World Health Organization (WHO) in 2010, recommended 0.75 mg/kg single dose primaquine for killing gametocytes after ruling out glucose-6-phosphate dehydrogenase (G6PD) deficiency. However, considering the practical feasibility of G6PD testing, WHO revised the recommendation in 2012 to 0.25 mg/kg single dose primaquine on day-1. This study aims to investigate the efficacy and safety of single-low dose primaquine (0.25 mg/kg) administered on day-1 to intervention arm compared to standard regimen, high-dose primaquine (0.75 mg/kg) administered on day-2 to control arm. This is a hospital based, open-label, multi-centric, randomized-controlled trial being conducted at four different sites in India, with a target sample size of 496 i.e., 124 participants per site. Participants above 18 years of age with uncomplicated P. falciparum malaria and normal glucose-6-phosphate dehydrogenase (G6PD) activity, defined as > 4.0 IU/g Hb using the point-of-care test, weight > 40 kg, haemoglobin > 8 g/dL are treated with ACT and randomized to either control or intervention arm. Efficacy assessment is based on gametocytemia as inferred from examination of stained peripheral blood smears during enrolment and follow-up. In addition, quantitative nucleic acid sequence-based amplification (QT-NASBA) for Pfs25 mRNA, will be used to quantify the gametocytes on day 1, 2/3, 7, and 14. Safety assessment during 14-day follow-up will be based on percentage of participants with more than 25

Background: India has a high burden of P. vivax malaria. Current guidelines recommend a total primaquine dose of 3·5 mg/kg administered over 14 days, however, adherence is poor, impacting effectiveness. The efficacy and safety of the same total dose administered over 7 days in India is unknown. Methods: We conducted a multicentre, open-label randomised controlled non-inferiority trial at two sites in India. Febrile patients aged 16 years or older with microscopically confirmed P. vivax monoinfection and ≥30% G6PD activity were eligible for enrolment. Patients were randomly assigned (1:1) using block randomisation stratified by site to either 3·5 mg/kg primaquine over 7 days or 3·5 mg/kg primaquine over 14 days, the current standard of care. Primaquine was administered in combination with chloroquine as per national treatment guideline. The primary endpoint was the cumulative incidence of symptomatic recurrent microscopy-confirmed P. vivax parasitaemia within six months. The study was registered with the Clinical Trials Registry of India (CTRI/2022/12/048283). Findings: Between September 2023 and October 2024, a total of 400 patients were enrolled (201 randomised to the 7-day group and 199 to the 14-day group). The cumulative incidence of symptomatic parasitaemia by day 180 was 1·1% (95% CI 0·0-4·1) following 7-day primaquine and 1·1% (95% CI 0·0-4·4) following 14-day primaquine. Sixteen patients treated with 7-day primaquine missed a primaquine dose (8%) compared with 40 patients treated with 14-day primaquine (20%). There were 35 adverse events in each group, 11 of which were reported to be drug-related in the 7-day group compared with 13 in the 14-day group. Gastrointestinal side effects at day 7 were rare in both the 7-day (0·5% [1/183]) and in the 14-day group (1·1% [2/180]). No patients had a haemoglobin fall from day 0 to days 1-14 by >5 g/dL or required a blood transfusion. One patient in the 14-day group had a haemoglobin fall to <8 g/dL .Interpretation: Compared with a 14-day primaquine regimen, a 7-day regimen of 3·5 mg/kg total dose was well-tolerated and non-inferior. Adherence was greater in patients with the 7-day regimen. These findings support the use of 7-day primaquine regimens in India.Funding: Bill & Melinda Gates Foundation

