Dataset Information

Tuberculous Lymphadenitis in Ethiopia Predominantly Caused by Strains Belonging to the Delhi/CAS Lineage and Newly Identified Ethiopian Clades of the Mycobacterium tuberculosis Complex.

ABSTRACT:

Background

Recently, newly defined clades of Mycobacterium tuberculosis complex (MTBC) strains, namely Ethiopia 1-3 and Ethiopia H37Rv-like strains, and other clades associated with pulmonary TB (PTB) were identified in Ethiopia. In this study, we investigated whether these new strain types exhibit an increased ability to cause TB lymphadenitis (TBLN) and raised the question, if particular MTBC strains derived from TBLN patients in northern Ethiopia are genetically adapted to their local hosts and/or to the TBLN.

Methods

Genotyping of 196 MTBC strains isolated from TBLN patients was performed by spoligotyping and 24-loci mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) typing. A statistical analysis was carried out to see possible associations between patient characteristics and phylogenetic MTBC strain classification.

Results

Among 196 isolates, the majority of strains belonged to the Delhi/CAS (38.8%) lineage, followed by Ethiopia 1 (9.7%), Ethiopia 3 (8.7%), Ethiopia H37RV-like (8.2%), Ethiopia 2 and Haarlem (7.7% each), URAL (3.6%), Uganda l and LAM (2% each), S-type (1.5%), X-type (1%), and 0.5% isolates of TUR, EAI, and Beijing genotype, respectively. Overall, 15 strains (7.7%) could not be allocated to a previously described phylogenetic lineage. The distribution of MTBC lineages is similar to that found in studies of PTB samples. The cluster rate (35%) in this study is significantly lower (P = 0.035) compared to 45% in the study of PTB in northwestern Ethiopia.

Conclusion

In the studied area, lymph node samples are dominated by Dehli/CAS genotype strains and strains of largely not yet defined clades based on MIRU-VNTR 24-loci nomenclature. We found no indication that strains of particular genotypes are specifically associated with TBLN. However, a detailed analysis of specific genetic variants of the locally contained Ethiopian clades by whole genome sequencing may reveal new insights into the host-pathogen co-evolution and specific features that are related to the local host immune system.

SUBMITTER: Biadglegne F

PROVIDER: S-EPMC4573740 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Tuberculous Lymphadenitis in Ethiopia Predominantly Caused by Strains Belonging to the Delhi/CAS Lineage and Newly Identified Ethiopian Clades of the Mycobacterium tuberculosis Complex.

Biadglegne Fantahun F Merker Matthias M Sack Ulrich U Rodloff Arne C AC Niemann Stefan S

PloS one 20150916 9

<h4>Background</h4>Recently, newly defined clades of Mycobacterium tuberculosis complex (MTBC) strains, namely Ethiopia 1-3 and Ethiopia H37Rv-like strains, and other clades associated with pulmonary TB (PTB) were identified in Ethiopia. In this study, we investigated whether these new strain types exhibit an increased ability to cause TB lymphadenitis (TBLN) and raised the question, if particular MTBC strains derived from TBLN patients in northern Ethiopia are genetically adapted to their local ...[more]

