Judy Stone, MD

Life-threatening fungal bloodstream infections associated with probiotic supplements have been reported in the journal Emerging Infectious Diseases by a group of researchers in Finland. While individuals consume these mixtures of bacteria and yeast in the hopes of “balancing” their microbiome or preventing diarrhea from antibiotic use, some died or developed yeast infections requiring prolonged antifungal treatment.

In a retrospective registry study at five university hospitals in Finland, the researchers found 46 patients between 2009 and 2018 with Saccharomyces sp. of yeast in their blood associated with ingesting probiotics. At least 20 (43%) had been using S. cerevisiae var. boulardii as a probiotic, with the organism then causing a bloodstream infection. Overall, 37% of the fungemic patients died.

Juha Rannikko, MD, lead author and infectious disease faculty member at Tampere University Hospital, Finland, said in an interview that there were an additional 1,153 nonblood isolates of Saccharomyces. He expressed surprise at the large number of nonblood isolates, saying: “If extrapolated ... it is about 10 nonblood Saccharomyces boulardii–associated findings for each Saccharomyces boulardii–associated fungemia.”

Most of the yeast infections (59%) occurred in patients with underlying gastrointestinal disease. Prior studies suggested that patients receiving enteral nutrition might become ill from translocation of the yeast from the inflamed GI tract.

If there were positive cultures for yeast from sites other than blood, physicians changed the antibiotics in 38% of patients.

Conventional wisdom has been that patients receiving broad-spectrum antibiotics should also receive an S. cerevisiae var. boulardii probiotic to prevent Clostridioides difficile infections. Dr. Rannikko and coauthors questioned this, noting results of such studies of prophylaxis were equivocal. “There is not enough evidence that clinicians should use Saccharomyces (probiotics) alongside antibiotics,” Dr. Rannikko concluded.

Laila Woc-Colburn, MD, associate professor at the Emory University School of Medicine, Atlanta, told this news organization that although the study was well done and was published in Emerging Infectious Diseases, the findings do not represent an “emerging” infectious disease. “We have known this for a while – since the 1990s,” she said. Warnings about probiotics are part of the standard advice Dr. Woc-Colburn gives transplant, chemotherapy, or immunosuppressed patients. “Don’t do these probiotics, because this is what’s going to happen,” she tells them. And she told this news organization, “If I see this in the blood, the first question I’m going to ask my patients is ... what probiotic were you drinking?”

Dr. Woc-Colburn said the Finnish researchers “did their due diligence” when conducting the study. “They were clear on their limitations. And they came out to the same conclusion as the 2005 Muñoz paper: That if we have some GI disruption, we should not be taking probiotics.”

She acknowledged that the Emerging Infectious Diseases study adds a substantial number of cases to those previously reported in the literature and confirms previous findings and recommendations to avoid probiotics if immunosuppressed or acutely ill.

Dr. Rannikko and Dr. Woc-Coburn have reported no relevant financial relationships. Dr. Rannikko has received a lecture fee from Novo Nordisk and a virtual congress attendance fee from Roche.

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

Life-threatening fungal bloodstream infections associated with probiotic supplements have been reported in the journal Emerging Infectious Diseases by a group of researchers in Finland. While individuals consume these mixtures of bacteria and yeast in the hopes of “balancing” their microbiome or preventing diarrhea from antibiotic use, some died or developed yeast infections requiring prolonged antifungal treatment.

In a retrospective registry study at five university hospitals in Finland, the researchers found 46 patients between 2009 and 2018 with Saccharomyces sp. of yeast in their blood associated with ingesting probiotics. At least 20 (43%) had been using S. cerevisiae var. boulardii as a probiotic, with the organism then causing a bloodstream infection. Overall, 37% of the fungemic patients died.

Juha Rannikko, MD, lead author and infectious disease faculty member at Tampere University Hospital, Finland, said in an interview that there were an additional 1,153 nonblood isolates of Saccharomyces. He expressed surprise at the large number of nonblood isolates, saying: “If extrapolated ... it is about 10 nonblood Saccharomyces boulardii–associated findings for each Saccharomyces boulardii–associated fungemia.”

Most of the yeast infections (59%) occurred in patients with underlying gastrointestinal disease. Prior studies suggested that patients receiving enteral nutrition might become ill from translocation of the yeast from the inflamed GI tract.

If there were positive cultures for yeast from sites other than blood, physicians changed the antibiotics in 38% of patients.

Conventional wisdom has been that patients receiving broad-spectrum antibiotics should also receive an S. cerevisiae var. boulardii probiotic to prevent Clostridioides difficile infections. Dr. Rannikko and coauthors questioned this, noting results of such studies of prophylaxis were equivocal. “There is not enough evidence that clinicians should use Saccharomyces (probiotics) alongside antibiotics,” Dr. Rannikko concluded.

Laila Woc-Colburn, MD, associate professor at the Emory University School of Medicine, Atlanta, told this news organization that although the study was well done and was published in Emerging Infectious Diseases, the findings do not represent an “emerging” infectious disease. “We have known this for a while – since the 1990s,” she said. Warnings about probiotics are part of the standard advice Dr. Woc-Colburn gives transplant, chemotherapy, or immunosuppressed patients. “Don’t do these probiotics, because this is what’s going to happen,” she tells them. And she told this news organization, “If I see this in the blood, the first question I’m going to ask my patients is ... what probiotic were you drinking?”

Dr. Woc-Colburn said the Finnish researchers “did their due diligence” when conducting the study. “They were clear on their limitations. And they came out to the same conclusion as the 2005 Muñoz paper: That if we have some GI disruption, we should not be taking probiotics.”

She acknowledged that the Emerging Infectious Diseases study adds a substantial number of cases to those previously reported in the literature and confirms previous findings and recommendations to avoid probiotics if immunosuppressed or acutely ill.

Dr. Rannikko and Dr. Woc-Coburn have reported no relevant financial relationships. Dr. Rannikko has received a lecture fee from Novo Nordisk and a virtual congress attendance fee from Roche.

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

Life-threatening fungal bloodstream infections associated with probiotic supplements have been reported in the journal Emerging Infectious Diseases by a group of researchers in Finland. While individuals consume these mixtures of bacteria and yeast in the hopes of “balancing” their microbiome or preventing diarrhea from antibiotic use, some died or developed yeast infections requiring prolonged antifungal treatment.