Background India has a high burden of Plasmodium vivax malaria. Current malaria treatment guidelines recommend a total primaquine dose of 3·5 mg/kg administered over 14 days to prevent relapse in P. vivax infection, however, adherence is generally poor, impacting effectiveness. We aimed to determine the efficacy and safety of the same total dose of 3·5 mg/kg administered over 7 days in India. Methods We conducted an open label, non-inferiority, randomised controlled trial at two sites in India. Febrile patients older than 16 years with microscopically confirmed P. vivax mono-infection and normal (≥30%) G6PD activity were eligible for enrolment. Patients were randomly assigned (1:1) using block randomisation, stratified by site, to either 3·5 mg/kg primaquine over 7 days or 3·5 mg/kg primaquine over 14 days, which is the current standard of care. Primaquine was administered in combination with chloroquine as per national treatment guidelines. The primary endpoint was the cumulative incidence of symptomatic recurrent microscopy-confirmed P. vivax parasitaemia within 6 months. Efficacy analyses were conducted on the intention-to-treat population. The study was registered with the Clinical Trials Registry of India (CTRI/2022/12/048283). Findings Between September 2023 and October 2024, a total of 400 patients were enrolled (201 randomised to the 7-day group and 199 to the 14-day group). By 180 days of follow up, there were a total of four P. vivax recurrences, with two in each arm. The cumulative incidence of symptomatic parasitaemia by day 180 was 1·1% (95% confidence interval [CI] 0·0–4·1) in the 7-day primaquine group and 1·1% (95% CI 0·0–4·4) in the 14-day primaquine group. Sixteen patients (8%) treated with 7-day primaquine missed a primaquine dose compared with 40 patients (20%) treated with 14-day primaquine. There were 35 adverse events reported in each group, 11 of which were reported to be drug-related in the 7-day group compared with 13 in the 14-day group. Gastrointestinal side effects at day 7 were rare in both the 7-day (0·5% [1/183]) and the 14-day group (1·1% [2/180]). None of the patients had a haemoglobin fall from day 0 to days 1–14 by more than 5 g/dL or required blood transfusion. Interpretation Compared with a 14-day primaquine regimen, a 7-day regimen of 3·5 mg/kg was well-tolerated and non-inferior within the observed 180 days of follow up. Adherence was greater among patients in the 7-day regimen. Although the overall number of recurrences was lower than anticipated, limiting the precision of the estimates, these findings are consistent with and support the current WHO recommendation for a 7-day primaquine regimen. Future studies with longer follow up could provide additional evidence for efficacy of this regimen against late P. vivax relapses. Funding Infectious Diseases Data Observatory (University of Oxford) through a grant from the Bill & Melinda Gates Foundation (INV-004713).

We enrich a standard debt overhang model with liquidity constraints to guide the design and interpretation of a collateralized debt modification experiment on a publicly traded lender’s delinquent vehicle loans to minibus entrepreneurs. Liquidity constraints add another borrower incentive compatibility constraint that interacts with debt overhang to shape repayment and effort. Consistent with model predictions, we find: debt reduction does not affect liquidity constrained borrowers; payment reduction improves both repayment and effort for borrowers with sufficient vehicle equity; payment reduction induces repayment without effort increases for low-equity borrowers. These results suggest a pecking order strategy for modification practice and policy. Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

Disease surveillance activities are usually resource-constrained and should be optimised to achieve spatial and real-time situational awareness. Such optimisation would help with better resource allocation, reduced logistics, and other costs. India has a high population density, diverse geography and climatic conditions, and difficult terrain. With respect to malaria, Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) are endemic, with substantial variability of transmission across the country. While for Pv, drug efficacy appears to be homogenous within the country, for Pf malaria, the resistance pattern varies from the northeastern region to the central region. These factors make accurate mapping of antimalarial drug resistance difficult. To account for these complexities, we develop a targeted and adaptive methodology to identify prospective study sites for Pf antimalarial drug resistance surveillance. We retrieve existing data on the prevalence of validated markers of resistance to Artesunate (AS) and Sulfadoxine-Pyrimethamine (SP) from the WorldWide Antimalarial Resistance Network (WWARN) systematic review database. We incorporate these data into a geostatistical model to estimate the prevalence of these markers across India and identify areas with high projected median resistance marker prevalence and low uncertainty. Finally, we create an interactive dashboard using the RShiny software package to simplify the process of selecting sites for future molecular surveillance. This methodology helps to ensure that decision-making is supported by data and modelling outputs while facilitating the generation of knowledge about the current state of antimalarial drug resistance with wide geographic coverage. We demonstrate the utility of our method by selecting sites for surveillance of drug resistance in Pf malaria in India. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by a grant from Bill & Melinda Gates Foundation (grant no. INV-004713). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The source data used for modelling is available from Artemisinin Molecular Surveyor (http://www.wwarn.org/molecular/surveyor/k13/index.html?t=201608031200#0) and SP Molecular Surveyor (http://www.wwarn.org/dhfr-dhps-surveyor/#0). R code is available on GitHub and can be access through below link (https://github.com/lu-harr/pf\_drug\_resistance). At present the dashboard has not been uploaded online due to data protection issues but a proof of concept on simulated data can be accessed through https://lucyharrison.shinyapps.io/pf\_drug\_resistance_shiny/. [https://lucyharrison.shinyapps.io/pf\_drug\_resistance_shiny/][1] [1]: https://lucyharrison.shinyapps.io/pf_drug_resistance_shiny/

