Biology subjects

Merker, M.

Publications and source records attributed to Merker, M..

3 recordsLinked to original sources

bioRxiv2018

Compensatory evolution drives multidrug-resistant tuberculosis in Central Asia

Bacterial factors favoring the unprecedented multidrug-resistant tuberculosis (MDR-TB) epidemic in the former Soviet Union remain unclear.\n\nWe utilized whole genome sequencing and Bayesian statistics to analyze the evolutionary history, temporal emergence of resistance and transmission networks of MDR-MTBC strains from Karakalpakstan, Uzbekistan (2001-2006).\n\nOne MTBC-clone (termed Central Asian outbreak, CAO) with resistance mediating mutations to eight anti-TB drugs existed prior the worldwide introduction of standardized WHO-endorsed directly observed treatment, short-course (DOTS). DOTS implementation in Karakalpakstan in 1998 likely selected for these CAO-strains, comprising 75% of sampled MDR-TB strains in 2005/2006. CAO-strains were also identified in a previously published cohort from Samara, Russia (2008-2010). Similarly, transmission success and resistance development was linked to mutations compensating fitness deficits associated with rifampicin resistance.\n\nThe genetic make-up of these outbreak clades threatens the success of both empirical and standardized guideline driven MDR-TB therapies, including the newly WHO-endorsed short MDR-TB regimen in Uzbekistan.

evolutionary biology↗

bioRxiv2018

Molecular epidemiology and drug resistance patterns of Mycobacterium tuberculosis complex isolates from university students and the local community in Eastern Ethiopia

BackgroundPrevious studies suggest the burden of pulmonary tuberculosis (PTB) in Ethiopia may be greater in university students relative to the overall population. However, little is known about the transmission dynamics of PTB among students and members of the communities surrounding university campuses in Eastern Ethiopia.\n\nMethodsA cross sectional study was conducted in Eastern Ethiopia among culture-confirmed PTB cases from university students (n=36) and community members diagnosed at one of four hospitals (n=152) serving the surrounding area. Drug susceptibility testing (DST) was performed on Mycobacterium Tuberculosis Complex (MTBC) isolates using BD Bactec MGIT 960 and molecular genotyping was performed using spoligotyping and 24-loci MIRU-VNTR. MTBC strains with Identical genotyping patterns were assigned to molecular clusters as surrogate marker for recent transmission and further contact tracing was initiated among clustered patients.\n\nResultsAmong all study participants, four MTBC lineages and 11 sub-lineages were identified, with Ethiopia_3 being most common sub-lineage (29.4%) and associated with strain clustering (P= 0.016). We identified 13 (8.1%) strains phylogenetically related to the known Ethiopian sub-lineages with a distinct Spoligotyping patterns and designated as Ethiopia_4. The clustering rate of MTB strains was 52.9% for university students and 66.7% for community members with a Recent Transmission Index (RTI) of 17.6% and 48.4%, respectively. Female gender, urban residence, and new TB cases were significantly associated with strain clustering (p<0.05). Forty-eight (30%) of the study participants were resistant to one or more first line anti TB drugs, three patients were classified as multidrug resistant (MDR), defined by isoniazid and rifampicin resistance.\n\nConclusionWe found evidence of significant PTB cases clustering and recent transmission among Ethiopian university students and the local community in eastern Ethiopia; with Ethiopia_3 being the predominant circulating sub-lineage. A country wide comprehensive molecular surveillance and drug resistance profiling of MTBC strains and Implementation of TB control programs within universities and the surrounding community should be considered to decrease TB transmission.

epidemiology↗

bioRxiv2018

The relationship between transmission time and clustering methods in Mycobacterium tuberculosis epidemiology

BackgroundTracking recent transmission is a vital part of controlling widespread pathogens such as Mycobacterium tuberculosis. Multiple methods with specific performance characteristics exist for detecting recent transmission chains, usually by clustering strains based on genotype similarities. With such a large variety of methods available, informed selection of an appropriate approach for determining transmissions within a given setting/time period is difficult.\n\nMethodsThis study combines whole genome sequence (WGS) data derived from 324 isolates collected 2005-2010 in Kinshasa, Democratic Republic of Congo (DRC), a high endemic setting, with phylodynamics to unveil the timing of transmission events posited by a variety of standard genotyping methods. Clustering data based on Spoligotyping, 24-loci MIRU-VNTR typing, WGS based SNP (Single Nucleotide Polymorphism) and core genome multi locus sequence typing (cgMLST) typing were evaluated.\n\nFindingsOur results suggest that clusters based on Spoligotyping could encompass transmission events that occurred over 70 years prior to sampling while 24-loci-MIRU-VNTR often represented two or more decades of transmission. Instead, WGS based genotyping applying low SNP or cgMLST allele thresholds allows for determination of recent transmission events in timespans of up to 10 years e.g. for a 5 SNP/allele cut-off.\n\nInterpretationWith the rapid uptake of WGS methods in surveillance and outbreak tracking, the findings obtained in this study can guide the selection of appropriate clustering methods for uncovering relevant transmission chains within a given time-period. For high resolution cluster analyses, WGS-SNP and cgMLST based analyses have similar clustering/timing characteristics even for data obtained from a high incidence setting.

epidemiology↗