Time to implement tailored interventions in Chhattisgarh, east-central India to reach malaria elimination.

BACKGROUND OBJECTIVES: Despite significant progress in malaria control throughout India, Chhattisgarh state continues to be a significant contributor to both malaria morbidity and mortality. This study aims to identify key factors associated with malaria endemicity, with a goal of focusing on these factors for malaria elimination by 2030. METHODS: We employed an analysis and narrative review methodology to summarize the existing evidence on malaria epidemiology in Chhattisgarh. Data encompassing environmental conditions, dominant malaria vectors and their distribution, and the impact of previous interventions on malaria control, were extracted from published literature using PubMed and Google Scholar. This information was subsequently correlated with malaria incidence data using appropriate statistical and geographical methods. RESULTS: Much of the malaria burden in Chhattisgarh state is concentrated in a few specific districts. The primary malaria vectors in these regions are Anopheles culicifacies and An. fluviatilis. High transmission areas are found in tribal belts which are challenging to access and are characterized by densely forested areas that provide a conducive habitat for malaria vectors. INTERPRETATION CONCLUSION: Conducive environmental conditions characterized by high forest cover, community behavior, and insurgency, contribute to high malaria endemicity in the area. Challenges include insecticide resistance in malaria vectors and asymptomatic malaria. Allocating additional resources to high-endemic districts is crucial. Innovative and focused malaria control programs of the country, such as DAMAN and Malaria Mukt Abhiyan, hold immense importance.

Spatiotemporal Epidemiology of Malaria in India from 2007 to 2022.

India is a major contributor to the global burden of malaria, especially Plasmodium vivax infection. Understanding the spatiotemporal trends of malaria across India over the last two decades may assist in targeted intervention. The population-normalized spatiotemporal trends of malaria epidemiology in India from 2007 to 2022 were analyzed using a geographic information system with the publicly available "malaria situation" report of the National Vector Borne Disease Control Program (NVBDCP). The NVBDCP data showed malaria cases to have steeply declined from 1.17 million in 2015 to 0.18 million cases in 2022; this is 10.1 and 18.7 fold lower than the WHO's estimate of 11.93 million and 3.38 million cases in 2015 and 2022, respectively. From 2007 to 2022, Mizoram, Meghalaya, Tripura, Odisha, Chhattisgarh, and Jharkhand consistently reported high caseloads of Plasmodium falciparum. In the same period, the P. vivax caseload was high in Arunachal Pradesh, Mizoram, Nagaland, Jharkhand, Odisha, Chhattisgarh, Goa, Daman and Diu, Dadra and Nagar Haveli, and Andaman and Nicobar Islands. The distribution of forest cover, annual rainfall, and proportion of the Scheduled Tribe population (the most underprivileged in Indian society) spatially correlated with malaria cases and deaths. Mizoram is the only state where cases were higher in 2022 than in 2007. Overall, India has made tremendous progress in controlling malaria and malaria-related deaths in the last decade. The decline could be attributed to the effective vector and parasite control strategies implemented across the country.

Malaria elimination: situation analysis of cases in India, the state of Madhya Pradesh in central India, and district Mandla of Madhya Pradesh.

India contributed approximately 66% of the malaria cases in the WHO South-East Asia region in 2022. In India, approximately 44% of cases have been reported to be disproportionately contributed by approximately 27 districts. A comparative analysis of reported malaria cases between January 2017 and December 2022 was performed in Mandla district, which is the site of a model malaria elimination demonstration project (MEDP) in Madhya Pradesh (MP), India. Compared to 2017, the decrease in malaria cases in Mandla from 2018 to 2022 was higher than MP and the rest of the country. The reduction of cases was significant in 2018, 2019, and 2021 (p < 0.01) (Mandla vs. MP) and was highly significant during 2018-2022 (p < 0.001) (Mandla vs. India). Robust surveillance and real-time data-based decisions accompanied by appropriate management, operational controls, and independent reviews, all designed for resource optimisation, were the reasons for eliminating indigenous malaria in Mandla district. The increase in infection rates during the months immediately following rains suggests that surveillance, vector control, and case management efforts should be specifically intensified for eliminating imported and indigenous cases in the near-elimination districts to work towards achieving the national elimination goal of 2030.