We show that the age composition of the population can shape the speed at which businesses adopt new technologies, using evidence from mobile payments in India. Consumers' propensity to use new payment technologies declines with age, creating stronger incentives for businesses serving younger customers to accept these technologies. We document this pattern in the rollout of a mobile payment option by a major fintech company. A model where consumer attitudes toward technology vary by age implies that business adoption is inefficiently low, with the young bearing disproportionate welfare losses from network externalities. Jointly subsidizing transaction and adoption costs restores efficiency. Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

Surveillance for genetic markers of resistance can provide valuable information on the likely efficacy of antimalarials but needs to be targeted to ensure optimal use of resources. We conducted a systematic search and review of publications in seven databases to compile resistance marker data from studies in India. The sample collection from the studies identified from this search was conducted between 1994 and 2020, and these studies were published between 1994 and 2022. In all, Plasmodium falciparum Kelch13 (PfK13), P. falciparum dihydropteroate synthase, and P. falciparum dihydrofolate reductase (PfDHPS) genotype data from 2,953, 4,148, and 4,222 blood samples from patients with laboratory-confirmed malaria, respectively, were extracted from these publications and uploaded onto the WorldWide Antimalarial Resistance Network molecular surveyors. These data were fed into hierarchical geostatistical models to produce maps with a predicted prevalence of the PfK13 and PfDHPS markers, and of the associated uncertainty. Zones with a predicted PfDHPS 540E prevalence of > 15% were identified in central, eastern, and northeastern India. The predicted prevalence of PfK13 mutants was nonzero at only a few locations, but were within or adjacent to the zones with > 15% prevalence of PfDHPS 540E. There may be a greater probability of artesunate-sulfadoxine-pyrimethamine failures in these regions, but these predictions need confirmation. This work can be applied in India and elsewhere to help identify the treatments most likely to be effective for malaria elimination.

We study the effect of language barriers on the ability of farmers to access information about agricultural technologies in rural areas of India. We use the introduction of government-sponsored call centers (Kisan Call Centers) which offer agricultural advice in the official language of each Indian state. For identification, we compare geographically contiguous areas that sit across state borders, and exploit differences in the language spoken by farmers and call center advisors. We document that language barriers limit the adoption of modern agricultural technologies – such as high-yielding variety seeds – and negatively affect crop yields.

