August 11, 2022 Stewardship/Resistance Analysis

Study: Treatment of limited and costly drug-resistant tuberculosis in Europe

A survey of tuberculosis (TB) treatment centers in Europe revealed that the availability of drug susceptibility testing (DST) for new and reused anti-TB drugs in Europe is very limited, that drugs and treatment regimens for drug-resistant tuberculosis are limited and treatment costs for anti-tuberculosis drugs resistant tuberculosis are very high, according to a study published this week in Clinical microbiology and infection.

For the study, a team of researchers from the Tuberculosis Network European Trials Group (TBNET) surveyed 43 tuberculosis treatment centers in 40 countries in the European region of the World Health Organization (WHO), collecting data on DST, availability of TB drugs and cost. They focused on treatment regimens for drug-susceptible tuberculosis (DS-TB), multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB), extensively drug-resistant tuberculosis (XDR-TB) and pre-XDR-TB.

For WHO Group A drugs (levofloxacin/moxifloxacin, bedaquiline and linezolid), the frequency of countries with phenotypic DSTs was as follows: 30/40 (75%) for levofloxacin, 33/40 (82%) for moxifloxacin, 19/40 (48%) for bedaquiline and 29/40 (72%) for linezolid. Overall, 36/43 (84%) and 24/43 (56%) countries had access to bedaquiline and delamanid, while only 6/43 (14%) had access to rifapentine. Treatment of patients with extensively drug-resistant tuberculosis with a regimen including carbapenem was only available in 17/43 (40%) countries.

The median cost of regimens for DS-TB, MDR/RR-TB (shorter regimen, including bedaquiline for 6 months) and XDR-TB (including bedaquiline, delamanid and a carbapenem) was €44 (45. 50 US$), 764 € (789 US$) and 8,709 € (9,004 US$) respectively in middle-income countries, and 280 € (289 US$), 29,765 € (30,733 US$) and 217 €591 (US$224,963) in high-income countries.

The study authors note that the lack of DST for drugs like bedaquiline and linezolid will result in an inability to detect patients with extensively drug-resistant tuberculosis who have the worst prognosis, while the high cost of shorter treatment for multidrug-resistant/RR-TB have enormous financial implications for countries with a high burden of drug-resistant tuberculosis. They say the data provided by the study underscores the need for “urgent action”.

“Strong political support and coordinated action from supranational institutions, countries and their TB programs, nongovernmental organizations and civil society are needed to ensure access to the best care for patients affected by TB “, they wrote.
August 9 Clin Microbiol Infect study

The TB vaccine is only effective in children under 5 years old

The bacille Calmette-Guérin (BCG) vaccine, when given at birth, is effective in preventing tuberculosis in children under 5 years of age, but ineffective in adolescents and adults, researchers reported in Lancet Global Health.

To estimate the effectiveness of the BCG vaccine, which is about 100 years old and one of the most widely used vaccines in the world, a team led by researchers from the Boston University School of Public Health analyzed individual data from 26 studies. longitudinal studies that included more than 68,000 participants exposed to TB from 1998 to 2018. The primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) TB. baseline) in exposed contacts. Secondary endpoints were pulmonary tuberculosis, extrapulmonary tuberculosis and mortality.

Among 68,552 participants, 1,309 (2.6%) of 49,686 BCG-vaccinated participants developed tuberculosis, compared to 473 (2.5%) of 18,866 unvaccinated participants. The overall effectiveness of BCG vaccination against all forms of tuberculosis was 18% (adjusted odds ratio [aOR]0.82: 95% confidence interval [CI], 0.74 to 0.91). When stratified by age, BCG vaccination only significantly protected against all forms of tuberculosis in children under 5 years of age (aOR, 0.63; 95% CI, 0.49 to 0.81).

BCG vaccination significantly protected against pulmonary tuberculosis in all participants (916 [2.2%] in 41,119 vaccinated participants versus 334 [2.1%] in 16,161 unvaccinated participants; aOR, 0.81; 95% CI, 0.70 to 0.94) but not against extrapulmonary tuberculosis (106 [0.3%] in 40,318 vaccinated participants versus 38 [0.2%] in 15,865 unvaccinated participants; aOR, 0.96; 95% CI, 0.65 to 1.41). In the four studies with mortality data, BCG vaccination was significantly protective against death (aOR, 0.25; 95% CI, 0.13 to 0.49).

The authors say that while the results confirm the value of BCG vaccination in children in settings where TB is endemic, they also underscore the need for new TB vaccines.

“These results suggest that infant BCG vaccination, although important for young children at high risk of tuberculosis, does not prevent adult-type cavitary tuberculosis and is therefore insufficient to prevent the tuberculosis epidemic, providing a further evidence that new vaccines are urgently needed,” the study authors concluded. They also suggest that until new TB vaccines are developed, children over 10 and adults should be given a BCG booster.
September 2022 Lancet Glob Health study

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