Systematic Review and Geospatial Modeling of Molecular Markers of Resistance to Artemisinins and Sulfadoxine-Pyrimethamine in Plasmodium falciparum in India.

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.

Malaria Slide Bank to Strengthen and Improve the Quality of Malaria Diagnosis: A National Slide Repository in India.

Malaria elimination is one of the top health care priorities in India, necessitating accessible and accurate diagnosis for effective treatment. A malaria slide bank in India is a collection of quality-controlled malaria-positive and -negative slides and is considered a vital asset for quality diagnosis. The collection of blood samples, preparation of blood smears, staining, quality control, molecular characterizations, and slide validation were carried out according to standard operating procedures in accordance with the WHO reference laboratory. The true count and parasite density per microliter were computed in accordance with WHO guidelines. Over 27 months, 48 batches (8,196 slides) were prepared. Overall, the majority of slide batches were Plasmodium vivax (45.9%; 22/48), followed by Plasmodium falciparum (25%; 12/48), malaria-negative infections (25%; 12/48), and mixed infections (4.1%; 2/48). All 48 batches passed internal validation by WHO-certified level-1 microscopists. For a batch, the true count was the median of the validators' counts (range, 111-280,795 parasites/µL). Except for mixed infections, the PCR results agreed with the verified microscopy results. Malaria slide bank slides would be a valuable tool for quality control, assurance, and microscopist training.

Repurposing FDA-approved drugs to target malaria through inhibition of dihydrofolate reductase in the folate biosynthesis pathway: A prospective approach.

Dihydrofolate reductase (DHFR) is a ubiquitous enzyme that regulates the biosynthesis of tetrahydrofolate among various species of Plasmodium parasite. It is a validated target of the antifolate drug pyrimethamine (Pyr) in Plasmodium falciparum (Pf), but its clinical efficacy has been hampered due to the emergence of drug resistance. This has made the attempt to screen Food & Drug Administration-approved drugs against wild- and mutant PfDHFR by employing an in-silico pipeline to identify potent candidates. The current study has followed a virtual screening approach for identifying potential DHFR inhibitors from DrugBank database, based on a structure similarity search of candidates, followed by absorption, distribution, metabolism, and excretion estimation. The screened drugs were subjected to various parameters like docking, molecular mechanics with generalized born and surface area solvation calculations, and molecular simulations. We have thus identified two potential drug candidates, duloxetine and guanethidine, which can be repurposed to be tested for their efficacy against wild type and drug resistant falciparum malaria.

Time series analysis of malaria cases to assess the impact of various interventions over the last three decades and forecasting malaria in India towards the 2030 elimination goals.

BACKGROUND: Despite the progress made in this decade towards malaria elimination, it remains a significant public health concern in India and many other countries in South Asia and Asia Pacific region. Understanding the historical trends of malaria incidence in relation to various commodity and policy interventions and identifying the factors associated with its occurrence can inform future intervention strategies for malaria elimination goals. METHODS: This study analysed historical malaria cases in India from 1990 to 2022 to assess the annual trends and the impact of key anti-malarial interventions on malaria incidence. Factors associated with malaria incidence were identified using univariate and multivariate linear regression analyses. Generalized linear, smoothing, autoregressive integrated moving averages (ARIMA) and Holt's models were used to forecast malaria cases from 2023 to 2030. RESULTS: The reported annual malaria cases in India during 1990-2000 were 2.38 million, which dropped to 0.73 million cases annually during 2011-2022. The overall reduction from 1990 (2,018,783) to 2022 (176,522) was 91%. The key interventions of the Enhanced Malaria Control Project (EMCP), Intensified Malaria Control Project (IMCP), use of bivalent rapid diagnostic tests (RDT-Pf/Pv), artemisinin-based combination therapy (ACT), and involvement of the Accredited Social Health Activists (ASHAs) as front-line workers were found to result in the decline of malaria significantly. The ARIMA and Holt's models projected a continued decline in cases with the potential for reaching zero indigenous cases by 2027-2028. Important factors influencing malaria incidence included tribal population density, literacy rate, health infrastructure, and forested and hard-to-reach areas. CONCLUSIONS: Studies aimed at assessing the impact of major commodity and policy interventions on the incidence of disease and studies of disease forecasting will inform programmes and policymakers of steps needed during the last mile phase to achieve malaria elimination. It is proposed that these time series and disease forecasting studies should be performed periodically using granular (monthly) and meteorological data to validate predictions of prior studies and suggest any changes needed for elimination efforts at national and sub-national levels.