In a retrospective registry study at five university hospitals in Finland, the researchers found 46 patients between 2009 and 2018 with Saccharomyces sp. of yeast in their blood associated with ingesting probiotics. At least 20 (43%) had been using S. cerevisiae var. boulardii as a probiotic, with the organism then causing a bloodstream infection. Overall, 37% of the fungemic patients died.

Juha Rannikko, MD, lead author and infectious disease faculty member at Tampere University Hospital, Finland, said in an interview that there were an additional 1,153 nonblood isolates of Saccharomyces. He expressed surprise at the large number of nonblood isolates, saying: “If extrapolated ... it is about 10 nonblood Saccharomyces boulardii–associated findings for each Saccharomyces boulardii–associated fungemia.”

Most of the yeast infections (59%) occurred in patients with underlying gastrointestinal disease. Prior studies suggested that patients receiving enteral nutrition might become ill from translocation of the yeast from the inflamed GI tract.

If there were positive cultures for yeast from sites other than blood, physicians changed the antibiotics in 38% of patients.

Conventional wisdom has been that patients receiving broad-spectrum antibiotics should also receive an S. cerevisiae var. boulardii probiotic to prevent Clostridioides difficile infections. Dr. Rannikko and coauthors questioned this, noting results of such studies of prophylaxis were equivocal. “There is not enough evidence that clinicians should use Saccharomyces (probiotics) alongside antibiotics,” Dr. Rannikko concluded.

Laila Woc-Colburn, MD, associate professor at the Emory University School of Medicine, Atlanta, told this news organization that although the study was well done and was published in Emerging Infectious Diseases, the findings do not represent an “emerging” infectious disease. “We have known this for a while – since the 1990s,” she said. Warnings about probiotics are part of the standard advice Dr. Woc-Colburn gives transplant, chemotherapy, or immunosuppressed patients. “Don’t do these probiotics, because this is what’s going to happen,” she tells them. And she told this news organization, “If I see this in the blood, the first question I’m going to ask my patients is ... what probiotic were you drinking?”

Dr. Woc-Colburn said the Finnish researchers “did their due diligence” when conducting the study. “They were clear on their limitations. And they came out to the same conclusion as the 2005 Muñoz paper: That if we have some GI disruption, we should not be taking probiotics.”

She acknowledged that the Emerging Infectious Diseases study adds a substantial number of cases to those previously reported in the literature and confirms previous findings and recommendations to avoid probiotics if immunosuppressed or acutely ill.

Dr. Rannikko and Dr. Woc-Coburn have reported no relevant financial relationships. Dr. Rannikko has received a lecture fee from Novo Nordisk and a virtual congress attendance fee from Roche.

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

A 1-week course of doxycycline is more effective than single-dose azithromycin to treat rectal chlamydia in men who have sex with men (MSM), according to newly published results in the New England Journal of Medicine.

Chlamydia is the most commonly reported bacterial STI in the United States, with 4 million cases reported in 2018, and 127 million globally. Most infections are asymptomatic.

Rates of rectal chlamydia among MSM screened for infection range from 3% to 10.5%.

The most recent Centers for Disease Control and Prevention chlamydia guidelines recommend either a single dose of azithromycin (1 g) or doxycycline 100 mg twice daily for 7 days. These 2015 guidelines were based on a meta-analysis of urogenital chlamydia infections, which showed comparable efficacy of 97% or 98%, respectively.

Study coauthor Jane S. Hocking, PhD, head of the sexual health unit at the University of Melbourne, told this news organization that “observational studies had suggested that azithromycin was about 20% less effective than doxycycline,” prompting this clinical trial.

The study, conducted at five sexual health clinics in Australia, was a double-blind, randomized, controlled trial of doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose).

Because 85% of infected men are asymptomatic, the study’s primary outcome was a negative nucleic acid amplification test at 4 weeks, confirming a microbiologic cure.

Using a modified intention-to-treat population, the study showed a microbiologic cure in 281 of 290 men (96.9%) in the doxycycline group and 227 of 297 (76.4%) in the azithromycin group (P < .001).

Adverse events were more common in the azithromycin group. Nausea, diarrhea, and vomiting occurred in 134 (45.1%) men in that group versus 98 men (33.8%) in those receiving doxycycline (P = .006).

A similar study was reported in Clinical Infectious Diseases in February 2021 by Dombrowski and colleagues. It was also randomized, double blinded, and placebo controlled but was smaller and conducted in Seattle and Boston. A 20% difference was found, with 80/88 (91%) in the doxycycline group and 63/89 (71%) in the azithromycin group having a microbiologic cure at 4 weeks of follow-up.

Jeanne Marrazzo, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, said in an interview that the researchers focused solely on asymptomatic proctitis because “other symptoms might indicate need for broader presumptive antibiotics” for coinfections. Similarly, symptomatic proctitis “could indicate LGV [lymphogranuloma venereum] chlamydia, which ... automatically mandates that 3-weeks of doxycycline be used.” Dr. Marrazzo concluded: “The fact that this was a blinded study obviously strengthens the conclusions/findings, which is great. It’s very reassuring that results overall are so consistent with the CID paper.” Dr. Marrazzo was not involved in either the New England Journal of Medicine investigation or CID study.

Ina Park, MD, associate professor in the department of family and community medicine at the University of California, San Francisco, and author of “Strange Bedfellows: Adventures in the Science, History, and Surprising Secrets of STDs,” (New York: Flatiron Books, 2021) was not involved in either study but has a long history of working with adolescents in clinics for STDs. Based on that experience, she told this news organization that, while doxycycline now clearly appears to be the drug of choice, “if compliance is an issue and rectal chlamydia is not likely, then I think azithromycin is still something we need to consider, particularly for younger patients, and folks for whom compliance is going to be an issue.” She added: “with adolescent patients, there are issues of parents possibly discovering the antibiotic and asking lots of questions. So, it’s very nice for folks to be able to get therapy, sort of a one and done approach in the clinic.”

