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Background: On January 30, 2023, 26 acute diarrheal disease (ADD) cases and a death were reported from a village in Dibrugarh, Assam, India. We investigated and described the outbreak by time, place and person, identified the potential exposures, and formulated recommendations. Methods: We defined a case of ADD as the occurrence of loose stools (≥3 episodes) between January 27, 2023 and February 11, 2023. We conducted a door-to-door case search, calculated attack rates by age and gender, drew an epidemic curve, and plotted cases by residence. We performed a case-control study to identify possible exposure variables, calculated odds ratio (OR) with 95 % confidence interval (CI), and collected stool and water specimens from households and schools for laboratory testing. Results: We identified a total of 55 cases, with an overall attack rate of 5.6 % and one death (case fatality rate of 1.8 %). School-going children exhibited a higher attack rate of 39 %. Shigella flexneri was isolated from one of the stool specimens. Furthermore, the water obtained from households' tube wells exceeded the permissible limits of E. coli for consumption. Consuming prasadam (Sacred food) at a school religious event (OR = 6.2, 95 % CI = 2.6–15.2) and not washing hands after defecation (OR = 8.2, 95 % CI = 1.7–38) were associated with ADD. Conclusion: The results indicated that the food served during the school religious event could potentially be the source of the ADD outbreak. The food served during the event likely acted as a medium for community transmission, possibly due to unhygienic practices and contaminated drinking water.

Abstract Introduction HIV self‐testing (HIVST) has been shown to increase the uptake of HIV testing and help achieve the UNAIDS 95‐95‐95 targets. This study assessed the acceptability, usability (ease of use and result interpretation) and the willingness to pay for HIVST kits distributed through three distribution models, namely the community‐based, PLHIV network‐led and private practitioners models, in India. Methods This cross‐sectional study was implemented across 14 states in India between September 2021 and June 2022. All participants could choose between blood‐based or oral‐fluid‐based test kits. Participants were shown a test‐kit usage demonstration video, and pre‐ and post‐test counselling was provided for all. Participants were followed‐up after testing, and if reported reactive, were further supported for linkage to confirmatory testing and antiretroviral therapy (ART) initiation. Results Among the 90,605 participants found eligible, 88,080 (97%) accepted an HIVST kit. Among the 87,976 who reported using an HIVST kit, 45,207 (51%) preferred a blood‐based kit, and 42,120 (48%) reported testing for the first time. For future testing, 77,064 (88%) reported preferring HIVST over other HIV testing methods. Among those who used the kit, 83,308 (95%) found the kit easy to use, and 83,237 (95%) reported that the test results were easy to interpret. Among those who preferred HIVST for future use, 52,136 (69%) were willing to pay for the kit, with 35,854 (69%) of those willing to pay less than US$ 1.20. Only one instance of social harm was reported, with a participant reporting suicidal tendencies due to discord with their partner. Out of 328 participants (0.4%) who tested reactive with HIVST, 291 (89%) were linked to confirmatory testing; of these, 254 were confirmed HIV positive, and 216 (85%) successfully initiated ART. Conclusions Overall, we report that nearly all participants were willing to accept HIVST, found the test kits easy to use and interpret, and about two‐thirds were willing to pay for HIVST. Given the high levels of acceptance and the ability to reach a large proportion of first‐time testers, HIVST in India could contribute to achieving the UNAIDS first 95 and ending the HIV epidemic.

In India, the incidence of mucormycosis reached high levels during 2021–2022, coinciding with the COVID-19 pandemic. In response to this, we established a multicentric ambispective cohort of patients hospitalised with mucormycosis across India. In this paper, we report their baseline profile, clinical characteristics and outcomes at discharge. Patients hospitalized for mucormycosis during March–July 2021 were included. Mucormycosis was diagnosed based on mycological confirmation on direct microscopy (KOH/Calcofluor white stain), culture, histopathology, or supportive evidence from endoscopy or imaging. After consent, trained data collectors used medical records and telephonic interviews to capture data in a pre-tested structured questionnaire. At baseline, we recruited 686 patients from 26 study hospitals, of whom 72.3% were males, 78% had a prior history of diabetes, 53.2% had a history of corticosteroid treatment, and 80% were associated with COVID-19. Pain, numbness or swelling of the face were the commonest symptoms (73.3%). Liposomal Amphotericin B was the commonest drug formulation used (67.1%), and endoscopic sinus surgery was the most common surgical procedure (73.6%). At discharge, the disease was stable in 43.3%, in regression for 29.9% but 9.6% died during hospitalization. Among survivors, commonly reported disabilities included facial disfigurement (18.4%) and difficulties in chewing/swallowing (17.8%). Though the risk of mortality was only 1 in 10, the disability due to the disease was very high. This cohort study could enhance our understanding of the disease’s clinical progression and help frame standard treatment guidelines.

IntroductionPrimary Human Papilloma Virus (HPV) testing offers higher sensitivity and specificity over Visual Inspection using Acetic acid (VIA) in cervical cancer screening. Self-sampling is a promising strategy to boost participation and reduce disparities. However, concerns about the initial costs hinder HPV testing adoption in low and middle-income countries. This study assesses the cost-utility of home-based HPV self-sampling versus VIA for cervical cancer screening in India.MethodsA cross-sectional study was conducted in East district, Sikkim, India, comparing the costs and utility outcomes of population-based cervical cancer screening through VIA and primary HPV screening through self-sampling. Cost-related data were collected from April 2021 to March 2022 using the bottom-up micro-costing method, while utility measures were collected prospectively using the EuroQoL-5D-5L questionnaire. The utility values were converted into quality-adjusted life days (QALDs) for an 8-day period. The willingness to pay threshold (WTP) was based on per capita GDP for 2022. If the calculated Incremental Cost-Effectiveness Ratio (ICER) value is lower than the WTP threshold, it signifies that the intervention is cost-effective.ResultsThe study included 95 women in each group of cervical cancer screening with VIA & HPV self-sampling. For eight days, the QALD was found to be 7.977 for the VIA group and 8.0 for the HPV group. The unit cost per woman screened by VIA and HPV self-testing was ₹1,597 (US$ 19.2) and ₹1,271(US$ 15.3), respectively. The ICER was ₹-14,459 (US$ -173.6), which was much below the WTP threshold for eight QALDs, i.e. ₹ 4,193 (US$ 50.4).ConclusionThe findings support HPV self-sampling as a cost-effective alternative to VIA. This informs policymakers and healthcare providers for better resource allocation in cervical cancer screening in Sikkim.

Due to the workload and lack of a critical mass of trained operational researchers within their ranks, health systems and programmes may not be able to dedicate sufficient time to conducting operational research (OR). Hence, they may need the technical support of operational researchers from research/academic organisations. Additionally, there is a knowledge gap regarding implementing differentiated tuberculosis (TB) care in programme settings. In this ‘how we did it’ paper, we share our experience of implementing a differentiated TB care model along with an inbuilt OR component in Tamil Nadu, a southern state in India. This was a health system initiative through a collaboration of the State TB cell with the Indian Council of Medical Research institutes and the World Health Organisation country office in India. The learnings are in the form of eleven tips: four broad principles (OR on priority areas and make it a health system initiative, implement simple and holistic ideas, embed OR within routine programme settings, aim for long-term engagement), four related to strategic planning (big team of investigators, joint leadership, decentralised decision-making, working in advance) and three about implementation planning (conducting pilots, smart use of e-tools and operational research publications at frequent intervals). These may act as a guide for other Indian states, high TB burden countries that want to implement differentiated care, and for operational researchers in providing technical assistance for strengthening implementation and conducting OR in health systems and programmes (TB or other health programmes). Following these tips may increase the chances of i) an enriching engagement, ii) policy/practice change, and iii) sustainable implementation.

Abstract Background Plasmacytoid and myeloid dendritic cells play a vital role in the protection against viral infections. In COVID-19, there is an impairment of dendritic cell (DC) function and interferon secretion which has been correlated with disease severity. Results In this study, we described the frequency of DC subsets and the plasma levels of Type I (IFNα, IFNβ) and Type III Interferons (IFNλ1), IFNλ2) and IFNλ3) in seven groups of COVID-19 individuals, classified based on days since RT-PCR confirmation of SARS-CoV2 infection. Our data shows that the frequencies of pDC and mDC increase from Days 15–30 to Days 61–90 and plateau thereafter. Similarly, the levels of IFNα, IFNβ, IFNλ1, IFNλ2 and IFNλ3 increase from Days 15–30 to Days 61–90 and plateau thereafter. COVID-19 patients with severe disease exhibit diminished frequencies of pDC and mDC and decreased levels of IFNα, IFNβ, IFNλ1, IFNλ2 and IFNλ3. Finally, the percentages of DC subsets positively correlated with the levels of Type I and Type III IFNs. Conclusion Thus, our study provides evidence of restoration of homeostatic levels in DC subset frequencies and circulating levels of Type I and Type III IFNs in convalescent COVID-19 individuals.

Objectives: India introduced BBV152/Covaxin and AZD1222/Covishield vaccines in January 2021. We estimated the effectiveness of these vaccines against severe COVID-19 among individuals aged ≥45 years. Methods: We did a multi-centric, hospital-based, case-control study between May and July 2021. Cases were severe COVID-19 patients, and controls were COVID-19 negative individuals from 11 hospitals. Vaccine effectiveness (VE) was estimated for complete (2 doses ≥ 14 days) and partial (1 dose ≥ 21 days) vaccination; interval between two vaccine doses and vaccination against the Delta variant. We used the random effects logistic regression model to calculate the adjusted odds ratios (aOR) with a 95% confidence interval (CI) after adjusting for relevant known confounders. Results: We enrolled 1143 cases and 2541 control patients. The VE of complete vaccination was 85% (95% CI: 79-89%) with AZD1222/Covishield and 71% (95% CI: 57-81%) with BBV152/Covaxin. The VE was highest for 6-8 weeks between two doses of AZD1222/Covishield (94%, 95% CI: 86-97%) and BBV152/Covaxin (93%, 95% CI: 34-99%). The VE estimates were similar against the Delta strain and sub-lineages. Conclusion: BBV152/Covaxin and AZD1222/Covishield were effective against severe COVID-19 among the Indian population during the period of dominance of the highly transmissible Delta variant in the second wave of the pandemic. An escalation of two-dose coverage with COVID-19 vaccines is critical to reduce severe COVID-19 and further mitigate the pandemic in the country.

