. Here’s what Ukrainians, and their neighbors, are facing on the infectious disease front.

Andrey Zinchuk, MD, MHS, a pulmonary/critical care physician at Yale and a native of Ukraine who immigrated to the U.S. at the age of 14 with his family, set the background for understanding this crisis. He said that TB and HIV rates in Ukraine have long been especially high, even before the current conflict: “Part of the challenge of the health care system in Ukraine is that it’s difficult to maintain a steady policy because of political instability,” he said. “We’ve had three revolutions in the last 20 years,” not counting the current Russian invasion.

The first was the breakup of the Soviet Union, which led to “an epidemic of people with HIV, hepatitis, and opioid use.” Next was the Orange Revolution in 2004 over fraud during a presidential election. In 2014 came the Maiden Revolution, after the government chose closer ties to Russia rather than Europe. Then-president Viktor Yanukovych fled to Russia.

“That’s when Russia annexed Crimea. There was essentially infiltration in Russian propaganda in the east of the country,” Dr. Zinchuk said. “This helped the Russians manufacture uprisings there to create a separatist state (the Luhansk and Donetsk People’s Republics) which were mostly Russian-speaking parts of the country,” an area known as the Donbas. This resulted in a war in eastern Ukraine that began 2014, with more than 10,000 deaths.

After the 2014 revolution, Dr. Zinchuk said, “There was a tremendous change in the way ... medical care was provided, and tremendous growth and stability in the medical supply for those chronic medical conditions.”

Nevertheless, health care expenditures in Ukraine have been quite low. Even before the current conflict, Dr. Zinchuk noted, annual health care expenditures in Ukraine were about $600 per capita. In comparison, it’s about $4,500 per person in Germany and $12,530 in the United States.

Despite those low per-capita expenditures in Ukraine, access to medicines – such as insulin for diabetes and antibiotics for tuberculosis – was stable before the war. But now, Dr. Zinchuk said, his aunt and uncle have had to flee Kyiv for the countryside and, while safe, they have “no plumbing and have to heat the house by burning firewood.” More significantly, their supply of medicine is unstable.

Asked what infections are of most immediate concern, Sten Vermund, MD, PhD, Dean of the Yale School of Public Health, told this news organization that it was “diarrheal diseases, especially in kids ... The water supply [of Mariupol] is no longer potable, but people are drinking it anyway. And sewage systems are destroyed, and raw sewage is just released into the rivers and streams. So the whole family of diarrheal diseases and war are bedfellows. So are respiratory diseases, whenever we have mass migrations and mixing of ... homeless people and transients.” 

There is one notable piece of good news that may reduce the spread of infectious diseases. Unlike the aftermath of World War II or the ongoing conflicts in the Middle East, Africa, and South Asia, refugees from the war in Ukraine are being taken into individual households throughout Poland, Germany, and other countries and are not being held in large displaced-persons camps. Dr. Vermund added, “The Syrian refugee camps in Lebanon are just tent camps with a million, 2 million people in them ... In theory, what the Poles are doing is a good thing from the point of view of preventing the spread of infection.”

One way of examining infections in war zones is by considering them based on how they are spread.
 

Respiratory infections

Although not as high on the list of concerns as TB or HIV, COVID-19 remains a big problem for infectious disease experts. Last fall, Ukraine ranked just behind the U.S. and Russia in deaths from COVID and in the top 10 in infections. Despite these dismal numbers, only 35% of people had completed the initial vaccination series.

The same conditions that fuel TB and COVID – crowding, especially in poorly ventilated settings – could lead to another measles outbreak. One occurred in Ukraine from 2017-2020, resulting in more than 115,000 cases. Even though the immunization rate for measles has now reached about 80%, the CDC considers Ukraine at high risk for another large outbreak since measles is so highly contagious.

According to the European Centre for Disease Prevention and Control (ECDC), Ukraine reported the second-highest number of TB cases in Europe (28,539). It is also one of the top 10 countries globally with the highest burden of multidrug-resistant tuberculosis (MDR-TB) – 27%. Equally disturbing is its ranking as having the second-highest rate of HIV/TB co-infection (26%) even before the war. Experts say war is a perfect breeding ground for TB, since starvation and overcrowding in poorly ventilated spaces encourages its spread.

Before the war, COVID had already caused severe disruptions in TB diagnosis and treatment access in Ukraine, and the World Health Organization suggested that the pandemic has set back efforts to end TB by more than a decade. 

Drug-resistant TB has been one of the biggest worries. In their report on TB in Ukraine, British tuberculosis experts Tom Wingfield, MBChB, PhD, from the Liverpool School of Tropical Medicine, and Jessica Potter MBBCh, PhD, from Queen Mary University of London, pointed out that “drug resistance thrives on fractured health systems and sporadic medicine supply.”

Frederick Altice, MD, a Yale epidemiologist and addiction specialist, noted, “[if] medication for tuberculosis is discontinued, that not only causes potential recurrence of disease but multidrug-resistant TB disease,” and patients could become infectious again.

Dr. Wingfield expressed concern that people will not seek care because they see it as unaffordable, although he told this news organization that he’s impressed at the Polish government’s efforts to ensure care. Especially with the triad of HIV, TB, and opioid use, Dr. Wingfield and Dr. Potter emphasized that these problems reflect the social determinants of health – “the experiences and conditions in which people live.” These medical conditions are all quite treatable with support, and once treated they pose no risk to others.
 

HIV and opioid use

Before the war, an estimated 260,000 people were living with HIV in Ukraine. Their rate of new HIV diagnoses in 2017 was second highest in the world – 37 out of every 100,000, exceeded only by Russia, with 71 out of 100,000.

Dr. Vermund told this news organization that “when Crimea was seized by the Russians in 2014, there was an immediate crisis among injection drug users who were in drug treatment programs, because it’s illegal in Russia to use buprenorphine or methadone ... So immediately, those programs were shut down, and all the drug users who were holding jobs, supporting their families, were withdrawing from their addictions and searching for a replacement, which was illegal heroin.”

Dr. Altice added that of 800 patients in the region who had to go cold turkey, “ten percent were dead within 6 months. Dependent on unreliable street drugs, some overdosed or committed suicide because they could not get treatment. They went through terrible withdrawal and stress.”

And as they relapsed, the HIV rate soared. “Fifty percent of the methadone patients have got HIV,” Dr. Altice said, “and if they stop taking the methadone, they’re going to stop taking their HIV medications as well. Their lives will become chaotic and very destabilized.”

This experience may soon repeat itself. There were two methadone factories in Ukraine – in Odessa and Kharkiv – that are now shut down by the war. Although there are efforts to import methadone and many other drugs, supply chain issues are “devastating,” Dr. Altice said. “If their medication for tuberculosis is discontinued, that not only causes potential recurrence of disease but multidrug-resistant TB disease,” and they could become infectious again. “[With a] lack of medication, lack of sterile syringes, people will be sharing syringes; they’ll be desperate. So as the desperation level goes up, the risk environment goes up, so that people have decreased opportunities to protect themselves,” and there will be an explosion in HIV.

Dr. Altice observed that with the immigration to Poland and the west, many Ukrainian refugees “are relying on the kindness of strangers.” They are likely to be “fearful to disclose either their HIV or their TB treatment status,” being afraid of being regarded as modern-day lepers, even though they are likely not infectious. Both Dr. Altice and Dr. Potter emphasized the need for the governments of Poland and other receiving countries to provide the refugees with “reassurance that their health information will not be shared with others.” Dr. Altice emphasized that “this is one of the things that I would say that these other countries have to get right.”

Dr. Potter echoed that, noting that extraordinary care needs to be taken so that shared information is not used for deportation.

When refugees are housed with rural hosts, transportation problems sometimes arise, creating major barriers to accessing care and treatment. In particular, refugees with TB, HIV, and addiction who are placed in small, remote locations may have difficulty securing transportation to sites where treatments for their complex illnesses are available, including specialists and medications.

Ukrainian-born microbiologist Olena Rzhepishevska, PhD, of Umeå University in Sweden, said in an interview that a network of European TB researchers have developed a database on TBNet where patients with TB can be specifically placed with understanding and helpful hosts outside of Ukraine. They can receive housing and medication through this network.

So far, 4 million Ukrainians have fled the country and millions more have been displaced internally. Dr. Altice noted that there is an “increased vulnerability beyond the vulnerability that they already [have] just by being a refugee” that we generally don’t recognize. Additionally, Poland and Hungary are not very progressive about methadone therapy nor are those nations well-equipped to provide it.

Dr. Altice explained that even within Ukraine, those who want to move to better their chance of getting their methadone are then at risk of being conscripted. He spoke of the grave calculations men must make, choosing to become internally displaced and risk conscription or losing life-saving methadone or medicines for HIV or TB.

One other unfortunate consequence of war might be a spike in rape, sexual abuse, prostitution, unwanted pregnancies, HIV, and sexually transmitted infections.

There were an estimated 80,100 female sex workers in Ukraine in 2016, with 5.2% HIV positive. In times of war, with no home or income, some women turn to prostitution to survive. Others are victims of sex trafficking, both within Ukraine and as refugees. The Russian invasion increased the risks of a surge in HIV infections, unwanted pregnancies, and abortions. Women who find themselves pregnant due to rape (a common tool of war) or sex trafficking may also struggle to access safe abortions. Poland, for example, has severe restrictions on abortion, and Ukrainian women may turn to unsafe, back-alley abortions, with their resulting high risk of infection.
 

Waterborne infections

Another concern involves waterborne infections. In addition to the common diarrheal diseases such as E coli, which can be expected from poor sanitation, polio is a significant concern. In the fall of 2021, Ukraine had an outbreak of vaccine-derived polio, with two cases of paralysis and 20 additional cases. As polio only paralyzes 1 person in 200 of those infected, many other cases were likely undetected. A vaccination campaign was just beginning when the war began.

Wound infections and antimicrobial resistance

The ECDC also reports high rates of antimicrobial resistance (AMR) in Ukraine, particularly involving common gram-negative bacteria, including Escherichia coli (53% resistance to third-generation cephalosporins), Klebsiella pneumoniae (54% resistance to carbapenems), and Acinetobacter spp. (77% resistance to carbapenems). Because of this, they recommend refugees requiring hospital admission be isolated on admission and screened for AMR. These AMR often complicate traumatic injuries of war.

Prevention

Many of these potential problems stemming from the war in Ukraine and the displacement of millions of its citizens can be avoided.

Attempts are being made to immunize refugees. WHO has made working with countries receiving refugees a priority, particularly by vaccinating children against measles, rubella, and COVID. The European Union has also purchased vaccines for polio and tuberculosis.

But Russia has waged an active anti-vaccine campaign against COVID in Ukraine, while at the same time advocating for vaccines in Russia. According to UNICEF, other countries with relatively low vaccination rates and high vaccine skepticism – Moldova, Romania, and Bulgaria – are at higher risk of polio and measles than those with high vaccination levels.

The continuing war in Ukraine has exacerbated the medical challenges the citizens of Ukraine face at home and as refugees fleeing to neighboring countries. Improving communication among agencies and governments and building trust with the refugees could go a long way toward limiting the spread of preventable infectious diseases as a result of the war.

Continuing to try to keep supply chains open within Ukraine and ensuring adequate supplies of medications and vaccines to refugees will also be essential. But, of course, the better solution is to end the war.

Dr. Altice, Dr. Potter, Dr. Wingfield, Dr. Vermund, and Dr. Zinchuk all report no relevant financial relationships.

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

Every day we see stark images of the war in Ukraine – bombed-out buildings, explosions, and bodies lying in the streets. But there’s another, less visible war against the bacteria and viruses that are gathering their forces together. They, too, will infect parts of the population and may spread throughout Europe. Here’s what Ukrainians, and their neighbors, are facing on the infectious disease front.

Andrey Zinchuk, MD, MHS, a pulmonary/critical care physician at Yale and a native of Ukraine who immigrated to the U.S. at the age of 14 with his family, set the background for understanding this crisis. He said that TB and HIV rates in Ukraine have long been especially high, even before the current conflict: “Part of the challenge of the health care system in Ukraine is that it’s difficult to maintain a steady policy because of political instability,” he said. “We’ve had three revolutions in the last 20 years,” not counting the current Russian invasion.

The first was the breakup of the Soviet Union, which led to “an epidemic of people with HIV, hepatitis, and opioid use.” Next was the Orange Revolution in 2004 over fraud during a presidential election. In 2014 came the Maiden Revolution, after the government chose closer ties to Russia rather than Europe. Then-president Viktor Yanukovych fled to Russia.

“That’s when Russia annexed Crimea. There was essentially infiltration in Russian propaganda in the east of the country,” Dr. Zinchuk said. “This helped the Russians manufacture uprisings there to create a separatist state (the Luhansk and Donetsk People’s Republics) which were mostly Russian-speaking parts of the country,” an area known as the Donbas. This resulted in a war in eastern Ukraine that began 2014, with more than 10,000 deaths.

After the 2014 revolution, Dr. Zinchuk said, “There was a tremendous change in the way ... medical care was provided, and tremendous growth and stability in the medical supply for those chronic medical conditions.”

Nevertheless, health care expenditures in Ukraine have been quite low. Even before the current conflict, Dr. Zinchuk noted, annual health care expenditures in Ukraine were about $600 per capita. In comparison, it’s about $4,500 per person in Germany and $12,530 in the United States.

Despite those low per-capita expenditures in Ukraine, access to medicines – such as insulin for diabetes and antibiotics for tuberculosis – was stable before the war. But now, Dr. Zinchuk said, his aunt and uncle have had to flee Kyiv for the countryside and, while safe, they have “no plumbing and have to heat the house by burning firewood.” More significantly, their supply of medicine is unstable.

Asked what infections are of most immediate concern, Sten Vermund, MD, PhD, Dean of the Yale School of Public Health, told this news organization that it was “diarrheal diseases, especially in kids ... The water supply [of Mariupol] is no longer potable, but people are drinking it anyway. And sewage systems are destroyed, and raw sewage is just released into the rivers and streams. So the whole family of diarrheal diseases and war are bedfellows. So are respiratory diseases, whenever we have mass migrations and mixing of ... homeless people and transients.” 

There is one notable piece of good news that may reduce the spread of infectious diseases. Unlike the aftermath of World War II or the ongoing conflicts in the Middle East, Africa, and South Asia, refugees from the war in Ukraine are being taken into individual households throughout Poland, Germany, and other countries and are not being held in large displaced-persons camps. Dr. Vermund added, “The Syrian refugee camps in Lebanon are just tent camps with a million, 2 million people in them ... In theory, what the Poles are doing is a good thing from the point of view of preventing the spread of infection.”

One way of examining infections in war zones is by considering them based on how they are spread.
 

Respiratory infections

Although not as high on the list of concerns as TB or HIV, COVID-19 remains a big problem for infectious disease experts. Last fall, Ukraine ranked just behind the U.S. and Russia in deaths from COVID and in the top 10 in infections. Despite these dismal numbers, only 35% of people had completed the initial vaccination series.

The same conditions that fuel TB and COVID – crowding, especially in poorly ventilated settings – could lead to another measles outbreak. One occurred in Ukraine from 2017-2020, resulting in more than 115,000 cases. Even though the immunization rate for measles has now reached about 80%, the CDC considers Ukraine at high risk for another large outbreak since measles is so highly contagious.

According to the European Centre for Disease Prevention and Control (ECDC), Ukraine reported the second-highest number of TB cases in Europe (28,539). It is also one of the top 10 countries globally with the highest burden of multidrug-resistant tuberculosis (MDR-TB) – 27%. Equally disturbing is its ranking as having the second-highest rate of HIV/TB co-infection (26%) even before the war. Experts say war is a perfect breeding ground for TB, since starvation and overcrowding in poorly ventilated spaces encourages its spread.

Before the war, COVID had already caused severe disruptions in TB diagnosis and treatment access in Ukraine, and the World Health Organization suggested that the pandemic has set back efforts to end TB by more than a decade. 

