India’s national COVID death totals remain undetermined. Using an independent nationally representative survey of 0.14 million (M) adults, we compared COVID mortality during the 2020 and 2021 viral waves to expected all-cause mortality. COVID constituted 29% (95% confidence interval, 28 to 31%) of deaths from June 2020 to July 2021, corresponding to 3.2 M (3.1 to 3.4) deaths, of which 2.7 M (2.6 to 2.9) occurred in April to July 2021 (when COVID doubled all-cause mortality). A subsurvey of 57,000 adults showed similar temporal increases in mortality, with COVID and non-COVID deaths peaking similarly. Two government data sources found that, when compared to prepandemic periods, all-cause mortality was 27% (23 to 32%) higher in 0.2 M health facilities and 26% (21 to 31%) higher in civil registration deaths in 10 states; both increases occurred mostly in 2021. The analyses find that India’s cumulative COVID deaths by September 2021 were six to seven times higher than reported officially.

Verbal autopsies with physician assignment of cause of death (COD) are commonly used in settings where medical certification of deaths is uncommon. It remains unanswered if automated algorithms can replace physician assignment. We randomized verbal autopsy interviews for deaths in 117 villages in rural India to either physician or automated COD assignment. Twenty-four trained lay (non-medical) surveyors applied the allocated method using a laptop-based electronic system. Two of 25 physicians were allocated randomly to independently code the deaths in the physician assignment arm. Six algorithms (Naïve Bayes Classifier (NBC), King-Lu, InSilicoVA, InSilicoVA-NT, InterVA-4, and SmartVA) coded each death in the automated arm. The primary outcome was concordance with the COD distribution in the standard physician-assigned arm. Four thousand six hundred fifty-one (4651) deaths were allocated to physician (standard), and 4723 to automated arms. The two arms were nearly identical in demographics and key symptom patterns. The average concordances of automated algorithms with the standard were 62%, 56%, and 59% for adult, child, and neonatal deaths, respectively. Automated algorithms showed inconsistent results, even for causes that are relatively easy to identify such as road traffic injuries. Automated algorithms underestimated the number of cancer and suicide deaths in adults and overestimated other injuries in adults and children. Across all ages, average weighted concordance with the standard was 62% (range 79–45%) with the best to worst ranking automated algorithms being InterVA-4, InSilicoVA-NT, InSilicoVA, SmartVA, NBC, and King-Lu. Individual-level sensitivity for causes of adult deaths in the automated arm was low between the algorithms but high between two independent physicians in the physician arm. While desirable, automated algorithms require further development and rigorous evaluation. Lay reporting of deaths paired with physician COD assignment of verbal autopsies, despite some limitations, remains a practicable method to document the patterns of mortality reliably for unattended deaths. ClinicalTrials.gov , NCT02810366. Submitted on 11 April 2016.

Haemolysis risk with single dose or short course primaquine was evaluated in glucose-6-phosphate dehydrogenase (G6PD) deficient people. Major electronic databases (to August 2016) were searched for single or short course 8-aminoquinolines (8-AQ) in (1) randomized comparisons against placebo in G6PD deficient people; and (2) observational comparisons in G6PD deficient compared to replete people. Two authors independently assessed eligibility, risk-of-bias, and extracted data. Five randomized controlled trials and four controlled observational cohorts were included. In G6PD deficient individuals, high-dose (0.75 mg/kg) PQ resulted in lower average haemoglobin levels at 7 days (mean difference [MD] −1.45 g/dl, 95% CI −2.17 to −0.74, 2 trials) and larger percentage fall from baseline to day 7 (MD −10.31%, 95% CI −17.69 to −2.92, 3 trials) compared to placebo. In G6PD deficient compared to replete people, average haemoglobin was lower at 7 days (MD −1.19 g/dl, 95% CI −1.94 to −0.44, 2 trials) and haemoglobin change from baseline to day 7 was greater (MD −9.10%, 95% CI −12.55 to −5.65, 5 trials). One small trial evaluated mid-range PQ dose (0.4–0.5 mg/kg) in G6PD deficient people, with no difference detected in average haemoglobin at day 7 compared to placebo. In one cohort comparing G6PD deficient and replete people there was a greater fall with G6PD deficiency (MD −4.99%, 95% CI −9.96 to −0.02). For low-dose PQ (0.1–0.25 mg/kg) in G6PD deficient people, haemoglobin change from baseline was similar to the placebo group (MD 1.72%, 95% CI −1.89 to 5.34, 2 trials). Comparing low dose PQ in G6PD deficient with replete people, the average haemoglobin was lower in the G6PD deficient group at 7 days (−0.57 g (95% CI −0.97 to −0.17, 1 trial)); although change from baseline was similar (MD −1.45%, 95% CI −5.69 to 2.78, 3 trials). Falls in average haemoglobin are less marked with the 0.1 to 0.25 mg/kg PQ than with the 0.75 mg/kg dose, and severe haemolytic events are not common. However, data were limited and the evidence GRADE was low or very low certainty.

Objectives We sought to understand the spread of SARS-CoV-2 infection in urban India, which has surprisingly low COVID-19 deaths. Design Cross-sectional and trend analyses of seroprevalence in self-referred test populations, and of reported cases and COVID mortality data. Participants 448,518 self-referred individuals using a nationwide chain of private laboratories with central testing of SARS-CoV-2 antibodies and publicly available case and mortality data. Setting 12 populous cities with nearly 92 million total population. Main outcome measures Seropositivity trends and predictors (using a Bayesian geospatial model) and prevalence derived from mortality data and infection fatality rates (IFR). Results For the whole of India, 31% of the self-referred individuals undergoing antibody testing were seropositive for SARS-CoV-2 antibodies. Seropositivity was higher in females (35%) than in males (30%) overall and in nearly every age group. In these 12 cities, seroprevalence rose from about 18% in July to 41% by December, with steeper increases at ages <20 and 20-44 years than at older ages. The “M-shaped” age pattern is consistent with intergenerational transmission. Areas of higher childhood measles vaccination in earlier years had lower seropositivity. The patterns of increase in seropositivity and in peak cases and deaths varied substantially across cities. In Delhi, death rates and cases first peaked in June and again in November; Chennai had a single peak in July. Based local IFRs and COVID deaths (adjusted for undercounts), we estimate that 43%-65% of adults above age 20 had been infected (range of mid-estimates of 12%-77%) corresponding 26 to 36 million infected adults in these cities, or an average of 9-12 infected adults per confirmed case. Conclusion Even with relatively low death rates, the large cities of India had remarkably high levels of SARS-CoV-2 infection. Vaccination strategies need to consider widespread intergenerational transmission.

A long-held assumption has been that nearly all malaria deaths in high-transmission areas are of children younger than 5 years and pregnant women. Most global malaria mortality estimates incorporate this assumption in their calculations. In 2010, the Indian Million Death Study, which assigns cause of death by verbal autopsy (VA), challenged the reigning perception, producing a U-shaped mortality age curve, with rates rising after age 45 years in areas of India with substantial malaria transmission. Similar patterns are seen in Africa in the International Network for the Demographic Evaluation of Populations and Their Health (INDEPTH) network, also relying on VA. Whether these results are accurate or are misidentified deaths can be resolved by improving the evidence for assigning causes for adult acute infectious deaths in high malaria transmission areas. The options for doing so include improving the accuracy of VA and adding postmortem biological evidence, steps we believe should be initiated without delay.