Background & objectives: Population-based seroepidemiological studies measure the extent of SARS-CoV-2 infection in a country. We report the findings of the first round of a national serosurvey, conducted to estimate the seroprevalence of SARS-CoV-2 infection among adult population of India. Methods: From May 11 to June 4, 2020, a randomly sampled, community-based survey was conducted in 700 villages/wards, selected from the 70 districts of the 21 States of India, categorized into four strata based on the incidence of reported COVID-19 cases. Four hundred adults per district were enrolled from 10 clusters with one adult per household. Serum samples were tested for IgG antibodies using COVID Kavach ELISA kit. All positive serum samples were re-tested using Euroimmun SARS-CoV-2 ELISA. Adjusting for survey design and serial test performance, weighted seroprevalence, number of infections, infection to case ratio (ICR) and infection fatality ratio (IFR) were calculated. Logistic regression was used to determine the factors associated with IgG positivity. Results: Total of 30,283 households were visited and 28,000 individuals were enrolled. Population-weighted seroprevalence after adjusting for test performance was 0.73 per cent [95% confidence interval (CI): 0.34-1.13]. Males, living in urban slums and occupation with high risk of exposure to potentially infected persons were associated with seropositivity. A cumulative 6,468,388 adult infections (95% CI: 3,829,029-11,199,423) were estimated in India by the early May. The overall ICR was between 81.6 (95% CI: 48.3-141.4) and 130.1 (95% CI: 77.0-225.2) with May 11 and May 3, 2020 as plausible reference points for reported cases. The IFR in the surveyed districts from high stratum, where death reporting was more robust, was 11.72 (95% CI: 7.21-19.19) to 15.04 (9.26-24.62) per 10,000 adults, using May 24 and June 1, 2020 as plausible reference points for reported deaths. Interpretation & conclusions: Seroprevalence of SARS-CoV-2 was low among the adult population in India around the beginning of May 2020. Further national and local serosurveys are recommended to better inform the public health strategy for containment and mitigation of the epidemic in various parts of the country.

The Thailand-Cambodia border is the epicenter for drug-resistant falciparum malaria. Previous studies have shown that chloroquine (CQ) and pyrimethamine resistance originated in this region and eventually spread to other Asian countries and Africa. However, there is a dearth in understanding the origin and evolution of dhps alleles associated with sulfadoxine resistance. The present study was designed to reveal the origin(s) of sulfadoxine resistance in Cambodia and its evolutionary relationship to African and South American dhps alleles. We sequenced 234 Cambodian Plasmodium falciparum isolates for the dhps codons S436A/F, A437G, K540E, A581G and A613S/T implicated in sulfadoxine resistance. We also genotyped 10 microsatellite loci around dhps to determine the genetic backgrounds of various alleles and compared them with the backgrounds of alleles prevalent in Africa and South America. In addition to previously known highly-resistant triple mutant dhps alleles SGEGA and AGEAA (codons 436, 437, 540, 581, 613 are sequentially indicated), a large proportion of the isolates (19.3%) contained a 540N mutation in association with 437G/581G yielding a previously unreported triple mutant allele, SGNGA. Microsatellite data strongly suggest the strength of selection was greater on triple mutant dhps alleles followed by the double and single mutants. We provide evidence for at least three independent origins for the double mutants, one each for the SGKGA, AGKAA and SGEAA alleles. Our data suggest that the triple mutant allele SGEGA and the novel allele SGNGA have common origin on the SGKGA background, whereas the AGEAA triple mutant was derived from AGKAA on multiple, albeit limited, genetic backgrounds. The SGEAA did not share haplotypes with any of the triple mutants. Comparative analysis of the microsatellite haplotypes flanking dhps alleles from Cambodia, Kenya, Cameroon and Venezuela revealed an independent origin of sulfadoxine resistant alleles in each of these regions.

Artemisinin combination therapies (ACTs) have recently been adopted as first-line therapy for Plasmodium falciparum infections in most malaria-endemic countries. In this study, we estimated the association between artesunate-mefloquine therapy failure and genetic changes in the putative transporter, pfmdr1. Blood samples were acquired from 80 patients enrolled in an 2004 in vivo efficacy study in Pailin, Cambodia, and genotyped for pfmdr1 copy number and haplotype. Having parasites with three or more copies of pfmdr1 before treatment was strongly associated with recrudescence (hazard ratio [HR] = 8.30; 95% CI: 2.60-26.43). This relationship was maintained when controlling for initial parasite density and hematocrit (HR = 7.91; 95% CI: 2.38-26.29). Artesunate-mefloquine treatment selected for increased pfmdr1 copy number, because isolates from recurrent episodes had higher copy numbers than the paired enrollment samples (Wilcoxon rank test, P = 0.040). pfmdr1 copy number should be evaluated further as a surveillance tool for artesunate-mefloquine resistance in Cambodia.