A randomised controlled trial to compare the efficacy, safety, and tolerability of low dose, short course primaquine in adults with uncomplicated P. vivax malaria in two hospitals in India.

BACKGROUND: Plasmodium vivax remains a major challenge for malaria control and elimination due to its ability to cause relapsing illness. To prevent relapses the Indian National Center for Vector Borne Diseases Control (NCVBDC) recommends treatment with primaquine at a dose of 0.25 mg/kg/day provided over 14 days. Shorter treatment courses may improve adherence and treatment effectiveness. METHODS: This is a hospital-based, randomised, controlled, open-label trial in two centres in India. Patients above the age of 16 years, with uncomplicated vivax malaria, G6PD activity of ≥ 30% of the adjusted male median (AMM) and haemoglobin levels ≥ 8 g/dL will be recruited into the study and randomised in a 1:1 ratio to receive standard schizonticidal treatment plus 7-day primaquine at 0.50 mg/kg/day or standard care with schizonticidal treatment plus 14-day primaquine at 0.25 mg/kg/day. Patients will be followed up for 6 months. The primary endpoint is the incidence risk of any P. vivax parasitaemia at 6 months. Safety outcomes include the incidence risk of severe anaemia (haemoglobin < 8 g/dL), the risk of blood transfusion, a > 25% fall in haemoglobin and an acute drop in haemoglobin of > 5 g/dL during primaquine treatment. DISCUSSION: This study will evaluate the efficacy and safety of a 7-day primaquine regimen compared to the standard 14-day regimen in India. Results from this trial are likely to directly inform national treatment guidelines. TRIAL REGISTRATION: Trial is registered on CTRI portal, Registration No: CTRI/2022/12/048283.

A computational strategy for systematic virtual screening of plasmodium falciparum heme detoxification protein inhibitors from the Drugbank database.

Antimalarial drug resistance poses one of the greatest threats to malaria treatment, resulting in increased morbidity and mortality. Heme Detoxification Protein (HDP) is among the essential hemoglobinases of P. falciparum (Pf), a vital molecular target for the treatment of malaria. In this study, we utilized the virtual screening workflow tool of the Schrodinger suite to find the best hits for the PfHDP from the DrugBank library. A total of 14,942 compounds were identified against the PfHDP. The top compounds with the highest docking scores and least energy scores were subjected to molecular simulations for 500 nanosecond to check the stability of the protein-drug complexes. The top three DrugBank compounds were found to be stable over 500 ns, namely DB09298 (silibinin), DB07426 (1-Hydroxy-2-(1,1':3',1''-Terphenyl-3-Yloxy) Ethane-1,1-Diyl] Bis (Phosphonic Acid), and DB07410 [(2-(3-Dibenzofuran-4-yl-Phenyl)-1-Hydroxy-1-Phosphono-Ethyl]-Phosphonic Acid). Overall analysis suggests that the top three compounds, DB09298, DB07426, and DB07410, have good stability for 500 ns. Their scaffolds can be used to design and develop new analogs of the target HDP protein. Silibinin, the anti-cancer drug, was found to be highly stable for the entire simulation period as compared to the other compounds. DB07426 shows its therapeutic effect on bones, especially in the treatment of osteoporosis, and DB07410 has anti-tumor, antibacterial, anti-oxidative, and anti-viral activities. All three compounds can be considered for repurposing as antimalarial drugs to evaluate the binding capacity or inhibition potential of these compounds. Further in-vivo and in-vitro analysis against the PfHDP protein should be conducted.Communicated by Ramaswamy H. Sarma.