The 2020 CDC Guidelines for Gonococcal Infections says: “CDC recommends a single 500 mg intramuscular dose of ceftriaxone for uncomplicated gonorrhea. Treatment for coinfection with Chlamydia trachomatis with oral doxycycline (100 mg twice daily for 7 days) should be administered when chlamydial infection has not been excluded.”

Hocking concluded – and Dr. Marrazzo and Dr. Park concur – that this study “provides conclusive evidence that doxycycline should be the first-line treatment for rectal chlamydia, but probably for just any chlamydia infection,” with specific exceptions.

The University of Melbourne researchers also noted that the doxycycline course requires more compliant patients, as adherence isn’t assured. The issue of compliance and need for directly observed therapy, allergy to doxycycline, and pregnancy (where doxycycline is contraindicated) will remain the primary indications for continued use of azithromycin.

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

A 1-week course of doxycycline is more effective than single-dose azithromycin to treat rectal chlamydia in men who have sex with men (MSM), according to newly published results in the New England Journal of Medicine.

Chlamydia is the most commonly reported bacterial STI in the United States, with 4 million cases reported in 2018, and 127 million globally. Most infections are asymptomatic.

Rates of rectal chlamydia among MSM screened for infection range from 3% to 10.5%.

The most recent Centers for Disease Control and Prevention chlamydia guidelines recommend either a single dose of azithromycin (1 g) or doxycycline 100 mg twice daily for 7 days. These 2015 guidelines were based on a meta-analysis of urogenital chlamydia infections, which showed comparable efficacy of 97% or 98%, respectively.

Study coauthor Jane S. Hocking, PhD, head of the sexual health unit at the University of Melbourne, told this news organization that “observational studies had suggested that azithromycin was about 20% less effective than doxycycline,” prompting this clinical trial.

The study, conducted at five sexual health clinics in Australia, was a double-blind, randomized, controlled trial of doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose).

Because 85% of infected men are asymptomatic, the study’s primary outcome was a negative nucleic acid amplification test at 4 weeks, confirming a microbiologic cure.

Using a modified intention-to-treat population, the study showed a microbiologic cure in 281 of 290 men (96.9%) in the doxycycline group and 227 of 297 (76.4%) in the azithromycin group (P < .001).

Adverse events were more common in the azithromycin group. Nausea, diarrhea, and vomiting occurred in 134 (45.1%) men in that group versus 98 men (33.8%) in those receiving doxycycline (P = .006).

A similar study was reported in Clinical Infectious Diseases in February 2021 by Dombrowski and colleagues. It was also randomized, double blinded, and placebo controlled but was smaller and conducted in Seattle and Boston. A 20% difference was found, with 80/88 (91%) in the doxycycline group and 63/89 (71%) in the azithromycin group having a microbiologic cure at 4 weeks of follow-up.

Jeanne Marrazzo, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, said in an interview that the researchers focused solely on asymptomatic proctitis because “other symptoms might indicate need for broader presumptive antibiotics” for coinfections. Similarly, symptomatic proctitis “could indicate LGV [lymphogranuloma venereum] chlamydia, which ... automatically mandates that 3-weeks of doxycycline be used.” Dr. Marrazzo concluded: “The fact that this was a blinded study obviously strengthens the conclusions/findings, which is great. It’s very reassuring that results overall are so consistent with the CID paper.” Dr. Marrazzo was not involved in either the New England Journal of Medicine investigation or CID study.

Ina Park, MD, associate professor in the department of family and community medicine at the University of California, San Francisco, and author of “Strange Bedfellows: Adventures in the Science, History, and Surprising Secrets of STDs,” (New York: Flatiron Books, 2021) was not involved in either study but has a long history of working with adolescents in clinics for STDs. Based on that experience, she told this news organization that, while doxycycline now clearly appears to be the drug of choice, “if compliance is an issue and rectal chlamydia is not likely, then I think azithromycin is still something we need to consider, particularly for younger patients, and folks for whom compliance is going to be an issue.” She added: “with adolescent patients, there are issues of parents possibly discovering the antibiotic and asking lots of questions. So, it’s very nice for folks to be able to get therapy, sort of a one and done approach in the clinic.”

The 2020 CDC Guidelines for Gonococcal Infections says: “CDC recommends a single 500 mg intramuscular dose of ceftriaxone for uncomplicated gonorrhea. Treatment for coinfection with Chlamydia trachomatis with oral doxycycline (100 mg twice daily for 7 days) should be administered when chlamydial infection has not been excluded.”

Hocking concluded – and Dr. Marrazzo and Dr. Park concur – that this study “provides conclusive evidence that doxycycline should be the first-line treatment for rectal chlamydia, but probably for just any chlamydia infection,” with specific exceptions.

The University of Melbourne researchers also noted that the doxycycline course requires more compliant patients, as adherence isn’t assured. The issue of compliance and need for directly observed therapy, allergy to doxycycline, and pregnancy (where doxycycline is contraindicated) will remain the primary indications for continued use of azithromycin.

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

A 1-week course of doxycycline is more effective than single-dose azithromycin to treat rectal chlamydia in men who have sex with men (MSM), according to newly published results in the New England Journal of Medicine.

Chlamydia is the most commonly reported bacterial STI in the United States, with 4 million cases reported in 2018, and 127 million globally. Most infections are asymptomatic.

Rates of rectal chlamydia among MSM screened for infection range from 3% to 10.5%.

The most recent Centers for Disease Control and Prevention chlamydia guidelines recommend either a single dose of azithromycin (1 g) or doxycycline 100 mg twice daily for 7 days. These 2015 guidelines were based on a meta-analysis of urogenital chlamydia infections, which showed comparable efficacy of 97% or 98%, respectively.

Study coauthor Jane S. Hocking, PhD, head of the sexual health unit at the University of Melbourne, told this news organization that “observational studies had suggested that azithromycin was about 20% less effective than doxycycline,” prompting this clinical trial.

The study, conducted at five sexual health clinics in Australia, was a double-blind, randomized, controlled trial of doxycycline (100 mg twice daily for 7 days) or azithromycin (1-g single dose).

Because 85% of infected men are asymptomatic, the study’s primary outcome was a negative nucleic acid amplification test at 4 weeks, confirming a microbiologic cure.

Using a modified intention-to-treat population, the study showed a microbiologic cure in 281 of 290 men (96.9%) in the doxycycline group and 227 of 297 (76.4%) in the azithromycin group (P < .001).