Drug-resistant TB has been one of the biggest worries. In their report on TB in Ukraine, British tuberculosis experts Tom Wingfield, MBChB, PhD, from the Liverpool School of Tropical Medicine, and Jessica Potter MBBCh, PhD, from Queen Mary University of London, pointed out that “drug resistance thrives on fractured health systems and sporadic medicine supply.”

Frederick Altice, MD, a Yale epidemiologist and addiction specialist, noted, “[if] medication for tuberculosis is discontinued, that not only causes potential recurrence of disease but multidrug-resistant TB disease,” and patients could become infectious again.

Dr. Wingfield expressed concern that people will not seek care because they see it as unaffordable, although he told this news organization that he’s impressed at the Polish government’s efforts to ensure care. Especially with the triad of HIV, TB, and opioid use, Dr. Wingfield and Dr. Potter emphasized that these problems reflect the social determinants of health – “the experiences and conditions in which people live.” These medical conditions are all quite treatable with support, and once treated they pose no risk to others.
 

HIV and opioid use

Before the war, an estimated 260,000 people were living with HIV in Ukraine. Their rate of new HIV diagnoses in 2017 was second highest in the world – 37 out of every 100,000, exceeded only by Russia, with 71 out of 100,000.

Dr. Vermund told this news organization that “when Crimea was seized by the Russians in 2014, there was an immediate crisis among injection drug users who were in drug treatment programs, because it’s illegal in Russia to use buprenorphine or methadone ... So immediately, those programs were shut down, and all the drug users who were holding jobs, supporting their families, were withdrawing from their addictions and searching for a replacement, which was illegal heroin.”

Dr. Altice added that of 800 patients in the region who had to go cold turkey, “ten percent were dead within 6 months. Dependent on unreliable street drugs, some overdosed or committed suicide because they could not get treatment. They went through terrible withdrawal and stress.”

And as they relapsed, the HIV rate soared. “Fifty percent of the methadone patients have got HIV,” Dr. Altice said, “and if they stop taking the methadone, they’re going to stop taking their HIV medications as well. Their lives will become chaotic and very destabilized.”

This experience may soon repeat itself. There were two methadone factories in Ukraine – in Odessa and Kharkiv – that are now shut down by the war. Although there are efforts to import methadone and many other drugs, supply chain issues are “devastating,” Dr. Altice said. “If their medication for tuberculosis is discontinued, that not only causes potential recurrence of disease but multidrug-resistant TB disease,” and they could become infectious again. “[With a] lack of medication, lack of sterile syringes, people will be sharing syringes; they’ll be desperate. So as the desperation level goes up, the risk environment goes up, so that people have decreased opportunities to protect themselves,” and there will be an explosion in HIV.

Dr. Altice observed that with the immigration to Poland and the west, many Ukrainian refugees “are relying on the kindness of strangers.” They are likely to be “fearful to disclose either their HIV or their TB treatment status,” being afraid of being regarded as modern-day lepers, even though they are likely not infectious. Both Dr. Altice and Dr. Potter emphasized the need for the governments of Poland and other receiving countries to provide the refugees with “reassurance that their health information will not be shared with others.” Dr. Altice emphasized that “this is one of the things that I would say that these other countries have to get right.”

Dr. Potter echoed that, noting that extraordinary care needs to be taken so that shared information is not used for deportation.

When refugees are housed with rural hosts, transportation problems sometimes arise, creating major barriers to accessing care and treatment. In particular, refugees with TB, HIV, and addiction who are placed in small, remote locations may have difficulty securing transportation to sites where treatments for their complex illnesses are available, including specialists and medications.

Ukrainian-born microbiologist Olena Rzhepishevska, PhD, of Umeå University in Sweden, said in an interview that a network of European TB researchers have developed a database on TBNet where patients with TB can be specifically placed with understanding and helpful hosts outside of Ukraine. They can receive housing and medication through this network.

So far, 4 million Ukrainians have fled the country and millions more have been displaced internally. Dr. Altice noted that there is an “increased vulnerability beyond the vulnerability that they already [have] just by being a refugee” that we generally don’t recognize. Additionally, Poland and Hungary are not very progressive about methadone therapy nor are those nations well-equipped to provide it.

Dr. Altice explained that even within Ukraine, those who want to move to better their chance of getting their methadone are then at risk of being conscripted. He spoke of the grave calculations men must make, choosing to become internally displaced and risk conscription or losing life-saving methadone or medicines for HIV or TB.

One other unfortunate consequence of war might be a spike in rape, sexual abuse, prostitution, unwanted pregnancies, HIV, and sexually transmitted infections.

There were an estimated 80,100 female sex workers in Ukraine in 2016, with 5.2% HIV positive. In times of war, with no home or income, some women turn to prostitution to survive. Others are victims of sex trafficking, both within Ukraine and as refugees. The Russian invasion increased the risks of a surge in HIV infections, unwanted pregnancies, and abortions. Women who find themselves pregnant due to rape (a common tool of war) or sex trafficking may also struggle to access safe abortions. Poland, for example, has severe restrictions on abortion, and Ukrainian women may turn to unsafe, back-alley abortions, with their resulting high risk of infection.
 

Waterborne infections

Another concern involves waterborne infections. In addition to the common diarrheal diseases such as E coli, which can be expected from poor sanitation, polio is a significant concern. In the fall of 2021, Ukraine had an outbreak of vaccine-derived polio, with two cases of paralysis and 20 additional cases. As polio only paralyzes 1 person in 200 of those infected, many other cases were likely undetected. A vaccination campaign was just beginning when the war began.

Wound infections and antimicrobial resistance

The ECDC also reports high rates of antimicrobial resistance (AMR) in Ukraine, particularly involving common gram-negative bacteria, including Escherichia coli (53% resistance to third-generation cephalosporins), Klebsiella pneumoniae (54% resistance to carbapenems), and Acinetobacter spp. (77% resistance to carbapenems). Because of this, they recommend refugees requiring hospital admission be isolated on admission and screened for AMR. These AMR often complicate traumatic injuries of war.

Prevention

Many of these potential problems stemming from the war in Ukraine and the displacement of millions of its citizens can be avoided.

Attempts are being made to immunize refugees. WHO has made working with countries receiving refugees a priority, particularly by vaccinating children against measles, rubella, and COVID. The European Union has also purchased vaccines for polio and tuberculosis.

But Russia has waged an active anti-vaccine campaign against COVID in Ukraine, while at the same time advocating for vaccines in Russia. According to UNICEF, other countries with relatively low vaccination rates and high vaccine skepticism – Moldova, Romania, and Bulgaria – are at higher risk of polio and measles than those with high vaccination levels.

The continuing war in Ukraine has exacerbated the medical challenges the citizens of Ukraine face at home and as refugees fleeing to neighboring countries. Improving communication among agencies and governments and building trust with the refugees could go a long way toward limiting the spread of preventable infectious diseases as a result of the war.

Continuing to try to keep supply chains open within Ukraine and ensuring adequate supplies of medications and vaccines to refugees will also be essential. But, of course, the better solution is to end the war.

Dr. Altice, Dr. Potter, Dr. Wingfield, Dr. Vermund, and Dr. Zinchuk all report no relevant financial relationships.

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

The World Health Organization now recommends shortened treatment for children with mild tuberculosis, as well as two oral TB treatments (bedaquiline and delamanid) for use in children of all ages. The updated guidelines for TB management in children and adolescents were announced March 21 ahead of World Tuberculosis Day on March 24.

The agency also called for increased investment in global TB programs, noting that in 2020, TB deaths increased for the first time in over a decade. “We cannot falter in our commitment to reach and save every man, woman, child, family, and community impacted by this deadly disease,” said Tereza Kasaeva, MD, PhD, director of the WHO Global Tuberculosis Programme during a press conference.

TB is the 13th-leading cause of death and the second top infectious killer after COVID-19, with more than 4,100 people dying from TB every day. WHO estimates that 1.1 million children fall ill with TB each year.
 

Calls for investment

The increase in TB deaths from 1.4 million in 2019 to 1.5 million in 2020 was coupled with a decrease in funding. From 2019-2020, global spending for TB diagnostic, treatment, and prevention services fell from $5.8 billion to $5.3 billion. This is less than half of the $13 billion target funding amount for 2022, Dr. Kasaeva said.

Efforts to expand access to TB care have fallen short mainly because of this lack of funding, especially for children. In 2020, about 63% of children under 15 years of age with TB either did not receive or were not reported to have access to TB diagnosis and treatment services, which rose to 72% in children under age 5. Almost two-thirds of children under age 5 also did not receive TB preventive treatment in 2022, according to WHO statistics.

The socioeconomic ramifications of the COVID-19 pandemic as well as ongoing conflict in Eastern Europe, Africa, and the Middle East have “further exacerbated the situation,” Dr. Kasaeva said. “This conveys the urgent need to dramatically increase investments to ramp up the fight against TB and achieve commitments to end TB made by global leaders.”

Dr. Kasaeva laid out WHO’s main points for global investment in TB care:

• Increase domestic and international funding to close gaps in TB research and program implementation. For countries with smaller economies, increased international investment will be necessary in the short or medium term to help regain progress.
• Double funding for TB research, including vaccines.
• Invest in sustaining TB programs and services during the COVID-19 pandemic and ongoing crises so care is not disrupted.

New guidelines

Dr. Kasaeva also noted that adoption of WHO’s new guidelines for children and adolescents should be fast-tracked to improve access to and quality of care. The updates include:

• Rapid molecular tests called Xpert Ultra should be used as the initial test for TB in children and adolescents.
• Diagnostic testing can now include noninvasive specimens, like stool samples.
• Children with mild TB can be treated with a , rather than 6 months. This shortened regimen will allow children to return to school faster and save money for families and the health care system, said Kerri Viney, MD, PhD, a team lead for the WHO Tuberculosis Programme, with a focus on vulnerable populations, including children. She presented the new guidelines during the WHO press conference.
• The recommended treatment regimen for TB meningitis has also been shortened from 12 to 6 months.

Two oral medications for drug-resistant TB (bedaquiline and delamanid) are now recommended for use in children of all ages. “There is no longer a need for painful injections that can have serious side effects, including deafness,” Dr. Viney said.

Health systems should develop new models of decentralized and integrated TB care to bring TB care closer to where children live.

The guidelines are available on the WHO website.

“The WHO guidelines issued today are a game changer for children and adolescents with TB,” Dr. Kasaeva said. The next step is assisting countries in implementing these updates so that children and adolescents globally have access to high quality TB care,” Dr. Viney added. “We have the policy recommendations. We have the implementation guidance, we have child-friendly formulations of TB medicines,” she said. “Let us not wait any longer. Let us invest to end TB in children and adolescents.”

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

The World Health Organization now recommends shortened treatment for children with mild tuberculosis, as well as two oral TB treatments (bedaquiline and delamanid) for use in children of all ages. The updated guidelines for TB management in children and adolescents were announced March 21 ahead of World Tuberculosis Day on March 24.

The agency also called for increased investment in global TB programs, noting that in 2020, TB deaths increased for the first time in over a decade. “We cannot falter in our commitment to reach and save every man, woman, child, family, and community impacted by this deadly disease,” said Tereza Kasaeva, MD, PhD, director of the WHO Global Tuberculosis Programme during a press conference.

TB is the 13th-leading cause of death and the second top infectious killer after COVID-19, with more than 4,100 people dying from TB every day. WHO estimates that 1.1 million children fall ill with TB each year.
 

Calls for investment

The increase in TB deaths from 1.4 million in 2019 to 1.5 million in 2020 was coupled with a decrease in funding. From 2019-2020, global spending for TB diagnostic, treatment, and prevention services fell from $5.8 billion to $5.3 billion. This is less than half of the $13 billion target funding amount for 2022, Dr. Kasaeva said.

Efforts to expand access to TB care have fallen short mainly because of this lack of funding, especially for children. In 2020, about 63% of children under 15 years of age with TB either did not receive or were not reported to have access to TB diagnosis and treatment services, which rose to 72% in children under age 5. Almost two-thirds of children under age 5 also did not receive TB preventive treatment in 2022, according to WHO statistics.

The socioeconomic ramifications of the COVID-19 pandemic as well as ongoing conflict in Eastern Europe, Africa, and the Middle East have “further exacerbated the situation,” Dr. Kasaeva said. “This conveys the urgent need to dramatically increase investments to ramp up the fight against TB and achieve commitments to end TB made by global leaders.”

Dr. Kasaeva laid out WHO’s main points for global investment in TB care:

• Increase domestic and international funding to close gaps in TB research and program implementation. For countries with smaller economies, increased international investment will be necessary in the short or medium term to help regain progress.
• Double funding for TB research, including vaccines.
• Invest in sustaining TB programs and services during the COVID-19 pandemic and ongoing crises so care is not disrupted.

New guidelines

Dr. Kasaeva also noted that adoption of WHO’s new guidelines for children and adolescents should be fast-tracked to improve access to and quality of care. The updates include:

• Rapid molecular tests called Xpert Ultra should be used as the initial test for TB in children and adolescents.
• Diagnostic testing can now include noninvasive specimens, like stool samples.
• Children with mild TB can be treated with a , rather than 6 months. This shortened regimen will allow children to return to school faster and save money for families and the health care system, said Kerri Viney, MD, PhD, a team lead for the WHO Tuberculosis Programme, with a focus on vulnerable populations, including children. She presented the new guidelines during the WHO press conference.
• The recommended treatment regimen for TB meningitis has also been shortened from 12 to 6 months.

Two oral medications for drug-resistant TB (bedaquiline and delamanid) are now recommended for use in children of all ages. “There is no longer a need for painful injections that can have serious side effects, including deafness,” Dr. Viney said.

Health systems should develop new models of decentralized and integrated TB care to bring TB care closer to where children live.

The guidelines are available on the WHO website.

“The WHO guidelines issued today are a game changer for children and adolescents with TB,” Dr. Kasaeva said. The next step is assisting countries in implementing these updates so that children and adolescents globally have access to high quality TB care,” Dr. Viney added. “We have the policy recommendations. We have the implementation guidance, we have child-friendly formulations of TB medicines,” she said. “Let us not wait any longer. Let us invest to end TB in children and adolescents.”

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

The World Health Organization now recommends shortened treatment for children with mild tuberculosis, as well as two oral TB treatments (bedaquiline and delamanid) for use in children of all ages. The updated guidelines for TB management in children and adolescents were announced March 21 ahead of World Tuberculosis Day on March 24.

The agency also called for increased investment in global TB programs, noting that in 2020, TB deaths increased for the first time in over a decade. “We cannot falter in our commitment to reach and save every man, woman, child, family, and community impacted by this deadly disease,” said Tereza Kasaeva, MD, PhD, director of the WHO Global Tuberculosis Programme during a press conference.

TB is the 13th-leading cause of death and the second top infectious killer after COVID-19, with more than 4,100 people dying from TB every day. WHO estimates that 1.1 million children fall ill with TB each year.
 

Calls for investment

The increase in TB deaths from 1.4 million in 2019 to 1.5 million in 2020 was coupled with a decrease in funding. From 2019-2020, global spending for TB diagnostic, treatment, and prevention services fell from $5.8 billion to $5.3 billion. This is less than half of the $13 billion target funding amount for 2022, Dr. Kasaeva said.

Efforts to expand access to TB care have fallen short mainly because of this lack of funding, especially for children. In 2020, about 63% of children under 15 years of age with TB either did not receive or were not reported to have access to TB diagnosis and treatment services, which rose to 72% in children under age 5. Almost two-thirds of children under age 5 also did not receive TB preventive treatment in 2022, according to WHO statistics.

The socioeconomic ramifications of the COVID-19 pandemic as well as ongoing conflict in Eastern Europe, Africa, and the Middle East have “further exacerbated the situation,” Dr. Kasaeva said. “This conveys the urgent need to dramatically increase investments to ramp up the fight against TB and achieve commitments to end TB made by global leaders.”

Dr. Kasaeva laid out WHO’s main points for global investment in TB care:

• Increase domestic and international funding to close gaps in TB research and program implementation. For countries with smaller economies, increased international investment will be necessary in the short or medium term to help regain progress.
• Double funding for TB research, including vaccines.
• Invest in sustaining TB programs and services during the COVID-19 pandemic and ongoing crises so care is not disrupted.

New guidelines

Dr. Kasaeva also noted that adoption of WHO’s new guidelines for children and adolescents should be fast-tracked to improve access to and quality of care. The updates include:

• Rapid molecular tests called Xpert Ultra should be used as the initial test for TB in children and adolescents.
• Diagnostic testing can now include noninvasive specimens, like stool samples.
• Children with mild TB can be treated with a , rather than 6 months. This shortened regimen will allow children to return to school faster and save money for families and the health care system, said Kerri Viney, MD, PhD, a team lead for the WHO Tuberculosis Programme, with a focus on vulnerable populations, including children. She presented the new guidelines during the WHO press conference.
• The recommended treatment regimen for TB meningitis has also been shortened from 12 to 6 months.

Two oral medications for drug-resistant TB (bedaquiline and delamanid) are now recommended for use in children of all ages. “There is no longer a need for painful injections that can have serious side effects, including deafness,” Dr. Viney said.

Health systems should develop new models of decentralized and integrated TB care to bring TB care closer to where children live.

The guidelines are available on the WHO website.

“The WHO guidelines issued today are a game changer for children and adolescents with TB,” Dr. Kasaeva said. The next step is assisting countries in implementing these updates so that children and adolescents globally have access to high quality TB care,” Dr. Viney added. “We have the policy recommendations. We have the implementation guidance, we have child-friendly formulations of TB medicines,” she said. “Let us not wait any longer. Let us invest to end TB in children and adolescents.”

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

The World Health Organization is expected to recommend truncating treatment of children with mild tuberculosis by 2 months – from 6 months to 4 – after a randomized trial found similar outcomes with the shorter regimen.

An international team of investigators found the abbreviated course of antibiotics was no less effective or safe than conventional treatment and saved an average of $17.34 per child – money that could be used to mitigate the toll of TB, which is estimated to sicken 1.1 million children worldwide each year.

The findings come as deaths from TB are rising as a result of the COVID-19 pandemic, which has hindered efforts to find and treat patients. In 2020, according to the WHO, an estimated 1.5 million people died from TB, the first year-over-year increase in such deaths since 2005.

Nearly a quarter of children with TB die, primarily because they go undiagnosed, according to the researchers, who published the study in the New England Journal of Medicine. Shorter treatment “translates into very large cost savings that could be used to improve screening and diagnosis to address the current case detection gap,” first author Anna Turkova, MD, of University College London, told this news organization.

The standard TB regimen is based on trials in adults with severe respiratory disease. However, about two-thirds of children have nonsevere infections.

For the study, Dr. Turkova and colleagues assigned 1,204 children with TB in four countries – Uganda, Zambia, South Africa, and India – to either a 4- or 6-month regimen with first-line medications rifampin, isoniazid, pyrazinamide, and ethambutol. Participants were aged 2 months to 15 years and had symptomatic nonsevere lung or lymph node infections with a negative test on a sputum smear microscopy. Eleven percent also had HIV.

After 18 months, 16 participants in the group that received the shortened treatment and 18 in the standard treatment group had experienced an unfavorable outcome – defined as treatment failure, recurrence of TB, loss to follow-up, or death (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5).

Similar numbers – 47 in the 4-month group and 48 in the 6-month group – experienced severe or life-threatening adverse events, most commonly chest infections, such as pneumonia, and liver problems, during treatment or up to 30 days after the last dose.  
 

New guidelines coming soon

The WHO plans to issue new guidelines and a handbook for TB management in children and adolescents on March 24, World Tuberculosis Day, a spokesman for the agency told Medscape.

Anna Mandalakas, MD, PhD, director of the Global Tuberculosis Program at Baylor College of Medicine, department of pediatrics, Houston, said the shorter regimen should enable more children to successfully complete TB treatment.

“It can be challenging to convince young children to take medications on a regular basis for 6 months,” Dr. Mandalakas, a member of a WHO guidelines development group that reviewed the study, told this news organization. “Despite best intentions, parents often become fatigued and give up the medicine battle.”

Leo Martinez, PhD, an epidemiologist at Boston University School of Public Health who studies pediatric TB, noted that study’s cost-effectiveness analysis applies only to health care costs. Families often suffer financially through lost wages, transportation to health care facilities, and lost employment, fueling a cycle of poverty and disease in low-income countries, he said.

A WHO statement noted that long treatment regimens can add toxicity and risk of drug interactions for children with HIV.

Separate efforts have been underway to hasten TB treatment in different groups of patients. A study published in NEJM showed that 4 months of the potent antibiotic rifapentine, along with another antibiotic, moxifloxacin, was non-inferior to the standard 6-month regimen in patients aged 12 and older. According to the editorial accompanying that study, the research illustrated the potential for shorter treatment courses that would be cheaper and less cumbersome, although that particular combination poses hurdles such as adherence issues and potential bacterial resistance.

Experts agreed that improved diagnostic procedures are critical to significantly reducing TB pediatric deaths – an issue that Dr. Turkova said will be addressed in WHO’s forthcoming handbook.

Because no gold-standard test exists for TB, and symptoms often overlap with other infections, widespread screening of children in households where adults have been diagnosed with TB has been found to improve detection of the disease. “Training of health care workers, easy-to-implement diagnostic algorithms, and widely accessible training materials on chest radiography in childhood TB should also improve case finding and treatment initiation,” she said.

The trial was supported by U.K. government and charitable research funders. Dr. Turkova and Dr. Martinez reported no financial disclosures. Dr. Mandalakas reported honoraria from WHO to support the preparation of diagnostics and treatment chapters in the operational handbook, for providing lectures for Medscape, and for serving on a data safety monitoring board for Janssen Pharmaceuticals.

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

The World Health Organization is expected to recommend truncating treatment of children with mild tuberculosis by 2 months – from 6 months to 4 – after a randomized trial found similar outcomes with the shorter regimen.

An international team of investigators found the abbreviated course of antibiotics was no less effective or safe than conventional treatment and saved an average of $17.34 per child – money that could be used to mitigate the toll of TB, which is estimated to sicken 1.1 million children worldwide each year.

The findings come as deaths from TB are rising as a result of the COVID-19 pandemic, which has hindered efforts to find and treat patients. In 2020, according to the WHO, an estimated 1.5 million people died from TB, the first year-over-year increase in such deaths since 2005.

Nearly a quarter of children with TB die, primarily because they go undiagnosed, according to the researchers, who published the study in the New England Journal of Medicine. Shorter treatment “translates into very large cost savings that could be used to improve screening and diagnosis to address the current case detection gap,” first author Anna Turkova, MD, of University College London, told this news organization.

The standard TB regimen is based on trials in adults with severe respiratory disease. However, about two-thirds of children have nonsevere infections.

For the study, Dr. Turkova and colleagues assigned 1,204 children with TB in four countries – Uganda, Zambia, South Africa, and India – to either a 4- or 6-month regimen with first-line medications rifampin, isoniazid, pyrazinamide, and ethambutol. Participants were aged 2 months to 15 years and had symptomatic nonsevere lung or lymph node infections with a negative test on a sputum smear microscopy. Eleven percent also had HIV.

After 18 months, 16 participants in the group that received the shortened treatment and 18 in the standard treatment group had experienced an unfavorable outcome – defined as treatment failure, recurrence of TB, loss to follow-up, or death (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5).

Similar numbers – 47 in the 4-month group and 48 in the 6-month group – experienced severe or life-threatening adverse events, most commonly chest infections, such as pneumonia, and liver problems, during treatment or up to 30 days after the last dose.  
 

New guidelines coming soon

The WHO plans to issue new guidelines and a handbook for TB management in children and adolescents on March 24, World Tuberculosis Day, a spokesman for the agency told Medscape.

Anna Mandalakas, MD, PhD, director of the Global Tuberculosis Program at Baylor College of Medicine, department of pediatrics, Houston, said the shorter regimen should enable more children to successfully complete TB treatment.

“It can be challenging to convince young children to take medications on a regular basis for 6 months,” Dr. Mandalakas, a member of a WHO guidelines development group that reviewed the study, told this news organization. “Despite best intentions, parents often become fatigued and give up the medicine battle.”

Leo Martinez, PhD, an epidemiologist at Boston University School of Public Health who studies pediatric TB, noted that study’s cost-effectiveness analysis applies only to health care costs. Families often suffer financially through lost wages, transportation to health care facilities, and lost employment, fueling a cycle of poverty and disease in low-income countries, he said.

A WHO statement noted that long treatment regimens can add toxicity and risk of drug interactions for children with HIV.

Separate efforts have been underway to hasten TB treatment in different groups of patients. A study published in NEJM showed that 4 months of the potent antibiotic rifapentine, along with another antibiotic, moxifloxacin, was non-inferior to the standard 6-month regimen in patients aged 12 and older. According to the editorial accompanying that study, the research illustrated the potential for shorter treatment courses that would be cheaper and less cumbersome, although that particular combination poses hurdles such as adherence issues and potential bacterial resistance.

Experts agreed that improved diagnostic procedures are critical to significantly reducing TB pediatric deaths – an issue that Dr. Turkova said will be addressed in WHO’s forthcoming handbook.

Because no gold-standard test exists for TB, and symptoms often overlap with other infections, widespread screening of children in households where adults have been diagnosed with TB has been found to improve detection of the disease. “Training of health care workers, easy-to-implement diagnostic algorithms, and widely accessible training materials on chest radiography in childhood TB should also improve case finding and treatment initiation,” she said.

The trial was supported by U.K. government and charitable research funders. Dr. Turkova and Dr. Martinez reported no financial disclosures. Dr. Mandalakas reported honoraria from WHO to support the preparation of diagnostics and treatment chapters in the operational handbook, for providing lectures for Medscape, and for serving on a data safety monitoring board for Janssen Pharmaceuticals.

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

The World Health Organization is expected to recommend truncating treatment of children with mild tuberculosis by 2 months – from 6 months to 4 – after a randomized trial found similar outcomes with the shorter regimen.

An international team of investigators found the abbreviated course of antibiotics was no less effective or safe than conventional treatment and saved an average of $17.34 per child – money that could be used to mitigate the toll of TB, which is estimated to sicken 1.1 million children worldwide each year.

The findings come as deaths from TB are rising as a result of the COVID-19 pandemic, which has hindered efforts to find and treat patients. In 2020, according to the WHO, an estimated 1.5 million people died from TB, the first year-over-year increase in such deaths since 2005.

Nearly a quarter of children with TB die, primarily because they go undiagnosed, according to the researchers, who published the study in the New England Journal of Medicine. Shorter treatment “translates into very large cost savings that could be used to improve screening and diagnosis to address the current case detection gap,” first author Anna Turkova, MD, of University College London, told this news organization.

The standard TB regimen is based on trials in adults with severe respiratory disease. However, about two-thirds of children have nonsevere infections.

For the study, Dr. Turkova and colleagues assigned 1,204 children with TB in four countries – Uganda, Zambia, South Africa, and India – to either a 4- or 6-month regimen with first-line medications rifampin, isoniazid, pyrazinamide, and ethambutol. Participants were aged 2 months to 15 years and had symptomatic nonsevere lung or lymph node infections with a negative test on a sputum smear microscopy. Eleven percent also had HIV.

After 18 months, 16 participants in the group that received the shortened treatment and 18 in the standard treatment group had experienced an unfavorable outcome – defined as treatment failure, recurrence of TB, loss to follow-up, or death (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5).

Similar numbers – 47 in the 4-month group and 48 in the 6-month group – experienced severe or life-threatening adverse events, most commonly chest infections, such as pneumonia, and liver problems, during treatment or up to 30 days after the last dose.  
 

New guidelines coming soon

The WHO plans to issue new guidelines and a handbook for TB management in children and adolescents on March 24, World Tuberculosis Day, a spokesman for the agency told Medscape.

Anna Mandalakas, MD, PhD, director of the Global Tuberculosis Program at Baylor College of Medicine, department of pediatrics, Houston, said the shorter regimen should enable more children to successfully complete TB treatment.

“It can be challenging to convince young children to take medications on a regular basis for 6 months,” Dr. Mandalakas, a member of a WHO guidelines development group that reviewed the study, told this news organization. “Despite best intentions, parents often become fatigued and give up the medicine battle.”

Leo Martinez, PhD, an epidemiologist at Boston University School of Public Health who studies pediatric TB, noted that study’s cost-effectiveness analysis applies only to health care costs. Families often suffer financially through lost wages, transportation to health care facilities, and lost employment, fueling a cycle of poverty and disease in low-income countries, he said.

A WHO statement noted that long treatment regimens can add toxicity and risk of drug interactions for children with HIV.

Separate efforts have been underway to hasten TB treatment in different groups of patients. A study published in NEJM showed that 4 months of the potent antibiotic rifapentine, along with another antibiotic, moxifloxacin, was non-inferior to the standard 6-month regimen in patients aged 12 and older. According to the editorial accompanying that study, the research illustrated the potential for shorter treatment courses that would be cheaper and less cumbersome, although that particular combination poses hurdles such as adherence issues and potential bacterial resistance.

Experts agreed that improved diagnostic procedures are critical to significantly reducing TB pediatric deaths – an issue that Dr. Turkova said will be addressed in WHO’s forthcoming handbook.

Because no gold-standard test exists for TB, and symptoms often overlap with other infections, widespread screening of children in households where adults have been diagnosed with TB has been found to improve detection of the disease. “Training of health care workers, easy-to-implement diagnostic algorithms, and widely accessible training materials on chest radiography in childhood TB should also improve case finding and treatment initiation,” she said.

The trial was supported by U.K. government and charitable research funders. Dr. Turkova and Dr. Martinez reported no financial disclosures. Dr. Mandalakas reported honoraria from WHO to support the preparation of diagnostics and treatment chapters in the operational handbook, for providing lectures for Medscape, and for serving on a data safety monitoring board for Janssen Pharmaceuticals.

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

Infectious disease specialist and humanitarian, Paul Edward Farmer, MD, PhD, who cofounded Partners In Health, died suddenly on Feb. 21. To celebrate his life, this news organization interviewed Serena Koenig, MD, MPH, who met Dr. Farmer when she was an internal medicine resident at Brigham and Women’s Hospital. Dr. Koenig had worked closely with Dr. Farmer ever since they met.

Q. Can you please share one of your best memories of Dr. Farmer?

Dr. Serena Koenig: There are so many memories it is hard to choose. One that was very formative for me occurred during one of my first trips to Haiti, in 2001. Paul and some other incredible colleagues at Partners IN Health (PIH) had started the HIV Equity Initiative, which was one of the first programs in the world to provide free, comprehensive treatment for HIV. This was at the time when millions of people in Africa were dying of HIV and many experts said it was not feasible to treat HIV in a poor country, because it was too complicated and expensive. Paul took me on some home visits with patients who had what he called the Lazarus effect, coming back from death’s door from advanced AIDS to vigorous health on antiretroviral therapy. I had just started working in Haiti with Paul and PIH, and I felt the enormous magnitude of what he was doing.

Q. What aspects of him and his work do you find most admirable?

Dr. Koenig: I most admired Paul’s humanity, his belief that every person matters and has the right to high-quality health care, and his vision of global health equity.

He said: “The idea that some lives matter less is the root of all that is wrong with the world.” Paul lived this philosophy. He has spoken extensively about harms of socialization for scarcity on behalf of those who are poor, leading policy makers to decisions regarding the feasibility of treating some diseases, but not others.

He said in an interview with the Harvard Gazette in 2018: “The most compelling thing to fight socialization for scarcity on behalf of others is health system strengthening. Health systems that integrate prevention and quality care.”

A few weeks ago, I asked him his thoughts about the high-level resources we have invested in some patients who have needed specialty care over the years, and he said: “No way that we should waste all of our emotional energy responding only to those constant, nagging critics that it’s not cost effective, not feasible, not sustainable, not even prudent. Because you know what they would have done if it was their child or family member.”
 

Q. When did you first meet Dr. Farmer, and what inspired you to work with him?

Dr. Koenig: When I was an internal medicine resident at the Brigham, Paul and I bonded over the care of one of my clinic patients who I followed very closely, and who was admitted to his inpatient service.

