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Background Mycobacterium tuberculosis strain diversity and drug resistance among people living with human immunodeficiency virus (HIV) in Vietnam have not been described previously. Methods We examined M. tuberculosis isolates from TB/HIV co-infected patients in Ho Chi Minh City, Vietnam. Drug susceptibility testing (DST), spoligotyping and 24-locus Mycobacterial Interspersed Repetitive Unit (MIRU-24 typing) were performed, and the rpoB, katG, inhA and inhA promoter, rpsL, rrs and embB genes were sequenced in all drug resistant isolates identified. Results In total, 84/200 (42.0%) strains demonstrated "any drug resistance"; 17 (8.5%) were multi-drug resistant (MDR). Streptomycin resistance was present in 80 (40.0%) isolates; 95.2% (80/84) with "any drug resistance" and 100% with MDR. No rifampicin monoresistance was detected. Of the rifampicin resistant strains 16/18 (88.9%) had mutations in the 81-bp Rifampicin Resistance Defining Region (RRDR) of the rpoB gene. Isoniazid resistance was mostly associated with Ser315Thr mutations in the katG gene (15/17; 88.2%). Beijing (49.0%) and East African Indian (EAI) lineage strains (35.0%; 56/70 EAI-5) were most common. Conclusion TB/HIV co-infection in Vietnam was associated with high rates of TB drug resistance, although we were unable to differentiate new from retreatment cases.

Background Improved and affordable diagnostic or triage tests are urgently needed at the microscopy centre level. Automated digital microscopy has the potential to overcome issues related to conventional microscopy, including training time requirement and inconsistencies in results interpretation. Methods For this blinded prospective study, sputum samples were collected from adults with presumptive pulmonary tuberculosis in Lima, Peru and Ho Chi Minh City, Vietnam. TBDx performance was evaluated as a stand-alone and as a triage test against conventional microscopy and Xpert, with culture as the reference standard. Xpert was used to confirm positive cases. Findings A total of 613 subjects were enrolled between October 2014 and March 2015, with 539 included in the final analysis. The sensitivity of TBDx was 62·2% (95% CI 56·6–67·4) and specificity was 90·7% (95% CI 85·9–94·2) compared to culture. The algorithm assessing TBDx as a triage test achieved a specificity of 100% while maintaining sensitivity. Interpretation While the diagnostic performance of TBDx did not reach the levels obtained by experienced microscopists in reference laboratories, it is conceivable that it would exceed the performance of less experienced microscopists. In the absence of highly sensitive and specific molecular tests at the microscopy centre level, TBDx in a triage-testing algorithm would optimize specificity and limit overall cost without compromising the number of patients receiving up-front drug susceptibility testing for rifampicin. However, the algorithm would miss over one third of patients compared to Xpert alone.

Background The GeneXpertMTB/RIF (Xpert) assay is now recommended by WHO for diagnosis of tuberculosis (TB) in children but evaluation data is limited. Methods One hundred and fifty consecutive HIV negative children (

Human ADAM19 (MADDAM) is a molecular marker for human dendritic cells and not expressed in macrophages. To investigate its cell-type-specific expression, we defined the transcriptional start site and the proximal promoter. Sequence analysis of the promoter revealed putative binding sites for several transcription factors including Sp1, Sp3, NF-κB, and VDR. A minimal promoter construct of 150 bp showed little difference in reporter activity between macrophages and dendritic cells. Transfection of monocytic THP-1 with the 150-bp fragment also resulted in significant reporter activity, despite the lack of endogenous MADDAM expression. TSA, a known inhibitor of histone deacetylation, led to a dose-dependent induction of MADDAM mRNA in THP-1. ChIP assays demonstrated high levels of acetylated histone H3 in the proximal promoter region of the MADDAM gene in TSA-treated THP-1 cells and dendritic cells as compared to macrophages, indicating an important role of histone acetylation in the regulation of the MADDAM gene.

Background To control multidrug resistant tuberculosis (MDR-TB), the drug susceptibility profile is needed to guide therapy. Classical drug susceptibility testing (DST) may take up to 2 to 4 months. The GenoType® MTBDRplus test is a commercially available line-probe assay that rapidly detects Mycobacterium tuberculosis (MTB) complex, as well as the most common mutations associated with rifampin and isoniazid resistance. We assessed sensitivity and specificity of the assay by using a geographically representative set of MTB isolates from the South of Vietnam. Methods We re-cultured 111 MTB isolates that were MDR, rifampin-resistant or pan-susceptible according to conventional DST and tested these with the GenoType® MTBDRplus test. Results By conventional DST, 55 strains were classified as MDR-TB, four strains were rifampicin mono-resistant and 52 strains were susceptible to all first-line drugs. The sensitivity of the GenoType® MTBDRplus was 93.1% for rifampicin, 92.6% for isoniazid and 88.9% for the combination of both; its specificity was 100%. The positive predictive value of the GenoType® MTBDRplus test for MDR-TB was 100% and the negative predictive value 90.3%. Conclusions We found a high specificity and positive predictive value of the GenoType® MTBDRplus test for MDR-TB which merits its use in the MDR-TB treatment program in Vietnam.