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Background The first national severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurvey in India, done in May-June, 2020, among adults aged 18 years or older from 21 states, found a SARS-CoV-2 IgG antibody seroprevalence of 0•73% (95% CI 0•34-1•13). We aimed to assess the more recent nationwide seroprevalence in the general population in India. MethodsWe did a second household serosurvey among individuals aged 10 years or older in the same 700 villages or wards within 70 districts in India that were included in the first serosurvey. Individuals aged younger than 10 years and households that did not respond at the time of survey were excluded. Participants were interviewed to collect information on sociodemographics, symptoms suggestive of COVID-19, exposure history to laboratoryconfirmed COVID-19 cases, and history of COVID-19 illness. 3-5 mL of venous blood was collected from each participant and blood samples were tested using the Abbott SARS-CoV-2 IgG assay. Seroprevalence was estimated after applying the sampling weights and adjusting for clustering and assay characteristics. We randomly selected one adult serum sample from each household to compare the seroprevalence among adults between the two serosurveys.Findings Between Aug 18 and Sept 20, 2020, we enrolled and collected serum samples from 29 082 individuals from 15 613 households. The weighted and adjusted seroprevalence of SARS-CoV-2 IgG antibodies in individuals aged 10 years or older was 6•6% (95% CI 5•8-7•4). Among 15 084 randomly selected adults (one per household), the weighted and adjusted seroprevalence was 7•1% (6•2-8•2). Seroprevalence was similar across age groups, sexes, and occupations. Seroprevalence was highest in urban slum areas followed by urban non-slum and rural areas. We estimated a cumulative 74•3 million infections in the country by Aug 18, 2020, with 26-32 infections for every reported COVID-19 case.Interpretation Approximately one in 15 individuals aged 10 years or older in India had SARS-CoV-2 infection by Aug 18, 2020. The adult seroprevalence increased approximately tenfold between May and August, 2020. Lower infection-to-case ratio in August than in May reflects a substantial increase in testing across the country.

Background: The combination of artesunate and mefloquine was introduced as the national firstline treatment for Plasmodium falciparum malaria in Cambodia in 2000. However, recent clinical trials performed at the Thai-Cambodian border have pointed to the declining efficacy of both artesunate-mefloquine and artemether-lumefantrine. Since pfmdr1 modulates susceptibility to mefloquine and artemisinin derivatives, the aim of this study was to assess the link between pfmdr1 copy number, in vitro susceptibility to individual drugs and treatment failure to combination therapy.

Background Earlier serosurveys in India revealed SARS-CoV-2 seroprevalence of 0.73% during May-June and 7.1% during August-September 2020. We conducted the third serosurvey during Dec 2020 and Jan 2021, to estimate the seroprevalence of SARS-CoV-2 infection among general population and healthcare workers (HCWs) in India. Methods We conducted the serosurvey in the same 70 districts selected for the first and second serosurveys. From each district, we enrolled at least 400 individuals aged ≥ 10 years from general population and 100 HCWs from sub-district level health facilities. Sera from general population were tested for presence of IgG antibodies against nucleocapsid (N) and spike protein (S1-RBD) of SARS-CoV-2, whereas sera from HCWs were tested for anti-S1-RBD. We estimated weighted seroprevalence adjusted for assay characteristics. Results Of the 28,598 sera from general population, 4585 (16%) had IgG antibodies against N, 6647 (23.2%) against S1-RBD and 7436 (26%) against either. The weighted and assay characteristic adjusted seroprevalence against either of the antibodies was 24.1 (95%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 general population as well as HCWs in India were exposed to SARS-CoV-2 by December 2020.

After the launch of the National Malaria Control Programme in 1953, the number of malaria cases reported in India fell to an all-time low of 0·1 million in 1965. However, the initial success could not be maintained and a resurgence of malaria began in the late 1960s. Resistance of Plasmodium falciparum to chloroquine was first reported in 1973 and increases in antimalarial resistance, along with rapid urbanisation and labour migration, complicated the challenge that India's large geographical area and population size already pose for malaria control. Although several institutions have done drug-resistance monitoring in India, a complete analysis of countrywide data across institutions does not exist. We did a systematic review of P falciparum malaria drugefficacy studies in India to summarise drug-resistance data and describe changes over the past 30 years to inform future policy. Continued use of chloroquine for treatment of P falciparum malaria in India will likely be ineffective. Resistance to sulfa-pyrimethamine should be closely monitored to protect the effectiveness of treatment with artesunate plus sulfadoxine-pyrimethamine, which is the new first-line treatment for P falciparum malaria. Strategies to reduce the emergence and spread of future drug resistance need to be proactive and supported by intensive monitoring.