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Abstract Background Differences in rural and urban settings could account for distinct characteristics in the epidemiology of tuberculosis (TB). We comparatively studied epidemiological features of TB and helminth co-infections in adult patients from rural and urban settings of Tanzania. Methods Adult patients (≥ 18 years) with microbiologically confirmed pulmonary TB were consecutively enrolled into two cohorts in Dar es Salaam, with ~ 4.4 million inhabitants (urban), and Ifakara in the sparsely populated Kilombero District with ~ 400 000 inhabitants (rural). Clinical data were obtained at recruitment. Stool and urine samples were subjected to diagnose helminthiases using Kato-Katz, Baermann, urine filtration, and circulating cathodic antigen tests. Differences between groups were assessed by χ 2, Fisher’s exact, and Wilcoxon rank sum tests. Logistic regression models were used to determine associations. Results Between August 2015 and February 2017, 668 patients were enrolled, 460 (68.9%) at the urban and 208 (31.1%) at the rural site. Median patient age was 35 years (interquartile range [IQR]: 27–41.5 years), and 454 (68%) were males. Patients from the rural setting were older (median age 37 years vs. 34 years, P = 0.003), had a lower median body mass index (17.5 kg/m2 vs. 18.5 kg/m2, P

Abstract Background Large sequence datasets are difficult to visualize and handle. Additionally, they often do not represent a random subset of the natural diversity, but the result of uncoordinated and convenience sampling. Consequently, they can suffer from redundancy and sampling biases. Results Here we present Treemmer, a simple tool to evaluate the redundancy of phylogenetic trees and reduce their complexity by eliminating leaves that contribute the least to the tree diversity. Conclusions Treemmer can reduce the size of datasets with different phylogenetic structures and levels of redundancy while maintaining a sub-sample that is representative of the original diversity. Additionally, it is possible to fine-tune the behavior of Treemmer including any kind of meta-information, making Treemmer particularly useful for empirical studies.

Abstract Background Culture contamination with environmental bacteria is a major challenge in tuberculosis (TB) laboratories in hot and humid climate zones. We studied the effect of cetylpyridinium chloride (CPC) preservation on culture results and performance of Xpert MTB/RIF. Methods Consecutive sputum samples from microscopy smear-positive TB patients were collected. Two-hundred samples were equally split in two aliquots, one aliquot was treated with CPC and stored at ambient temperature for 7 days. The second aliquot was immediately processed. Samples were decontaminated for 20, 15 or 10 min, and subsequently cultured on Löwenstein-Jensen medium. Furthermore, 50 samples were stored for 7, 14 and 21 days, and 100 CPC-pretreated samples tested by Xpert MTB/RIF. Results CPC pretreated samples showed a higher culture yield compared to non-treated sputum samples across all decontamination times: 94% vs. 73% at 10 min (p = 0.01), 94% vs. 64% at 15 min (p = 0.004), and 90% vs. 52% at 20 min (p

Abstract Background Bovine tuberculosis (BTB) is caused by Mycobacterium bovis, which belongs to the Mycobacterium tuberculosis complex. Mycobacterium bovis have been described to be responsible of most cases of bovine tuberculosis. Although M. tuberculosis, M. africanum and non-complex mycobacteria were isolated from cattle. In Morocco, so far, no molecular studies were conducted to characterize the strains responsible of BTB. The present study aims to characterize M. bovis in Morocco. The present study was conducted in slaughterhouses in Rabat and El Jadida. Samples were collected from 327 slaughtered animals with visible lesions suggesting BTB. Results A total of 225 isolates yielded cultures, 95% (n = 215) of them were acid-fast (AF). Sixty eight per cent of the AF positive samples were confirmed as tuberculous mycobacteria (n = 147), 99% of these (n = 146) having RD9 and among the latter, 98% (n = 143) positive while 2% (n = 3) negative for RD4 A total of 134 samples were analyzed by spoligotyping of which 14 were in cluster and with 41 different spoligotypes, ten of them were new patterns (23%). The most prevalent spoligotypes were SB0121, SB0265, and SB0120, and were already identified in many other countries, such as Algeria, Spain, Tunisia, the United States and Argentina. Conclusion The shared borders between Algeria and Morocco, in addition to the previous importation of cattle from Europe and the US could explain the similarities found in M. bovis spoligotypes. On the other hand, the desert of Morocco could be considered as an efficient barrier preventing the introduction of BTB to Morocco from West Central and East Africa. Our findings suggest a low level endemic transmission of BTB similar to other African countries. However, more research is needed for further knowledge about the transmission patterns of BTB in Morocco.

Abstract Background Combination therapy is one of the most effective tools for limiting the emergence of drug resistance in pathogens. Despite the widespread adoption of combination therapy across diseases, drug resistance rates continue to rise, leading to failing treatment regimens. The mechanisms underlying treatment failure are well studied, but the processes governing successful combination therapy are poorly understood. We address this question by studying the population dynamics of Mycobacterium tuberculosis within tuberculosis patients undergoing treatment with different combinations of antibiotics. Results By combining very deep whole genome sequencing (~1000-fold genome-wide coverage) with sequential sputum sampling, we were able to detect transient genetic diversity driven by the apparently continuous turnover of minor alleles, which could serve as the source of drug-resistant bacteria. However, we report that treatment efficacy has a clear impact on the population dynamics: sufficient drug pressure bears a clear signature of purifying selection leading to apparent genetic stability. In contrast, M. tuberculosis populations subject to less drug pressure show markedly different dynamics, including cases of acquisition of additional drug resistance. Conclusions Our findings show that for a pathogen like M. tuberculosis, which is well adapted to the human host, purifying selection constrains the evolutionary trajectory to resistance in effectively treated individuals. Nonetheless, we also report a continuous turnover of minor variants, which could give rise to the emergence of drug resistance in cases of drug pressure weakening. Monitoring bacterial population dynamics could therefore provide an informative metric for assessing the efficacy of novel drug combinations.

Abstract Background Vitamin D level is inversely associated with tuberculosis (TB) and diabetes (DM). Vitamin D could be a mediator in the association between TB and DM. We examined the associations between vitamin D, TB and DM. Methods Consecutive adults with TB and sex- and age-matched volunteers were included in a case-control study in Dar es Salaam, Tanzania. Glycemia and total vitamin D (25(OH)D) were measured at enrolment and after TB treatment in cases. The association between low 25(OH)D (