Risk factors of tuberculosis in Mizoram: First report of the possible role of water source.

BACKGROUND: Various risk factors of tuberculosis have been studied across the globe, but these may be altered over time and can be specific to geographical regions and there is not much information available from Northeastern region of India. This study aims to investigate the various risk factors of tuberculosis and analyze the presence of any less-established risk factors. METHODS: A total of 400 TB cases and 840 healthy controls were interviewed from December 2017 - June 2020. Logistic regression model was used to analyze associated risk factors. Patients were categorized into pulmonary and extrapulmonary TB. RESULTS: Clinical presentation such as fever, cough, weight loss, chest pain and night sweats were more prominent among pulmonary TB patients. The most common mode of diagnosis among pulmonary and extrapulmonary TB were GeneXpert and X-ray, respectively. Tuberculosis was found to be strongly prevalent among patients from lower socio-economic status, less educated, unemployed and improper housing condition. Other risk factors associated were alcohol consumption, neighbours with TB, travel history, no BCG vaccine, mass gathering, and non-ideal weight. An interesting less-established risk factor that demands attention is the source of water supply (p-0.017, OR-2.313, CI: 1.160-4.613), which was significant in this study. CONCLUSION: Our data suggests that apart from all the well-established risk factors for TB, water supply might play a crucial role towards the transmission of TB, since proper hospital waste water treatment is yet to be adopted in Mizoram, Northeast India. From a public health standpoint, this highlights the need for further research in this area.

Distribution and frequency of common mutations in rpoB gene of Mycobacterium tuberculosis detected by Xpert MTB/RIF and identification of residential areas of rifampicin resistant-TB cases: A first retrospective study from Mizoram, Northeast India.

Background: Rifampicin resistance (RR) is a surrogate marker of multidrug-resistant tuberculosis. The aim of this study is to determine the frequency of the commonly mutated probes for rpoB gene and locate the residential areas of the Rifampicin Resistant-TB (RR-TB) patients in a high endemic zone of Northeast India. Methods: Archived data of 13,454 Xpert MTB/RIF reports were evaluated retrospectively between 2014 and 2021. Socio-demographic and available clinical information were reviewed and analyzed for RR-TB cases only. Logistic Regression was used to analyze the parameters with respect to probe types. P-value ≤ 0.05 was considered to be statistically significant. Results: 2,894 patients had Mycobacterium tuberculosis infection out of which 460 were RR-TB, which was most prevalent among 25-34 years. The most common mutation occurred in probe A (25.9 %) followed by E (23.5 %), D (9.8 %), B (2.6 %) and the least in C (0.2 %). High prevalence (34.3 %) of probe mutation combinations were also found: probes AB (0.4 %), AD (32.8 %), AE (0.4 %), DE (0.2 %) and ADE (0.4 %). Seventeen patients (3.7 %) were found without any missing probes. RR-TB patients were mostly located in Aizawl North -III, South -II and East -II constituencies. Conclusion: This study provides genetic pattern of drug resistance accountable for RR over the past years in Mizoram which will help local clinicians in the initiation of correct treatment. Also, our findings provide a baseline data on the magnitude of RR-TB within the state and identification of the residential areas can help local health authorities in planning surveillance programs to control the spread of RR-TB.

MGIT sensitivity testing and genotyping of drug resistant Mycobacterium tuberculosis isolates from Mizoram, Northeast India.