Like everyone else who has worked with Paul, I was touched by his kindness and warmth.

A couple of years later, he asked me to help him raise money to bring a young man named Wilnot from Haiti to the Brigham for an aortic valve replacement. After we raised the money, he asked me to go to Haiti to help Wilnot get his medical visa and to escort him to Boston.

That short trip to Haiti had an enormous impact on my life. I was shattered to see the poverty that the people of Haiti were enduring – and in a country a short plane flight from Miami.

Shortly after this, Paul asked me to help him find treatment for another patient, a young boy named John, who presented with neck masses that were later diagnosed as nasopharyngeal carcinoma.

It took us some time to make the diagnosis and then to arrange free care at Mass General.

When I returned to Haiti with two PIH colleagues to help John get a visa and escort him back to Boston, we found that John’s condition was much worse. We ended up medically evacuating him to Boston, because he was too sick for a commercial flight.

Tracy Kidder wrote about this heartbreaking experience in the book “Mountains Beyond Mountains.”

Throughout all of these experiences, I was deeply impressed with Paul’s commitment to do whatever it took to provide the best care for patients, as if they were members of his own family. He said “Tout Moun Se Moun” (Haitian Creole for “every person is a person”), and I could tell that he meant it.
 

Q. How did you collaborate with him professionally?

Dr. Koenig: I spent the first few years after residency working with Paul and Partners In Health. Initially, I served as a liaison between PIH in Haiti and the Brigham, bringing several more patients to Boston for care, and arranging specialty surgical trips to Haiti.

Later, when HIV funding became available from the Global Fund for HIV, Tuberculosis, and Malaria, I moved to rural Haiti to provide treatment for patients with HIV and/or TB at one of the first PIH expansion sites. We treated many patients with advanced stages of HIV and/or TB, and many of them recovered remarkably quickly with antiretroviral therapy.

When I returned to Boston to complete an infectious disease fellowship I switched my focus to conducting clinical research to improve HIV and TB treatment outcomes. Paul emailed his mentor and friend, Jean “Bill” Pape, the director of a Haitian NGO called GHESKIO (Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections), which is an internationally celebrated center of excellence in HIV-related research and clinical care, to ask if I could collaborate with them.

Ever since that time, I have been based between the Brigham’s division of global health equity, which was led by Paul, and GHESKIO.

Paul was very supportive of our research, which aims to improve health service delivery and treatment regimens for HIV and TB.
 

Q. What lessons do you think other physicians can learn from him?

Dr. Koenig: As Joia Mukherjee, chief medical officer of Partners In Health, has said, Paul left us a roadmap. He wrote many books, and he was very eloquent in expressing his philosophy about equity and justice in numerous interviews. This is relevant not only for international sites, but in the United States as well, with our major disparities in health outcomes by race, geography, and socioeconomic status.

No one will be able to replace Paul, but he left us with a vision of what is achievable.

Dr. Koenig is associate physician, Brigham and Women’s Hospital, Boston, with faculty appointments in the divisions of global health equity and infectious diseases. She is also associate professor at Harvard Medical School.

Infectious disease specialist and humanitarian, Paul Edward Farmer, MD, PhD, who cofounded Partners In Health, died suddenly on Feb. 21. To celebrate his life, this news organization interviewed Serena Koenig, MD, MPH, who met Dr. Farmer when she was an internal medicine resident at Brigham and Women’s Hospital. Dr. Koenig had worked closely with Dr. Farmer ever since they met.

Q. Can you please share one of your best memories of Dr. Farmer?

Dr. Serena Koenig: There are so many memories it is hard to choose. One that was very formative for me occurred during one of my first trips to Haiti, in 2001. Paul and some other incredible colleagues at Partners IN Health (PIH) had started the HIV Equity Initiative, which was one of the first programs in the world to provide free, comprehensive treatment for HIV. This was at the time when millions of people in Africa were dying of HIV and many experts said it was not feasible to treat HIV in a poor country, because it was too complicated and expensive. Paul took me on some home visits with patients who had what he called the Lazarus effect, coming back from death’s door from advanced AIDS to vigorous health on antiretroviral therapy. I had just started working in Haiti with Paul and PIH, and I felt the enormous magnitude of what he was doing.

Q. What aspects of him and his work do you find most admirable?

Dr. Koenig: I most admired Paul’s humanity, his belief that every person matters and has the right to high-quality health care, and his vision of global health equity.

He said: “The idea that some lives matter less is the root of all that is wrong with the world.” Paul lived this philosophy. He has spoken extensively about harms of socialization for scarcity on behalf of those who are poor, leading policy makers to decisions regarding the feasibility of treating some diseases, but not others.

He said in an interview with the Harvard Gazette in 2018: “The most compelling thing to fight socialization for scarcity on behalf of others is health system strengthening. Health systems that integrate prevention and quality care.”

A few weeks ago, I asked him his thoughts about the high-level resources we have invested in some patients who have needed specialty care over the years, and he said: “No way that we should waste all of our emotional energy responding only to those constant, nagging critics that it’s not cost effective, not feasible, not sustainable, not even prudent. Because you know what they would have done if it was their child or family member.”
 

Q. When did you first meet Dr. Farmer, and what inspired you to work with him?

Dr. Koenig: When I was an internal medicine resident at the Brigham, Paul and I bonded over the care of one of my clinic patients who I followed very closely, and who was admitted to his inpatient service.

Like everyone else who has worked with Paul, I was touched by his kindness and warmth.

A couple of years later, he asked me to help him raise money to bring a young man named Wilnot from Haiti to the Brigham for an aortic valve replacement. After we raised the money, he asked me to go to Haiti to help Wilnot get his medical visa and to escort him to Boston.

That short trip to Haiti had an enormous impact on my life. I was shattered to see the poverty that the people of Haiti were enduring – and in a country a short plane flight from Miami.

Shortly after this, Paul asked me to help him find treatment for another patient, a young boy named John, who presented with neck masses that were later diagnosed as nasopharyngeal carcinoma.

It took us some time to make the diagnosis and then to arrange free care at Mass General.

When I returned to Haiti with two PIH colleagues to help John get a visa and escort him back to Boston, we found that John’s condition was much worse. We ended up medically evacuating him to Boston, because he was too sick for a commercial flight.

Tracy Kidder wrote about this heartbreaking experience in the book “Mountains Beyond Mountains.”

Throughout all of these experiences, I was deeply impressed with Paul’s commitment to do whatever it took to provide the best care for patients, as if they were members of his own family. He said “Tout Moun Se Moun” (Haitian Creole for “every person is a person”), and I could tell that he meant it.
 

Q. How did you collaborate with him professionally?

Dr. Koenig: I spent the first few years after residency working with Paul and Partners In Health. Initially, I served as a liaison between PIH in Haiti and the Brigham, bringing several more patients to Boston for care, and arranging specialty surgical trips to Haiti.

Later, when HIV funding became available from the Global Fund for HIV, Tuberculosis, and Malaria, I moved to rural Haiti to provide treatment for patients with HIV and/or TB at one of the first PIH expansion sites. We treated many patients with advanced stages of HIV and/or TB, and many of them recovered remarkably quickly with antiretroviral therapy.

When I returned to Boston to complete an infectious disease fellowship I switched my focus to conducting clinical research to improve HIV and TB treatment outcomes. Paul emailed his mentor and friend, Jean “Bill” Pape, the director of a Haitian NGO called GHESKIO (Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections), which is an internationally celebrated center of excellence in HIV-related research and clinical care, to ask if I could collaborate with them.

Ever since that time, I have been based between the Brigham’s division of global health equity, which was led by Paul, and GHESKIO.

Paul was very supportive of our research, which aims to improve health service delivery and treatment regimens for HIV and TB.
 

Q. What lessons do you think other physicians can learn from him?

Dr. Koenig: As Joia Mukherjee, chief medical officer of Partners In Health, has said, Paul left us a roadmap. He wrote many books, and he was very eloquent in expressing his philosophy about equity and justice in numerous interviews. This is relevant not only for international sites, but in the United States as well, with our major disparities in health outcomes by race, geography, and socioeconomic status.

No one will be able to replace Paul, but he left us with a vision of what is achievable.

Dr. Koenig is associate physician, Brigham and Women’s Hospital, Boston, with faculty appointments in the divisions of global health equity and infectious diseases. She is also associate professor at Harvard Medical School.

Infectious disease specialist and humanitarian, Paul Edward Farmer, MD, PhD, who cofounded Partners In Health, died suddenly on Feb. 21. To celebrate his life, this news organization interviewed Serena Koenig, MD, MPH, who met Dr. Farmer when she was an internal medicine resident at Brigham and Women’s Hospital. Dr. Koenig had worked closely with Dr. Farmer ever since they met.

Q. Can you please share one of your best memories of Dr. Farmer?

Dr. Serena Koenig: There are so many memories it is hard to choose. One that was very formative for me occurred during one of my first trips to Haiti, in 2001. Paul and some other incredible colleagues at Partners IN Health (PIH) had started the HIV Equity Initiative, which was one of the first programs in the world to provide free, comprehensive treatment for HIV. This was at the time when millions of people in Africa were dying of HIV and many experts said it was not feasible to treat HIV in a poor country, because it was too complicated and expensive. Paul took me on some home visits with patients who had what he called the Lazarus effect, coming back from death’s door from advanced AIDS to vigorous health on antiretroviral therapy. I had just started working in Haiti with Paul and PIH, and I felt the enormous magnitude of what he was doing.

Q. What aspects of him and his work do you find most admirable?

Dr. Koenig: I most admired Paul’s humanity, his belief that every person matters and has the right to high-quality health care, and his vision of global health equity.

He said: “The idea that some lives matter less is the root of all that is wrong with the world.” Paul lived this philosophy. He has spoken extensively about harms of socialization for scarcity on behalf of those who are poor, leading policy makers to decisions regarding the feasibility of treating some diseases, but not others.

He said in an interview with the Harvard Gazette in 2018: “The most compelling thing to fight socialization for scarcity on behalf of others is health system strengthening. Health systems that integrate prevention and quality care.”

A few weeks ago, I asked him his thoughts about the high-level resources we have invested in some patients who have needed specialty care over the years, and he said: “No way that we should waste all of our emotional energy responding only to those constant, nagging critics that it’s not cost effective, not feasible, not sustainable, not even prudent. Because you know what they would have done if it was their child or family member.”
 

Q. When did you first meet Dr. Farmer, and what inspired you to work with him?

Dr. Koenig: When I was an internal medicine resident at the Brigham, Paul and I bonded over the care of one of my clinic patients who I followed very closely, and who was admitted to his inpatient service.

Like everyone else who has worked with Paul, I was touched by his kindness and warmth.

A couple of years later, he asked me to help him raise money to bring a young man named Wilnot from Haiti to the Brigham for an aortic valve replacement. After we raised the money, he asked me to go to Haiti to help Wilnot get his medical visa and to escort him to Boston.

That short trip to Haiti had an enormous impact on my life. I was shattered to see the poverty that the people of Haiti were enduring – and in a country a short plane flight from Miami.

Shortly after this, Paul asked me to help him find treatment for another patient, a young boy named John, who presented with neck masses that were later diagnosed as nasopharyngeal carcinoma.

It took us some time to make the diagnosis and then to arrange free care at Mass General.

When I returned to Haiti with two PIH colleagues to help John get a visa and escort him back to Boston, we found that John’s condition was much worse. We ended up medically evacuating him to Boston, because he was too sick for a commercial flight.

Tracy Kidder wrote about this heartbreaking experience in the book “Mountains Beyond Mountains.”

Throughout all of these experiences, I was deeply impressed with Paul’s commitment to do whatever it took to provide the best care for patients, as if they were members of his own family. He said “Tout Moun Se Moun” (Haitian Creole for “every person is a person”), and I could tell that he meant it.
 

Q. How did you collaborate with him professionally?

Dr. Koenig: I spent the first few years after residency working with Paul and Partners In Health. Initially, I served as a liaison between PIH in Haiti and the Brigham, bringing several more patients to Boston for care, and arranging specialty surgical trips to Haiti.

Later, when HIV funding became available from the Global Fund for HIV, Tuberculosis, and Malaria, I moved to rural Haiti to provide treatment for patients with HIV and/or TB at one of the first PIH expansion sites. We treated many patients with advanced stages of HIV and/or TB, and many of them recovered remarkably quickly with antiretroviral therapy.

When I returned to Boston to complete an infectious disease fellowship I switched my focus to conducting clinical research to improve HIV and TB treatment outcomes. Paul emailed his mentor and friend, Jean “Bill” Pape, the director of a Haitian NGO called GHESKIO (Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections), which is an internationally celebrated center of excellence in HIV-related research and clinical care, to ask if I could collaborate with them.

Ever since that time, I have been based between the Brigham’s division of global health equity, which was led by Paul, and GHESKIO.

Paul was very supportive of our research, which aims to improve health service delivery and treatment regimens for HIV and TB.
 

Q. What lessons do you think other physicians can learn from him?

Dr. Koenig: As Joia Mukherjee, chief medical officer of Partners In Health, has said, Paul left us a roadmap. He wrote many books, and he was very eloquent in expressing his philosophy about equity and justice in numerous interviews. This is relevant not only for international sites, but in the United States as well, with our major disparities in health outcomes by race, geography, and socioeconomic status.

No one will be able to replace Paul, but he left us with a vision of what is achievable.

Dr. Koenig is associate physician, Brigham and Women’s Hospital, Boston, with faculty appointments in the divisions of global health equity and infectious diseases. She is also associate professor at Harvard Medical School.

Potential immigrants to the United States from countries with high rates of tuberculosis tend to follow through with TB tests and treatment before they travel, and their compliance helps control TB spread, according to a study published online Feb. 16, 2022, in Emerging Infectious Diseases.

“In our study of U.S.-bound immigrants in Vietnam during their required overseas medical examination prior to migration to the United States, we identified a high proportion of U.S.-bound immigrants with latent TB infection (LTBI) and offered them preventive TB treatment,” coauthor Christina R. Phares, PhD, of the Centers for Disease Control and Prevention, Atlanta, said in an interview.

“Overall, 88% of those who started treatment completed their treatment,” she said in an interview. “This is a higher treatment completion rate than has been found in many postarrival strategies in the U.S.”

“This study demonstrated that providing LTBI testing and treatment during the overseas medical examination is feasible, yields high initiation and completion rates, and should be considered as a viable strategy to address LTBI in U.S.-bound migrants,” lead author Amera Khan, DrPH, of the Stop TB Partnership in Geneva, said in an interview.

The research team began the 1-year Preventing Tuberculosis Overseas Pilot Study (PTOPS) in Vietnam in 2018 among applicants for U.S. immigrant visas. Study participants were 12 years of age or older and were undergoing required medical examinations, which included the interferon-gamma release assay (IGRA) tuberculosis blood test.

Eligible IGRA-positive participants who planned to complete their LTBI treatment before traveling to the United States were offered free 3HP (12 weekly doses of isoniazid and rifapentine). Of 5,311 people recruited into the study, 2,438 (46%) enrolled; 2,276 had an IGRA processed; and 484 (21%) tested positive. Of the 452 participants eligible for 3HP, 304 (67%) began, and 268 (88%) completed, their treatment.
 

Preimmigration strategies needed

Worldwide, TB is now the second-leading cause of death by infectious disease, behind COVID-19, Dr. Khan said. The U.S. has seen a slow, steady decline in incidence with an increasing proportion of TB found in people born outside the country.

“Approximately 70% of U.S. TB cases occur in persons born outside the U.S., with the vast majority due to reactivation of latent TB infection acquired prior to their travel to the U.S.,” she said. “To progress towards elimination TB in the U.S., we need innovative strategies to address the high burden of LTBI among immigrants.”

Jonathan E. Golub, PhD, MPH, an infectious diseases specialist and a professor of medicine, epidemiology, and international health at Johns Hopkins University, Baltimore, was not involved in the study but welcomed its results. “This study clearly shows that a predeparture screening and treatment strategy for LTBI can be successfully implemented,” he told this news organization. “While the study highlights areas of the LTBI care cascade that need improvement, the message is clear that predeparture screening and treatment has the potential to significantly impact TB rates among non–U.S.-born persons in the U.S.”