Adverse events were more common in the azithromycin group. Nausea, diarrhea, and vomiting occurred in 134 (45.1%) men in that group versus 98 men (33.8%) in those receiving doxycycline (P = .006).

A similar study was reported in Clinical Infectious Diseases in February 2021 by Dombrowski and colleagues. It was also randomized, double blinded, and placebo controlled but was smaller and conducted in Seattle and Boston. A 20% difference was found, with 80/88 (91%) in the doxycycline group and 63/89 (71%) in the azithromycin group having a microbiologic cure at 4 weeks of follow-up.

Jeanne Marrazzo, MD, director of the division of infectious diseases at the University of Alabama at Birmingham, said in an interview that the researchers focused solely on asymptomatic proctitis because “other symptoms might indicate need for broader presumptive antibiotics” for coinfections. Similarly, symptomatic proctitis “could indicate LGV [lymphogranuloma venereum] chlamydia, which ... automatically mandates that 3-weeks of doxycycline be used.” Dr. Marrazzo concluded: “The fact that this was a blinded study obviously strengthens the conclusions/findings, which is great. It’s very reassuring that results overall are so consistent with the CID paper.” Dr. Marrazzo was not involved in either the New England Journal of Medicine investigation or CID study.

Ina Park, MD, associate professor in the department of family and community medicine at the University of California, San Francisco, and author of “Strange Bedfellows: Adventures in the Science, History, and Surprising Secrets of STDs,” (New York: Flatiron Books, 2021) was not involved in either study but has a long history of working with adolescents in clinics for STDs. Based on that experience, she told this news organization that, while doxycycline now clearly appears to be the drug of choice, “if compliance is an issue and rectal chlamydia is not likely, then I think azithromycin is still something we need to consider, particularly for younger patients, and folks for whom compliance is going to be an issue.” She added: “with adolescent patients, there are issues of parents possibly discovering the antibiotic and asking lots of questions. So, it’s very nice for folks to be able to get therapy, sort of a one and done approach in the clinic.”

The 2020 CDC Guidelines for Gonococcal Infections says: “CDC recommends a single 500 mg intramuscular dose of ceftriaxone for uncomplicated gonorrhea. Treatment for coinfection with Chlamydia trachomatis with oral doxycycline (100 mg twice daily for 7 days) should be administered when chlamydial infection has not been excluded.”

Hocking concluded – and Dr. Marrazzo and Dr. Park concur – that this study “provides conclusive evidence that doxycycline should be the first-line treatment for rectal chlamydia, but probably for just any chlamydia infection,” with specific exceptions.

The University of Melbourne researchers also noted that the doxycycline course requires more compliant patients, as adherence isn’t assured. The issue of compliance and need for directly observed therapy, allergy to doxycycline, and pregnancy (where doxycycline is contraindicated) will remain the primary indications for continued use of azithromycin.

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

Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose. 

Now the Centers for Disease Control and Prevention has published the first comprehensive guide to the diagnosis and treatment of botulism. The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in  Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.

In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.

Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”

While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.

Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
 

Diagnosis

Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.

Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).

Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.

Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.

With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.

Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”

It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.

Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
 

Treatment

Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.

Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.

While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.

Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.

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. You can find her at drjudystone.com or on Twitter @drjudystone.

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

Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose. 

Now the Centers for Disease Control and Prevention has published the first comprehensive guide to the diagnosis and treatment of botulism. The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in  Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.

In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.

Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”

While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.

Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
 

Diagnosis

Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.

Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).

Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.

Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.

With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.

Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”

It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.

Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
 

Treatment

Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.

Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.

While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.

Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.

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. You can find her at drjudystone.com or on Twitter @drjudystone.

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

Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose. 

Now the Centers for Disease Control and Prevention has published the first comprehensive guide to the diagnosis and treatment of botulism. The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in  Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.

In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.

Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”

While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.

Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
 

Diagnosis

Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.

Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).

Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.

Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.

With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.

Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”

It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.

Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
 

Treatment

Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.

Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.

While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.

Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.

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. You can find her at drjudystone.com or on Twitter @drjudystone.

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

In a surprising study from the Amazon rain forest, Brazilian scientists found that symptomatic COVID-19 infections were twice as likely to occur in people who had prior dengue.

The study, led by Marcelo Urbano Ferreira, MD, PhD, of the University of São Paulo Biomedical Sciences Institute, was conducted in Mâncio Lima, a town in the Amazon region of Brazil, and published May 6, 2021, in Clinical Infectious Diseases.

In the study, supported by the São Paulo Research Foundation, Ferreira’s team looked at sequential blood samples from 1,285 residents of Mâncio Lima.

An earlier study by Miguel Nicolelis, MD, PhD, and colleagues (published as a preprint) had analyzed data from the first COVID-19 wave in Brazil in 2020. It was an “ecological study” and examined dengue cases in different geographic regions of Brazil. That study concluded that dengue actually seemed to protect people from later developing COVID-19.

Dr. Ferreira anticipated finding a similar effect. Instead, he found the opposite effect. Although dengue did not increase the risk of subsequent COVID-19 infection, symptomatic COVID-19 became twice as likely in people with prior dengue. His study was longitudinal, following a single group of patients in Mâncio Lima over time.

Dr. Ferreira explained that ecological studies are inherently less accurate, as they look at populations in different places. “All the older cases are diagnosed on clinical grounds ... Because most infections are either asymptomatic or symptoms can be easily confused with” other diseases, many cases are missed. So, during the dengue transmission season, “We have some overestimation of the actual number of cases, and outside the transmission season, we have underestimation of the cases.”

On the apparent discrepancy with the earlier study by Dr. Nicolelis, Dr. Ferreira commented, “It’s a wonderful study because it’s something you can do quickly and test a hypothesis [in a] very, very timely [manner], but the problem is if your diagnosis is not very reliable.”

Dr. Ferreira had another advantage: Knowing from sequential blood samples that his patients were exposed to dengue within the past 5 years. He also could tell serologically when they became infected with the SARS-CoV-2 virus, which causes COVID-19.

Dr. Ferreira told this news organization that very few of their patients became seriously ill or required hospitalization. Because their sample size was too small, he could not say if prior dengue made the COVID-19 infection worse.

