The Stop TB Partnership's Global Drug Facility (GDF) has cut the price of a key component of multidrug-resistant tuberculosis (MDR-TB) treatment regimens by 25%.

The reduction, announced last week, cuts the price of pretomanid produced by generic drugmaker Lupin to $169 per treatment course when purchased through the GDF, down from $224 in October 2024. Developed by the TB Alliance, pretomanid is part of two shorter, all-oral treatment regimens recommended by the World Health Organization for treating MDR-TB—BPaL (bedaquiline, pretomanid, and linezolid) and BPaLM (bedaquiline, pretomanid, linezolid, and moxifloxacin).

The Stop TB Partnership, which created the GDF in 2001 to promote equitable access to TB drugs and diagnostics, says the price reduction will save its clients upwards of $3 million per year. In addition, it establishes a reference price that high-burden TB countries can use in price negotiations when they are procuring pretomanid directly from suppliers.

Combined with recent price reductions for bedaquiline, linezolid, and moxifloxacin, the price of a 6-month BPaLM treatment course has now been reduced by 47%, an amount the Stop TB Partnership says will save national TB programs roughly $37 million a year.

"This is a remarkable feat that couldn’t have come at a better time as future TB funding hangs in the balance," Stop TB Partnership Executive Director Lucica Ditiu, MD, said in a press release.

An estimated 176,000 people globally are treated for MDR-TB each year.

Analysis of data from a randomized clinical trial in Kenya suggests that the presence of a macrolide resistance gene in the gut microbiome may reduce the efficacy of empiric azithromycin in children discharged from the hospital, researchers reported yesterday in the Journal of Infectious Diseases.

The Toto Bora trial (June 2016 to November 2019) tested whether a 5-day course of azithromycin reduced the risk of re-hospitalization or death in the 6 months following hospitalization in Kenyan children ages 5 and under compared with placebo. Despite evidence from other trials suggesting azithromycin may reduce childhood mortality in high-mortality settings in sub-Saharan Africa, the trial found no evidence of benefit. 

Hypothesizing that the results may be tied to the presence of macrolide resistance genes in the gut microbiome, a team of researchers from Kenya and the United States analyzed DNA from fecal samples of children enrolled in the trial. Their aim was to determine whether the presence of macrolide resistance genes was associated with increased risk of re-hospitalization or death.

Gene could explain differences in treatment effect

Among 1,394 children enrolled in the trial (699 in the azithromycin group and 696 in the placebo group), 94.7% had at least one macrolide resistance–conferring gene detected, and macrolide-resistance gene carriage distribution was equal across both arms. The Mef(A) gene was found in 23.7% of children and was the only macrolide-resistance gene that modified azithromycin's effect on re-hospitalization or death. 

In children without the Mef(A) gene, azithromycin reduced the hazard of rehospitalization or death by a third (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.45 to 0.99). But among children with the Mef(A) gene, there was a nearly three-fold higher risk in those randomized to azithromycin (HR, 2.72; 95% CI, 1.21 to 6.09). No major differences were observed in azithromycin's effect across other macrolide-resistance genes.

"Our study is the first to systematically evaluate the potentially modifiable effect of macrolide resistance gene carriage on the efficacy of azithromycin for post-hospital re-hospitalization and mortality," the study authors wrote. "If confirmed, this finding could explain sources of variability in treatment effects in empiric azithromycin trials targeting children at high risk of mortality."

Testing of more than 36,000 deer has detected 243 cases of chronic wasting disease (CWD) in 35 Missouri counties—including 7 previously unaffected areas, the Missouri Department of Conservation (MDC) announced yesterday.

Counties reporting their first CWD cases are Audrain, Callaway, Lewis, Marion, Miller, Morgan, and Texas, all of which abut CWD-positive areas. The first four counties are in northeastern Missouri, while Miller and Morgan counties are centrally located, and Texas county is in the central lower third of the state.

• Malawi on April 17 declared an mpox outbreak after detecting its first three confirmed cases, the World Health Organization (WHO) Malawi office said today on X. With support from the United Kingdom and the UN Central Emergency Response Fund, response teams from the WHO and Malawi’s health ministry are setting up an emergency treatment center at Kamuzu Hospital. The cases in Malawi make it the 23^rd country in Africa to report mpox cases. On its Facebook page, Malawi’s health ministry said cases were reported from Lilongwe district in the central part of the country, where the first suspected case was reported from Bwaila Hospital on March 20 and another case reported on April 9. Samples tested positive for mpox at Malawi’s National Reference Laboratory on April 16. 
• The US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) today reported four more H5N1 avian flu detections in dairy cattle, three from Idaho and one from California, raising the national total since March 2024 to 1,025 detections from 17 states. Idaho has now reported 65 detections, making it the second most affected state behind California, which has reported 765. The Idaho Department of Agriculture says 25 herds are currently quarantined, with 16 in Gooding County, 7 in Jerome County, and 2 in Twin Falls County. In poultry developments, APHIS over the past few days has reported one more H5N1 detection, which involves a live bird market in New York’s Queens County.