Summary: Background: The COVID-19 pandemic showcased the power of genomic sequencing to tackle the emergence and spread of infectious diseases. However, metagenomic sequencing of total microbial RNAs in wastewater has the potential to assess multiple infectious diseases simultaneously and has yet to be explored. Methods: A retrospective RNA-Seq epidemiological survey of 140 untreated composite wastewater samples was performed across urban (n = 112) and rural (n = 28) areas of Nagpur, Central India. Composite wastewater samples were prepared by pooling 422 individual grab samples collected prospectively from sewer lines of urban municipality zones and open drains of rural areas from 3rd February to 3rd April 2021, during the second COVID-19 wave in India. Samples were pre-processed and total RNA was extracted prior to genomic sequencing. Findings: This is the first study that has utilised culture and/or probe-independent unbiased RNA-Seq to examine Indian wastewater samples. Our findings reveal the detection of zoonotic viruses including chikungunya, Jingmen tick and rabies viruses, which have not previously been reported in wastewater. SARS-CoV-2 was detectable in 83 locations (59%), with stark abundance variations observed between sampling sites. Hepatitis C virus was the most frequently detected infectious virus, identified in 113 locations and co-occurring 77 times with SARS-CoV-2; and both were more abundantly detected in rural areas than urban zones. Concurrent identification of segmented virus genomic fragments of influenza A virus, norovirus, and rotavirus was observed. Geographical differences were also observed for astrovirus, saffold virus, husavirus, and aichi virus that were more prevalent in urban samples, while the zoonotic viruses chikungunya and rabies, were more abundant in rural environments. Interpretation: RNA-Seq can effectively detect multiple infectious diseases simultaneously, facilitating geographical and epidemiological surveys of endemic viruses that could help direct healthcare interventions against emergent and pre-existent infectious diseases as well as cost-effectively and qualitatively characterising the health status of the population over time. Funding: UK Research and Innovation (UKRI) Global Challenges Research Fund (GCRF) grant number H54810, as supported by Research England.

Due to the primary closure of the fragile tissues, large postoperative drainage is unexpected following a periodontal medical procedure. This case study elaborately illustrates the formation of a “liver coagulation” or “currant jam clot” following a periodontal fold surgical operation. Contamination, internal damage, and the presence of foreign particles such as bone splinters or bits of dental restorative dressing can all increase the risk of an incident happening.

Abstract Background In view of the growing popularity, reach and access for Massive Open Online Courses (MOOCs), India’s apex body for medical education, the National Medical Commission (NMC) mandated uniform foundational course on research methods for the medical post graduates (PGs) and faculty members of the medical institutions under NMC as MOOC. This course is a pioneering effort in the field of India’s PG medical education. NMC entrusted Indian Council of Medical Research (ICMR)-National Institute of Epidemiology (NIE) to design and offer the MOOC, named as Basic Course in Biomedical Research (BCBR). We describe the experience of designing and that of implementation challenges in the inaugural cycle of the course. Methods The course objective was to inculcate the fundamental concepts in research methods covering epidemiology and biostatistics in the form of video lectures, resource materials, discussion forum, assignments, feedback and a final proctored examination. The course was delivered over 16 weeks through MOOCs platform under the Indian Ministry of Education. We reviewed records, documents and faculty notes and described the course conceptualization, development, design and implementation process. We abstracted information from course portal on enrolment profile of the participants, self-reported course feedback (structured and open-ended on format, lectures and quality of contents), examination registration form, scores obtained in the assignments/examination and that of the participant queries. We described quantitative data using descriptive statistics. We presented the thematic analysis of qualitative data from open-ended questions in the feedback system and that of email interactions. Results The inaugural cycle (September-December 2019) was taken by 24,385 participants. Majority, 15,879 (65%) were from medical background. 13,242 (54%) were medical postgraduates and 2637 (11%) were medical teachers. Among the enrolled, 14,720 (60%) cleared the assignments. A total of 11,392 (47%), 8,205 (62%) medical PGs and 896 (34%) faculty members successfully completed the course. Feedback from 1305 (5%) participants had mean score of 4.5/5 (±0.7) for quality of teaching. We faced challenges in customizing the course for medical participants, unawareness among target group, digital illiteracy and the ongoing pandemic. Conclusions During the inaugural cycle of the online Basic Course in Biomedical Research course, nearly half of the enrolled participants successfully completed and received the certificate. India’s MOOC for enhancing research capabilities of future medical researchers encountered successes and challenges. Lessons learnt from the inaugural cycle will guide future directions and to address larger issues in terms of sustainability and replication by stakeholders in medical education in India or elsewhere.

Introduction: India experienced 2 waves of COVID-19 pandemic caused by SARS-CoV-2 and reported the second highest caseload globally. Seroepidemiologic studies were done to track the course of the pandemic. We systematically reviewed and synthesized the seroprevalence of SARS-CoV-2 in the Indian population.Methods: We included studies reporting seroprevalence of IgG antibodies against SARS-CoV-2 from March 1, 2020 to August 11, 2021 and excluded studies done only among patients with COVID-19 and vaccinated individuals. We searched published databases, preprint servers, and government documents using a combination of keywords and medical subheading (MeSH) terms of “Seroprevalence AND SARS-CoV-2 AND India”. We assessed risk of bias using the Newcastle-Ottawa scale, the appraisal tool for cross-sectional studies (AXIS), the Joanna Briggs Institute (JBI) critical appraisal tool, and WHO's statement on the Reporting of Seroepidemiological Studies for SARS-CoV-2 (ROSES-S). We calculated pooled seroprevalence along with 95% Confidence Intervals (CI) during the first (March 2020 to February 2021) and second wave (March to August 2021). We also estimated seroprevalence by selected demographic characteristics.Results: We identified 3821 studies and included 53 studies with 905379 participants after excluding duplicates, screening of titles and abstracts and full-text screening. Of the 53, 20 studies were of good quality. Some of the reviewed studies did not report adequate information on study methods (sampling = 24% (13/53); laboratory = 83% [44/53]). Studies of ‘poor’ quality had more than one of the following issues: unjustified sample size, nonrepresentative sample, nonclassification of nonrespondents, results unadjusted for demographics and methods insufficiently explained to enable replication. Overall pooled seroprevalence was 20.7% in the first (95% CI = 16.1 to 25.3) and 69.2% (95% CI = 64.5 to 73.8) in the second wave. Seroprevalence did not differ by age in first wave, whereas in the second, it increased with age. Seroprevalence was slightly higher among women in the second wave. In both the waves, the estimate was higher in urban than in rural areas.Conclusion: Seroprevalence increased by 3-fold between the 2 waves of the pandemic in India. Our review highlights the need for designing and reporting studies using standard protocols.

