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Dengue is the most extensively spread mosquito-borne disease; endemic in more than 100 countries. Information about dengue disease burden, its prevalence, incidence and geographic distribution is critical in planning appropriate control measures against dengue fever. We conducted a systematic review and meta-analysis of dengue fever in India. We searched for studies published until 2017 reporting the incidence, the prevalence or case fatality of dengue in India. Our primary outcomes were (a) prevalence of laboratory confirmed dengue infection among clinically suspected patients, (b) seroprevalence in the general population and (c) case fatality ratio among laboratory confirmed dengue patients. We used binomial-normal mixed effects regression model to estimate the pooled proportion of dengue infections. Forest plots were used to display pooled estimates. The metafor package of R software was used to conduct meta-analysis. Of the 2285 identified articles on dengue, we included 233 in the analysis wherein 180 reported prevalence of laboratory confirmed dengue infection, seven reported seroprevalence as evidenced by IgG or neutralizing antibodies against dengue and 77 reported case fatality. The overall estimate of the prevalence of laboratory confirmed dengue infection among clinically suspected patients was 38.3% (95% CI: 34.8%-41.8%). The pooled estimate of dengue seroprevalence in the general population and CFR among laboratory confirmed patients was 56.9% (95% CI: 37.5-74.4) and 2.6% (95% CI: 2-3.4) respectively. There was significant heterogeneity in reported outcomes (p-values<0.001). Identified gaps in the understanding of dengue epidemiology in India emphasize the need to initiate community-based cohort studies representing different geographic regions to generate reliable estimates of age-specific incidence of dengue and studies to generate dengue seroprevalence data in the country.

As of February 29, 2020, more than 85,000 cases of coronavirus disease 2019 (COVID-19) have been reported from China and 53 other countries with 2,924 deaths. On January 30, 2020, the first laboratory-confirmed case of COVID was reported from Kerala, India. In view of the earlier evidence about effectiveness of repurposed lopinavir/ritonavir against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus (CoV), as well as preliminary docking studies conducted by the ICMR-National Institute of Virology, Pune, the Central Drugs Standard Control Organization approved the restricted public health use of lopinavir/ritonavir combination amongst symptomatic COVID-19 patients detected in the country. Hospitalized adult patients with laboratory-confirmed SARS-CoV-2 infection with any one of the following criteria will be eligible to receive lopinavir/ritonavir for 14 days after obtaining written informed consent: (i) respiratory distress with respiratory rate ≥22/min or SpO2of <94 per cent; (ii) lung parenchymal infiltrates on chest X-ray; (iii) hypotension defined as systolic blood pressure <90 mmHg or need for vasopressor/inotropic medication; (iv) new-onset organ dysfunction; and (v) high-risk groups - age >60 yr, diabetes mellitus, renal failure, chronic lung disease and immunocompromised persons. Patients will be monitored to document clinical (hospital length of stay and mortality at 14, 28 and 90 days), laboratory (presence of viral RNA in serial throat swab samples) and safety (adverse events and serious adverse events) outcomes. Treatment outcomes amongst initial cases would be useful in providing guidance about the clinical management of patients with COVID-19. If found useful in managing initial SARS-CoV-2-infected patients, further evaluation using a randomized control trial design is warranted to guide future therapeutic use of this combination.

•Vaccine effectiveness (VE) of single dose of JE vaccine was evaluated among Indian adults.•Vaccine provided adequate protection for at least six years.•A significant reduction in incidence of JE among adults was noted.•However, coverage of vaccine was low.•Periodic mass vaccination campaigns will further reduce the disease burden. Japanese encephalitis virus (JEV) remains the major etiology of encephalitis throughout Asia. In India, the state of Assam alone contributes more than one-third of the national burden of JE. Between 2011 and 2014, a single dose of JE vaccine SA 14-14-2 (LAJEV) was administered among adults aged 15–65 years residing in Sivasagar and Dibrugarh districts of Assam, India. We monitored the trend of JE incidence between 2009 and 2018 using JE surveillance data, estimated the long-term effectiveness of the single dose of LAJEV and estimated the coverage of JE vaccine in two districts. We compared the JE vaccination status of laboratory-confirmed hospitalized JE patients (case) and age, sex and locality matched healthy individuals (controls) to estimate the effectiveness of single dose of JE vaccine. We used surveillance data for 2009–2018 to calculate the incidence of JE among adults. We conducted a community-based survey to estimate the coverage of JE vaccine in the two districts. A total of 452 laboratory-confirmed JE case-patients and 904 matched healthy controls were enrolled in the study between 2012 and 2018. The effectiveness of a single dose of JE vaccine over the 7-year period was 77.0 (95% CI: 67.0–83.0). Vaccine effectiveness decreased from 91% (95% CI: 73.0–97.0) in first year of vaccination to 71% (95% CI: 21.0–90.0) at six years post-vaccination. The incidence of adults JE cases declined from 10.5 per 100,000 in the pre-vaccination period to 5.7 per 100,000 in the years following vaccination. The coverage of vaccine among adults in two districts was 40.1% (36.8–43.5). A single dose of JE vaccine offered adequate protection for at least six years. Conducting mass vaccination campaigns periodically would further reduce the incidence of JE in endemic districts in Assam.