The type of interaction between two infections like dengue and COVID-19 is called a “syndemic,” which the CDC defines as “synergistically interacting epidemics.” Dr. Ferreira hypothesized about some of the factors that might be at play but does not yet have enough data. For example, he speculated about a biologic basis, such as a link to autoimmunity or vasculitis from prior dengue, but “has no real data to either support or reject these things.”

Dr. Ferreira added that perhaps there are social factors that put certain people at higher risk of infection; for example, maybe some people are “more exposed to high viral loads.”

In Brazil’s first wave of COVID-19, Dr. Ferreira’s team calculated dengue seroconversion as about 10%; many cases of dengue were asymptomatic. Ferreira expects they will “have a very different clinical spectrum during the second wave,” with young people becoming much more ill from the P1 variant of concern.

Scott O’Neill, PhD, founder and director of the World Mosquito Program, told this news organization that, while he found the Brazil results intriguing, at present they are not sufficient to say that there’s a causal relationship between dengue and COVID-19. He expressed concern that the results seem counterintuitive and doubts there’s a biological or mechanistic cause. Instead, Dr. O’Neill wondered if “there could be something about social or economic conditions or living conditions” that might account for the correlation. For example, perhaps poverty increases exposure to both dengue and COVID-19.

Furthermore, Dr. O’Neill said in an interview that he suspects that, with the COVID-19 lockdowns, “You might expect to see more dengue.” This is because “most transmission occurs around the house, and so [with] having more people confined to houses, you might expect to see more dengue.” Such appears to be the case in Singapore.

In an article in the Journal of Infectious Diseases,  Jue Tao Lim and colleagues described increased dengue in Singapore during COVID-19. They noted that most employees in Singapore work in air-conditioned settings. With social distancing enforced to try to reduce COVID-19, people stayed at home. The mosquito that transmits dengue, Aedes aegypti, gathers in wet spots in residential areas and bites during the daytime. The authors hypothesized that the spike in dengue was because of this change in habits, which shifted people’s exposure.

The syndemic in Brazil is complicated, with malaria and multiple arboviral diseases (chikungunya, dengue, Zika) overlapping with COVID-19 in areas of high population density, poverty, and poor sanitation, among other social ills. Such overlapping factors make it harder to distinguish correlations from causations. Prospective longitudinal studies might be needed to provide definitive answers.

Dr. Ferreira and Dr. O’Neill have disclosed no relevant financial relationships.

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

In a surprising study from the Amazon rain forest, Brazilian scientists found that symptomatic COVID-19 infections were twice as likely to occur in people who had prior dengue.

The study, led by Marcelo Urbano Ferreira, MD, PhD, of the University of São Paulo Biomedical Sciences Institute, was conducted in Mâncio Lima, a town in the Amazon region of Brazil, and published May 6, 2021, in Clinical Infectious Diseases.

In the study, supported by the São Paulo Research Foundation, Ferreira’s team looked at sequential blood samples from 1,285 residents of Mâncio Lima.

An earlier study by Miguel Nicolelis, MD, PhD, and colleagues (published as a preprint) had analyzed data from the first COVID-19 wave in Brazil in 2020. It was an “ecological study” and examined dengue cases in different geographic regions of Brazil. That study concluded that dengue actually seemed to protect people from later developing COVID-19.

Dr. Ferreira anticipated finding a similar effect. Instead, he found the opposite effect. Although dengue did not increase the risk of subsequent COVID-19 infection, symptomatic COVID-19 became twice as likely in people with prior dengue. His study was longitudinal, following a single group of patients in Mâncio Lima over time.

Dr. Ferreira explained that ecological studies are inherently less accurate, as they look at populations in different places. “All the older cases are diagnosed on clinical grounds ... Because most infections are either asymptomatic or symptoms can be easily confused with” other diseases, many cases are missed. So, during the dengue transmission season, “We have some overestimation of the actual number of cases, and outside the transmission season, we have underestimation of the cases.”

On the apparent discrepancy with the earlier study by Dr. Nicolelis, Dr. Ferreira commented, “It’s a wonderful study because it’s something you can do quickly and test a hypothesis [in a] very, very timely [manner], but the problem is if your diagnosis is not very reliable.”

Dr. Ferreira had another advantage: Knowing from sequential blood samples that his patients were exposed to dengue within the past 5 years. He also could tell serologically when they became infected with the SARS-CoV-2 virus, which causes COVID-19.

Dr. Ferreira told this news organization that very few of their patients became seriously ill or required hospitalization. Because their sample size was too small, he could not say if prior dengue made the COVID-19 infection worse.

The type of interaction between two infections like dengue and COVID-19 is called a “syndemic,” which the CDC defines as “synergistically interacting epidemics.” Dr. Ferreira hypothesized about some of the factors that might be at play but does not yet have enough data. For example, he speculated about a biologic basis, such as a link to autoimmunity or vasculitis from prior dengue, but “has no real data to either support or reject these things.”

Dr. Ferreira added that perhaps there are social factors that put certain people at higher risk of infection; for example, maybe some people are “more exposed to high viral loads.”

In Brazil’s first wave of COVID-19, Dr. Ferreira’s team calculated dengue seroconversion as about 10%; many cases of dengue were asymptomatic. Ferreira expects they will “have a very different clinical spectrum during the second wave,” with young people becoming much more ill from the P1 variant of concern.

Scott O’Neill, PhD, founder and director of the World Mosquito Program, told this news organization that, while he found the Brazil results intriguing, at present they are not sufficient to say that there’s a causal relationship between dengue and COVID-19. He expressed concern that the results seem counterintuitive and doubts there’s a biological or mechanistic cause. Instead, Dr. O’Neill wondered if “there could be something about social or economic conditions or living conditions” that might account for the correlation. For example, perhaps poverty increases exposure to both dengue and COVID-19.

Furthermore, Dr. O’Neill said in an interview that he suspects that, with the COVID-19 lockdowns, “You might expect to see more dengue.” This is because “most transmission occurs around the house, and so [with] having more people confined to houses, you might expect to see more dengue.” Such appears to be the case in Singapore.