Introduction: Coronavirus disease-2019 (COVID-19) had a multidimensional impact on human life. It affects the health-related quality of life (HRQoL) which is a perceived measure of physical and mental health. We estimated the EuroQol utility value for COVID-19 and the associated factors for those managed at Siddha COVID care centres in Tamil Nadu. Methods: A cross-sectional study was conducted by a telephonic interview of 2000 randomly selected COVID-19 adults tested positive during June 2020 to Jan 2021. We collected sociodemographic, clinical and EQ-5D-5L profile. Mean EQ-5D-5L summary utility values and EQ-VAS scores were estimated. Multivariate regression was used to examine the factors associated with EQ-5D-5L. Study protocol was approved by the Institutional ethics committee of Government Siddha Medical College, Chennai (GSMC–CH–3401/ME-2/050/2021). The committee waived the written informed consent considering the pandemic situation of emerging infectious diseases. Results: We interviewed 1047 participants. Of the total 68% were males with the median age (IQR) of 38 (29–51) years. The mean EQ-5D-5L utility score and EQ-VAS scores are 0.98 ± 0.05 and 92.14 ± 0.39 respectively. COVID-19 asymptomatic group reported a mean utility score of 0.99 ± 0.03 which is relatively more than the symptomatic group (0.97 ± 0.06),. EQ-VAS score was also reported high among the asymptomatic (95.45 ± 5.95) than the symptomatic (91.40 ± 8.69COVID-19. Conclusion: The severity of illness and the comorbidity are significantly associated with a low HRQoL of COVID-19 patients.

A complete sampling frame (CSF) is needed for the development of probability sampling structures; utilisation of a spatial sampling frame (SSF) was the objective of the present study. We used two sampling methods, simple random sampling (SRS) and stratified random sampling (STRS), to compare the prevalence estimates delivered by a CSF to that by a SSF when applied to self-reported hypertension and diabetes mellitus in a semi-urban setting and in a rural one. A CSF based on Geodatabase of all households and all individuals was available for our study that focused on adults aged 18-69 years in the two settings. A single digitized shapefile of solely household regions/structures as SSF was developed using Google Earth and employed for the study. The results from the two sampling frames were similar and not significantly different. All 95%CI calculations contained the prevalence rates of the two medical conditions except for one occasion based on STRS and CSF. The SRS based on CSF showed a minimum 95% CI width for diabetes mellitus, whereas SSF showed a minimum 95% CI width for hypertension. The coefficient of variation exceeded 10.0% on six occasions for CSF but only once for SSF, which was found to be as efficient as CSF.

Abstract Monocytes are thought to play an important role in host defence and pathogenesis of COVID-19. However, a comprehensive examination of monocyte numbers and function has not been performed longitudinally in acute and convalescent COVID-19. We examined the absolute counts of monocytes, the frequency of monocyte subsets, the plasma levels of monocyte activation markers using flowcytometry and ELISA in seven groups of COVID-19 individuals, classified based on days since RT-PCR confirmation of SARS-CoV2 infection. Our data shows that the absolute counts of total monocytes and the frequencies of intermediate and non-classical monocytes increases from Days 15–30 to Days 61–90 and plateau thereafter. In contrast, the frequency of classical monocytes decreases from Days 15–30 till Days 121–150. The plasma levels of sCD14, CRP, sCD163 and sTissue Factor (sTF)—all decrease from Days 15–30 till Days 151–180. COVID-19 patients with severe disease exhibit higher levels of monocyte counts and higher frequencies of classical monocytes and lower frequencies of intermediate and non-classical monocytes and elevated plasma levels of sCD14, CRP, sCD163 and sTF in comparison with mild disease. Thus, our study provides evidence of dynamic alterations in monocyte counts, subset frequencies and activation status in acute and convalescent COVID-19 individuals.

