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In 2020, fecal (stool) testing was recommended for diagnosing Mycobacterium tuberculosis complex (MTBC) infection in children by using the Cepheid Xpert MTB/RIF assay; since then, countries have begun implementing stool-based testing, often as part of a comprehensive strategy to enhance TB case finding among children. On the basis of an experience-sharing workshop in November 2023, we determined insights of 9 early-adopter countries. Across those countries, 71,757 children underwent stool testing over a combined period of 121 months, October 2020-September 2023. A total of 2,892 children were positive for MTBC, and rifampin resistance was confirmed for 43 stool samples. The overall yield of MTBC detection across the countries was 4.1% (range 1.1%-17.3%). Stool collection for Xpert testing was considered noninvasive and as easy as sputum testing. Stool-based testing can be integrated into peripheral healthcare levels as a routine test to increase bacteriologic confirmation among children with presumptive TB.

Individuals exposed to a person with infectious multidrug-resistant or rifampicin-resistant (MDR-RR) tuberculosis are at risk of developing tuberculosis disease. Historically, insufficient empirical evidence for preventive treatment in this group has permitted inadequate guidance for clinical decision making. However, several high-quality studies have been published detailing preventive treatment options for these contacts at high risk. In this Review, we discuss the management of individuals exposed to patients with infectious MDR-RR tuberculosis. We pay particular attention to the entire spectrum of clinical care for this population, including baseline assessment, possible preventive treatments, follow-up, and shared decision making. We discuss the available evidence, the rationales for different management strategies, and the interactions with (and implications of) secondary comorbidities such as HIV or malnutrition.

Like many countries, Ukraine faces challenges with diagnosing tuberculosis (TB) in children due to the paucibacillary nature of the disease and difficulty obtaining respiratory samples. To improve diagnostic efficiency, stool testing is being integrated into routine pediatric TB services. This started with a pilot introduction at 12 regional TB facilities, where stool was collected for children with a preliminary diagnosis of TB, based on clinical and/or radiological or laboratory findings, in addition to routine testing. For 168 children, a stool test was conducted between November 2021 and September 2022, with samples submitted in all 12 pilot regions. For 132 children, other samples were available in addition to stool. Mycobacterium tuberculosis (MTB) was bacteriologically confirmed in 37 children (in stool for 18 children). For 7 of the 18 children with MTB in stool, stool was the only sample in which MTB was detected. Rifampicin resistance was detected in seven children (in stool for three). This noninvasive TB diagnostic sample is especially beneficial for young children who cannot produce sputum. Early detection of TB and its drug-resistant strains in children will allow medical workers to provide safer and more effective treatment and save more lives. Based on the pilot implementation, Ukraine's national TB program began implementing stool testing throughout the country.

Globally, there is substantial concern regarding the challenges of treating complex drug resistance patterns in multidrug resistant tuberculosis cases. Utilising data from three different settings (Estonia, Latvia, Romania) we sought to contrast drug susceptibility profiles for multidrug resistant tuberculosis cases, highlight the difficulties in designing universal regimen, and inform future regimen selection. Demographic and microbiological surveillance data for multidrug resistant tuberculosis cases from 2004-13 were analysed. High levels of additional resistance to currently recommended second line drugs were seen in all settings, with extensive variability between countries. Accurate drug susceptibility testing and drug susceptibility testing data are vital to inform the development of comprehensive, flexible, multidrug resistant tuberculosis guidance.

In 2020, WHO guidelines prioritised the use of a standard fully oral short treatment regimen (STR) consisting of bedaquiline, levofloxacin or moxifloxacin, ethionamide, ethambutol, high-dose isoniazid, pyrazinamide, and clofazimine for the management of rifampicin-resistant tuberculosis. A high prevalence of resistance to constituent drugs precluded its widespread use by countries in the WHO European region. We evaluated three 9-month fully oral modified STRs (mSTRs) in which ethionamide, ethambutol, isoniazid, and pyrazinamide were replaced by linezolid, cycloserine, or delamanid (or a combination). This multicountry, prospective, single-arm, cohort study examined the effectiveness and safety of mSTRs for fluoroquinolone-susceptible, rifampicin-resistant pulmonary tuberculosis in 13 countries in the WHO European region during 2020–23. We enrolled adults and children of all ages with bacteriologically confirmed rifampicin-resistant, fluoroquinolone-susceptible pulmonary tuberculosis, and children (aged 0–18 years) with clinically diagnosed disease and a confirmed contact with rifampicin-resistant, fluoroquinolone-susceptible tuberculosis. Participants aged 6 years or older received one of two regimens: bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine; or bedaquiline, linezolid, levofloxacin, clofazimine, and delamanid. Children younger than 6 years received delamanid, linezolid, levofloxacin, and clofazimine. Participants were followed up for 12 months after successful treatment completion to detect recurrence and death. The primary outcome was the cumulative probability of not having an unsuccessful study outcome (defined as treatment failure, on-treatment loss to follow-up, death, or recurrence) before 22 months of study follow-up. The primary safety outcome was the incidence of each adverse event of interest (peripheral neuropathy, optic neuritis, myelosuppression, hepatitis, prolonged QT interval, hypokalaemia, and acute kidney injury) of grade 3 or higher severity during the treatment course. Between Aug 28, 2020 and May 26, 2021, 7272 patients were screened and 2636 were included in the treatment cohort. 1966 (74·6%) were male, 670 (25·4%) were female, and median age was 43 years (IQR 33–53). Treatment success was recorded for 2181 (82·7%) participants. The cumulative probability of not having an unsuccessful study outcome 22 months after treatment initiation was 79% (95% CI 78–81). Increasing age (adjusted hazard ratio 2·61 [95% CI 1·70–4·04] for people aged >64 years vs 35–44 years), HIV-positive status (1·53 [1·16–2·01]), presence of bilateral cavities (1·68 [1·29–2·19]), smoking history (1·34 [1·05–1·71]), baseline anaemia (1·46 [1·15–1·86]), unemployment (1·37 [1·04–1·80]), elevated baseline liver enzymes (1·40 [1·13–1·73]), and excessive alcohol use (1·47 [1·14–1·89]) were positively associated with unsuccessful study outcomes. In the safety cohort of 2813 participants who received at least one dose, 301 adverse events of interest were recorded in 252 (9·0%) participants with the most frequent being myelosuppression (139 [4·9%] participants, 157 [52·2%] events). The high treatment success and good safety results indicate considerable potential for the use of mSTRs in programmatic conditions, especially for individuals not eligible for the current WHO-recommended 6-month regimen and in settings with a need for alternative options. The Global Fund to Fight AIDS, Tuberculosis and Malaria; United States Agency for International Development; Government of Germany; and WHO. For the Russian translation of the abstract see Supplementary Materials section.

Background. Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. Methods. To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. Results. In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16–.47) for XDR tuberculosis, 0.28 (.17–.45) for FQ, and 0.15 (.06–.39) to 0.60 (.34–1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07–.62) for acquired XDR tuberculosis and 0.23 (.09–.59) for acquired FQ resistance. Conclusions. Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards.