Explore the vast range of titles available.

Thierry Wirth, Philip Supply, Stefan Niemann and colleagues analyze 4,987 Mycobacterium tuberculosis strains of the Beijing lineage isolated from 99 countries. They report whole-genome sequencing of 110 representative strains, characterize global population structure and reconstruct the evolutionary history of this lineage. Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.

Proper treatment of tuberculosis requires a combination of drugs to which the causative organism is susceptible. In this report, genotypic assessment of antimicrobial susceptibility of more than 10,000 M. tuberculosis isolates was correlated with phenotypic test results.

Rapid diagnosis of drug-resistant tuberculosis is important in determining proper management. This letter reports on limitations of the Xpert MTB/RIF assay in determining rifampin resistance in tuberculosis isolates in Swaziland. To the Editor: Tuberculosis is a major global health problem that has worsened with the increasing emergence of Mycobacterium tuberculosis (MTB) complex strains that are resistant to rifampin (RIF) and isoniazid. As recommended by the World Health Organization (WHO), the timely detection of drug resistance with the use of rapid molecular diagnostic tests, such as the Xpert MTB/RIF assay (Cepheid), is essential for appropriate treatment of patients with tuberculosis and for limiting the further spread of multidrug-resistant disease. 1 , 2 We used 24-loci mycobacterial interspersed repetitive unit–variable number tandem repeat (MIRU-VNTR) analysis and spoligotyping to perform classic genotypic analysis of MTB . . .

Current guidelines recommend the use of the lateral flow urine lipoarabinomannan assay (LAM) in HIV-positive, ambulatory patients with signs and symptoms of tuberculosis (TB) only if they are seriously ill or have CD4 count ≤ 100 cells/μl. We assessed the diagnostic yield of including LAM in TB diagnostic algorithms in HIV-positive, ambulatory patients with CD4 < 200 cells/μl, as well as the risk of mortality in LAM-positive patients who were not diagnosed using other diagnostic tools and not treated for TB. We conducted a prospective observational study including HIV-positive adult patients with signs and symptoms of TB and CD4 < 200 cells/μl attending 6 health facilities in Malawi and Mozambique. Patients were included consecutively from 18 September 2015 to 27 October 2016 in Malawi and from 3 December 2014 to 22 August 2016 in Mozambique. All patients had a clinical exam and LAM, chest X-ray, sputum microscopy, and Xpert MTB/RIF assay (Xpert) requested. Culture in sputum was done for a subset of patients. The diagnostic yield was defined as the proportion of patients with a positive assay result among those with laboratory-confirmed TB. For the 456 patients included in the study, the median age was 36 years (IQR 31-43) and the median CD4 count was 50 cells/μl (IQR 21-108). Forty-five percent (205/456) of the patients had laboratory-confirmed TB. The diagnostic yields of LAM, microscopy, and Xpert were 82.4% (169/205), 33.7% (69/205), and 40.0% (84/205), respectively. In total, 50.2% (103/205) of the patients with laboratory-confirmed TB were diagnosed only through LAM. Overall, the use of LAM in diagnostic algorithms increased the yield of algorithms with microscopy and with Xpert by 38.0% (78/205) and 34.6% (71/205), respectively, and, specifically among patients with CD4 100-199 cells/μl, by 27.5% (14/51) and 29.4% (15/51), respectively. LAM-positive patients not diagnosed through other tools and not treated for TB had a significantly higher risk of mortality than LAM-positive patients who received treatment (adjusted risk ratio 2.57, 95% CI 1.27-5.19, p = 0.009). Although the TB diagnostic conditions in the study sites were similar to those in other resource-limited settings, the added value of LAM may depend on the availability of microscopy or Xpert results. LAM has diagnostic value for identifying TB in HIV-positive patients with signs and symptoms of TB and advanced immunodeficiency, including those with a CD4 count of 100-199 cells/μl. In this study, the use of LAM enabled the diagnosis of TB in half of the patients with confirmed TB disease; without LAM, these patients would have been missed. The rapid identification and treatment of TB enabled by LAM may decrease overall mortality risk for these patients.

The emergence of resistance to anti-tuberculosis (DR-TB) drugs and the HIV epidemic represent a serious threat for reducing the global burden of TB. Although data on HIV-negative DR-TB treatment outcomes are well published, few data on DR-TB outcomes among HIV co-infected people is available despite the great public health importance. We retrospectively reported and compared the DR-TB treatment outcomes of HIV-positive and HIV-negative patients treated with an individualized regimen based on WHO guidelines in seven countries: Abkhazia, Armenia, Colombia, Kenya, Kyrgyzstan, Swaziland and Uzbekistan. Of the 1,369 patients started DRTB treatment, 809 (59.1%) were multi-drug resistant (MDR-TB) and 418 (30.5%) were HIV-positive. HIV-positive patients were mainly from African countries (90.1%) while HIV-negative originated from Former Soviet Union (FSU) countries. Despite a higher case fatality rate (19.0% vs 9.4%), HIV-positive MDR-TB patients had a 10% higher success rate than HIV-negative patients (64.0% vs 53.2%, p = 0.007). No difference in treatment success was found among polydrug-resistant (PDR-TB) patients. Overall, lost to follow-up rate was much higher among HIV-negative (22.0% vs. 8.4%). Older age and not receiving ART were the only factors associated with unfavorable treatment outcome among HIV-positive patients. As already known for HIV-negative patients, success rate of DR-TB HIV-positive patients remains low and requires more effective DR-TB regimen using new drugs also suitable to HIV-infected patients on ART. The study also confirms the need of ART introduction in HIV co-infected patients.