Dr. Golub went on to explain that new technologies for LTBI screening have been underutilized. “New, shorter LTBI treatment regimens provide more feasible choices for both providers and people applying for immigration visas. Combining IGRA with 3HP creates an efficient and effective strategy. This strategy had not been tested prior to the study and the results are exciting.”

Dr. Golub highlighted one important aspect of the study: that many participants started treatment in Vietnam and completed it in the U.S. “This shows that such a protocol provides needed flexibility and can be followed by the health care systems and patients,” Dr. Golub said. “If TB is to ever be eliminated in the U.S., reducing TB among non–U.S.-born persons must be prioritized.”

The rifapentine used in the study was donated by Sanofi, the drug’s manufacturer. Dr. Khan, Dr. Phares, and Dr. Golub reported no relevant financial relationships. The study was supported by a CDC Cooperative Agreement.

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

Potential immigrants to the United States from countries with high rates of tuberculosis tend to follow through with TB tests and treatment before they travel, and their compliance helps control TB spread, according to a study published online Feb. 16, 2022, in Emerging Infectious Diseases.

“In our study of U.S.-bound immigrants in Vietnam during their required overseas medical examination prior to migration to the United States, we identified a high proportion of U.S.-bound immigrants with latent TB infection (LTBI) and offered them preventive TB treatment,” coauthor Christina R. Phares, PhD, of the Centers for Disease Control and Prevention, Atlanta, said in an interview.

“Overall, 88% of those who started treatment completed their treatment,” she said in an interview. “This is a higher treatment completion rate than has been found in many postarrival strategies in the U.S.”

“This study demonstrated that providing LTBI testing and treatment during the overseas medical examination is feasible, yields high initiation and completion rates, and should be considered as a viable strategy to address LTBI in U.S.-bound migrants,” lead author Amera Khan, DrPH, of the Stop TB Partnership in Geneva, said in an interview.

The research team began the 1-year Preventing Tuberculosis Overseas Pilot Study (PTOPS) in Vietnam in 2018 among applicants for U.S. immigrant visas. Study participants were 12 years of age or older and were undergoing required medical examinations, which included the interferon-gamma release assay (IGRA) tuberculosis blood test.

Eligible IGRA-positive participants who planned to complete their LTBI treatment before traveling to the United States were offered free 3HP (12 weekly doses of isoniazid and rifapentine). Of 5,311 people recruited into the study, 2,438 (46%) enrolled; 2,276 had an IGRA processed; and 484 (21%) tested positive. Of the 452 participants eligible for 3HP, 304 (67%) began, and 268 (88%) completed, their treatment.
 

Preimmigration strategies needed

Worldwide, TB is now the second-leading cause of death by infectious disease, behind COVID-19, Dr. Khan said. The U.S. has seen a slow, steady decline in incidence with an increasing proportion of TB found in people born outside the country.

“Approximately 70% of U.S. TB cases occur in persons born outside the U.S., with the vast majority due to reactivation of latent TB infection acquired prior to their travel to the U.S.,” she said. “To progress towards elimination TB in the U.S., we need innovative strategies to address the high burden of LTBI among immigrants.”

Jonathan E. Golub, PhD, MPH, an infectious diseases specialist and a professor of medicine, epidemiology, and international health at Johns Hopkins University, Baltimore, was not involved in the study but welcomed its results. “This study clearly shows that a predeparture screening and treatment strategy for LTBI can be successfully implemented,” he told this news organization. “While the study highlights areas of the LTBI care cascade that need improvement, the message is clear that predeparture screening and treatment has the potential to significantly impact TB rates among non–U.S.-born persons in the U.S.”

Dr. Golub went on to explain that new technologies for LTBI screening have been underutilized. “New, shorter LTBI treatment regimens provide more feasible choices for both providers and people applying for immigration visas. Combining IGRA with 3HP creates an efficient and effective strategy. This strategy had not been tested prior to the study and the results are exciting.”

Dr. Golub highlighted one important aspect of the study: that many participants started treatment in Vietnam and completed it in the U.S. “This shows that such a protocol provides needed flexibility and can be followed by the health care systems and patients,” Dr. Golub said. “If TB is to ever be eliminated in the U.S., reducing TB among non–U.S.-born persons must be prioritized.”

The rifapentine used in the study was donated by Sanofi, the drug’s manufacturer. Dr. Khan, Dr. Phares, and Dr. Golub reported no relevant financial relationships. The study was supported by a CDC Cooperative Agreement.

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

Potential immigrants to the United States from countries with high rates of tuberculosis tend to follow through with TB tests and treatment before they travel, and their compliance helps control TB spread, according to a study published online Feb. 16, 2022, in Emerging Infectious Diseases.

“In our study of U.S.-bound immigrants in Vietnam during their required overseas medical examination prior to migration to the United States, we identified a high proportion of U.S.-bound immigrants with latent TB infection (LTBI) and offered them preventive TB treatment,” coauthor Christina R. Phares, PhD, of the Centers for Disease Control and Prevention, Atlanta, said in an interview.

“Overall, 88% of those who started treatment completed their treatment,” she said in an interview. “This is a higher treatment completion rate than has been found in many postarrival strategies in the U.S.”

“This study demonstrated that providing LTBI testing and treatment during the overseas medical examination is feasible, yields high initiation and completion rates, and should be considered as a viable strategy to address LTBI in U.S.-bound migrants,” lead author Amera Khan, DrPH, of the Stop TB Partnership in Geneva, said in an interview.

The research team began the 1-year Preventing Tuberculosis Overseas Pilot Study (PTOPS) in Vietnam in 2018 among applicants for U.S. immigrant visas. Study participants were 12 years of age or older and were undergoing required medical examinations, which included the interferon-gamma release assay (IGRA) tuberculosis blood test.

Eligible IGRA-positive participants who planned to complete their LTBI treatment before traveling to the United States were offered free 3HP (12 weekly doses of isoniazid and rifapentine). Of 5,311 people recruited into the study, 2,438 (46%) enrolled; 2,276 had an IGRA processed; and 484 (21%) tested positive. Of the 452 participants eligible for 3HP, 304 (67%) began, and 268 (88%) completed, their treatment.
 

Preimmigration strategies needed

Worldwide, TB is now the second-leading cause of death by infectious disease, behind COVID-19, Dr. Khan said. The U.S. has seen a slow, steady decline in incidence with an increasing proportion of TB found in people born outside the country.

“Approximately 70% of U.S. TB cases occur in persons born outside the U.S., with the vast majority due to reactivation of latent TB infection acquired prior to their travel to the U.S.,” she said. “To progress towards elimination TB in the U.S., we need innovative strategies to address the high burden of LTBI among immigrants.”

Jonathan E. Golub, PhD, MPH, an infectious diseases specialist and a professor of medicine, epidemiology, and international health at Johns Hopkins University, Baltimore, was not involved in the study but welcomed its results. “This study clearly shows that a predeparture screening and treatment strategy for LTBI can be successfully implemented,” he told this news organization. “While the study highlights areas of the LTBI care cascade that need improvement, the message is clear that predeparture screening and treatment has the potential to significantly impact TB rates among non–U.S.-born persons in the U.S.”

Dr. Golub went on to explain that new technologies for LTBI screening have been underutilized. “New, shorter LTBI treatment regimens provide more feasible choices for both providers and people applying for immigration visas. Combining IGRA with 3HP creates an efficient and effective strategy. This strategy had not been tested prior to the study and the results are exciting.”

Dr. Golub highlighted one important aspect of the study: that many participants started treatment in Vietnam and completed it in the U.S. “This shows that such a protocol provides needed flexibility and can be followed by the health care systems and patients,” Dr. Golub said. “If TB is to ever be eliminated in the U.S., reducing TB among non–U.S.-born persons must be prioritized.”

The rifapentine used in the study was donated by Sanofi, the drug’s manufacturer. Dr. Khan, Dr. Phares, and Dr. Golub reported no relevant financial relationships. The study was supported by a CDC Cooperative Agreement.

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

From testing to treatment, Global Fund HIV services have been hampered by COVID-19. “We’ve been set back by COVID but we’ve seen remarkable resilience, a lot of innovation and creativity,” Siobhan Crowley MD, head of HIV at the Global Fund, said in an interview. 

“If you consider that 21.9 million people are getting antiretrovirals at this point through the Global Fund, I think that needs to be appreciated. Ten years ago, that wouldn’t have been the case; all of those people would have disappeared into the ethers,” she said.

Through close partnerships with the U.S. Agency for International Development, the U.S. President’s Emergency Plan for AIDS Relief, and other Western countries and organizations, the Global Fund has invested $22.7 billion in programs to prevent and treat HIV and AIDS, and $3.8 billion in tuberculosis (TB)/HIV programs, according to the organization’s 2021 Results Report. 

But the report also underscores the significant effect that the COVID-19 pandemic has had on funded countries’ progress toward achieving renewed 90-90-90 targets for HIV testing/diagnosis, treatment, and viral suppression by 2030.

The setbacks have been challenging and have touched nearly every service from prevention to treatment. According to the report, between 2019 and 2020:

• Voluntary male circumcision declined by 27%.
• Numbers reached by HIV prevention programs fell by 11%.
• 4.5% fewer mothers received medications to prevent HIV transmission to their babies.
• HIV testing services, including initiation, decreased by 22%.

The numbers tell only a part of the story, according to Dr. Crowley.

“We put in place an emergency mechanism to make funds available for countries to do everything except vaccines in support of COVID,” Dr. Crowley explained. (As of August 2021, these funds had been allocated to 107 countries and 16 multicountry programs.)

Countries were advised that they could use the emergency funds three different ways: 1) for COVID-specific purposes (e.g., diagnostics, oxygen, personal protective equipment; 2) to support mitigation strategies geared toward protecting existing HIV, tuberculosis, and malaria programs and getting them back on track; and 3) for so-called “health system fixes,” such as investing in data systems to track COVID, HIV, and other core diseases, as well as the community workforce.

With regard to HIV, each country supported by the Global Fund was asked to ensure that multimonth (3-6 months) dispensing was implemented and/or accelerated so that patients could avoid congested facilities, and, wherever possible, that drugs were delivered or accessed outside the facility. One example of the success of this effort was found in South Africa, where the number of people on antiretrovirals increased almost threefold, from 1.2 million to 4.2 million people.

Countries also were asked to adapt HIV testing procedures by, for example, moving organized testing out of the facilities and into neighborhoods to meet people where they are. Rapid diagnostic testing and triage care linkage using technologies such as WhatsApp were the result, as were opportunities for home testing which, Dr. Crowley noted, remains a critical component of the overall strategy. 

“The self-test is important for two reasons, not just because you are trying to find people with HIV, but also, when people know that they’re negative, they know what they can or should do to stay negative,” she said. “It’s quite a powerful motivator.” 

Self-testing might also help countries motivate the 6 million people who know that they have HIV but are not on treatment. But there are still 4.1 million residing in these countries who aren’t aware that they are infected, according to the report. This figure is especially troubling, considering that some may also be harboring TB coinfections, including multidrug-resistant TB (MDR-TB).
 

The imperfect storm globally and in the U.S.

“One of the things that was striking in the report was the decline in the number of people reached with testing and prevention services,” Chris Beyrer, MD, MPH, the Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. Dr. Beyrer was not involved in the report’s development.

“You know, a 10% decline in 1 year to reach people in need is substantial,” he said. “Let’s say it continues; many people are predicting that we won’t have reasonable coverage for low-income countries with COVID until 2023. That adds up to a substantial decline in people reached with these services.”

Dr. Beyrer also expressed concern about the convergence of HIV and TB in already overburdened, fragile health care systems. “Globally, the No. 1 cause of death for people living with HIV is TB, and of course, it’s highly transmissible. So, in many high-burden countries, children are exposed, typically from household members early on, and so the number of people with latent TB infection is just enormous.

“If you look at the report, the worst outcomes are MDR-TB. Those multidrug-resistant and extensively-drug-resistant strains are really a threat to everybody,” Dr. Beyrer said.

But it’s not time for U.S. providers to rest on their laurels either. Dr. Beyrer noted that the 22% decline in HIV testing reported by the Global Fund is similar to what has been happening in the United States with elective procedures such as HIV testing and even preventive procedures like medical male circumcision. 

“It’s very clear here in the Global Fund data that the majority of new infections worldwide are in key populations [that] include gay and bisexual men, men who have sex with men, transgender women who have sex with men, people who inject drugs, and sex workers of all genders. Those are people who already faced barriers to health care access and were made worse by COVID.”

Dr. Beyrer noted that, according to the Centers for Disease Control and Prevention, in 2019 in the United States, 68% of new HIV infections occurred in gay and bisexual men, and the effect that COVID-19 will have is still unknown. He also noted the similarity between the most marginalized populations in the Global Fund report and African American men, who have not realized the same increase in the use of preexposure prophylaxis or the same decline in new infections as have their White counterparts. 

“It’s also where we are seeing the worst of COVID, low immunization coverage, and high rates of hospitalization and death. ... It’s a dark, dark time for many,” Dr. Crowley said. “And there has also been some amazing resilience and adaptation. The weird thing is, the HIV platform is a natural platform; I mean, if we can keep 21.9 million people on treatment, we can probably deliver them a COVID test and a vaccine.”

Dr. Crowley and Dr. Beyrer report no relevant financial relationships.

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

From testing to treatment, Global Fund HIV services have been hampered by COVID-19. “We’ve been set back by COVID but we’ve seen remarkable resilience, a lot of innovation and creativity,” Siobhan Crowley MD, head of HIV at the Global Fund, said in an interview. 

“If you consider that 21.9 million people are getting antiretrovirals at this point through the Global Fund, I think that needs to be appreciated. Ten years ago, that wouldn’t have been the case; all of those people would have disappeared into the ethers,” she said.

Through close partnerships with the U.S. Agency for International Development, the U.S. President’s Emergency Plan for AIDS Relief, and other Western countries and organizations, the Global Fund has invested $22.7 billion in programs to prevent and treat HIV and AIDS, and $3.8 billion in tuberculosis (TB)/HIV programs, according to the organization’s 2021 Results Report. 

But the report also underscores the significant effect that the COVID-19 pandemic has had on funded countries’ progress toward achieving renewed 90-90-90 targets for HIV testing/diagnosis, treatment, and viral suppression by 2030.

The setbacks have been challenging and have touched nearly every service from prevention to treatment. According to the report, between 2019 and 2020:

• Voluntary male circumcision declined by 27%.
• Numbers reached by HIV prevention programs fell by 11%.
• 4.5% fewer mothers received medications to prevent HIV transmission to their babies.
• HIV testing services, including initiation, decreased by 22%.

The numbers tell only a part of the story, according to Dr. Crowley.

“We put in place an emergency mechanism to make funds available for countries to do everything except vaccines in support of COVID,” Dr. Crowley explained. (As of August 2021, these funds had been allocated to 107 countries and 16 multicountry programs.)

Countries were advised that they could use the emergency funds three different ways: 1) for COVID-specific purposes (e.g., diagnostics, oxygen, personal protective equipment; 2) to support mitigation strategies geared toward protecting existing HIV, tuberculosis, and malaria programs and getting them back on track; and 3) for so-called “health system fixes,” such as investing in data systems to track COVID, HIV, and other core diseases, as well as the community workforce.

With regard to HIV, each country supported by the Global Fund was asked to ensure that multimonth (3-6 months) dispensing was implemented and/or accelerated so that patients could avoid congested facilities, and, wherever possible, that drugs were delivered or accessed outside the facility. One example of the success of this effort was found in South Africa, where the number of people on antiretrovirals increased almost threefold, from 1.2 million to 4.2 million people.

Countries also were asked to adapt HIV testing procedures by, for example, moving organized testing out of the facilities and into neighborhoods to meet people where they are. Rapid diagnostic testing and triage care linkage using technologies such as WhatsApp were the result, as were opportunities for home testing which, Dr. Crowley noted, remains a critical component of the overall strategy. 