Millions of people worldwide visit, live or work in the hypoxic environment encountered at high altitudes and it is important to understand the biomolecular responses to this stress. This would help design mitigation strategies for high altitude illnesses. In spite of a number of studies spanning over 100 years, still the complex mechanisms controlling acclimatization to hypoxia remain largely unknown. To identify potential diagnostic, therapeutic and predictive markers for HA stress, it is important to comprehensively compare and analyse these studies. Towards this goal, HighAltitudeOmicsDB is a unique resource that provides a comprehensive, curated, user-friendly and detailed compilation of various genes/proteins which have been experimentally validated to be associated with various HA conditions, their protein–protein interactions (PPIs) and gene ontology (GO) semantic similarities. For each database entry, HighAltitudeOmicsDB additionally stores the level of regulation (up/down-regulation), fold change, study control group, duration and altitude of exposure, tissue of expression, source organism, level of hypoxia, method of experimental validation, place/country of study, ethnicity, geographical location etc. The database also collates information on disease and drug association, tissue-specific expression level, GO and KEGG pathway associations. The web resource is a unique server platform that offers interactive PPI networks and GO semantic similarity matrices among the interactors.These unique features help to offer mechanistic insights into the disease pathology. Hence, HighAltitudeOmicsDBis a unique platform for researchers working in this area to explore, fetch, compare and analyse HA-associated genes/proteins, their PPI networks, and GO semantic similarities. The database is available at http://www.altitudeomicsdb.in .

We provide evidence on the importance of coordination frictions in technology adoption, using data from a large provider of electronic wallets during the Indian demonetization. Exploiting geographical variation in exposure to the demonetization, we show that adoption of the wallet increased persistently in response to the large but temporary cash contraction, consistent with the predictions of a technology adoption model with complementarities. Model estimates indicate that adoption would have been 45% lower without complementarities. Our results illustrate how large but temporary interventions can help overcome coordination frictions, though we caution that such interventions may also exacerbate initial differences in adoption.

BACKGROUND:The optimal dosing of primaquine to prevent relapsing Plasmodium vivax malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to prevent P. vivax relapse. METHODS:A systematic review identified P. vivax efficacy studies from South Asia published between 1 January 2000 and 23 August 2021. In a one-stage meta-analysis of available individual patient data, the cumulative risks of P. vivax recurrence at day 42 and 180 were assessed by primaquine total mg/kg dose and duration. The risk of recurrence by day 180 was also determined in a two-stage meta-analysis. Patients with a >25% drop in haemoglobin to <70 g/L, or an absolute drop of >50 g/L between days 1 and 14 were categorised by daily mg/kg primaquine dose. RESULTS:In 791 patients from 7 studies in the one-stage meta-analysis, the day 180 cumulative risk of recurrence was 61.1% (95% CI 42.2% to 80.4%; 201 patients; 25 recurrences) after treatment without primaquine, 28.8% (95% CI 8.2% to 74.1%; 398 patients; 4 recurrences) following low total (2 to <5 mg/kg) and 0% (96 patients; 0 recurrences) following high total dose primaquine (≥5 mg/kg). In the subsequent two-stage meta-analysis of nine studies (3529 patients), the pooled proportions of P. vivax recurrences by day 180 were 12.1% (95% CI 7.7% to 17.2%), 2.3% (95% CI 0.3% to 5.4%) and 0.7% (95% CI 0% to 6.1%), respectively. No patients had a >25% drop in haemoglobin to <70 g/L. CONCLUSIONS:Primaquine treatment led to a marked decrease in P. vivax recurrences following low (~3.5 mg/kg) and high (~7 mg/kg) total doses, with no reported severe haemolytic events. PROSPERO REGISTRATION NUMBER:CRD42022313730.

We analyze the effects of a debt restructuring program that relaxed liquidity constraints — by reducing immediate payments without changing the long-run debt — for financially distressed small firms in South Africa’s minibus industry. We combine novel administrative data on business owners of small informal firms — including their loan performance, driving effort and labor supply, risk-taking behavior, and credit bureau information — with a cut-off rule that generated discontinuity in the program eligibility. We find that one year later small business owners that receive payment reductions (i) have higher repayments and lower defaults on minibus debt; (ii) increase their effort on the job; and (iii) have improved overall financial health. We do not find any evidence of borrowers indulging in misconduct or putting passenger safety at risk, suggesting an improvement in overall welfare for borrowers. These findings run counter to the view that short-run liquidity constraints induce higher borrower effort. We rationalize these findings in the context of a framework where penalties imposed due to late payments in the presence of liquidity constraints lead to future debt overhang, thereby, generating moral hazard in effort. Our findings present payment reduction as a potential low-cost tool that benefits both borrowers and creditors, at least in the short-run.

