Recurrence of pulmonary tuberculosis in India: Findings from the 2019-2021 nationwide community-based TB prevalence survey.

Recurrent Tuberculosis patients contribute to a significant proportion of TB burden in India. A nationwide survey was conducted during 2019-2021 across India among adults to estimate the prevalence of TB. A total of 322480 individuals were screened and 1402 were having TB. Of this, 381 (27.1%) had recurrent TB. The crude prevalence (95% CI) of recurrent TB was 118 (107-131) per 100,000 population. The median duration between episodes of TB was 24 months. The proportion of drug resistant TB was 11.3% and 3.6% in the recurrent group and new TB patients respectively. Higher prevalence of recurrent TB was observed in elderly, males, malnourished, known diabetics, smokers, and alcohol users. (p<0.001). To prevent TB recurrence, all treated tuberculosis patients must be followed at least for 24 months, with screening for Chest X-ray, liquid culture every 6 months, smoking cessation, alcohol cessation, nutritional interventions and good diabetic management.

Understanding complexities in the uptake of indigenously developed rapid point-of-care diagnostics for containment of antimicrobial resistance in India.

A good point-of-care diagnostic test holds a promise to reduce inappropriate use of antibiotics by enabling early detection of the pathogen and facilitating rapid testing of antimicrobial susceptibility. India has taken many initiatives in the recent past to augment the development and deployment of diagnostics in Indian health care system. Funding opportunities to promote innovation in diagnostics development were started in early 2000s through various ministries and departments. India released National Essential Diagnostics List which enlists essential tests and there is now Free Diagnostics Service Initiative of Government of India under National Health Mission that mandates to provide all essential tests free of cost. We wanted to understand how these initiatives have impacted the diagnostics that could be of use in containment of antimicrobial resistance (AMR) and whether there is a smooth process for bringing indigenously developed products relevant to AMR into the healthcare system. We conducted a longitudinal survey (January 2019 and January 2021) to understand the availability of market ready indigenous rapid diagnostics for AMR in the country and their progress towards introduction in the private market or uptake in healthcare system. We found that many innovators and developers are working towards development of rapid tests that can be useful in the containment of AMR in India. While there are many promising diagnostics on the horizon, the pathway for uptake of indigenously developed diagnostics in healthcare system remains disjointed and needs to be harmonised for the investments made towards development to translate as tangible gains. Since most of these efforts are government funded, it is incumbent upon the government to also provide a seamless pathway to make these diagnostics available in health care system. In absence of this guidance, most of these diagnostics will sit with the innovators/developers and will never be used for the purpose they were intended to serve.

Sequential determination of viral load, humoral responses and phylogenetic analysis in fatal and non-fatal cases of Crimean-Congo hemorrhagic fever patients from Gujarat, India, 2019.

BACKGROUND: Thirty-four CCHF cases (17 fatal; 17 survived) were confirmed from Gujarat state, India during the year 2019. We aimed to find out the viral load, antibody kinetics, cytokine profile and phylogenetic analysis between fatal and non- fatal cases. METHODS: Thirty four cases were included in this study. Blood and urine samples were collected from all the cases on the day of admission to hospital. Non-fatal cases were followed weekly for understanding the profile of viral kinetics, anti-CCHFV IgM and IgG antibodies. We also quantified the cytokines in both fatal and non-fatal cases. For epidemiological correlation, livestock were screened for anti-CCHF IgG antibodies and the tick pool specimens were tested by real time RT-PCR. Virus isolation was attempted on tick pools and human specimens and phylogenetic analysis performed on human and ticks complete genome sequences. RESULTS: CCHF cases were detected throughout year in 2019 with the peak in August. Out of 34 cases, eight secondary CCHF cases were reported. Cases were predominantly detected in males and in 19-45 years age group (55.88%). The persistence of viremia was observed till 76th POD (post onset date) in one case whereas anti-CCHFV IgM and IgG was detected amongst these cases from the 2nd and 20th POD respectively. Positivity observed amongst livestock and tick pools were was 21.57% and 7.4% respectively. The cytokine analysis revealed a significant increase in the level of serum IL-6, IL-10 and IFN-γ during the acute phase of the infection, but interestingly IL-10 lowered to normal upon clearance of the virus in the clinically recovered case. Fatal cases had high viral RNA copy numbers. Bleeding from one or two mucosal sites was significantly associated with fatality (OR-16.47;p-0.0034 at 95% CI). We could do CCHF virus isolation from two cases. Phylogenetic analysis revealed circulation of re-assortment of Asian-West African genotypes in humans and ticks. CONCLUSIONS: The persistence of CCHF viral RNA was detected till 76th POD in one of the survivors. The circulation of a re-assortment Asian-West African genotype in a CCHF case is also reported first time from India.