In 2022, India's national tuberculosis (TB) elimination program (NTEP) commissioned a national level evaluation of active case finding (ACF) for TB to guide evidence-based strategic planning. As part of this evaluation, based on secondary data analysis we observed that the quality of ACF was suboptimal in 2021. Hence, this study aimed to understand the enablers, barriers, and suggested solutions to improve ACF for TB in India from NTEP staff (provider) perspective. This was a descriptive qualitative study involving key informant interviews from six districts and eight states, conducted between February and August 2023. We purposively selected key state- district- and sub-district-level program managers and implementers who were experienced and vocal. The interviews were audio recorded and transcribed verbatim by research interns and investigators. Two investigators independently did manual descriptive thematic analysis, and a third investigator resolved inconsistencies. The themes and categories emerged by collating together the results of the coding process. A total of 34 key informant interviews were conducted and of these, four were repeat interviews. Adequate budgets for ACF including incentives, performance review mechanism, engagement of all stakeholders, adopting a community friendly approach, use of rapid diagnostic tests and digitalization were the perceived enablers. In some states ACF was implemented in general population (not restricted to high-risk population) following directives at state level. There were limited mechanisms to ensure ACF quality indicators were met before disbursing incentives and cross-verification of the aggregate ACF care cascade numbers that were reported in Ni-kshay (electronic TB information management system under NTEP). In addition to the state and district level implementers having limited understanding of concepts around ACF (quality indicators, number needed to screen and yield), we also inferred the presence of a 'know-do' gap for many activities under ACF. The suggested solutions were around capacity building and quality improvement strategies. The existing national ACF guidance should be revised to emphasize capacity building, need to carry out ACF in high-risk (not general) population, quality control-linked incentives, and regular implementation monitoring of the activities. This should contribute towards better coverage and improved quality translating into better ACF outcomes.

India 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). We 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. Nearly 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.

Background Patients with TB have additional nutritional requirements and thus additional costs to the household. Ni-kshay Poshan Yojana (NPY) is a Direct Benefit Transfer (DBT) scheme under the National Tuberculosis Elimination Programme(NTEP) in India which offers INR 500 monthly to all notified patients with TB for nutritional support during the period of anti-TB treatment. Five years after its implementation, we conducted the first nationwide evaluation of NPY. Methods In our retrospective cohort study using programmatic data of patients notified with TB in nine randomly selected Indian states between 2018 and 2022, we estimated the proportion of patients who received at least one NPY instalment and the median time to receive the first instalment. We determined the factors associated (i) with non-receipt of NPY using a generalised linear model with Poisson family and log link and (ii) with time taken to receive first NPY benefit in 2022 using quantile regression at 50th percentile. Results Overall, 3,712,551 patients were notified between 2018 and 2022. During this period, the proportion who received at least one NPY instalment had increased from 56.9% to 76.1%. Non-receipt was significantly higher among patients notified by private sector (aRR 2.10;2.08,2.12), reactive for HIV (aRR 1.69;1.64,1.74) and with missing/undetermined diabetic status (aRR 2.02;1.98,2.05). The median(IQR) time to receive the first instalment had reduced from 200(109,331) days in 2018 to 91(51,149) days in 2022. Patients from private sector(106.9;106.3,107.4days), those with HIV-reactive (103.7;101.8,105.7days), DRTB(104.6;102.6,106.7days) and missing/undetermined diabetic status (115.3;114,116.6days) experienced longer delays. Conclusions The coverage of NPY among patients with TB had increased and the time to receipt of benefit had halved in the past five years. Three-fourths of the patients received at least one NPY instalment, more than half of whom had waited over three months to receive the first instalment. NTEP has to focus on timely transfer of benefits to enable patients to meet their additional nutritional demands, experience treatment success and avoid catastrophic expenditure.