Abstract Background Antimicrobial resistance is a global health emergency. Persons colonized with multidrug-resistant organisms (MDROs) are at risk for developing subsequent multidrug-resistant infections, as colonization represents an important precursor to invasive infection. Despite reports documenting the worldwide dissemination of MDROs, fundamental questions remain regarding the burden of resistance, metrics to measure prevalence, and determinants of spread. We describe a multi-site colonization survey protocol that aims to quantify the population-based prevalence and associated risk factors for colonization with high-threat MDROs among community dwelling participants and patients admitted to hospitals within a defined population-catchment area. Methods Researchers in five countries (Bangladesh, Chile, Guatemala, Kenya, and India) will conduct a cross-sectional, population-based prevalence survey consisting of a risk factor questionnaire and collection of specimens to evaluate colonization with three high-threat MDROs: extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Healthy adults residing in a household within the sampling area will be enrolled in addition to eligible hospitalized adults. Colonizing isolates of these MDROs will be compared by multilocus sequence typing (MLST) to routinely collected invasive clinical isolates, where available, to determine potential pathogenicity. A colonizing MDRO isolate will be categorized as potentially pathogenic if the MLST pattern of the colonizing isolate matches the MLST pattern of an invasive clinical isolate. The outcomes of this study will be estimates of the population-based prevalence of colonization with ESCrE, CRE, and MRSA; determination of the proportion of colonizing ESCrE, CRE, and MRSA with pathogenic characteristics based on MLST; identification of factors independently associated with ESCrE, CRE, and MRSA colonization; and creation an archive of ESCrE, CRE, and MRSA isolates for future study. Discussion This is the first study to use a common protocol to evaluate population-based prevalence and risk factors associated with MDRO colonization among community-dwelling and hospitalized adults in multiple countries with diverse epidemiological conditions, including low- and middle-income settings. The results will be used to better describe the global epidemiology of MDROs and guide the development of mitigation strategies in both community and healthcare settings. These standardized baseline surveys can also inform future studies seeking to further characterize MDRO epidemiology globally.

Background: Earlier serosurveys in India revealed seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) of 0.73% in May–June 2020 and 7.1% in August–September 2020. A third serosurvey was conducted between December 2020 and January 2021 to estimate the seroprevalence of SARS-CoV-2 infection among the general population and healthcare workers (HCWs) in India. Methods: The third serosurvey was conducted in the same 70 districts as the first and second serosurveys. For each district, at least 400 individuals aged ≥10 years from the general population and 100 HCWs from subdistrict-level health facilities were enrolled. Serum samples from the general population were tested for the presence of immunoglobulin G (IgG) antibodies against the nucleocapsid (N) and spike (S1-RBD) proteins of SARS-CoV-2, whereas serum samples from HCWs were tested for anti-S1-RBD. Weighted seroprevalence adjusted for assay characteristics was estimated. Results: Of the 28,598 serum samples from the general population, 4585 (16%) had IgG antibodies against the N protein, 6647 (23.2%) had IgG antibodies against the S1-RBD protein, and 7436 (26%) had IgG antibodies against either the N protein or the S1-RBD protein. Weighted and assay-characteristic-adjusted seroprevalence against either of the antibodies was 24.1% [95% confidence interval (CI) 23.0–25.3%]. Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI 23.5–27.8%). Conclusions: Nearly one in four individuals aged ≥10 years from the general population as well as HCWs in India had been exposed to SARS-CoV-2 by December 2020.

We conducted a cross-sectional survey to estimate the seroprevalence of IgG against severe acute respiratory syndrome coronavirus 2 in Chennai, India. Among 12,405 serum samples tested, weighted seroprevalence was 18.4% (95% CI 14.8%–22.6%). These findings indicate most of the population of Chennai is still susceptible to this virus.

Introduction: The EQ-5D-5L questionnaire is a tool that is a very generic and preference-based instrument to describe the health-related quality of life. We have generated the stratified index utility value for the Tamil Nadu population and compared the utility values based on socio-demographic and clinical characteristics. Methods: We conducted a community-based analytical cross-sectional study using telephonic interviews from November 2020 till December 2020 among individuals aged 18 years and above who were infected by the coronavirus confirmed with an RT-PCR within 30 days in Tamil Nadu State. EQ-5D-5L profile, socio-demographic and clinical characteristics of the study participants were collected and analysed. Results: We interviewed 372 participants, with 57.5% were males, and their mean age was 44.5 ± 15.3 years. About 40% of participants reported as having comorbidities, such as diabetes (19.4%), hypertension (12.4%), heart disease (2.4%), kidney disease (0.8%) and others. The mean EQ-5D utility score was 0.925 ± 0.150, and the mean EQ-VAS was 90.68 ± 11.81. Overall, men had a higher utility value (0.938 ± 0.130) than women, (0.907 ± 0.170). Individuals with comorbidities, requiring longer hospitalisation were having lower utility scores than their counterparts. Conclusion: We report the EQ-5D-5L utility values for the COVID-19 illness. These values would help to estimate quality-adjusted life years in health economic evaluation studies.

BackgroundIn the ongoing COVID-19 pandemic, an increased incidence of ROCM was noted in India among those infected with COVID. We determined risk factors for rhino-orbito-cerebral mucormycosis (ROCM) post Coronavirus disease 2019 (COVID-19) among those never and ever hospitalized for COVID-19 separately through a multicentric, hospital-based, unmatched case-control study across India.MethodsWe defined cases and controls as those with and without post-COVID ROCM, respectively. We compared their socio-demographics, co-morbidities, steroid use, glycaemic status, and practices. We calculated crude and adjusted odds ratio (AOR) with 95% confidence intervals (CI) through logistic regression. The covariates with a p-value for crude OR of less than 0·20 were considered for the regression model.ResultsAmong hospitalised, we recruited 267 cases and 256 controls and 116 cases and 231 controls among never hospitalised. Risk factors (AOR; 95% CI) for post-COVID ROCM among the hospitalised were age 45-59 years (2·1; 1·4 to 3·1), having diabetes mellitus (4·9; 3·4 to 7·1), elevated plasma glucose (6·4; 2·4 to 17·2), steroid use (3·2; 2 to 5·2) and frequent nasal washing (4·8; 1·4 to 17). Among those never hospitalised, age ≥ 60 years (6·6; 3·3 to 13·3), having diabetes mellitus (6·7; 3·8 to 11·6), elevated plasma glucose (13·7; 2·2 to 84), steroid use (9·8; 5·8 to 16·6), and cloth facemask use (2·6; 1·5 to 4·5) were associated with increased risk of post-COVID ROCM.ConclusionsHyperglycemia, irrespective of having diabetes mellitus and steroid use, was associated with an increased risk of ROCM independent of COVID-19 hospitalisation. Rational steroid usage and glucose monitoring may reduce the risk of post-COVID.

