Transborder molecular analysis of drug-resistant tuberculosis in Mongolia and Eastern Siberia, Russia.

Eastern Siberia (Russia) and Mongolia are borderline regions in Asia with a high incidence of tuberculosis (TB). In this study, we investigated the transborder transmission of Mycobacterium tuberculosis with a focus on endemic and epidemic clones and drug resistance. M. tuberculosis isolates (287 from Mongolia and 754 from Russia) were collected using cross-sectional population-based surveys between 2010 and 2016. The isolates were genotyped using 24 variable number of tandem repeat loci and by testing of the key markers to discriminate within the Beijing genotype. All isolates were divided into 427 mycobacterial interspersed repetitive units types that were assigned to Lineage 2 (Beijing) and Lineage 4 (Ural, Haarlem, Latin American-Mediterranean [LAM], S, unclassified). The Beijing genotype was dominant in both countries (69% in Russia, 75% in Mongolia). However, the Beijing isolates differed significantly between the countries, in terms of the identified subtypes. LAM was the most common non-Beijing genotype (11.1% in Mongolia and 14.9% in Russia) and LAM isolates mostly belonged to the LAM-RUS branch in both countries. The multidrug-resistance (MDR) rate was higher in Russia than in Mongolia among newly diagnosed patients: 29.4% versus 5.6% (p < .001). In Mongolia, the MDR rate was similar in Beijing (29.7%) and non-Beijing (27.5%) genotypes. In Russia, a higher MDR rate was observed in (i) Beijing compared with non-Beijing (48.7% versus 38.3%, p = .03) and (ii) Beijing B0/W148 compared with Beijing Central Asian/Russian (63.4% versus 37.3%, p < .001). In conclusion, the M. tuberculosis population structure in Mongolia was shaped by mainly historical interaction with China (dominance of the Beijing genotype) and Northern Eurasia (presence of the LAM-RUS branch). In contrast, the transborder transmission of M. tuberculosis since the 1990s between Mongolia and its neighbours has been negligible, and the adverse trends of MDR-TB in Russia did not impact the current situation in Mongolia.

Risk factors associated with drug-resistant tuberculosis in Ethiopia: A systematic review and meta-analysis.

The emergence of drug-resistant tuberculosis (DR-TB) is becoming a challenge to the national TB control programmes including Ethiopia. Different risk factors are associated with DR-TB. Identifying these risk factors in a local setting is important to strengthen the effort to prevent and control DR-TB. Thus, this study aimed to assess the risk factors associated with DR-TB in Ethiopia. The Preferred Reporting Items for Systematic Reviews and Meta-analyses checklist was followed to conduct this study. We systematically searched the articles from electronic databases and grey literature sources. We used the JBI tools to assess the quality of studies. Data were analysed using STATA version 15. We estimated the pooled odds ratio (OR) along with 95% Confidence Interval (CI). The forest plot and I2 heterogeneity test were used to assess heterogeneity among studies. We explored the presence of publication bias through visual inspection of the funnel plot and Egger's regression test. After screening 2238 articles, 27 studies were included in the final analysis. Based on the pooled analysis of the OR, unemployment (OR; 2.71, 95% CI; 1.64, 3.78), previous TB history (OR; 4.83, 95% CI; 3.02, 6.64), contact with known TB patient (OR; 1.72, 95% CI; 1.05, 2.40), contact with the known multi-drug resistant (MDR) TB patient (OR; 2.54, 95% CI; 1.46, 3.63) and having pulmonary TB (PTB; OR; 1.80, 95% CI; 1.14, 2.45) were found to be the risk factors of DR-TB, while elders (OR; 0.77, 95%CI; 0.60, 0.95) including above 45 years (OR; 0.76, 95%CI; 0.55, 0.97) and males (OR; 0.86, 95%CI; 0.76, 0.97) had lower DR-TB risk, compared to their counterparts. A previous history of TB treatment is a major risk factor for acquiring DR-TB in Ethiopia that might be due to poor adherence during the first-line anti-TB treatment. Besides, having contact with a TB patient, contact with an MDR-TB patient, having PTB and being unemployed were the risk factors of DR-TB in Ethiopia. Thus, active screening of TB contacts for DR-TB might help to detect DR-TB cases as early as possible and could help to mitigate its further transmission across the community.

Recurrences of multidrug-resistant tuberculosis: Strains involved, within-host diversity, and fine-tuned allocation of reinfections.

Recurrent tuberculosis occurs due to exogenous reinfection or reactivation/persistence. We analysed 90 sequential MDR Mtb isolates obtained in Argentina from 27 patients with previously diagnosed MDR-TB that recurred in 2018 (1-10 years, 2-10 isolates per patient). Three long-term predominant strains were responsible for 63% of all MDR-TB recurrences. Most of the remaining patients were infected by strains different from each other. Reactivation/persistence of the same strain caused all but one recurrence, which was due to a reinfection with a predominant strain. One of the prevalent strains showed marked stability in the recurrences, while in another strain higher SNP-based diversity was observed. Comparisons of intra- versus inter-patient SNP distances identified two possible reinfections with closely related variants circulating in the community. Our results show a complex scenario of MDR-TB infections in settings with predominant MDR Mtb strains.