Seasonal changes in the human cardiovascular system are known to play an important role in the onset of many diseases. Confounding variables include behavioral and environmental factors; failing to address such variables makes measuring the true temporal impact of these diseases difficult. On the other hand, numerous clinical studies imply that only specific groups of people are more seasonal sensitive and that their maladaptation might contribute to various illnesses. As a result, it is critical to evaluate the etiological and seasonal sensitive patterns of cardiovascular diseases (CVD), which impact the majority of the human population. The hypothesis for this study formulated that cardiovascular and associated illnesses had substantial connections with seasonal and etiological variations. Thus in the present study, 4519 systematic screen-eligible studies were analyzed using data mining to uncover 852 disease association relationships between cardiovascular and associated disorders. A disease ontology-based semantic similarity network (DSN) analysis was performed to narrow down the identified CVDs. Further, topological analysis was used to predict the seven CVDs, including myocardial infarction (MI), in three clusters. Following that, Mann-Kendall and Cox-Stuart analyses were used to investigate the seasonal sensitivity and temporal relationship of these seven CVDs. Finally, temporal relationships were confirmed using LOESS and TBATS, as well as seasonal breakdown utilizing autocorrelation and fast Fourier transform results. The study provides indirect evidence of a severe etiological association among the three cardiovascular diseases, including MI, atrial fibrillation, and atherosclerosis, which are winter season sensitive in most of the world population. Hypertension has two seasonal falls and peaks due to its seasonal nature, that is, summer and winter hypertension. While, heart failure was also identified, with minor temporal trends. Hence, all five diseases could be classified as seasonal cardiovascular comorbid diseases (SCCD). Furthermore, these diseases could be studied for potential common risk factors such as biochemical, genetic, and physiological factors.

Most governments in developing countries offer subsidized credit programs to the agricultural sector. We document that farmers often lack information on how these programs work, their eligibility criteria and loan terms offered. We study the impact of information frictions on credit take-up by exploiting plausibly exogenous variation in the construction of new mobile phone towers in rural areas of India without previous mobile phone coverage. Areas receiving coverage experience higher take-up of agricultural credit. The effects are concentrated in short-term credit to small land holders, which have been the target of a major Indian government credit program, the Kisan credit cards.

Seasonal variations in human cardiovascular system are known to play a key role in the onset of many maladies. Behavioural and environmental factors act as confounding variables, failing to address such variables makes it challenging to measure the true temporal impact of these diseases. Conversely, numerous clinical investigations suggest that only certain groups of people are more seasonal sensitive and their maladaptation can contribute to a range of sicknesses. Therefore, it is crucial to assess the etiological and seasonal sensitive patterns among cardiovascular diseases (CVD) affecting most of the human population. For this study, it was hypothesized that cardiovascular and related disorders have strong associations with seasonal sensitive physiological changes. Data mining was performed to extract the relevant information on the association between cardiovascular and related diseases. Disease ontology-based semantic similarity network (DSN) analysis was performed to narrow down the consequent CVDs. Furthermore, topological analysis was carried out to predict the seven CVDs in three clusters including myocardial infarction. Further, these seven CVDs were assessed for their seasonal sensitivity and temporal association among themselves using Mann-Kendall and cox-Stuart analyses. Moreover, temporal associations were verified using LOESS and TBATS. While seasonal decomposition was assessed by autocorrelation and fast Fourier transform outcomes. The study provides indirect evidence of severe seasonal cardiovascular comorbidity among the three cardiovascular diseases, including myocardial infarction, atrial fibrillation, and atherosclerosis, which are all prevalent in the world population. While two other CVDs i.e. hypertension and heart failure were also identified, with minor temporal trends. Hence, all five diseases could be classified as seasonal cardiovascular comorbid diseases (SCCD). Furthermore, these diseases could be studied for potential common risk factors such as biochemical, genetic, and physiological factors.