Background India has experienced the second largest outbreak of COVID-19 globally, yet there is a paucity of studies analysing contact tracing data in the region which can optimise public health interventions (PHI’s). Methods We analysed contact tracing data from Karnataka, India between 9 March and 21 July 2020. We estimated metrics of transmission including the reproduction number (R), overdispersion (k), secondary attack rate (SAR), and serial interval. R and k were jointly estimated using a Bayesian Markov Chain Monte Carlo approach. We studied determinants of risk of further transmission and risk of being symptomatic using Poisson regression models. Findings Up to 21 July 2020, we found 111 index cases that crossed the super-spreading threshold of ≥8 secondary cases. Among 956 confirmed traced cases, 8.7% of index cases had 14.4% of contacts but caused 80% of all secondary cases. Among 16715 contacts, overall SAR was 3.6% [95% CI, 3.4–3.9] and symptomatic cases were more infectious than asymptomatic cases (SAR 7.7% vs 2.0%; aRR 3.63 [3.04–4.34]). As compared to infectors aged 19–44 years, children were less infectious (aRR 0.21 [0.07–0.66] for 0–5 years and 0.47 [0.32–0.68] for 6–18 years). Infectors who were confirmed ≥4 days after symptom onset were associated with higher infectiousness (aRR 3.01 [2.11–4.31]). As compared to asymptomatic cases, symptomatic cases were 8.16 [3.29–20.24] times more likely to cause symptomatic infection in their secondary cases. Serial interval had a mean of 5.4 [4.4–6.4] days, and case fatality rate was 2.5% [2.4–2.7] which increased with age. Conclusion We found significant heterogeneity in the individual-level transmissibility of SARS-CoV-2 which could not be explained by the degree of heterogeneity in the underlying number of contacts. To strengthen contact tracing in over-dispersed outbreaks, testing and tracing delays should be minimised and retrospective contact tracing should be implemented. Targeted measures to reduce potential superspreading events should be implemented. Interventions aimed at children might have a relatively small impact on reducing transmission owing to their low symptomaticity and infectivity. We propose that symptomatic cases could cause a snowballing effect on clinical severity and infectiousness across transmission generations; further studies are needed to confirm this finding.

BackgroundIndia began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March-June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs).Methods and findingsWe did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test-adjusted seroprevalence of IgG antibodies against SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6-9 years, 5,798 (20%) were aged 10-17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. The weighted and test-adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged ≥6 years was 67.6% (95% CI 66.4% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey.ConclusionsNearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June-July 2021 in India. As one-third of the population is still seronegative, it is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions.

Abstract COVID‐19 has affected over a billion people around the world, with over 2 million losing their lives (Worldometer). About 10% of patients infected with COVID‐19 develop a serious illness, including respiratory failure, that require advanced life‐supporting measures. Mortality among this subgroup exceeds 60%. We present a case of an otherwise healthy 34‐year‐old male who developed end‐stage pulmonary fibrosis following COVID‐19 infection. He achieved haemodynamic stability with mechanical ventilation and extracorporeal membrane oxygenation (ECMO) but did not show any sign of weaning off ECMO; however, he successfully underwent bilateral lung transplantation.

Objective Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma.Design Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease.Setting 39 public and private hospitals across India during the study period from 22 April to 14 July 2020.Participants Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed.Primary outcome measure Factors associated with all-cause mortality at 28 days after enrolment.Results The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3–7) and non-survivors (4 days; IQR 3–6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p10 (9.97, 3.65–27.13, p1.0 mg/L (2.50, 1.14–5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44–4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60–5.45, p=0.001) were significantly associated with death.Conclusion In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death.Trial registration number CTRI/2020/04/024775.

We conducted a serosurvey of 155 healthcare workers and 124 household and community members who had close contact with 18 patients who had laboratory-confirmed Nipah virus infections in Kerala, India. We detected 3 subclinical infections; 2 persons had IgM and IgG and 1 only IgM against Nipah virus.

Since the recent introduction of several viable vaccines for SARS-CoV-2, vaccination uptake has become the key factor that will determine our success in containing the COVID-19 pandemic. We argue that game theory and social network models should be used to guide decisions pertaining to vaccination programmes for the best possible results. In the months following the introduction of vaccines, their availability and the human resources needed to run the vaccination programmes have been scarce in many countries. Vaccine hesitancy is also being encountered from some sections of the general public. We emphasize that decision-making under uncertainty and imperfect information, and with only conditionally optimal outcomes, is a unique forte of established game-theoretic modelling. Therefore, we can use this approach to obtain the best framework for modelling and simulating vaccination prioritization and uptake that will be readily available to inform important policy decisions for the optimal control of the COVID-19 pandemic.