“The self-test is important for two reasons, not just because you are trying to find people with HIV, but also, when people know that they’re negative, they know what they can or should do to stay negative,” she said. “It’s quite a powerful motivator.” 

Self-testing might also help countries motivate the 6 million people who know that they have HIV but are not on treatment. But there are still 4.1 million residing in these countries who aren’t aware that they are infected, according to the report. This figure is especially troubling, considering that some may also be harboring TB coinfections, including multidrug-resistant TB (MDR-TB).
 

The imperfect storm globally and in the U.S.

“One of the things that was striking in the report was the decline in the number of people reached with testing and prevention services,” Chris Beyrer, MD, MPH, the Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. Dr. Beyrer was not involved in the report’s development.

“You know, a 10% decline in 1 year to reach people in need is substantial,” he said. “Let’s say it continues; many people are predicting that we won’t have reasonable coverage for low-income countries with COVID until 2023. That adds up to a substantial decline in people reached with these services.”

Dr. Beyrer also expressed concern about the convergence of HIV and TB in already overburdened, fragile health care systems. “Globally, the No. 1 cause of death for people living with HIV is TB, and of course, it’s highly transmissible. So, in many high-burden countries, children are exposed, typically from household members early on, and so the number of people with latent TB infection is just enormous.

“If you look at the report, the worst outcomes are MDR-TB. Those multidrug-resistant and extensively-drug-resistant strains are really a threat to everybody,” Dr. Beyrer said.

But it’s not time for U.S. providers to rest on their laurels either. Dr. Beyrer noted that the 22% decline in HIV testing reported by the Global Fund is similar to what has been happening in the United States with elective procedures such as HIV testing and even preventive procedures like medical male circumcision. 

“It’s very clear here in the Global Fund data that the majority of new infections worldwide are in key populations [that] include gay and bisexual men, men who have sex with men, transgender women who have sex with men, people who inject drugs, and sex workers of all genders. Those are people who already faced barriers to health care access and were made worse by COVID.”

Dr. Beyrer noted that, according to the Centers for Disease Control and Prevention, in 2019 in the United States, 68% of new HIV infections occurred in gay and bisexual men, and the effect that COVID-19 will have is still unknown. He also noted the similarity between the most marginalized populations in the Global Fund report and African American men, who have not realized the same increase in the use of preexposure prophylaxis or the same decline in new infections as have their White counterparts. 

“It’s also where we are seeing the worst of COVID, low immunization coverage, and high rates of hospitalization and death. ... It’s a dark, dark time for many,” Dr. Crowley said. “And there has also been some amazing resilience and adaptation. The weird thing is, the HIV platform is a natural platform; I mean, if we can keep 21.9 million people on treatment, we can probably deliver them a COVID test and a vaccine.”

Dr. Crowley and Dr. Beyrer report no relevant financial relationships.

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

From testing to treatment, Global Fund HIV services have been hampered by COVID-19. “We’ve been set back by COVID but we’ve seen remarkable resilience, a lot of innovation and creativity,” Siobhan Crowley MD, head of HIV at the Global Fund, said in an interview. 

“If you consider that 21.9 million people are getting antiretrovirals at this point through the Global Fund, I think that needs to be appreciated. Ten years ago, that wouldn’t have been the case; all of those people would have disappeared into the ethers,” she said.

Through close partnerships with the U.S. Agency for International Development, the U.S. President’s Emergency Plan for AIDS Relief, and other Western countries and organizations, the Global Fund has invested $22.7 billion in programs to prevent and treat HIV and AIDS, and $3.8 billion in tuberculosis (TB)/HIV programs, according to the organization’s 2021 Results Report. 

But the report also underscores the significant effect that the COVID-19 pandemic has had on funded countries’ progress toward achieving renewed 90-90-90 targets for HIV testing/diagnosis, treatment, and viral suppression by 2030.

The setbacks have been challenging and have touched nearly every service from prevention to treatment. According to the report, between 2019 and 2020:

• Voluntary male circumcision declined by 27%.
• Numbers reached by HIV prevention programs fell by 11%.
• 4.5% fewer mothers received medications to prevent HIV transmission to their babies.
• HIV testing services, including initiation, decreased by 22%.

The numbers tell only a part of the story, according to Dr. Crowley.

“We put in place an emergency mechanism to make funds available for countries to do everything except vaccines in support of COVID,” Dr. Crowley explained. (As of August 2021, these funds had been allocated to 107 countries and 16 multicountry programs.)

Countries were advised that they could use the emergency funds three different ways: 1) for COVID-specific purposes (e.g., diagnostics, oxygen, personal protective equipment; 2) to support mitigation strategies geared toward protecting existing HIV, tuberculosis, and malaria programs and getting them back on track; and 3) for so-called “health system fixes,” such as investing in data systems to track COVID, HIV, and other core diseases, as well as the community workforce.

With regard to HIV, each country supported by the Global Fund was asked to ensure that multimonth (3-6 months) dispensing was implemented and/or accelerated so that patients could avoid congested facilities, and, wherever possible, that drugs were delivered or accessed outside the facility. One example of the success of this effort was found in South Africa, where the number of people on antiretrovirals increased almost threefold, from 1.2 million to 4.2 million people.

Countries also were asked to adapt HIV testing procedures by, for example, moving organized testing out of the facilities and into neighborhoods to meet people where they are. Rapid diagnostic testing and triage care linkage using technologies such as WhatsApp were the result, as were opportunities for home testing which, Dr. Crowley noted, remains a critical component of the overall strategy. 

“The self-test is important for two reasons, not just because you are trying to find people with HIV, but also, when people know that they’re negative, they know what they can or should do to stay negative,” she said. “It’s quite a powerful motivator.” 

Self-testing might also help countries motivate the 6 million people who know that they have HIV but are not on treatment. But there are still 4.1 million residing in these countries who aren’t aware that they are infected, according to the report. This figure is especially troubling, considering that some may also be harboring TB coinfections, including multidrug-resistant TB (MDR-TB).
 

The imperfect storm globally and in the U.S.

“One of the things that was striking in the report was the decline in the number of people reached with testing and prevention services,” Chris Beyrer, MD, MPH, the Desmond M. Tutu Professor of Public Health and Human Rights at the Johns Hopkins Bloomberg School of Public Health in Baltimore, said in an interview. Dr. Beyrer was not involved in the report’s development.

“You know, a 10% decline in 1 year to reach people in need is substantial,” he said. “Let’s say it continues; many people are predicting that we won’t have reasonable coverage for low-income countries with COVID until 2023. That adds up to a substantial decline in people reached with these services.”

Dr. Beyrer also expressed concern about the convergence of HIV and TB in already overburdened, fragile health care systems. “Globally, the No. 1 cause of death for people living with HIV is TB, and of course, it’s highly transmissible. So, in many high-burden countries, children are exposed, typically from household members early on, and so the number of people with latent TB infection is just enormous.

“If you look at the report, the worst outcomes are MDR-TB. Those multidrug-resistant and extensively-drug-resistant strains are really a threat to everybody,” Dr. Beyrer said.

But it’s not time for U.S. providers to rest on their laurels either. Dr. Beyrer noted that the 22% decline in HIV testing reported by the Global Fund is similar to what has been happening in the United States with elective procedures such as HIV testing and even preventive procedures like medical male circumcision. 

“It’s very clear here in the Global Fund data that the majority of new infections worldwide are in key populations [that] include gay and bisexual men, men who have sex with men, transgender women who have sex with men, people who inject drugs, and sex workers of all genders. Those are people who already faced barriers to health care access and were made worse by COVID.”

Dr. Beyrer noted that, according to the Centers for Disease Control and Prevention, in 2019 in the United States, 68% of new HIV infections occurred in gay and bisexual men, and the effect that COVID-19 will have is still unknown. He also noted the similarity between the most marginalized populations in the Global Fund report and African American men, who have not realized the same increase in the use of preexposure prophylaxis or the same decline in new infections as have their White counterparts. 

“It’s also where we are seeing the worst of COVID, low immunization coverage, and high rates of hospitalization and death. ... It’s a dark, dark time for many,” Dr. Crowley said. “And there has also been some amazing resilience and adaptation. The weird thing is, the HIV platform is a natural platform; I mean, if we can keep 21.9 million people on treatment, we can probably deliver them a COVID test and a vaccine.”

Dr. Crowley and Dr. Beyrer report no relevant financial relationships.

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

Lower doses of linezolid in the BPaL drug regimen (bedaquiline, pretomanid, and linezolid) significantly reduce the adverse events associated with the treatment for patients with highly drug-resistant tuberculosis (TB) without compromising its high efficacy, new research shows.

“The ZeNix trial shows that reduced doses and/or shorter durations of linezolid appear to have high efficacy and improved safety,” said first author Francesca Conradie, MB, BCh, of the clinical HIV research unit, faculty of health sciences, University of Witwatersrand, Johannesburg, South Africa, in presenting the findings at the virtual meeting of the International AIDS Society conference.

As recently reported in the pivotal Nix-TB trial, the BPaL regimen yielded a 90% treatment success rate among people with highly drug-resistant forms of TB.

However, a 6-month regimen that included linezolid 1,200 mg resulted in toxic effects: 81% of patients in the study experienced peripheral neuropathy, and myelosuppression occurred in 48%. These effects often led to dose reductions or treatment interruption.

Adjustments in the dose of linezolid in the new ZeNix trial substantially reduced peripheral neuropathy to 13% and myelosuppression to 7%, with no significant reduction in the treatment response.

Importantly, the results were similar among patients with and those without HIV. This is of note because TB is the leading cause of death among patients with HIV.

“In the ZeNix trial, only 20% of patients were HIV infected, but in the [previous] Nix-TB trial, 30% were infected, so we have experience now in about 70 patients who were infected, and the outcomes were no different,” Dr. Conradie said in an interview.

Experts say the findings represent an important turn in the steep challenge of tackling highly resistant TB.

“In our opinion, these are exciting results that could change treatment guidelines for highly drug-resistant tuberculosis, with real benefits for the patients,” said Hendrik Streeck, MD, International AIDS Society cochair and director of the Institute of Virology and the Institute for HIV Research at the University Bonn (Germany), in a press conference.

Payam Nahid, MD, MPH, director of the Center for Tuberculosis at theUniversity of California, San Francisco, agreed.

“The results of this trial will impact global practices in treating drug-resistant TB as well as the design and conduct of future TB clinical trials,” Dr. Nahid said in an interview.
 

ZeNix trial

The phase 3 ZeNix trial included 181 patients with highly resistant TB in South Africa, Russia, Georgia, and Moldova. The mean age of the patients was 37 years; 67.4% were men, 63.5% were White, and 19.9% were HIV positive.

All patients were treated for 6 months with bedaquiline 200 mg daily for 8 weeks followed by 100 mg daily for 18 weeks, as well as pretomanid 200 mg daily.

The patients were randomly assigned to receive one of four daily doses of linezolid: 1,200 mg for 6 months (the original dose from the Nix-TB trial; n = 45) or 2 months (n = 46), or 600 mg for 6 or 2 months (45 patients each).

Percentages of patients with HIV were equal among the four groups, at about 20% each.

The primary outcomes – resolution of clinical disease and a negative culture status after 6 months – were observed across all linezolid dose groups. The success rate was 93% for those receiving 1,200 mg for 6 months, 89% for those receiving 1,200 mg for 2 months, 91% for those receiving 600 mg for 6 months, and 84% for those receiving 600 mg for 2 months.

With regard to the key adverse events of peripheral neuropathy and myelosuppression, manifested as anemia, the highest rates were among those who received linezolid 1,200 mg for 6 month, at 38% and 22%, respectively, compared with 24% and 17.4% among those who received 1,200 mg for 2 months, 24% and 2% among those who received 600 mg for 6 months, and 13% and 6.7% among those who received 600 mg for 2 months.

Four cases of optic neuropathy occurred among those who received 1,200 mg for 6 months; all cases resolved.

Patients who received 1,200 mg for 6 months required the highest number of linezolid dose modifications; 51% required changes that included reduction, interruption, or discontinuation, compared with 28% among those who received 1,200 mg for 2 months and 13% each in the other two groups.

On the basis of these results, “my personal opinion is that 600 mg at 6 months [of linezolid] is most likely the best strategy for the treatment of this highly resistant treatment population group,” Dr. Conradie told this news organization.
 

Findings represent ‘great news’ in addressing concerns

Dr. Nahid further commented that the results are highly encouraging in light of the ongoing concerns about the effects of linezolid in the BPaL regimen.

“This is great news,” he said. “The ZeNix trial addresses a key concern that providers and patients have had regarding the safety and tolerability of taking 6 months of linezolid at 1200 mg/d as part of the BPaL regimen.

“The findings that doses lower and durations shorter than the current 1,200 mg linezolid daily for 6 months will significantly expand the usability of the BPaL regimen worldwide.”

The inclusion of patients with HIV was essential in the trial, he noted.

“There are drug-drug interactions to be considered, among other factors that impact drug exposure,” Dr. Nahid said.

“Inclusion of patients living with HIV in this study means that any modifications to the BPaL regimen considered by the WHO [World Health Organization] and other policy decision makers will include data from this key population,” he said. “Of course, more data are needed on safety, tolerability, and efficacy on BPaL in general, and there are international cohorts and demonstration projects underway that will enhance our understanding of the regimen in HIV and in other special populations.”

The authors, Dr. Streeck, and Dr. Nahid have disclosed no relevant financial relationships.

This article was updated 7/21/21.

Lower doses of linezolid in the BPaL drug regimen (bedaquiline, pretomanid, and linezolid) significantly reduce the adverse events associated with the treatment for patients with highly drug-resistant tuberculosis (TB) without compromising its high efficacy, new research shows.

“The ZeNix trial shows that reduced doses and/or shorter durations of linezolid appear to have high efficacy and improved safety,” said first author Francesca Conradie, MB, BCh, of the clinical HIV research unit, faculty of health sciences, University of Witwatersrand, Johannesburg, South Africa, in presenting the findings at the virtual meeting of the International AIDS Society conference.

As recently reported in the pivotal Nix-TB trial, the BPaL regimen yielded a 90% treatment success rate among people with highly drug-resistant forms of TB.

However, a 6-month regimen that included linezolid 1,200 mg resulted in toxic effects: 81% of patients in the study experienced peripheral neuropathy, and myelosuppression occurred in 48%. These effects often led to dose reductions or treatment interruption.

Adjustments in the dose of linezolid in the new ZeNix trial substantially reduced peripheral neuropathy to 13% and myelosuppression to 7%, with no significant reduction in the treatment response.

Importantly, the results were similar among patients with and those without HIV. This is of note because TB is the leading cause of death among patients with HIV.

“In the ZeNix trial, only 20% of patients were HIV infected, but in the [previous] Nix-TB trial, 30% were infected, so we have experience now in about 70 patients who were infected, and the outcomes were no different,” Dr. Conradie said in an interview.

Experts say the findings represent an important turn in the steep challenge of tackling highly resistant TB.

“In our opinion, these are exciting results that could change treatment guidelines for highly drug-resistant tuberculosis, with real benefits for the patients,” said Hendrik Streeck, MD, International AIDS Society cochair and director of the Institute of Virology and the Institute for HIV Research at the University Bonn (Germany), in a press conference.

Payam Nahid, MD, MPH, director of the Center for Tuberculosis at theUniversity of California, San Francisco, agreed.

“The results of this trial will impact global practices in treating drug-resistant TB as well as the design and conduct of future TB clinical trials,” Dr. Nahid said in an interview.
 

ZeNix trial

The phase 3 ZeNix trial included 181 patients with highly resistant TB in South Africa, Russia, Georgia, and Moldova. The mean age of the patients was 37 years; 67.4% were men, 63.5% were White, and 19.9% were HIV positive.

All patients were treated for 6 months with bedaquiline 200 mg daily for 8 weeks followed by 100 mg daily for 18 weeks, as well as pretomanid 200 mg daily.