Assessment of Plasmodium falciparum drug resistance associated molecular markers in Mandla, Madhya Pradesh, India.

BACKGROUND: Resistance against artemisinin-based combination therapy is one of the challenges to malaria control and elimination globally. Mutations in different genes (Pfdhfr, Pfdhps, Pfk-13 and Pfmdr1) confer resistance to artesunate and sulfadoxine-pyrimethamine (AS + SP) were analysed from Mandla district, Madhya Pradesh, to assess the effectiveness of the current treatment regimen against uncomplicated Plasmodium falciparum. METHODS: Dried blood spots were collected during the active fever survey and mass screening and treatment activities as part of the Malaria Elimination Demonstration Project (MEDP) from 2019 to 2020. Isolated DNA samples were used to amplify the Pfdhfr, Pfdhps, Pfk13 and Pfmdr1 genes using nested PCR and sequenced for mutation analysis using the Sanger sequencing method. RESULTS: A total of 393 samples were subjected to PCR amplification, sequencing and sequence analysis; 199, 215, 235, and 141 samples were successfully sequenced for Pfdhfr, Pfdhps, Pfk13, Pfmdr1, respectively. Analysis revealed that the 53.3% double mutation (C59R, S108N) in Pfdhfr, 89.3% single mutation (G437A) in Pfdhps, 13.5% single mutants (N86Y), and 51.1% synonymous mutations in Pfmdr1 in the study area. Five different non-synonymous and two synonymous point mutations found in Pfk13, which were not associated to artemisinin resistance. CONCLUSION: The study has found that mutations linked to SP resistance are increasing in frequency, which may reduce the effectiveness of this drug as a future partner in artemisinin-based combinations. No evidence of mutations linked to artemisinin resistance in Pfk13 was found, suggesting that parasites are sensitive to artemisinin derivatives in the study area. These findings are a baseline for routine molecular surveillance to proactively identify the emergence and spread of artemisinin-resistant parasites.

Low prevalence of antimalarial-resistance mutations in India during 2014-15: Impact of combining first-line therapy with primaquine.

BACKGROUND: Antimalarial drug resistance surveillance and containment are crucial for countries aiming to eliminate malaria. Monitoring resistance evolution through studies before and after treatment policy changes is crucial. METHOD: A total of 939 P. falciparum-positive blood samples were collected between 2014 and 2015 across ten sites in India, categorized into four geographic clusters. PCR-amplified products were sequenced to identify point mutations at drug-resistance-conferring genes (Pfdhfr, Pfdhps, Pfmdr1, Pfk13). RESULT: Triple Pfdhfr mutants were found only in northeast India bordering Myanmar, while the wildtype was dominant in central India. Pfdhps wildtypes were prevalent in all areas, and no double mutants were found. Except in Northwest India, Pfmdr1 wildtype was dominant in all clusters. Nonsynonymous double mutations were only found in northwest India. Only synonymous mutations occurred in Pfk13. These were found in Central India at low frequency. The pattern of linkage disequilibrium and principal component analysis reflects low pressure for drug resistance and heterogeneity between the geographic clusters. CONCLUSION: Resistance levels were highest in Northeast India, close to the Myanmar border, where resistance is common. Primaquine has been widely used as a gametocidal and schizonticidal drug, has likely contributed to maintaining low drug resistance levels and preventing strong selection for resistance.

Safety and efficacy of primaquine in patients with Plasmodium vivax malaria from South Asia: a systematic review and individual patient data meta-analysis.

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.

Tracking district-level performance in the context of achieving zero indigenous case status by 2027.