BackgroundThe Indian Council of Medical Research set up a pan-national laboratory network to diagnose and monitor Coronavirus disease 2019 (COVID-19). Based on these data, we describe the epidemiology of the pandemic at national and sub-national levels and the performance of the laboratory network.MethodsWe included surveillance data for individuals tested and the number of tests from March 2020 to January 2021. We calculated the incidence of COVID-19 by age, gender and state and tests per 100,000 population, the proportion of symptomatic individuals among those tested, the proportion of repeat tests and test positivity. We computed median (Interquartile range-IQR) days needed for selected surveillance activities to describe timeliness.ResultsThe analysis included 176 million individuals and 188 million tests. The overall incidence of COVID-19 was 0.8%, and 12,584 persons per 100,000 population were tested. 6.1% of individuals tested returned a positive result. Ten of the 37 Indian States and Union Territories accounted for about 75.6% of the total cases. Daily testing scaled up from 40,000 initially to nearly one million in March 2021. The median duration between symptom onset and sample collection was two (IQR = 0,3) days, median duration between both sample collection and testing and between testing and data entry were less than or equal to one day. Missing or invalid entries ranged from 0.01% for age to 0.7% for test outcome.ConclusionThe laboratory network set-up by ICMR was scaled up massively over a short period, which enabled testing a large section of the population. Although all states and territories were affected, most cases were concentrated in a few large states. Timeliness between the various surveillance activities was acceptable, indicating good responsiveness of the surveillance system.

BackgroundRisk factors for the development of severe COVID-19 disease and death have been widely reported across several studies. Knowledge about the determinants of severe disease and mortality in the Indian context can guide early clinical management.MethodsWe conducted a hospital-based case control study across nine sites in India to identify the determinants of severe and critical COVID-19 disease.FindingsWe identified age above 60 years, duration before admission >5 days, chronic kidney disease, leucocytosis, prothrombin time > 14 sec, serum ferritin >250 ng/mL, d-dimer >0.5 ng/mL, pro-calcitonin >0.15 μg/L, fibrin degradation products >5 μg/mL, C-reactive protein >5 mg/L, lactate dehydrogenase >150 U/L, interleukin-6 >25 pg/mL, NLR ≥3, and deranged liver function, renal function and serum electrolytes as significant factors associated with severe COVID-19 disease.InterpretationWe have identified a set of parameters that can help in characterising severe COVID-19 cases in India. These parameters are part of routinely available investigations within Indian hospital settings, both public and private. Study findings have the potential to inform clinical management protocols and identify patients at high risk of severe outcomes at an early stage.

Background: Examination of CD4+ T cell responses during the natural course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection offers useful information for the improvement of vaccination strategies against this virus and the protective effect of these T cells. Methods: We characterized the SARS-CoV-2-specific CD4+ T cell activation marker, multifunctional cytokine and cytotoxic marker expression in recovered coronavirus disease 2019 (COVID-19) individuals. Results: CD4+ T-cell responses in late convalescent (>6 months of diagnosis) individuals are characterized by elevated frequencies of activated as well as mono, dual- and multi-functional Th1 and Th17 CD4+ T cells in comparison to early convalescent (+ T cells were also enhanced in late convalescent compared to early convalescent individuals. Conclusion: Our findings from a low-to middle-income country suggest protective adaptive immune responses following natural infection of SARS-CoV-2 are elevated even at six months following initial symptoms, indicating the CD4+ T cell mediated immune protection lasts for six months or more in natural infection.

Scrub typhus is associated with outbreaks of acute encephalitis syndrome in Uttar Pradesh, India. A case-control study indicated that children residing, playing, or visiting fields; living with firewood stored indoors; handling cattle fodder; and practicing open defecation were at increased risk for scrub typhus. Communication messages should focus on changing these behaviors.

Background: Migration has been linked to the spread of HIV epidemic from the urban areas of western India to the rural areas of north India. Objectives: This is the first population-based study among the wives of migrant workers of Muzaffarpur district in Bihar with objectives to describe their sexual behavior within marriage, estimate the prevalence of HIV, and to know their awareness regarding HIV/AIDS. Methods: A two-stage cluster survey was conducted by randomly selecting 25 eligible wives from each of the 34 selected villages. A total of 850 wives were interviewed and the blood samples were collected for HIV testing. To determine the factors associated with HIV/AIDS-awareness, we calculated adjusted odds ratios and 95% confidence intervals (CI) using multiple logistic regression analysis. Results: 34 (3%) of 850 wives reported condom use with their husband. HIV prevalence was 0.59% (95% CI: 0.19-1.37%) among the wives of migrant workers. Out of 850 wives, 132 (15.5%) had heard about HIV. Condoms use (OR = 3.21, 95% CI: 1.22-7.90) and premarital sex (OR=7.44, 95% CI: 1.6-33.67) were found significantly positively associated with HIV knowledge of wives. HIV awareness of the wives was significantly associated with age-group 15-24 years, literacy status, and possession of television and husbands’ literacy status. The knowledge about HIV among wives had significant positive impact on condoms use and premarital sex. HIV prevalence among the wives of migrant workers was higher than the prevalence among women in the general population. Education was found to be positively associated with awareness about HIV. Conclusions: Effective interventions are needed for increasing awareness of HIV among wives of migrant workers in Bihar.

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.