The patients were randomly assigned to receive one of four daily doses of linezolid: 1,200 mg for 6 months (the original dose from the Nix-TB trial; n = 45) or 2 months (n = 46), or 600 mg for 6 or 2 months (45 patients each).

Percentages of patients with HIV were equal among the four groups, at about 20% each.

The primary outcomes – resolution of clinical disease and a negative culture status after 6 months – were observed across all linezolid dose groups. The success rate was 93% for those receiving 1,200 mg for 6 months, 89% for those receiving 1,200 mg for 2 months, 91% for those receiving 600 mg for 6 months, and 84% for those receiving 600 mg for 2 months.

With regard to the key adverse events of peripheral neuropathy and myelosuppression, manifested as anemia, the highest rates were among those who received linezolid 1,200 mg for 6 month, at 38% and 22%, respectively, compared with 24% and 17.4% among those who received 1,200 mg for 2 months, 24% and 2% among those who received 600 mg for 6 months, and 13% and 6.7% among those who received 600 mg for 2 months.

Four cases of optic neuropathy occurred among those who received 1,200 mg for 6 months; all cases resolved.

Patients who received 1,200 mg for 6 months required the highest number of linezolid dose modifications; 51% required changes that included reduction, interruption, or discontinuation, compared with 28% among those who received 1,200 mg for 2 months and 13% each in the other two groups.

On the basis of these results, “my personal opinion is that 600 mg at 6 months [of linezolid] is most likely the best strategy for the treatment of this highly resistant treatment population group,” Dr. Conradie told this news organization.
 

Findings represent ‘great news’ in addressing concerns

Dr. Nahid further commented that the results are highly encouraging in light of the ongoing concerns about the effects of linezolid in the BPaL regimen.

“This is great news,” he said. “The ZeNix trial addresses a key concern that providers and patients have had regarding the safety and tolerability of taking 6 months of linezolid at 1200 mg/d as part of the BPaL regimen.

“The findings that doses lower and durations shorter than the current 1,200 mg linezolid daily for 6 months will significantly expand the usability of the BPaL regimen worldwide.”

The inclusion of patients with HIV was essential in the trial, he noted.

“There are drug-drug interactions to be considered, among other factors that impact drug exposure,” Dr. Nahid said.

“Inclusion of patients living with HIV in this study means that any modifications to the BPaL regimen considered by the WHO [World Health Organization] and other policy decision makers will include data from this key population,” he said. “Of course, more data are needed on safety, tolerability, and efficacy on BPaL in general, and there are international cohorts and demonstration projects underway that will enhance our understanding of the regimen in HIV and in other special populations.”

The authors, Dr. Streeck, and Dr. Nahid have disclosed no relevant financial relationships.

This article was updated 7/21/21.

Lower doses of linezolid in the BPaL drug regimen (bedaquiline, pretomanid, and linezolid) significantly reduce the adverse events associated with the treatment for patients with highly drug-resistant tuberculosis (TB) without compromising its high efficacy, new research shows.

“The ZeNix trial shows that reduced doses and/or shorter durations of linezolid appear to have high efficacy and improved safety,” said first author Francesca Conradie, MB, BCh, of the clinical HIV research unit, faculty of health sciences, University of Witwatersrand, Johannesburg, South Africa, in presenting the findings at the virtual meeting of the International AIDS Society conference.

As recently reported in the pivotal Nix-TB trial, the BPaL regimen yielded a 90% treatment success rate among people with highly drug-resistant forms of TB.

However, a 6-month regimen that included linezolid 1,200 mg resulted in toxic effects: 81% of patients in the study experienced peripheral neuropathy, and myelosuppression occurred in 48%. These effects often led to dose reductions or treatment interruption.

Adjustments in the dose of linezolid in the new ZeNix trial substantially reduced peripheral neuropathy to 13% and myelosuppression to 7%, with no significant reduction in the treatment response.

Importantly, the results were similar among patients with and those without HIV. This is of note because TB is the leading cause of death among patients with HIV.

“In the ZeNix trial, only 20% of patients were HIV infected, but in the [previous] Nix-TB trial, 30% were infected, so we have experience now in about 70 patients who were infected, and the outcomes were no different,” Dr. Conradie said in an interview.

Experts say the findings represent an important turn in the steep challenge of tackling highly resistant TB.

“In our opinion, these are exciting results that could change treatment guidelines for highly drug-resistant tuberculosis, with real benefits for the patients,” said Hendrik Streeck, MD, International AIDS Society cochair and director of the Institute of Virology and the Institute for HIV Research at the University Bonn (Germany), in a press conference.

Payam Nahid, MD, MPH, director of the Center for Tuberculosis at theUniversity of California, San Francisco, agreed.

“The results of this trial will impact global practices in treating drug-resistant TB as well as the design and conduct of future TB clinical trials,” Dr. Nahid said in an interview.
 

ZeNix trial

The phase 3 ZeNix trial included 181 patients with highly resistant TB in South Africa, Russia, Georgia, and Moldova. The mean age of the patients was 37 years; 67.4% were men, 63.5% were White, and 19.9% were HIV positive.

All patients were treated for 6 months with bedaquiline 200 mg daily for 8 weeks followed by 100 mg daily for 18 weeks, as well as pretomanid 200 mg daily.

The patients were randomly assigned to receive one of four daily doses of linezolid: 1,200 mg for 6 months (the original dose from the Nix-TB trial; n = 45) or 2 months (n = 46), or 600 mg for 6 or 2 months (45 patients each).

Percentages of patients with HIV were equal among the four groups, at about 20% each.

The primary outcomes – resolution of clinical disease and a negative culture status after 6 months – were observed across all linezolid dose groups. The success rate was 93% for those receiving 1,200 mg for 6 months, 89% for those receiving 1,200 mg for 2 months, 91% for those receiving 600 mg for 6 months, and 84% for those receiving 600 mg for 2 months.

With regard to the key adverse events of peripheral neuropathy and myelosuppression, manifested as anemia, the highest rates were among those who received linezolid 1,200 mg for 6 month, at 38% and 22%, respectively, compared with 24% and 17.4% among those who received 1,200 mg for 2 months, 24% and 2% among those who received 600 mg for 6 months, and 13% and 6.7% among those who received 600 mg for 2 months.

Four cases of optic neuropathy occurred among those who received 1,200 mg for 6 months; all cases resolved.

Patients who received 1,200 mg for 6 months required the highest number of linezolid dose modifications; 51% required changes that included reduction, interruption, or discontinuation, compared with 28% among those who received 1,200 mg for 2 months and 13% each in the other two groups.

On the basis of these results, “my personal opinion is that 600 mg at 6 months [of linezolid] is most likely the best strategy for the treatment of this highly resistant treatment population group,” Dr. Conradie told this news organization.
 

Findings represent ‘great news’ in addressing concerns

Dr. Nahid further commented that the results are highly encouraging in light of the ongoing concerns about the effects of linezolid in the BPaL regimen.

“This is great news,” he said. “The ZeNix trial addresses a key concern that providers and patients have had regarding the safety and tolerability of taking 6 months of linezolid at 1200 mg/d as part of the BPaL regimen.

“The findings that doses lower and durations shorter than the current 1,200 mg linezolid daily for 6 months will significantly expand the usability of the BPaL regimen worldwide.”

The inclusion of patients with HIV was essential in the trial, he noted.

“There are drug-drug interactions to be considered, among other factors that impact drug exposure,” Dr. Nahid said.

“Inclusion of patients living with HIV in this study means that any modifications to the BPaL regimen considered by the WHO [World Health Organization] and other policy decision makers will include data from this key population,” he said. “Of course, more data are needed on safety, tolerability, and efficacy on BPaL in general, and there are international cohorts and demonstration projects underway that will enhance our understanding of the regimen in HIV and in other special populations.”

The authors, Dr. Streeck, and Dr. Nahid have disclosed no relevant financial relationships.

This article was updated 7/21/21.

Médecins Sans Frontières (MSF/Doctors Without Borders) announced early closure of its phase 2/3 trial of a 6-month multidrug regimen for multidrug-resistant tuberculosis (MDR-TB) because an independent data safety and monitoring board (DSMB) determined that the drug combination in the study regimen was superior to current therapy, according to a press release.

The trial, called TB PRACTECAL, compared the current local standard of care with a 6-month regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin. The interim analysis included 242 patients and the randomized, controlled trial was conducted in sites in Belarus, South Africa, and Uzbekistan.

The preliminary data will be shared with the World Health Organization soon and will also be submitted to a peer-reviewed journal. If it withstands further reviews, as is anticipated, the trial would support the first solely oral regimen for MDR-TB.

In 2019, an estimated 465,000 people developed MDR-TB and 182,000 died. The global burden of TB at that time was about 10 million new cases, many with coexisting HIV.

Current treatment for MDR-TB lasts 9-20 months and is complicated by the need for painful shots and toxic antibiotics. Side effects can include psychiatric problems from quinolones, isoniazid, ethambutol, or cycloserine; deafness from aminoglycosides; and bone marrow suppression from linezolid, among other toxicities.

It’s hoped that the shorter regimen will reduce toxicity and improve patient compliance. Poor adherence to treatment is a major driver of further drug resistance. Current regimens require up to 20 pills per day as well as daily injections.

In a prepared statement from MSF, David Moore, MD, MSc, London School of Hygiene and Tropical Medicine, a member of the TB-PRACTECAL trial’s steering committee, concluded: “The findings could transform the way we treat patients with drug-resistant forms of TB worldwide, who have been neglected for too long.”

This good news is particularly welcome as, in the time of COVID-19, “an estimated 1.4 million fewer people received care for tuberculosis in 2020 than in 2019,” according to the WHO. The drop, an overall 21% reduction in patients beginning treatment, ranged as high as 42% in Indonesia.

Although awaiting complete data, Madhukar Pai, MD, PhD, associate director of the McGill International TB Centre, McGill University, Montreal, shares Dr. Moore’s enthusiasm. In an interview, Dr. Pai compared MDR-TB with extensively drug-resistant TB (XDR-TB).

“I’m excited about the possibility that these trial results might help shorten MDR-TB treatment to 6 months,” said Dr. Pai. “That will be a huge relief to all patients battling drug-resistant disease. The 6-month BPaL regimen (bedaquiline, pretomanid, and linezolid) regimen works well in XDR-TB. So, I would expect the TB PRACTECAL regimen with one added drug (moxifloxacin) to work well in MDR-TB, which is less severe than XDR-TB. Between these two regimens, if we can bring down MDR and XDR treatment to 6 months, all oral, that would be a huge advance.”

The expense of bedaquiline has been a long-standing concern in the global health community. Janssen, a subsidiary of Johnson & Johnson, has reduced the price to $340 per 6-month treatment course for more than 135 eligible low- and middle-income countries.

Previously, the tiered pricing structure was different for low-, middle-, and high-income countries (U.S. $900, $3,000, and $30,000, respectively). “The global TB community has asked Janssen to drop the price of bedaquiline to a level no higher than $32 per month – double the price at which researchers estimated bedaquiline could be sold for a profit,” according to the Treatment Action Group A major source of contention over pricing has been that there has been considerable public investment in the drug›s development.

Dr. Pai concluded: “Bedaquiline is likely the most important drug in both 6-month regimens. We need to work harder to make bedaquiline, an excellent drug, more affordable and accessible.”

While the full data is not yet publicly available, TB PRACTECAL was a randomized, controlled, multicenter study. The fact that enrollment was discontinued early by the DSMB suggests the efficacy data was compelling and that this completely oral regimen will become the standard of care.

Dr. Stone is an infectious disease specialist and author of Resilience: One Family’s Story of Hope and Triumph Over Evil and of Conducting Clinical Research, the essential guide to the topic. A version of this article first appeared on Medscape.com.

Médecins Sans Frontières (MSF/Doctors Without Borders) announced early closure of its phase 2/3 trial of a 6-month multidrug regimen for multidrug-resistant tuberculosis (MDR-TB) because an independent data safety and monitoring board (DSMB) determined that the drug combination in the study regimen was superior to current therapy, according to a press release.

The trial, called TB PRACTECAL, compared the current local standard of care with a 6-month regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin. The interim analysis included 242 patients and the randomized, controlled trial was conducted in sites in Belarus, South Africa, and Uzbekistan.

The preliminary data will be shared with the World Health Organization soon and will also be submitted to a peer-reviewed journal. If it withstands further reviews, as is anticipated, the trial would support the first solely oral regimen for MDR-TB.

In 2019, an estimated 465,000 people developed MDR-TB and 182,000 died. The global burden of TB at that time was about 10 million new cases, many with coexisting HIV.

Current treatment for MDR-TB lasts 9-20 months and is complicated by the need for painful shots and toxic antibiotics. Side effects can include psychiatric problems from quinolones, isoniazid, ethambutol, or cycloserine; deafness from aminoglycosides; and bone marrow suppression from linezolid, among other toxicities.

It’s hoped that the shorter regimen will reduce toxicity and improve patient compliance. Poor adherence to treatment is a major driver of further drug resistance. Current regimens require up to 20 pills per day as well as daily injections.

In a prepared statement from MSF, David Moore, MD, MSc, London School of Hygiene and Tropical Medicine, a member of the TB-PRACTECAL trial’s steering committee, concluded: “The findings could transform the way we treat patients with drug-resistant forms of TB worldwide, who have been neglected for too long.”

This good news is particularly welcome as, in the time of COVID-19, “an estimated 1.4 million fewer people received care for tuberculosis in 2020 than in 2019,” according to the WHO. The drop, an overall 21% reduction in patients beginning treatment, ranged as high as 42% in Indonesia.

Although awaiting complete data, Madhukar Pai, MD, PhD, associate director of the McGill International TB Centre, McGill University, Montreal, shares Dr. Moore’s enthusiasm. In an interview, Dr. Pai compared MDR-TB with extensively drug-resistant TB (XDR-TB).

“I’m excited about the possibility that these trial results might help shorten MDR-TB treatment to 6 months,” said Dr. Pai. “That will be a huge relief to all patients battling drug-resistant disease. The 6-month BPaL regimen (bedaquiline, pretomanid, and linezolid) regimen works well in XDR-TB. So, I would expect the TB PRACTECAL regimen with one added drug (moxifloxacin) to work well in MDR-TB, which is less severe than XDR-TB. Between these two regimens, if we can bring down MDR and XDR treatment to 6 months, all oral, that would be a huge advance.”

The expense of bedaquiline has been a long-standing concern in the global health community. Janssen, a subsidiary of Johnson & Johnson, has reduced the price to $340 per 6-month treatment course for more than 135 eligible low- and middle-income countries.

Previously, the tiered pricing structure was different for low-, middle-, and high-income countries (U.S. $900, $3,000, and $30,000, respectively). “The global TB community has asked Janssen to drop the price of bedaquiline to a level no higher than $32 per month – double the price at which researchers estimated bedaquiline could be sold for a profit,” according to the Treatment Action Group A major source of contention over pricing has been that there has been considerable public investment in the drug›s development.

Dr. Pai concluded: “Bedaquiline is likely the most important drug in both 6-month regimens. We need to work harder to make bedaquiline, an excellent drug, more affordable and accessible.”

While the full data is not yet publicly available, TB PRACTECAL was a randomized, controlled, multicenter study. The fact that enrollment was discontinued early by the DSMB suggests the efficacy data was compelling and that this completely oral regimen will become the standard of care.

Dr. Stone is an infectious disease specialist and author of Resilience: One Family’s Story of Hope and Triumph Over Evil and of Conducting Clinical Research, the essential guide to the topic. A version of this article first appeared on Medscape.com.

Médecins Sans Frontières (MSF/Doctors Without Borders) announced early closure of its phase 2/3 trial of a 6-month multidrug regimen for multidrug-resistant tuberculosis (MDR-TB) because an independent data safety and monitoring board (DSMB) determined that the drug combination in the study regimen was superior to current therapy, according to a press release.

The trial, called TB PRACTECAL, compared the current local standard of care with a 6-month regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin. The interim analysis included 242 patients and the randomized, controlled trial was conducted in sites in Belarus, South Africa, and Uzbekistan.