India has committed to zero indigenous malaria cases by 2027 and elimination by 2030. Of 28 states and 8 union territories of India, eleven states were targeted to reach the elimination phase by 2020. However, state-level epidemiology indicates that several states of India may not be on the optimum track, and few goals set in National Framework for Malaria Elimination (NFME) for 2020 remain to be addressed. Therefore, tracking the current progress of malaria elimination in India at the district level, and identifying districts that are off track is important in understanding possible shortfalls to malaria elimination. Annual malaria case data from 2017-20 of 686 districts of India were obtained from the National Center for Vector-Borne Diseases Control (NCVBDC) and analysed to evaluate the performance of districts to achieve zero case status by 2027. A district's performance was evaluated by calculating the annual percentage change in the total number of malaria cases for the years 2018, 2019 and 2020 considering the previous year as a base year. The mean, median and maximum of these annual changes were then used to project the number of malaria cases in 2027. Based on these, districts were classified into four groups: 1) districts that are expected to reach zero case status by 2027, 2) districts that would achieve zero case status between 2028 and 2030, 3) districts that would arrive at zero case status after 2030, and 4) districts where malaria cases are on the rise. Analysis suggest, a cohort of fifteen districts require urgent modification or improvement in their malaria control strategies by identifying foci of infection and customizing interventions. They may also require new interventional tools that are being developed recently so that malaria case reduction over the years may be increased.

Evaluation of the model malaria elimination strategy in Mandla district along with its neighbouring districts: a time series analysis from 2008 to 2020.

BACKGROUND: Compared to 2017, India achieved a significant reduction in malaria cases in 2020. Madhya Pradesh (MP) is a tribal dominated state of India with history of high malaria burden in some districts. District Mandla of MP state showed a considerable decline in malaria cases between 2000 and 2013, except in 2007. Subsequently, a resurgence of malaria cases was observed during 2014 and 2015. The Malaria Elimination Demonstration Project (MEDP) was launched in 2017 in Mandla with the goal to achieve zero indigenous malaria cases. This project used: (1) active surveillance and case management using T4 (Track fever, Test fever, Treat patient, and Track patient); (2) vector control using indoor residual sprays and long-lasting insecticidal nets; (3) information education communication and behaviour change communication; and (4) regular monitoring and evaluation with an emphasis on operational and management accountability. This study has investigated malaria prevalence trends from 2008 to 2020, and has predicted trends for the next 5 years for Mandla and its bordering districts. METHODS: The malaria prevalence data of the district Mandla for the period of January 2008 to August 2017 was obtained from District Malaria Office (DMO) Mandla and data for the period of September 2017 to December 2020 was taken from MEDP data repository. Further, the malaria prevalence data for the period of January 2008 to December 2020 was collected from DMOs of the neighbouring districts of Mandla. A univariate time series and forecast analysis was performed using seasonal autoregressive integrated moving average model. FINDINGS: Malaria prevalence in Mandla showed a sharp decline [- 87% (95% CI - 90%, - 84%)] from 2017 to 2020. The malaria forecast for Mandla predicts zero cases in the next 5 years (2021-2025), provided current interventions are sustained. By contrast, the model has forecasted a risk of resurgence of malaria in other districts in MP (Balaghat, Dindori, Jabalpur, Seoni, and Kawardha) that were not the part of MEDP. CONCLUSION: The interventions deployed as part of MEDP have resulted in a sustainable zero indigenous malaria cases in Mandla. Use of similar strategies in neighbouring and other malaria-endemic districts in India could achieve similar results. However, without adding extra cost to the existing intervention, sincere efforts are needed to sustain these interventions and their impact using accountability framework, data transparency, and programme ownership from state to district level.

A comparative assessment of the community frontline health workers for their knowledge and practices of malaria diagnosis and treatment in three contiguous districts Mandla, Balaghat, and Dindori of Madhya Pradesh, India.