PMID: 26376441

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Project description:BackgroundTuberculosis (TB), caused by the Mycobacterium tuberculosis complex (MTBC), is a chronic infectious disease with both pulmonary and extrapulmonary forms. This study set out to investigate and compare the genomic diversity and transmission dynamics of Mycobacterium tuberculosis (Mtb) isolates obtained from tuberculous lymphadenitis (TBLN) and pulmonary TB (PTB) cases in Northwest Ethiopia.MethodsA facility-based cross-sectional study was conducted using two groups of samples collected between February 2021 and June 2022 (Group 1) and between June 2020 and June 2022 (Group 2) in Northwest Ethiopia. Deoxyribonucleic acid (DNA) was extracted from 200 heat-inactivated Mtb isolates. Whole-genome sequencing (WGS) was performed from 161 isolates having ≥1 ng DNA/μl using Illumina NovaSeq 6000 technology.ResultsFrom the total 161 isolates sequenced, 146 Mtb isolates were successfully genotyped into three lineages (L) and 18 sub-lineages. The Euro-American (EA, L4) lineage was the prevailing (n = 100; 68.5%) followed by Central Asian (CAS, L3, n = 43; 25.3%) and then L7 (n = 3; 2.05%). The L4.2.2.ETH sub-lineage accounted for 19.9%, while Haarlem estimated at 13.7%. The phylogenetic tree revealed distinct Mtb clusters between PTB and TBLN isolates even though there was no difference at lineages and sub-lineages levels. The clustering rate (CR) and recent transmission index (RTI) for PTB were 30 and 15%, respectively. Similarly, the CR and RTI for TBLN were 31.1 and 18 %, respectively.Conclusion and recommendationsPTB and TBLN isolates showed no Mtb lineages and sub-lineages difference. However, at the threshold of five allelic distances, Mtb isolates obtained from PTB and TBLN form distinct complexes in the phylogenetic tree, which indicates the presence of Mtb genomic variation among the two clinical forms. The high rate of clustering and RTI among TBLN implied that TBLN was likely the result of recent transmission and/or reactivation from short latency. Hence, the high incidence rate of TBLN in the Amhara region could be the result of Mtb genomic diversity and rapid clinical progression from primary infection and/or short latency. To validate this conclusion, a similar community-based study with a large sample size and better sampling technique is highly desirable. Additionally, analysis of genomic variants other than phylogenetic informative regions could give insightful information. Combined analysis of the host and the pathogen genome (GXG) together with environmental (GxGxE) factors could give comprehensive co-evolutionary information.

Project description:Tuberculous lymphadenitis (TBLN) is the most common form of extrapulmonary tuberculosis. The cytomorphological features of lymph node smears have reduced specificity for the diagnosis of tuberculosis. The diagnosis of TBLN with direct smear microscopy lacks sensitivity due to the limited number of bacilli in lymph node aspirate. Therefore, we aimed to assess whether the concentration of lymph node aspirate improves the sensitivity of acid fast smear microscopy for the diagnosis of tuberculous lymphadenitis.A cross-sectional comparative study was conducted on 200 patients clinically suspected for tuberculous lymphadenitis in Jimma, Ethiopia. Lymph node aspirate was collected. The first two drops were used for cytomorphological study and direct acid fast staining. The remaining aspirate was treated with N-acetyl-L-cysteine (NALC) and concentrated by centrifugation at 3000 g for 15 minutes. The sediment was used for acid fast staining and culture. Differentiation of M. tuberculosis complex (MTBC) from non-tuberculous mycobacteria (NTM) was done by para-nitrobenzoic acid susceptibility test.Complete data were available for 187 study subjects. 68% (127/187) were positive for M. tuberculosis on culture. Four isolates, 2.1% (4/187), were identified as NTM. The detection rate of direct smear microscopy was 25.1% and that of the concentration method 49.7%. Cytomorphologically, 79.7% of cases were classified as TBLN. The sensitivity of direct smear microscopy was 34.6%, for concentrated smear microscopy 66.1%, and for cytomorphology 89.8%. Two AFB positive cases on concentration method were non-tuberculosis mycobacteria (NTM). The concentration method yielded a positive result from seven cases diagnosed as suppurative abscess by cytology. Both for the direct and concentration methods the highest rate of AFB positivity was observed in smears showing caseous necrosis alone. Smear positivity rate decreased with the appearance of epithelioid cell aggregates.The concentration of lymph node aspirates for acid fast smear microscopy had significantly higher sensitivity than direct microscopy.

Dataset Information

Tuberculous Lymphadenitis in Ethiopia Predominantly Caused by Strains Belonging to the Delhi/CAS Lineage and Newly Identified Ethiopian Clades of the Mycobacterium tuberculosis Complex.

Background

Methods

Results

Conclusion

Publications

Tuberculous Lymphadenitis in Ethiopia Predominantly Caused by Strains Belonging to the Delhi/CAS Lineage and Newly Identified Ethiopian Clades of the Mycobacterium tuberculosis Complex.

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