Characterization of mutations in the rpoB gene conferring rifampicin resistance in Mycobacterium tuberculosis complex isolated from lymph nodes of slaughtered cattle from South Africa.

Tuberculosis (TB) is an ongoing public health care, with the state of affairs exacerbated by the growth of anti-TB drug-resistant forms in South Africa. Not much attention is given to zoonotic TB. Thus, this study aimed to determine the presence of rpoB mutations among Mycobacterium tuberculosis complex (MTBC) isolates of lymph nodes from slaughtered cattle. A count of 14,950 carcasses from selected abattoirs were examined for nodular lesions and enlarged lymph nodes; 376 lymph nodes were cultured for MTBC. Positive isolates were tested for drug sensitivity against three anti-TB drugs, rifampicin, isoniazid, and ethambutol, using the Lowenstein-Jensen proportion method. Rifampicin-resistant isolates were sequenced, and spoligotyping was performed for lineage classification. A total of 162 isolates were confirmed as MTBC and 42 isolates were resistant to rifampicin. All rifampicin-resistant isolates carried the H526D rpoB mutation, and almost all of them carried an additional nonsynonymous nucleotide substitution in the hot spot region, in three other codons (510, 516 and 522). In total, 5 different mutations at four codons are reported, including one isolate showing 3 of them which has never been reported in South Africa. In addition, we report 4 different spoligo patterns, with 34 isolates known and 8 unknown spoligotype international types. From the known clades, 5 (11.9%) isolates were identified as Bov_4 caprae lineage, 29 (69%) Beijing, and 8 (19.1%) remaining unknown clades. The detection of MTBC-resistant patterns from cattle lymph nodes (Eastern Cape, South Africa) necessitates the investigation of other possible routes of MTBC transmission.

Detection of mycobacterial infection in non-human primates using the Xpert MTB/RIF molecular assay.

Tuberculosis is a major public health concern, and diagnostic strategies applied to animal populations are scarce. As part of ongoing efforts to control tuberculosis dissemination at our animal facility, two non-human primates (NHP, Saimiri sciureus) presenting cutaneous lesions were examined for mycobacterial infection. Both animals tested positive for acid-fast bacilli and Mycobacterium tuberculosis using a molecular assay (IS6110 PCR). Animals were euthanized and several samples were tested for M. tuberculosis using the Xpert MTB/RIF assay. Many samples were positive for M. tuberculosis and rifampicin resistance, and some produced mycobacterial growth. Oral swabs from cage mates were then tested with Xpert MTB/RIF, and the majority tested positive for M. tuberculosis and rifampicin resistance, and produced growth in culture. To our knowledge, this is the first report of multidrug-resistant mycobacterial infection in NHP. Additionally, our data shows that the Xpert MTB/RIF assay can be useful as a screening tool for tuberculosis infection in NHP.

Tuberculosis cross-species transmission in Tanzania: towards a One-Health concept.

For centuries, tuberculosis, which is a chronic infection caused by the bacillus Mycobacterium tuberculosis has remained a global health problem. The global burden of tuberculosis has increased, particularly in the Southern African region, mainly due to HIV, and inadequate health systems which has in turn given rise to emergent drug resistant tuberculosis (TB) strains. Bovine tuberculosis (BTB) has also emerged as a significant disease with the tendency for inter-species spread. The extent of interspecies BTB transmission both in urban and rural communities has not been adequately assessed. The phenomenon is of particular importance in rural communities where people share habitats with livestock and wildlife (particularly in areas near national parks and game reserves). Aerosol and oral intake are the major routes of transmission from diseased to healthy individuals, with health care workers often contracting infection nosocomially. Although TB control has increasingly been achieved in high-income countries, the disease, like other poverty-related infections, has continued to be a disaster in countries with low income economies. Transmission of infections occurs not only amongst humans but also between animals and humans (and occasionally vice versa) necessitating assessment of the extent of transmission at their interface. This review explores tuberculosis as a disease of humans which can cross-transmit between humans, livestock and wildlife. The review also addresses issues underlying the use of molecular biology, genetic sequencing and bioinformatics as t tools to understand the extent of inter-species cross-transmission of TB in a 'One Health' context.

Genitourinary and pulmonary multidrug resistant Mycobacterium tuberculosis infection in an Asian elephant (Elephas maximus).

A female Asian elephant (Elephas maximus) developed vaginal and trunk discharge. Cultures were positive for pan-susceptible Mycobacterium tuberculosis. Isoniazid and pyrazinamide were given rectally and monitored by serum levels. After being trained at 10 mo to accept oral dosing, treatment was changed and rifampin was added. Oral medications were administered for another 10 mo. A year after completion of therapy, the vaginal discharge increased and cultures yielded M. tuberculosis, resistant to isoniazid and rifampin. Treatment with oral ethambutol, pyrazinamide, and enrofloxacin and intramuscular amikacin was initiated. Although followup cultures became negative, adverse reactions to medications precluded treatment completion. Due to public health concerns related to multidrug resistant M. tuberculosis (MDR-TB), the elephant was euthanized. Postmortem smears from the lung, peribronchial, and abdominal lymph nodes yielded acid-fast bacteria, although cultures were negative. This case highlights important considerations in the treatment of M. tuberculosis in animals and the need for a consistent approach to diagnosis, treatment, and follow-up.