In an article in the Journal of Infectious Diseases,  Jue Tao Lim and colleagues described increased dengue in Singapore during COVID-19. They noted that most employees in Singapore work in air-conditioned settings. With social distancing enforced to try to reduce COVID-19, people stayed at home. The mosquito that transmits dengue, Aedes aegypti, gathers in wet spots in residential areas and bites during the daytime. The authors hypothesized that the spike in dengue was because of this change in habits, which shifted people’s exposure.

The syndemic in Brazil is complicated, with malaria and multiple arboviral diseases (chikungunya, dengue, Zika) overlapping with COVID-19 in areas of high population density, poverty, and poor sanitation, among other social ills. Such overlapping factors make it harder to distinguish correlations from causations. Prospective longitudinal studies might be needed to provide definitive answers.

Dr. Ferreira and Dr. O’Neill have disclosed no relevant financial relationships.

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

In a surprising study from the Amazon rain forest, Brazilian scientists found that symptomatic COVID-19 infections were twice as likely to occur in people who had prior dengue.

The study, led by Marcelo Urbano Ferreira, MD, PhD, of the University of São Paulo Biomedical Sciences Institute, was conducted in Mâncio Lima, a town in the Amazon region of Brazil, and published May 6, 2021, in Clinical Infectious Diseases.

In the study, supported by the São Paulo Research Foundation, Ferreira’s team looked at sequential blood samples from 1,285 residents of Mâncio Lima.

An earlier study by Miguel Nicolelis, MD, PhD, and colleagues (published as a preprint) had analyzed data from the first COVID-19 wave in Brazil in 2020. It was an “ecological study” and examined dengue cases in different geographic regions of Brazil. That study concluded that dengue actually seemed to protect people from later developing COVID-19.

Dr. Ferreira anticipated finding a similar effect. Instead, he found the opposite effect. Although dengue did not increase the risk of subsequent COVID-19 infection, symptomatic COVID-19 became twice as likely in people with prior dengue. His study was longitudinal, following a single group of patients in Mâncio Lima over time.

Dr. Ferreira explained that ecological studies are inherently less accurate, as they look at populations in different places. “All the older cases are diagnosed on clinical grounds ... Because most infections are either asymptomatic or symptoms can be easily confused with” other diseases, many cases are missed. So, during the dengue transmission season, “We have some overestimation of the actual number of cases, and outside the transmission season, we have underestimation of the cases.”

On the apparent discrepancy with the earlier study by Dr. Nicolelis, Dr. Ferreira commented, “It’s a wonderful study because it’s something you can do quickly and test a hypothesis [in a] very, very timely [manner], but the problem is if your diagnosis is not very reliable.”

Dr. Ferreira had another advantage: Knowing from sequential blood samples that his patients were exposed to dengue within the past 5 years. He also could tell serologically when they became infected with the SARS-CoV-2 virus, which causes COVID-19.

Dr. Ferreira told this news organization that very few of their patients became seriously ill or required hospitalization. Because their sample size was too small, he could not say if prior dengue made the COVID-19 infection worse.

The type of interaction between two infections like dengue and COVID-19 is called a “syndemic,” which the CDC defines as “synergistically interacting epidemics.” Dr. Ferreira hypothesized about some of the factors that might be at play but does not yet have enough data. For example, he speculated about a biologic basis, such as a link to autoimmunity or vasculitis from prior dengue, but “has no real data to either support or reject these things.”

Dr. Ferreira added that perhaps there are social factors that put certain people at higher risk of infection; for example, maybe some people are “more exposed to high viral loads.”

In Brazil’s first wave of COVID-19, Dr. Ferreira’s team calculated dengue seroconversion as about 10%; many cases of dengue were asymptomatic. Ferreira expects they will “have a very different clinical spectrum during the second wave,” with young people becoming much more ill from the P1 variant of concern.

Scott O’Neill, PhD, founder and director of the World Mosquito Program, told this news organization that, while he found the Brazil results intriguing, at present they are not sufficient to say that there’s a causal relationship between dengue and COVID-19. He expressed concern that the results seem counterintuitive and doubts there’s a biological or mechanistic cause. Instead, Dr. O’Neill wondered if “there could be something about social or economic conditions or living conditions” that might account for the correlation. For example, perhaps poverty increases exposure to both dengue and COVID-19.

Furthermore, Dr. O’Neill said in an interview that he suspects that, with the COVID-19 lockdowns, “You might expect to see more dengue.” This is because “most transmission occurs around the house, and so [with] having more people confined to houses, you might expect to see more dengue.” Such appears to be the case in Singapore.

In an article in the Journal of Infectious Diseases,  Jue Tao Lim and colleagues described increased dengue in Singapore during COVID-19. They noted that most employees in Singapore work in air-conditioned settings. With social distancing enforced to try to reduce COVID-19, people stayed at home. The mosquito that transmits dengue, Aedes aegypti, gathers in wet spots in residential areas and bites during the daytime. The authors hypothesized that the spike in dengue was because of this change in habits, which shifted people’s exposure.

The syndemic in Brazil is complicated, with malaria and multiple arboviral diseases (chikungunya, dengue, Zika) overlapping with COVID-19 in areas of high population density, poverty, and poor sanitation, among other social ills. Such overlapping factors make it harder to distinguish correlations from causations. Prospective longitudinal studies might be needed to provide definitive answers.

Dr. Ferreira and Dr. O’Neill have disclosed no relevant financial relationships.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A new study shows disturbing evidence that malaria is becoming resistant to artemisinin, a drug critical for treatment in Africa. Although artemisinin resistance has long plagued the Mekong Delta, it is relatively new to Africa.
 

In a study published online April 14 in The Lancet Infectious Diseases, researchers found that the typical 3-day course of treatment did not totally eradicate Plasmodium falciparum, the parasite that causes malaria. A delayed clearance of the parasite was shown and found to be associated with a genetic mutation called Pfkelch13 R561H.

P. falciparum isolates with this mutation were found in 7.5% of infected children in one area of Rwanda. Further genomic studies showed that this mutation was locally acquired and did not emerge from Southeast Asia. This is well illustrated in a genomic tree published in Nature Medicine in August, 2020. That study reported data collected from adults from 2013 to 2015.

The delay in reporting the mutation was due, in part, to the burdensome process of whole-genome sequencing and transfection studies, Pascal Ringwald, MD, PhD, coordinator of the Global Malaria Programme at WHO, and coauthor of the Nature Medicine study, said in an interview. In transfection studies, the mutation is inserted into parasites and the resultant effect is observed.

Aline Uwimana, MD, of Rwanda Biomedical Centre. is the lead author on both studies.

Meera Venkatesan, PhD, chief of the Case Management, Monitoring and Evaluation Branch, President’s Malaria Initiative, USAID, noted that the Lancet Infectious Diseases study was a therapeutic efficacy study (TES) on samples from children from 2018. In an interview, Dr. Venkatesan explained that the study is noteworthy because it demonstrated the clinical significance of this mutation with delayed parasite clearance. She did note that although there was a lag in publication of the initial reports of artemisinin resistance mutations, that information – and its implications – was promptly shared with the global malaria research community, as are other findings of public health importance.

Although most of the children got better, this “partial resistance” emerged while patients were taking artemether–lumefantrine. This is a type of artemisinin-based combination therapy (ACT) with two drugs intended to stall the emergence of resistance.

The delayed clearance will be a problem because it can contribute to the selection and spread of the partially resistant malaria parasite.

To slow the spread of artemisinin resistance, Dr. Ringwald emphasized the need to add a gametocidal drug to block the transmission to humans. “You give a single dose of primaquine, which will help stop the spread,” he said in an interview. “Continuing surveillance and mapping. These are priorities.”

So are following national guidelines and banning the use of artemisinin monotherapy. Dr. Ringwald stressed two additional priorities: the need for accurate diagnosis of malaria, and the need to use “good-quality drugs and to avoid substandard or fake medicines” by not purchasing drugs on the street.

Unscrupulous individuals are also selling artemisia preparations to treat or prevent COVID-19, when it has no such activity. Similarly, artemisia teas are sold as herbal remedies and nutraceuticals.

Philippe Guérin, MD, director of the Worldwide Antimalarial Resistance Network (WWARN), listed the same recommendations, focusing a bit more on accurate detection of malaria and treatment with a multidrug regimen plus primaquine. You need “to have different first-line treatment (different ACTs) to avoid drug pressure” and resistance to the partner drug emerging, he said in an interview.

Such multiple first-line treatments rely on artemisinin in combination with various drugs, but this can cause some logistical challenges. Resistance is so problematic that the MORU (Mahidol Oxford Tropical Medicine Research Unit) Tropical Health Network in Bangkok is studying triple drug combinations, adding amodiaquine or mefloquine to an artemisinin-based combination.

Dr. Guérin emphasized two other problems regarding the monitoring of malaria resistance in Africa (although not specifically Rwanda). One is the inability to do adequate surveillance in active conflict zones and areas of instability. The other is that COVID-19 is causing resources to be taken away from malaria and redirected to the more immediate crisis. By having to focus on the immediate viral pandemic, public-health authorities are missing the chance to address other critically important infectious diseases with large burdens – specifically malaria, TB, and HIV – which might have greater impacts on future generations.

Dr. Guérin noted that although we now have solid evidence of artemisinin resistance in Rwanda, and isolated cases in other African countries, we have little idea of the magnitude of the problem because testing is not widespread throughout parts of the continent.

What would widespread P. falciparum malaria resistance in Africa mean? Children are the most vulnerable to malaria, and account for two-thirds of the deaths. One study suggests there could be 78 million more cases over a 5-year period, along with far more deaths. Hence, there is a heightened urgency to implement the outlined strategies to prevent a looming catastrophe.

The authors have disclosed no relevant financial relationships.

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

A new study shows disturbing evidence that malaria is becoming resistant to artemisinin, a drug critical for treatment in Africa. Although artemisinin resistance has long plagued the Mekong Delta, it is relatively new to Africa.
 

In a study published online April 14 in The Lancet Infectious Diseases, researchers found that the typical 3-day course of treatment did not totally eradicate Plasmodium falciparum, the parasite that causes malaria. A delayed clearance of the parasite was shown and found to be associated with a genetic mutation called Pfkelch13 R561H.

P. falciparum isolates with this mutation were found in 7.5% of infected children in one area of Rwanda. Further genomic studies showed that this mutation was locally acquired and did not emerge from Southeast Asia. This is well illustrated in a genomic tree published in Nature Medicine in August, 2020. That study reported data collected from adults from 2013 to 2015.

The delay in reporting the mutation was due, in part, to the burdensome process of whole-genome sequencing and transfection studies, Pascal Ringwald, MD, PhD, coordinator of the Global Malaria Programme at WHO, and coauthor of the Nature Medicine study, said in an interview. In transfection studies, the mutation is inserted into parasites and the resultant effect is observed.

Aline Uwimana, MD, of Rwanda Biomedical Centre. is the lead author on both studies.

Meera Venkatesan, PhD, chief of the Case Management, Monitoring and Evaluation Branch, President’s Malaria Initiative, USAID, noted that the Lancet Infectious Diseases study was a therapeutic efficacy study (TES) on samples from children from 2018. In an interview, Dr. Venkatesan explained that the study is noteworthy because it demonstrated the clinical significance of this mutation with delayed parasite clearance. She did note that although there was a lag in publication of the initial reports of artemisinin resistance mutations, that information – and its implications – was promptly shared with the global malaria research community, as are other findings of public health importance.

Although most of the children got better, this “partial resistance” emerged while patients were taking artemether–lumefantrine. This is a type of artemisinin-based combination therapy (ACT) with two drugs intended to stall the emergence of resistance.

The delayed clearance will be a problem because it can contribute to the selection and spread of the partially resistant malaria parasite.

To slow the spread of artemisinin resistance, Dr. Ringwald emphasized the need to add a gametocidal drug to block the transmission to humans. “You give a single dose of primaquine, which will help stop the spread,” he said in an interview. “Continuing surveillance and mapping. These are priorities.”

So are following national guidelines and banning the use of artemisinin monotherapy. Dr. Ringwald stressed two additional priorities: the need for accurate diagnosis of malaria, and the need to use “good-quality drugs and to avoid substandard or fake medicines” by not purchasing drugs on the street.

Unscrupulous individuals are also selling artemisia preparations to treat or prevent COVID-19, when it has no such activity. Similarly, artemisia teas are sold as herbal remedies and nutraceuticals.