Background: Studies from India on sputum conversion and tuberculosis (TB) treatment outcomes among TB patients with diabetes are limited. Objective: The objective of this study is to estimate the proportion of sputum smear conversion and successful treatment outcomes among diabetic–TB patients treated under Revised National TB Control Programme (RNTCP). Methodology: Information on TB disease, diabetes, sputum conversion, and treatment outcomes were collected from treatment cards of adult TB patients (age >18 years) treated in the District TB Centre TB Unit, Tiruchirapalli, Tamil Nadu from July 1, 2014, to October 31, 2015. Results: Diabetes was documented in 163 (14%) of 1131 TB patients. Sputum conversion was in 107 (94%) of 114 smear positive-TB patients. Successful TB treatment outcome was in 116 (85%) of 136 patients and 107 (86%) of 124 new TB patients. Conclusion: Sputum conversion was as per RNTCP target while treatment success rate among the new TB patients with diabetes was suboptimal.

Objective: To estimate the prevalence of usage, unsafe practices and risk perception regarding household pesticides in a rural community of Tamil Nadu, India. Materials and Methods: In a cross-sectional survey we used a pre-tested questionnaire and trained interviewers to collect information on household pesticide use for the past 6 months from any adult member of randomly selected households. Results: Out of 143 households, 95% used at least one household pesticide (95% CI: 93.5-99.5) and 94% used at least one household pesticide specifically for mosquito control. The most commonly used pesticides were mosquito coils (75%), mosquito liquid vaporizers (36%), ant-killing powder (24%) and moth/naphthalene balls (18%). The major non-chemical methods of pest control were rat traps (12%) and mosquito bed nets (7.5%). Out of the mosquito coil users, 61% kept the windows and doors closed while the coil was burning. Out of the moth ball users, 88% left them in the place of use till they fully vaporized. Nearly half of the users did not know that household pesticides were harmful to their health and the health of their children. Conclusions: The use of household pesticides was highly prevalent in this rural community. The prevalence of unsafe practices while handling them was also high. We recommend that the users of household pesticides be educated about the health hazards and about safe practices and non-chemical methods of pest control be promoted.

Models are designed to provide evidence for strategic program planning by examining the impact of different interventions on projected HIV incidence. We employed the Goals Model to fit the HIV epidemic curves in Andhra Pradesh, Maharashtra and Tamil Nadu states of India where HIV epidemic is considered to have matured and in a declining phase. Input data in the Goals Model consisted of demographic, epidemiological, transmission-related and risk group wise behavioral parameters. The HIV prevalence curves generated in the Goals Model for each risk group in the three states were compared with the epidemic curves generated by the Estimation and Projection Package (EPP) that the national program is routinely using. In all the three states, the HIV prevalence trends for high-risk populations simulated by the Goals Model matched well with those derived using state-level HIV surveillance data in the EPP. However, trends for the low- and medium-risk populations differed between the two models. This highlights the need to generate more representative and robust data in these sub-populations and consider some structural changes in the modeling equation and parameters in the Goals Model to effectively use it to assess the impact of future strategies of HIV control in various sub-populations in India at the sub-national level.

Pleural Aspergillosis is a rare entity, with most of the cases occurring on a background of lung disease or surgery. We report a case of a 16-year-old boy who developed pleural Aspergillosis in the absence of any obvious pre-disposing factors. Patient presented with fever, dry cough and left sided chest discomfort of 6 weeks duration. A chest radiograph revealed features of the left pyopneumothorax. Despite being started on presumptive antituberculous treatment and intercostal drainage his symptoms failed to resolve. The sputum and pus were then subjected to fungal smears and culture, which indicated growth of Aspergillus fumigatus. We report this case in view of the extreme rarity of pleural Aspergillosis occurring in a young healthy individual with no evidence of prior lung pathology. Furthermore, the source of infection was traced back to a very unusual possible focus - a decayed tooth infected with A. fumigatus, thus making the case even more interesting.

It seems generally accepted that targeted interventions in India have been successful in raising condom use between female sex workers (FSWs) and their clients. Data from clients of FSWs have been under-utilised to analyse the risk environments and vulnerability of both partners.The 2009 Integrated Biological and Behavioural Assessment survey sampled clients of FSWs at hotspots in Andhra Pradesh, Maharashtra and Tamil Nadu (n=5040). The risk profile of clients in terms of sexual networking and condom use are compared across usual pick-up place. We used propensity score matching (PSM) to estimate the average treatment effect on treated (ATT) of intervention messages on clients' consistent condom use with FSW.Clients of the more hidden sex workers who solicit from home or via phone or agents had more extensive sexual networks, reporting casual female partners as well as anal intercourse with male partners and FSW. Clients of brothel-based sex workers, who were the least educated, reported the fewest number/categories of partners, least anal sex, and lowest condom use (41%). Consistent condom use varied widely by state: 65% in Andhra Pradesh, 36% in Maharashtra and 29% in Tamil Nadu. Exposure to intervention messages on sexually transmitted infections was lowest among men frequenting brothels (58%), and highest among men soliciting less visible sex workers (70%). Exposure had significant impact on consistent condom use, including among clients of home-based sex workers (ATT 21%; p=0.001) and among men soliciting other more hidden FSW (ATT 17%; p=0.001). In Tamil Nadu no impact could be demonstrated.Commercial sex happens between two partners and both need to be, and can be, reached by intervention messages. Commercial sex is still largely unprotected and as the sex industry gets more diffuse a greater focus on reaching clients of sex workers seems important given their extensive sexual networks.