BACKGROUND: Global malaria cases rose by 14 million, and deaths by 69,000, in 2020. In India, a 46% decline has been reported between 2020 and 2019. In 2017, the Malaria Elimination Demonstration Project conducted a needs-assessment of the Accredited Social Health Activists (ASHAs) of Mandla district. This survey revealed the inadequate level of knowledge in malaria diagnosis and treatment. Subsequently, a training programme was launched for enhancing malaria-related knowledge of ASHAs. The present study was conducted in 2021 to evaluate the impact of training on malaria-related knowledge and practices of ASHAs in Mandla. This assessment was also done in two adjoining districts: Balaghat and Dindori. METHODS: A cross-sectional survey using a structured questionnaire was administered to ASHAs to measure their knowledge and practices related to malaria etiology, prevention, diagnosis, and treatment. A comparison of information collected from these three districts was performed using simple descriptive statistics, comparison of means and multivariate logistic regression analysis. RESULTS: Significant improvement was noted amongst ASHAs of district Mandla between 2017 (baseline) and 2021 (endline) in knowledge related to malaria transmission, preventive measures, adherence to the national drug policy, diagnosis using rapid diagnostic tests, and identification of age group-specific, colour-coded artemisinin combination therapy blister packs (p < 0.05). The multivariate logistic regression analysis revealed that odds of Mandla baseline was 0.39, 0.48, 0.34, and 0.07 times lower for malaria-related knowledge on disease etiology, prevention, diagnosis, and treatment, respectively (p < 0.001). Further, participants in districts Balaghat and Dindori showed significantly lower odds for knowledge (p < 0.001) and treatment practices (p < 0.01) compared to Mandla endline. Education, attended training, having a malaria learner's guide, and minimum 10 years' work experience were potential predictors for good treatment practices. CONCLUSION: The findings of the study unequivocally establishes significant improvement in overall malaria-related knowledge and practices of ASHAs in Mandla as a result of periodic training and capacity building efforts. The study suggests that learnings from Mandla district could be helpful in improving level of knowledge and practices among frontline health workers.

A case report of late treatment failure in Plasmodium falciparum malaria in a traveler from the Democratic Republic of the Congo to India.

A young male returned from the Democratic Republic of the Congo (DRC) to India after four months during his official work. Within a week of his arrival, he developed a high-grade fever with nausea and was hospitalized in a private hospital in New Delhi. He was diagnosed with malaria, treated with an artesunate injection as antimalarial, and discharged on day 5th from the hospital. A week later, he was diagnosed with malaria and dengue positive at ICMR-National Institute of Malaria Research, New Delhi. Artesunate with sulphadoxine and pyrimethamine (AS+SP) was administered following India's malaria treatment policy. However, high-grade fever, along with the asexual stage of the P. falciparum parasite, was observed within 28 days of treatment with AS+SP, signifying late treatment failure (LTF). Further, the molecular analysis from both the days of episodes was analyzed using genomic DNA from dried blood spots, revealing resistance to sulphadoxine-pyrimethamine with mutations at codons pfdhfr 51I, pfdhfr 59 R, pfdhfr 108 N, pfdhps 437 A, pfdhps 581 G. No functional mutation associated was found in pfKelch13, but interestingly the sensitive codons to chloroquine (CQ) (wild type pfcrtK76 and pfmdrN86) revealed the probably reversible CQ sensitivity in the sample from DRC.

Linkages between malaria and malnutrition in co-endemic regions of India.

INTRODUCTION: Malaria and malnutrition are key public health challenges in India. However, the relationship between them is poorly understood. Here, we aimed to elucidate the potential interactions between the two health conditions by identifying the areas of their spatial overlap. METHODS: We have analysed the district-wise undernutrition and malaria data of 638 districts of India across 28 states and 8 union territories. Data on malnutrition parameters viz. stunting, wasting, underweight and anaemia, sourced from the fourth National Family Health Survey (2015-2016), and malaria Annual Parasite Index (API) data of the same year (i.e, 2015), sourced from National Center of Vector Borne Diseases Control were analysed using local Moran's I Index and logistic regression. RESULTS: Among all the malnutrition parameters, we found underweight in children and anaemia in men to co-occur with malaria in the districts of Chhattisgarh, Jharkhand, Madhya Pradesh and Odisha. Further, districts with more than 36% underweight children (OR (95% CI): 2.31 (1.53 to 3.48)) and/or more than 23.6% male population with anaemia (OR (95% CI): 2.06 (1.37 to 3.11)) had higher odds of being malaria endemic districts (ie, Annual Parasite Index >1). CONCLUSION: Malaria and malnutrition co-occur in the malaria-endemic parts of India. The high prevalence of undernutrition in children and anaemia among men may contribute to malaria endemicity in a particular region. Therefore, future research should be prioritised to generate data on the individual level. Further, malaria control interventions could be tailored to integrate nutrition programmes to disrupt indigenous malaria transmission in endemic districts.