PURPOSE: Tuberculosis, a crucial infectious disease is still a health concern globally. India is among the countries with high MDR-TB burden. Currently, sputum smear microscopy using Ziehl Neelsen stain and GeneXpert are the only diagnostic means in Mizoram. This study was done to characterize local tuberculosis strains circulating in Mizoram. METHODS: Sputum was cultured using MGIT 960 and DST was performed for Streptomycin, Isoniazid, Rifampicin, Ethambutol and Pyrazinamide. GeneXpert test was done simultaneously. DNA was extracted using Trueprep AUTO v2, molbio diagnostics. Antibiotic Resistance Genes and LSP were amplified and sequenced. RESULTS: Ser315Thr was the most common mutation in katG among MDR-TB isolates. GeneXpert probes A and D drop out upon sequencing showed L511P, H526Q and H526L mutation. The L511P and H526Q mutations were seen in new and treated cases. Discrepancy between MGIT 960 and GeneXpert were observed. LSP-PCR revealed that Indo-Oceanic, East-African Indian, Euro-American and Beijing lineages were found in Mizoram. CONCLUSION: This study provides mutation information on the resistant genotypes detected with GeneXpert as well as MGIT 960. It also provides information on the lineages of Mycobacterium tuberculosis circulating in the state. Utilization of sequencing technologies is essential in diagnostic laboratories to rule out discrepant results and as a cautionary measure to prevent wrong diagnosis and treatment.

Analysis of variants in mitochondrial genome and their putative pathogenicity in tuberculosis patients from Mizoram, North east India.

Tuberculosis caused by Mycobacterium tuberculosis is one of the main global health concerns. In this study, the entire mitochondrial genome from blood samples of tuberculosis patients was analyzed to understand the possible mtDNA variants. The potential impact of non-synonymous substitutions on protein functions were determined using prediction tools. 28 non- synonymous variants were found of which 2 variants (MT-ND2 g. A > G4824 p.T119A and MT-ND6 g. T > C14180 p.Y165C) were found to be deleterious among the cases only. Majority of the variants lie in the D-loop of the non-protein coding region of the mitochondrial DNA. We propose that mutations in the mitochondrial genome need to be validated further to understand their association with tuberculosis.

Intensified tuberculosis and HIV surveillance in a prison in Northeast India: Implementation research.

Structural and individual level factors in prisons create challenges towards detection and management of HIV/tuberculosis. WHO and India's HIV/tuberculosis control programs recommend intensified case finding in prisons. Low HIV and tuberculosis detection rates suggest poor implementation of existing surveillance strategies within the prison healthcare system in Mizoram's capital city of Aizawl. We explored the operational feasibility of implementing the intensified case finding strategy in Aizawl central prison. We implemented the intensified screening through entry screening of new inmates, mass screening of resident inmates and exit screening at release. We set up digital chest radiography, sputum smear microscopy and HIV testing facilities within the prison and referral to external facility for Cartridge Based Nucleic Acid Amplification Test (CBNAAT). We screened 738 inmates (Male: 626; Female: 112). Of 53% inmates having presumptive tuberculosis symptoms, 37% underwent sputum microscopy. We detected 14 new tuberculosis cases; overall tuberculosis positivity 1.9%. We tested 65% of 657 inmates for HIV, of which 41 new cases were detected; overall HIV positivity 16.5%. Three male inmates had HIV-tuberculosis co-infection. It is feasible to implement intensified case detection for tuberculosis/HIV in the prison with inter-departmental coordination, albeit with certain challenges.

Screening for haemoglobinopathies and G6PD deficiency among the Mizos of Mizoram: a preliminary study.

The population of North-eastern region of India is of different tribes, races and ethnic backgrounds. The study of abnormal haemoglobins and G6PD has been usefully utilized in population genetics to evaluate the nature and extent of selective forces operating in a population. Data on haemoglobinopathies and G6PD deficiency is still not available from the State of Mizoram. The present study was aimed to document the frequency of these genetic traits in the Mizos of Mizoram. Blood samples in the form of dried filter paper spots collected from 490 Mizos were subjected to haemoglobin electrophoresis in starch agar gel for detection of haemoglobin variants and fluorescent spot test was conducted for screening of G6PD deficiency. Hb E was the only haemoglobin variant detected. The prevalence of the carreer state was documented to be 1.5%. G6PD deficiency was prevalent in 17.5% of this population. The prevalence of Hb E was much lower and that of G-6PD deficiency was found to be much higher than what has been reported from most other states of the north-eastern region of India. This might point towards a different ethnic origin of this population.