A prospective multicentre diagnostic accuracy study for the Truenat tuberculosis assays.

BACKGROUND: Bringing reliable and accurate tuberculosis (TB) diagnosis closer to patients is a key priority for global TB control. Molbio Diagnostics have developed the Truenat point-of-care molecular assays for detection of TB and rifampicin (RIF) resistance. METHODS: We conducted a prospective multicentre diagnostic accuracy study at 19 primary healthcare centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to estimate the diagnostic accuracy of the point-of-care Truenat MTB, MTB Plus and MTB-RIF Dx assays for pulmonary TB using culture and phenotypic drug susceptibility testing as the reference standard, compared with Xpert MTB/RIF or Ultra. RESULTS: Of 1807 enrolled participants with TB signs/symptoms, 24% were culture-positive for Mycobacterium tuberculosis, of which 15% were RIF-resistant. In microscopy centres, the pooled sensitivity of Truenat MTB and Truenat MTB Plus was 73% (95% CI 67-78%) and 80% (95% CI 75-84%), respectively. Among smear-negative specimens, sensitivities were 36% (95% CI 27-47%) and 47% (95% CI 37-58%), respectively. Sensitivity of Truenat MTB-RIF was 84% (95% CI 62-95%). Truenat assays showed high specificity. Head-to-head comparison in the central reference laboratories suggested that the Truenat assays have similar performance to Xpert MTB/RIF. CONCLUSION: We found the performance of Molbio's Truenat MTB, MTB Plus and MTB-RIF Dx assays to be comparable to that of the Xpert MTB/RIF assay. Performing the Truenat tests in primary healthcare centres with very limited infrastructure was feasible. These data supported the development of a World Health Organization policy recommendation of the Molbio assays.

Self-reported and clinically identified loss of smell and taste among persons tested for COVID-19 in Chennai, southern India, July-August 2020: A cross sectional study.

BACKGROUND: Early detection of symptoms of loss of smell and taste lately added for Coronavirus disease 2019 (COVID-19) has the potential for improving pandemic response. In the Indian context, we compared proportion experiencing new loss of smell or taste among COVID-19 positive and negative individuals in Chennai city, Southern India. METHODS: We did an analytical cross-sectional study among individuals aged 18-80 years undergoing testing at COVID-19 sample collection centres. We ascertained loss of smell and taste using standardised self-reporting and clinical examination procedures. We administered Sino Nasal Outcome (SNOT 22) questionnaire for comprehensive understanding of these symptoms. We compared proportion having symptoms between COVID-19 positive and negative persons. We compared the two assessment methods to compute diagnostic validity indicators. RESULTS: Of the 277 participants, 169 (61%) were men and mean age of 40.7 years [SD = 13.3]. Fifty eight (21%) had COVID-19 and 12 (36%) of them were asymptomatic. Predominantly reported symptoms were fever (30%), headache (18%) and cough (18%). Self-reported or clinically identified new loss of smell or taste was higher among COVID-19 positive (n = 13; 22%) than negative persons (n = 23; 11%) [p = 0.02]. Sensitivity was higher for self-reported or clinically identified loss of smell (17.2%) than that of loss of taste (6.9%). Negative predictive value for loss of smell or taste, self-reported or clinically identified was 81%. Likelihood ratio of positive test was 2.13. CONCLUSION: Loss of smell or taste are predominantly reported by COVID-19 confirmed individuals. Objective and subjective assessments of smell and taste may be required to identify those requiring COVID-19 testing.

Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques.

The COVID-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. Safe and effective vaccines are needed to overcome this crisis. Here, we develop and assess the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine in rhesus macaques. Twenty macaques were divided into four groups of five animals each. One group was administered a placebo, while three groups were immunized with three different vaccine candidates of BBV152 at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which exhibited interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. This vaccine candidate BBV152 has completed Phase I/II (NCT04471519) clinical trials in India and is presently in phase III, data of this study substantiates the immunogenicity and protective efficacy of the vaccine candidates.

Successful integration of HIV pre-exposure prophylaxis into a community-based HIV prevention program for female sex workers in Kolkata, India.

We assessed the impact of pre-exposure prophylaxis (PrEP) in the context of a community-based HIV program among female sex workers (FSWs) in Kolkata, India. This was an open-label, uncontrolled demonstration trial. HIV seronegative FSWs over 18 years were eligible. Participants were administered daily tenofovir/emtricitabine (TDF-FTC) with follow-up visits at months 1, 3, 6, 9, 12, and 15. Drug adherence was monitored by self-report, and a random subset of participants underwent plasma TDF testing. 843 women were screened and 678 enrolled and started on PrEP. Seventy-nine women (11%) did not complete all scheduled visits: four women died of reasons unrelated to PrEP and 75 withdrew, for a 15-month retention rate of 89%. Self-reported daily adherence was over 70%. Among those tested for TDF, the percentage of women whose level reached ≥40 ng/mL was 65% by their final visit. There were no HIV seroconversions, and no evidence of significant changes in sexual behavior. This study demonstrated the feasibility and effectiveness of PrEP for FSWs in Kolkata, with very high levels of adherence to PrEP and no HIV seroconversions. The integration of PrEP into an existing community-based HIV prevention program ensured community support and facilitated adherence.

Multicentric validation of indigenous molecular test Truenat™ MTB for detection of Mycobacterium tuberculosis in sputum samples from presumptive pulmonary tuberculosis patients in comparison with reference standards.

BACKGROUND & OBJECTIVES: : Early case detection is essential to interrupt transmission and to prevent further spread of tuberculosis (TB) in high endemic settings. Nucleic acid amplification tests (NAATs) with visual read-outs are ideal as point-of-care tests. Truenat™ MTB is an indigenous chip-based NAAT for detection of Mycobacterium tuberculosis, which involves extraction of DNA and real-time polymerase chain reaction (PCR) using portable, automated, battery-operated instruments. The current multicentric study was aimed to evaluate Truenat for detection of MTB in sputum samples obtained from patients with presumptive pulmonary TB with reference to culture as gold standard and Xpert as a comparator. METHODS: : The study was conducted at four sites, namely ICMR-National Institute for Research in Tuberculosis, Chennai; All India Institute of Medical Sciences, New Delhi; ICMR-National JALMA Institute for Leprosy and Other Mycobacterial Diseases, Agra; and National Institute of TB and Respiratory Diseases, New Delhi. Patients suspected to have TB were screened for eligibility. Two sputum samples were collected from each patient. Tests included smear, Xpert and Truenat directly from the sputum sample and culture by Lowenstein-Jensen (L-J) medium and MGIT960 from decontaminated pellets. Sample used for Truenat assay was coded. Resolution of Truenat false positives was done using an in-house PCR with TRC4 primers. RESULTS: : The study enrolled 2419 presumptive TB patients after screening 2465 patients, and 3541 sputum samples were collected from the enrolled patients. Results of 2623 samples were available for analysis. Truenat showed a positivity rate of 48.5 per cent as compared to 37.0 per cent by Xpert. The sensitivities of Truenat and Xpert were was 88.3 and 79.7 per cent, respectively in comparison with culture. INTERPRETATION & CONCLUSIONS: : Truenat MTB identified more positives among culture-confirmed samples than Xpert and had higher sensitivity. In addition, other advantageous operational features of Truenat MTB were identified which would be useful in field settings.