Screening of potential antiplasmodial agents targeting cysteine protease-Falcipain 2: a computational pipeline.

The spread of antimalarial drug resistance is a substantial challenge in achieving global malaria elimination. Consequently, the identification of novel therapeutic candidates is a global health priority. Malaria parasite necessitates hemoglobin degradation for its survival, which is mediated by Falcipain 2 (FP2), a promising antimalarial target. In particular, FP2 is a key enzyme in the erythrocytic stage of the parasite's life cycle. Here, we report the screening of approved drugs listed in DrugBank using a computational pipeline that includes drug-likeness, toxicity assessments, oral toxicity evaluation, oral bioavailability, docking analysis, maximum common substructure (MCS) and molecular dynamics (MD) Simulations analysis to identify capable FP2 inhibitors, which are hence potential antiplasmodial agents. A total of 45 drugs were identified, which have positive drug-likeness, no toxic features and good bioavailability. Among these, six drugs showed good binding affinity towards FP2 compared to E64, an epoxide known to inhibit FP2. Notably, two of them, Cefalotin and Cefoxitin, shared the highest MCS with E64, which suggests that they possess similar biological activity as E64. In an investigation using MD for 100 ns, Cefalotin and Cefoxitin showed adequate protein compactness as well as satisfactory complex stability. Overall, these computational approach findings can be applied for designing and developing specific inhibitors or new antimalarial agents for the treatment of malaria infections.Communicated by Ramaswamy H. Sarma.

Age-specific malaria vulnerability and transmission reservoir among children.

Purpose: The pediatric population, especially under-five children, is highly susceptible to malaria and accounts for 76 % of global malaria deaths according to the World Malaria Report 2022. The purpose of this manuscript is to discuss the various factors involved in the susceptibility of the pediatric population to Malaria and the importance of this age group for malaria elimination. Methodology: Data on pediatric malaria epidemiology that includes prevalence, risk factors, immune factors, socioeconomic factors, control methods, etc. were extracted from published literature using PubMed and Google Scholar. This data was further correlated with malaria incidence data from the World Health Organization (WHO) and the National Center for Vector Borne Diseases Control (NCVBDC). Results: The younger age group is vulnerable to severe malaria due to an immature immune system. The risk of infection and clinical disease increases after the waning of maternal immunity. In the initial years of life, the developing brain is more susceptible to malaria infection and its after-effects. The pediatric population may act as a malaria transmission reservoir due to parasite density and asymptomatic infections. WHO recommended RTS,S/AS01 has limitations and may not be applicable in all settings to propel malaria elimination. Conclusion: The diagnosis of malaria is based on clinical suspicion and confirmed with microscopy and/or rapid diagnostic testing. The school-age pediatric population serves as a transmission reservoir in the form of asymptomatic malaria since they have acquired some immunity due to exposure in early childhood. Targeting the hidden reservoir in the pediatric population and protecting this vulnerable group will be essential for malaria elimination from the countries targeting elimination.

Science of malaria elimination: using knowledge of bottlenecks and enablers from the Malaria Elimination Demonstration Project in Central India for eliminating malaria in the Asia Pacific region.

Malaria poses a major public health challenge in the Asia Pacific. Malaria Elimination Demonstration Project was conducted as a public-private partnership initiative in Mandla between State government, ICMR, and FDEC India. The project employed controls for efficient operational and management decisions. IEC campaigns found crucial in schools and communities. Capacity building of local workers emphasized for better diagnosis and treatment. SOCH mobile app launched for complete digitalization. Better supervision for Indoor Residual Sprays and optimized Long Lasting Insecticidal Nets distribution. Significant malaria cases reduction in Mandla. Insights from MEDP crucial for malaria elimination strategies in other endemic regions of the Asia Pacific.