Philippe Guérin, MD, director of the Worldwide Antimalarial Resistance Network (WWARN), listed the same recommendations, focusing a bit more on accurate detection of malaria and treatment with a multidrug regimen plus primaquine. You need “to have different first-line treatment (different ACTs) to avoid drug pressure” and resistance to the partner drug emerging, he said in an interview.

Such multiple first-line treatments rely on artemisinin in combination with various drugs, but this can cause some logistical challenges. Resistance is so problematic that the MORU (Mahidol Oxford Tropical Medicine Research Unit) Tropical Health Network in Bangkok is studying triple drug combinations, adding amodiaquine or mefloquine to an artemisinin-based combination.

Dr. Guérin emphasized two other problems regarding the monitoring of malaria resistance in Africa (although not specifically Rwanda). One is the inability to do adequate surveillance in active conflict zones and areas of instability. The other is that COVID-19 is causing resources to be taken away from malaria and redirected to the more immediate crisis. By having to focus on the immediate viral pandemic, public-health authorities are missing the chance to address other critically important infectious diseases with large burdens – specifically malaria, TB, and HIV – which might have greater impacts on future generations.

Dr. Guérin noted that although we now have solid evidence of artemisinin resistance in Rwanda, and isolated cases in other African countries, we have little idea of the magnitude of the problem because testing is not widespread throughout parts of the continent.

What would widespread P. falciparum malaria resistance in Africa mean? Children are the most vulnerable to malaria, and account for two-thirds of the deaths. One study suggests there could be 78 million more cases over a 5-year period, along with far more deaths. Hence, there is a heightened urgency to implement the outlined strategies to prevent a looming catastrophe.

The authors have disclosed no relevant financial relationships.

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

A new study shows disturbing evidence that malaria is becoming resistant to artemisinin, a drug critical for treatment in Africa. Although artemisinin resistance has long plagued the Mekong Delta, it is relatively new to Africa.
 

In a study published online April 14 in The Lancet Infectious Diseases, researchers found that the typical 3-day course of treatment did not totally eradicate Plasmodium falciparum, the parasite that causes malaria. A delayed clearance of the parasite was shown and found to be associated with a genetic mutation called Pfkelch13 R561H.

P. falciparum isolates with this mutation were found in 7.5% of infected children in one area of Rwanda. Further genomic studies showed that this mutation was locally acquired and did not emerge from Southeast Asia. This is well illustrated in a genomic tree published in Nature Medicine in August, 2020. That study reported data collected from adults from 2013 to 2015.

The delay in reporting the mutation was due, in part, to the burdensome process of whole-genome sequencing and transfection studies, Pascal Ringwald, MD, PhD, coordinator of the Global Malaria Programme at WHO, and coauthor of the Nature Medicine study, said in an interview. In transfection studies, the mutation is inserted into parasites and the resultant effect is observed.

Aline Uwimana, MD, of Rwanda Biomedical Centre. is the lead author on both studies.

Meera Venkatesan, PhD, chief of the Case Management, Monitoring and Evaluation Branch, President’s Malaria Initiative, USAID, noted that the Lancet Infectious Diseases study was a therapeutic efficacy study (TES) on samples from children from 2018. In an interview, Dr. Venkatesan explained that the study is noteworthy because it demonstrated the clinical significance of this mutation with delayed parasite clearance. She did note that although there was a lag in publication of the initial reports of artemisinin resistance mutations, that information – and its implications – was promptly shared with the global malaria research community, as are other findings of public health importance.

Although most of the children got better, this “partial resistance” emerged while patients were taking artemether–lumefantrine. This is a type of artemisinin-based combination therapy (ACT) with two drugs intended to stall the emergence of resistance.

The delayed clearance will be a problem because it can contribute to the selection and spread of the partially resistant malaria parasite.

To slow the spread of artemisinin resistance, Dr. Ringwald emphasized the need to add a gametocidal drug to block the transmission to humans. “You give a single dose of primaquine, which will help stop the spread,” he said in an interview. “Continuing surveillance and mapping. These are priorities.”

So are following national guidelines and banning the use of artemisinin monotherapy. Dr. Ringwald stressed two additional priorities: the need for accurate diagnosis of malaria, and the need to use “good-quality drugs and to avoid substandard or fake medicines” by not purchasing drugs on the street.

Unscrupulous individuals are also selling artemisia preparations to treat or prevent COVID-19, when it has no such activity. Similarly, artemisia teas are sold as herbal remedies and nutraceuticals.

Philippe Guérin, MD, director of the Worldwide Antimalarial Resistance Network (WWARN), listed the same recommendations, focusing a bit more on accurate detection of malaria and treatment with a multidrug regimen plus primaquine. You need “to have different first-line treatment (different ACTs) to avoid drug pressure” and resistance to the partner drug emerging, he said in an interview.

Such multiple first-line treatments rely on artemisinin in combination with various drugs, but this can cause some logistical challenges. Resistance is so problematic that the MORU (Mahidol Oxford Tropical Medicine Research Unit) Tropical Health Network in Bangkok is studying triple drug combinations, adding amodiaquine or mefloquine to an artemisinin-based combination.

Dr. Guérin emphasized two other problems regarding the monitoring of malaria resistance in Africa (although not specifically Rwanda). One is the inability to do adequate surveillance in active conflict zones and areas of instability. The other is that COVID-19 is causing resources to be taken away from malaria and redirected to the more immediate crisis. By having to focus on the immediate viral pandemic, public-health authorities are missing the chance to address other critically important infectious diseases with large burdens – specifically malaria, TB, and HIV – which might have greater impacts on future generations.

Dr. Guérin noted that although we now have solid evidence of artemisinin resistance in Rwanda, and isolated cases in other African countries, we have little idea of the magnitude of the problem because testing is not widespread throughout parts of the continent.

What would widespread P. falciparum malaria resistance in Africa mean? Children are the most vulnerable to malaria, and account for two-thirds of the deaths. One study suggests there could be 78 million more cases over a 5-year period, along with far more deaths. Hence, there is a heightened urgency to implement the outlined strategies to prevent a looming catastrophe.

The authors have disclosed no relevant financial relationships.

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.

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.