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.

As of February 29, 2020, more than 85,000 cases of coronavirus disease 2019 (COVID-19) have been reported from China and 53 other countries with 2,924 deaths. On January 30, 2020, the first laboratory-confirmed case of COVID was reported from Kerala, India. In view of the earlier evidence about effectiveness of repurposed lopinavir/ritonavir against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus (CoV), as well as preliminary docking studies conducted by the ICMR-National Institute of Virology, Pune, the Central Drugs Standard Control Organization approved the restricted public health use of lopinavir/ritonavir combination amongst symptomatic COVID-19 patients detected in the country. Hospitalized adult patients with laboratory-confirmed SARS-CoV-2 infection with any one of the following criteria will be eligible to receive lopinavir/ritonavir for 14 days after obtaining written informed consent: (i) respiratory distress with respiratory rate ≥22/min or SpO of <94 per cent; (ii) lung parenchymal infiltrates on chest X-ray; (iii) hypotension defined as systolic blood pressure <90 mmHg or need for vasopressor/inotropic medication; (iv) new-onset organ dysfunction; and (v) high-risk groups - age >60 yr, diabetes mellitus, renal failure, chronic lung disease and immunocompromised persons. Patients will be monitored to document clinical (hospital length of stay and mortality at 14, 28 and 90 days), laboratory (presence of viral RNA in serial throat swab samples) and safety (adverse events and serious adverse events) outcomes. Treatment outcomes amongst initial cases would be useful in providing guidance about the clinical management of patients with COVID-19. If found useful in managing initial SARS-CoV-2-infected patients, further evaluation using a randomized control trial design is warranted to guide future therapeutic use of this combination.

We retrospectively data-mined the case records of Reverse Transcription Polymerase Chain Reaction (RT-PCR) confirmed COVID-19 patients hospitalized to a tertiary care centre to derive mortality predictors and formulate a risk score, for prioritizing admission. Data on clinical manifestations, comorbidities, vital signs, and basic lab investigations collected as part of routine medical management at admission to a COVID-19 tertiary care centre in Chengalpattu, South India between May and November 2020 were retrospectively analysed to ascertain predictors of mortality in the univariate analysis using their relative difference in distribution among 'survivors' and 'non-survivors'. The regression coefficients of those factors remaining significant in the multivariable logistic regression were utilised for risk score formulation and validated in 1000 bootstrap datasets. Among 746 COVID-19 patients hospitalised [487 \"survivors\" and 259 \"non-survivors\" (deaths)], there was a slight male predilection [62.5%, (466/746)], with a higher mortality rate observed among 40-70 years age group [59.1%, (441/746)] and highest among diabetic patients with elevated urea levels [65.4% (68/104)]. The adjusted odds ratios of factors [OR (95% CI)] significant in the multivariable logistic regression were SaO2<95%; 2.96 (1.71-5.18), Urea ≥50 mg/dl: 4.51 (2.59-7.97), Neutrophil-lymphocytic ratio (NLR) >3; 3.01 (1.61-5.83), Age ≥50 years;2.52 (1.45-4.43), Pulse Rate ≥100/min: 2.02 (1.19-3.47) and coexisting Diabetes Mellitus; 1.73 (1.02-2.95) with hypertension and gender not retaining their significance. The individual risk scores for SaO2<95-11, Urea ≥50 mg/dl-15, NLR >3-11, Age ≥50 years-9, Pulse Rate ≥100/min-7 and coexisting diabetes mellitus-6, acronymed collectively as 'OUR-ARDs score' showed that the sum of scores ≥ 25 predicted mortality with a sensitivity-90%, specificity-64% and AUC of 0.85. The 'OUR ARDs' risk score, derived from easily assessable factors predicting mortality, offered a tangible solution for prioritizing admission to COVID-19 tertiary care centre, that enhanced patient care but without unduly straining the health system.

Risk 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. We conducted a hospital-based case control study across nine sites in India to identify the determinants of severe and critical COVID-19 disease. We 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. We 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.