Epidemiology, diagnosis & treatment of non-tuberculous mycobacterial diseases.

Non-tuberculous mycobacteria (NTM) are ubiquitously present in the environment, but NTM diseases occur infrequently. NTM are generally considered to be less virulent than Mycobacterium tuberculosis, however, these organisms can cause diseases in both immunocompromised and immunocompetent hosts. As compared to tuberculosis, person-to-person transmission does not occur except with M. abscessus NTM species among cystic fibrosis patients. Lung is the most commonly involved organ, and the NTM-pulmonary disease (NTM-PD) occurs frequently in patients with pre-existing lung disease. NTM may also present as localized disease involving extrapulmonary sites such as lymph nodes, skin and soft tissues and rarely bones. Disseminated NTM disease is rare and occurs in individuals with congenital or acquired immune defects such as HIV/AIDS. Rapid molecular tests are now available for confirmation of NTM diagnosis at species and subspecies level. Drug susceptibility testing (DST) is not routinely done except in non-responsive disease due to slowly growing mycobacteria ( M. avium complex, M. kansasii) or infection due to rapidly growing mycobacteria, especially M. abscessus. While the decision to treat the patients with NTM-PD is made carefully, the treatment is given for 12 months after sputum culture conversion. Additional measures include pulmonary rehabilitation and correction of malnutrition. Treatment response in NTM-PD is variable and depends on isolated NTM species and severity of the underlying PD. Surgery is reserved for patients with localized disease with good pulmonary functions. Future research should focus on the development and validation of non-culture-based rapid diagnostic tests for early diagnosis and discovery of newer drugs with greater efficacy and lesser toxicity than the available ones.

A prospective study of non-tuberculous mycobacterial disease among tuberculosis suspects at a tertiary care centre in north India.

Background & objectives: The burden of non-tuberculous mycobacterial (NTM) disease is increasing worldwide. The disease shares clinicoradiological features with tuberculosis (TB), Nocardia and several fungal diseases, and its diagnosis is frequently delayed. The present study was performed to determine the frequency of NTM disease among TB suspects in a tertiary care centre in north India. Methods: In this prospective study, mycobacterial culture isolates from pulmonary and extrapulmonary specimens among TB suspects were tested with immunochromatographic assay (ICA). All ICA-negative isolates were considered as NTM suspects and further subjected to 16S-23S rRNA internal transcribed spacer gene sequencing for confirmation and species identification. Patients with active disease were treated with drug regimen as per the identified NTM species. Follow up of patients was done to determine clinical, radiological and microbiological outcomes. Results: Of the 5409 TB suspects, 42 (0.77%) were diagnosed with NTM disease. Patients with active disease consenting for treatment were treated and followed up. Thirty four patients had NTM pulmonary disease (NTM-PD) and the remaining eight had extrapulmonary NTM (EP-NTM) disease. Mycobacterium intracellulare and M. abscessus, respectively, were most frequently isolated from NTM-PD and EP-NTM patients. Fifteen NTM-PD and seven EP-NTM patients successfully completed the treatment. Ten patients died due to unrelated causes, five were lost to follow up and another four declined the treatment. Interpretation & conclusions: Our study showed that the frequency of NTM disease was low among TB suspects at a large tertiary care centre in north India and this finding was similar to other Indian studies. More studies need to be done in other parts of the country to know the geographical variation in NTM disease, if any.

A four year experience in narcolepsy from a sleep clinic at a tertiary care centre with a short review of contemporary Indian literature.

Narcolepsy is a common sleep disorder in Western countries but rarely reported from India. Here, we report a small case series of four narcolepsy patients seen over a four year period in the sleep clinic of a tertiary care hospital in north India. The diagnosis was established by clinical history and two or more sleep-onset rapid eye movements (SOREMs) on multiple sleep latency tests (MSLTs) following overnight polysomnography (PSG). The mean age of patients was 26.2±6.4 yr; one patient had associated cataplexy and another one had all four cardinal symptoms of narcolepsy. All these patients had a history of excessive daytime sleepiness (EDS). The mean body mass index was 24.2±4.7 kg/m[2]. The mean sleep latency during MSLT was 2.7±1.3 min, and the mean REM latency was 5.7±2.9 min. Narcolepsy, although rarely reported from India, should be suspected in young non-obese patients complaining of EDS and confirmed by performing MSLT following overnight PSG.

Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity.

BACKGROUND & OBJECTIVES: The N-acetyltransferase 2 (NAT2) gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH). METHODS: In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. RESULTS: Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8%) and non-DIH (77.2%) patients. However, the genotypic distribution of variant NAT2FNx015/FNx017 amongst slow-acetylator genotypes was significantly higher in DIH (56%) group as compared to non-DIH (39%) group (odds ratio 2.02; P=0.006). INTERPRETATION & CONCLUSIONS: The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.

Non-tuberculous mycobacteria: a disease beyond TB and preparedness in India.

BACKGROUND AND METHODS: Fifty-six Indian studies on NTM diseases were selected between 1981 and 2020 from various electronic databases (PubMed, EMBASE, Medline, BIOSIS preview, and Scopus) for systematic review. RESULTS: NTM isolation rates increased from 0.9% between 2001 and 2010 to 1.6% between 2011 and 2020. Prevalence of NTM-pulmonary disease (NTM-PD) among presumptive-TB patients in India was 1.1% (395/34,829). M. avium complex (MAC) (19%) was most commonly isolated from pulmonary specimens followed by M. chelonae (10%), M. fortuitum (9.8%), and M. abscessus (8.8%). M. fortuitum (35.5%), M. chelonae (23.6%) and M. abscessus (15%) were frequently reported from extra-pulmonary specimens. Patients with NTM-PD were mostly treated with a macrolide-based three-drug regimen. Clarithromycin-based-drug regimen in combination with amikacin, ciprofloxacin and several other drugs (rifampicin, imipenem, ofloxacin, linezolid, azithromycin) was used for treatment of EP-NTM. Median duration of the treatment in NTM-PD was 12 months, (6-18 months) whereas it was 6 months (3.1-8.7 months) in EP-NTM. Treatment was successful in 45% (19/42) of NTM-PD patients and 75% (93/124) of EP-NTM patients. CONCLUSION: It is concluded from this review that most Indian studies have published laboratory data on NTM isolation and speciation and lacked information on clinical, microbiological and radiological correlation and treatment outcome details. Future studies should address these issues while publishing on NTM diseases.

Urinary EPCR and dermcidin as potential novel biomarkers for severe adult OSA patients.

BACKGROUND: Due to low predictive values of obstructive sleep apnea (OSA) screening tools, there is a need for biomarker for screening of OSA patients at an early stage. The aim of the study was to evaluate differentially expressed proteins in blood and urine samples of OSA patients. METHODS: In this study, we used isobaric tagging for relative and absolute quantification (iTRAQ) based proteomics approach to identify differentially expressed proteins, which were subsequently verified and validated using enzyme-linked immunosorbent assay (ELISA) technique in adult OSA patients. RESULTS: Seventeen differentially expressed proteins were selected from iTRAQ data for verification, based on their clinical significance and reproducibility among different iTRAQ experiment sets. Five of these proteins (plasma = 2; urine = 3) were further validated in plasma (non-OSA- = 42; OSA = 198) and urine samples (non-OSA = 46; OSA = 197). ROC curve analysis for all OSA vs. non-OSA subjects ensured optimal diagnostic utility of two urinary proteins: Endothelial protein c receptor (EPCR) (AUC = 73%, cut-off: 35 pg/ml) and dermcidin (AUC = 74%, cut-off: 4.6 pg/ml). For severe OSA, diagnostic accuracy significantly improved with AUC as 88% and 82% for EPCR (cut-off: 46 pg/ml) and dermcidin (cut-off: 5.2 pg/ml) respectively. Sensitivity and specificity of combined performance of both urinary proteins for severe OSA were 94% and 91% respectively. CONCLUSION: In this study, urinary EPCR and dermcidin emerged as novel biomarkers for screening severe OSA patients.