The preliminary data will be shared with the World Health Organization soon and will also be submitted to a peer-reviewed journal. If it withstands further reviews, as is anticipated, the trial would support the first solely oral regimen for MDR-TB.

In 2019, an estimated 465,000 people developed MDR-TB and 182,000 died. The global burden of TB at that time was about 10 million new cases, many with coexisting HIV.

Current treatment for MDR-TB lasts 9-20 months and is complicated by the need for painful shots and toxic antibiotics. Side effects can include psychiatric problems from quinolones, isoniazid, ethambutol, or cycloserine; deafness from aminoglycosides; and bone marrow suppression from linezolid, among other toxicities.

It’s hoped that the shorter regimen will reduce toxicity and improve patient compliance. Poor adherence to treatment is a major driver of further drug resistance. Current regimens require up to 20 pills per day as well as daily injections.

In a prepared statement from MSF, David Moore, MD, MSc, London School of Hygiene and Tropical Medicine, a member of the TB-PRACTECAL trial’s steering committee, concluded: “The findings could transform the way we treat patients with drug-resistant forms of TB worldwide, who have been neglected for too long.”

This good news is particularly welcome as, in the time of COVID-19, “an estimated 1.4 million fewer people received care for tuberculosis in 2020 than in 2019,” according to the WHO. The drop, an overall 21% reduction in patients beginning treatment, ranged as high as 42% in Indonesia.

Although awaiting complete data, Madhukar Pai, MD, PhD, associate director of the McGill International TB Centre, McGill University, Montreal, shares Dr. Moore’s enthusiasm. In an interview, Dr. Pai compared MDR-TB with extensively drug-resistant TB (XDR-TB).

“I’m excited about the possibility that these trial results might help shorten MDR-TB treatment to 6 months,” said Dr. Pai. “That will be a huge relief to all patients battling drug-resistant disease. The 6-month BPaL regimen (bedaquiline, pretomanid, and linezolid) regimen works well in XDR-TB. So, I would expect the TB PRACTECAL regimen with one added drug (moxifloxacin) to work well in MDR-TB, which is less severe than XDR-TB. Between these two regimens, if we can bring down MDR and XDR treatment to 6 months, all oral, that would be a huge advance.”

The expense of bedaquiline has been a long-standing concern in the global health community. Janssen, a subsidiary of Johnson & Johnson, has reduced the price to $340 per 6-month treatment course for more than 135 eligible low- and middle-income countries.

Previously, the tiered pricing structure was different for low-, middle-, and high-income countries (U.S. $900, $3,000, and $30,000, respectively). “The global TB community has asked Janssen to drop the price of bedaquiline to a level no higher than $32 per month – double the price at which researchers estimated bedaquiline could be sold for a profit,” according to the Treatment Action Group A major source of contention over pricing has been that there has been considerable public investment in the drug›s development.

Dr. Pai concluded: “Bedaquiline is likely the most important drug in both 6-month regimens. We need to work harder to make bedaquiline, an excellent drug, more affordable and accessible.”

While the full data is not yet publicly available, TB PRACTECAL was a randomized, controlled, multicenter study. The fact that enrollment was discontinued early by the DSMB suggests the efficacy data was compelling and that this completely oral regimen will become the standard of care.

Dr. Stone is an infectious disease specialist and author of Resilience: One Family’s Story of Hope and Triumph Over Evil and of Conducting Clinical Research, the essential guide to the topic. A version of this article first appeared on Medscape.com.

Despite recent advances in the diagnosis, treatment, and prevention of pediatric tuberculosis in children living with HIV (CLHIV) and HIV-exposed uninfected children (HEU), several unmet needs remain, including studies evaluating the feasibility of shortened TB treatment regimens.

“Children living with HIV contribute disproportionately to pediatric TB mortality rates, accounting for 16% of child TB deaths, and many cases are underdiagnosed and underreported,” said Nicole Salazar-Austin, MD, of Johns Hopkins University in Baltimore. She provided an update on pediatric TB prevention and treatment during an educational symposium at this year’s virtual Conference on Retroviruses & Opportunistic Infections.

Dr. Salazar-Austin summarized current diagnostics for pediatric TB and reviewed options for the prevention and treatment of TB in CLHIV and HEU.
 

TB and CLHIV

Presently, TB is the most common opportunistic infection among CLHIV, and those with severe immune suppression have a fivefold greater risk of TB disease. While antiretroviral therapy (ART) is highly protective against TB disease in CLHIV, only about 50% of eligible children receive ART.

Dr. Salazar-Austin explained that many individuals with TB/HIV coinfection are unaware of their coinfection and not receiving treatment. Despite recommendations, TB preventive therapy is poorly implemented in CLHIV, especially in high-burden settings.
 

Pediatric TB diagnosis

Smear microscopy, culture, and Xpert MTB/RIF Ultra are the main diagnostic modalities for pediatric TB. The Xpert MTB/RIF test is an automated PCR-based assay that simultaneously and rapidly detects Mycobacterium tuberculosis complex and resistance to rifampin. The test is currently recommended by the World Health Organization as the initial diagnostic method for presumptive TB cases in both adults and children.

However, under optimal conditions, only 40% of TB cases will be detected. This is in part due to limited implementation of sputum collection procedures, but recent evidence has shown that collection of multiple specimens improves sensitivity for both culture and Xpert MTB/RIF Ultra across all specimen types, Dr. Salazar-Austin explained.

In 2020, the WHO endorsed the use of stool samples for the diagnosis of pediatric pulmonary TB. Stool Xpert is an emerging alternative, noninvasive method for ruling in pediatric TB disease, and has shown sensitivity and specificity similar to that of Xpert MTB/RIF Ultra.

“TB diagnostics have limited sensitivity in children, and efforts are ongoing to maximize current diagnostics, but new diagnostics are needed,” said Dr. Salazar-Austin.
 

Pediatric TB treatment

Despite the high frequency of TB as an opportunistic infection in CLHIV, current data on co-treatment strategies are limited.

Dolutegravir-based regimens are the preferred first-line regimen for CLHIV. In June 2020, the Food and Drug Administration approved the dispersible dolutegravir tablet, and it is expected to become widely available in 2021.

In children with TB/HIV coinfection who receive dolutegravir and rifampicin, dolutegravir is typically dosed twice daily because of a known drug interaction, based on data from the ODYSSEY study. The WHO recommendations for treatment of pediatric TB/HIV coinfection were recently updated to reflect twice-daily dosing of dolutegravir.

Despite these new recommendations, data are currently limited, and observational pharmacokinetic studies evaluating twice daily dolutegravir with TB treatment in young children are needed.

“More work is needed to evaluate the drug-drug interactions and proper dosing of rifamycins with dolutegravir for the treatment and prevention of TB in CLHIV,” Dr. Salazar-Austin said.

Based on data from TBTC Study 31/ACTG A5349, high-dose rifapentine (a rifamycin) with moxifloxacin (a fluoroquinolone) was noninferior to rifapentine alone in newly diagnosed, culture positive, drug-susceptible TB in children 12 years and older.

Whether rifapentine and moxifloxacin (RPT-Mox) can be used in children under 12 years remains unknown, but future studies may help answer this question, Dr. Salazar-Austin noted. The FDA has restricted the use of fluoroquinolones in children because of a possible effect on cartilage development, she explained.

Furthermore, recent data from the SHINE trial suggested that shortened treatment regimens may hold promise for children with TB.

“While shortened TB treatment regimens hold promise, much work needs to be done in children to implement RPT-Mox, but the results from SHINE can be implemented rapidly,” Dr. Salazar-Austin said.

Dr. Salazar-Austin disclosed no conflicts of interest. The presentation was funded by NICHD, UNITAID, Fogarty Institute, and the IMPAACT network.

Despite recent advances in the diagnosis, treatment, and prevention of pediatric tuberculosis in children living with HIV (CLHIV) and HIV-exposed uninfected children (HEU), several unmet needs remain, including studies evaluating the feasibility of shortened TB treatment regimens.

“Children living with HIV contribute disproportionately to pediatric TB mortality rates, accounting for 16% of child TB deaths, and many cases are underdiagnosed and underreported,” said Nicole Salazar-Austin, MD, of Johns Hopkins University in Baltimore. She provided an update on pediatric TB prevention and treatment during an educational symposium at this year’s virtual Conference on Retroviruses & Opportunistic Infections.

Dr. Salazar-Austin summarized current diagnostics for pediatric TB and reviewed options for the prevention and treatment of TB in CLHIV and HEU.
 

TB and CLHIV

Presently, TB is the most common opportunistic infection among CLHIV, and those with severe immune suppression have a fivefold greater risk of TB disease. While antiretroviral therapy (ART) is highly protective against TB disease in CLHIV, only about 50% of eligible children receive ART.

Dr. Salazar-Austin explained that many individuals with TB/HIV coinfection are unaware of their coinfection and not receiving treatment. Despite recommendations, TB preventive therapy is poorly implemented in CLHIV, especially in high-burden settings.
 

Pediatric TB diagnosis

Smear microscopy, culture, and Xpert MTB/RIF Ultra are the main diagnostic modalities for pediatric TB. The Xpert MTB/RIF test is an automated PCR-based assay that simultaneously and rapidly detects Mycobacterium tuberculosis complex and resistance to rifampin. The test is currently recommended by the World Health Organization as the initial diagnostic method for presumptive TB cases in both adults and children.

However, under optimal conditions, only 40% of TB cases will be detected. This is in part due to limited implementation of sputum collection procedures, but recent evidence has shown that collection of multiple specimens improves sensitivity for both culture and Xpert MTB/RIF Ultra across all specimen types, Dr. Salazar-Austin explained.

In 2020, the WHO endorsed the use of stool samples for the diagnosis of pediatric pulmonary TB. Stool Xpert is an emerging alternative, noninvasive method for ruling in pediatric TB disease, and has shown sensitivity and specificity similar to that of Xpert MTB/RIF Ultra.

“TB diagnostics have limited sensitivity in children, and efforts are ongoing to maximize current diagnostics, but new diagnostics are needed,” said Dr. Salazar-Austin.
 

Pediatric TB treatment

Despite the high frequency of TB as an opportunistic infection in CLHIV, current data on co-treatment strategies are limited.

Dolutegravir-based regimens are the preferred first-line regimen for CLHIV. In June 2020, the Food and Drug Administration approved the dispersible dolutegravir tablet, and it is expected to become widely available in 2021.

In children with TB/HIV coinfection who receive dolutegravir and rifampicin, dolutegravir is typically dosed twice daily because of a known drug interaction, based on data from the ODYSSEY study. The WHO recommendations for treatment of pediatric TB/HIV coinfection were recently updated to reflect twice-daily dosing of dolutegravir.

Despite these new recommendations, data are currently limited, and observational pharmacokinetic studies evaluating twice daily dolutegravir with TB treatment in young children are needed.

“More work is needed to evaluate the drug-drug interactions and proper dosing of rifamycins with dolutegravir for the treatment and prevention of TB in CLHIV,” Dr. Salazar-Austin said.

Based on data from TBTC Study 31/ACTG A5349, high-dose rifapentine (a rifamycin) with moxifloxacin (a fluoroquinolone) was noninferior to rifapentine alone in newly diagnosed, culture positive, drug-susceptible TB in children 12 years and older.

Whether rifapentine and moxifloxacin (RPT-Mox) can be used in children under 12 years remains unknown, but future studies may help answer this question, Dr. Salazar-Austin noted. The FDA has restricted the use of fluoroquinolones in children because of a possible effect on cartilage development, she explained.

Furthermore, recent data from the SHINE trial suggested that shortened treatment regimens may hold promise for children with TB.

“While shortened TB treatment regimens hold promise, much work needs to be done in children to implement RPT-Mox, but the results from SHINE can be implemented rapidly,” Dr. Salazar-Austin said.

Dr. Salazar-Austin disclosed no conflicts of interest. The presentation was funded by NICHD, UNITAID, Fogarty Institute, and the IMPAACT network.

Despite recent advances in the diagnosis, treatment, and prevention of pediatric tuberculosis in children living with HIV (CLHIV) and HIV-exposed uninfected children (HEU), several unmet needs remain, including studies evaluating the feasibility of shortened TB treatment regimens.

“Children living with HIV contribute disproportionately to pediatric TB mortality rates, accounting for 16% of child TB deaths, and many cases are underdiagnosed and underreported,” said Nicole Salazar-Austin, MD, of Johns Hopkins University in Baltimore. She provided an update on pediatric TB prevention and treatment during an educational symposium at this year’s virtual Conference on Retroviruses & Opportunistic Infections.

Dr. Salazar-Austin summarized current diagnostics for pediatric TB and reviewed options for the prevention and treatment of TB in CLHIV and HEU.
 

TB and CLHIV

Presently, TB is the most common opportunistic infection among CLHIV, and those with severe immune suppression have a fivefold greater risk of TB disease. While antiretroviral therapy (ART) is highly protective against TB disease in CLHIV, only about 50% of eligible children receive ART.

Dr. Salazar-Austin explained that many individuals with TB/HIV coinfection are unaware of their coinfection and not receiving treatment. Despite recommendations, TB preventive therapy is poorly implemented in CLHIV, especially in high-burden settings.
 

Pediatric TB diagnosis

Smear microscopy, culture, and Xpert MTB/RIF Ultra are the main diagnostic modalities for pediatric TB. The Xpert MTB/RIF test is an automated PCR-based assay that simultaneously and rapidly detects Mycobacterium tuberculosis complex and resistance to rifampin. The test is currently recommended by the World Health Organization as the initial diagnostic method for presumptive TB cases in both adults and children.

However, under optimal conditions, only 40% of TB cases will be detected. This is in part due to limited implementation of sputum collection procedures, but recent evidence has shown that collection of multiple specimens improves sensitivity for both culture and Xpert MTB/RIF Ultra across all specimen types, Dr. Salazar-Austin explained.

In 2020, the WHO endorsed the use of stool samples for the diagnosis of pediatric pulmonary TB. Stool Xpert is an emerging alternative, noninvasive method for ruling in pediatric TB disease, and has shown sensitivity and specificity similar to that of Xpert MTB/RIF Ultra.

“TB diagnostics have limited sensitivity in children, and efforts are ongoing to maximize current diagnostics, but new diagnostics are needed,” said Dr. Salazar-Austin.
 

Pediatric TB treatment

Despite the high frequency of TB as an opportunistic infection in CLHIV, current data on co-treatment strategies are limited.

Dolutegravir-based regimens are the preferred first-line regimen for CLHIV. In June 2020, the Food and Drug Administration approved the dispersible dolutegravir tablet, and it is expected to become widely available in 2021.

In children with TB/HIV coinfection who receive dolutegravir and rifampicin, dolutegravir is typically dosed twice daily because of a known drug interaction, based on data from the ODYSSEY study. The WHO recommendations for treatment of pediatric TB/HIV coinfection were recently updated to reflect twice-daily dosing of dolutegravir.

Despite these new recommendations, data are currently limited, and observational pharmacokinetic studies evaluating twice daily dolutegravir with TB treatment in young children are needed.

“More work is needed to evaluate the drug-drug interactions and proper dosing of rifamycins with dolutegravir for the treatment and prevention of TB in CLHIV,” Dr. Salazar-Austin said.

Based on data from TBTC Study 31/ACTG A5349, high-dose rifapentine (a rifamycin) with moxifloxacin (a fluoroquinolone) was noninferior to rifapentine alone in newly diagnosed, culture positive, drug-susceptible TB in children 12 years and older.

Whether rifapentine and moxifloxacin (RPT-Mox) can be used in children under 12 years remains unknown, but future studies may help answer this question, Dr. Salazar-Austin noted. The FDA has restricted the use of fluoroquinolones in children because of a possible effect on cartilage development, she explained.

Furthermore, recent data from the SHINE trial suggested that shortened treatment regimens may hold promise for children with TB.

“While shortened TB treatment regimens hold promise, much work needs to be done in children to implement RPT-Mox, but the results from SHINE can be implemented rapidly,” Dr. Salazar-Austin said.

Dr. Salazar-Austin disclosed no conflicts of interest. The presentation was funded by NICHD, UNITAID, Fogarty Institute, and the IMPAACT network.