Two new rotavirus vaccines have recently been licensed in many countries. However, their efficacy has only been shown against certain serotypes commonly circulating in Europe, North America, and Latin America, but thought to be globally important. To assess the potential impact of these vaccines in sub-Saharan Africa, where rotavirus mortality is high, knowledge of prevalent types is essential because an effective rotavirus vaccine is needed to protect against prevailing serotypes in the community. We did two systematic reviews and two meta-analyses of the most recent published data on the burden of rotavirus disease in children aged under 5 years and rotavirus serotypes circulating in countries in sub-Saharan Africa. Eligible studies were selected from PubMed/Medline, Cochrane Library, EmBase, LILACS, Academic Search Premier, Biological Abstracts, ISI Web of Science, and the African Index Medicus. Depending on the heterogeneity, DerSimonian–Laird random-effects or fixed-effects models were used for meta-analyses. Geographical variability in rotavirus burden within countries in sub-Saharan Africa is substantial, and most countries lack information on rotavirus epidemiology. We estimated that annual mortality for this region was 243·3 (95% CI 187·6–301·7) deaths per 100 000 under 5 years (ie, a total of 300 000 children die of rotavirus infection in this region each year). The most common G type detected was G1 (34·9%), followed by G2 (9·1%), and G3 (8·6%). The most common P types detected were P[8] (35·5%) and P[6] (27·5%). Accurate information should be collected from surveillance based on standardised methods in these countries to obtain comparable data on the burden of disease and the circulating strains to assess the potential impact of vaccine introduction.

Background. The success of the current treatment regimen for multidrug-resistant (MDR) tuberculosis is poor partly owing to a high default rate. Many studies have explored predictors of poor outcomes, but very few have assessed the effects of treatment interruptions on treatment outcomes for MDR tuberculosis. Methods. We conducted a retrospective analysis among patients with MDR tuberculosis enrolled in 2 MDR tuberculosis programs using regimens recommended by the World Health Organization under directly observed therapy. Treatment outcomes were defined as successful if the patient was cured or completed treatment and unsuccessful if the patient died or defaulted from treatment or if treatment failed. The effect of patterns of interruptions on treatment outcomes was assessed through multivariate logistic regression. Results. A total of 393 patients with MDR tuberculosis were included in the study; 171 (43.5%) had a successful outcome, and 222 (56.5%) an unsuccessful outcome: 39 (9.9%) died, 56 (14.3%) had failed treatment, and 127 (32.3%) defaulted from treatment. In multivariate analysis, long interruptions (≥3 days) (adjusted odds ratio, 3.87; 95% confidence interval, 1.66-8.98) and short gaps (<10 days) between interruptions (3.94; 1.76-8.81) were independently associated with an unsuccessful treatment outcome. Discussion. This study shows that in a directly observed therapy-based MDR tuberculosis program, treatment interruptions at short intervals of ≥3 days directly affect treatment outcome.

Colombia has been seriously affected by an internal armed conflict for more than 40 years affecting mainly the civilian population, who is forced to displace, suffers kidnapping, extortion, threats and assassinations. Between 2005 and 2008, Médecins Sans Frontières-France provided psychological care and treatment in the region of Tolima, a strategic place in the armed conflict. The mental health program was based on a short-term multi-faceted treatment developed according to the psychological and psychosomatic needs of the population. Here we describe the population attending during 2005-2008, in both urban and rural settings, as well as the psychological treatment provided during this period and its outcomes. We observed differences between the urban and rural settings in the traumatic events reported, the clinical expression of the disorders, the disorders diagnosed, and their severity. Although the duration of the treatment was limited due to security reasons and access difficulties, patient condition at last visit improved in most of the patients. These descriptive results suggest that further studies should be conducted to examine the role of short-term psychotherapy, adapted specifically to the context, can be a useful tool to provide psychological care to population affected by an armed conflict.

ObjectiveWe aimed to measure the prevalence and incidence of latent tuberculosis infection (LTBI) and tuberculosis (TB) disease in children in close contact with patients with drug-resistant TB (DR-TB) in a country with high DR-TB prevalence.Design and settingThis is a prospective cohort study of paediatric contacts of adult patients with pulmonary DR-TB in Armenia. Children were screened using tuberculin skin test, interferon-gamma release assay and chest X-ray at the initial consultation, and were reassessed every 3–6 months for a period of 24 months. Children did not receive preventive treatment.Main outcome measuresPrevalence and incidence of LTBI and TB disease; factors associated with prevalent LTBI.ResultsAt initial evaluation, 3 of the 150 children included were diagnosed with TB disease (2.0%). The prevalence of LTBI was 58.7%. The incidence of LTBI was 19.9 per 100 children per year, and was especially high during the first 6 months of follow-up (33.3 per 100 children per year). No additional cases with incident disease were diagnosed during follow-up. After adjustment, prevalent LTBI was significantly associated with the child’s age, sleeping in the same house, higher household density, the index case’s age, positive smear result and presence of lung cavities.ConclusionsChildren in close contact with patients with DR-TB or in contact with very contagious patients had an increased risk of prevalent LTBI. Although none of the children developed TB disease during a 2-year follow-up period, screening for symptoms of TB disease, based on the prevalence of disease at recruitment, together with follow-up and repeated testing of non-infected contacts, is highly recommended in paediatric contacts of patients with DR-TB.

Background Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini. Methods We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009–2010; (2) MDR strains from the Nhlangano region, 2014–2017). Results MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n  = 28; gCL10, n  = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987–1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2. Conclusion The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently.