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.

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.

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.

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.

Sinococuline, a bioactive compound of Cocculus hirsutus has potent anti-dengue activity.

Dengue virus (DENV) infection has increased worldwide, with over 400 million infections annually, and has become a serious public health concern. Several drug candidates, new and repurposed, have failed to meet the primary efficacy endpoints. We have recently shown that Aqueous Extract of the stem of Cocculus hirsutus (AQCH) was effective in vitro and in vivo against DENV and was safe in humans. We now report that an active ingredient of AQCH, Sinococuline, protects against the antibody-mediated secondary-DENV infection in the AG129 mouse model. DENV infection markers were assessed, viz. serum viremia and vital organs pathologies-viral load, proinflammatory cytokines and intestinal vascular leakage. The treatment with Sinococuline at 2.0 mg/kg/day; BID (twice a day), was the most effective in protecting the severely DENV-infected AG129 mice. Also, this dose effectively reduced serum viremia and tissue-viral load and inhibited the elevated expression levels of proinflammatory cytokines (TNF-α and IL-6) in several vital organs. Based on these findings, it could be explored further for pre-clinical and clinical developments for the treatment of dengue.

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.

Mass screening and treatment (MSaT) for identifying and treating asymptomatic cases of malaria-malaria elimination demonstration project (MEDP), Mandla, Madhya Pradesh.

BACKGROUND: Mass screening and treatment (MSaT) aims at reducing the spread of malaria in communities by identifying and treating infected persons regardless of the symptoms. This study was conducted to identify and treat asymptomatic cases using MSaT approaches in the community. METHODS: Three rounds of MSaT using cluster combination approaches were carried out during September 2018 to December 2019 to identify and treat asymptomatic malaria cases in the community. All individuals who were present in the household were screened using RDT irrespective of malaria related symptoms. Simultaneously thick and thin blood smear and blood spot were collected for further analysis using microscopy and diagnostic PCR done in a subset of the samples. RESULTS: Logistic regression analysis revealed that asymptomatic malaria cases significantly less among the older age groups compared with < 5 years children (OR ranged between 0.52 and 0.61; p < 0.05), lowest in cluster 4 (OR = 0.01; p < 0.0001); during third round of MSaT survey (OR = 0.11; p < 0.0001) and significantly higher in moderate to high endemic areas (OR = 88.30; p < 0.0001). CONCLUSION: Over the three rounds of MSaT, the number of asymptomatic cases were significantly less in the older age groups, and during third round. Similarly, the asymptomatic cases were significantly less in the low endemic area with API < 1 (cluster four). Therefore, the malaria elimination programme may consider the MSaT strategy to identify asymptomatic cases that would be otherwise missed by routine fever based surveillance. This MSaT strategy would help accomplish the malaria elimination goal in an expedited manner.

A qualitative study on community perceptions on quality of healthcare services they received in the Malaria Elimination Demonstration Project in district Mandla, India.

BACKGROUND: The utilization and impact of the healthcare services depend on the perceived quality, appropriateness, ease of availability, and cost of the services. This study aimed to understand the community's perception of the quality of healthcare services delivered as part of the Malaria Elimination Demonstration Project (MEDP), Mandla, Madhya Pradesh, India. METHODS: The study used qualitative techniques to analyze the community perceptions that emerged from the participants' narratives during the Focus Group Discussions (FGDs) and in-depth Interviews with Key Informants (IKIs) on the promptness and quality of healthcare service delivery, the behaviour of MEDP staff, Information, Education and Communication, and Behavioural Change Communication activities, coordination with community members and other health personnel, and capacity building of healthcare workers and the community. RESULTS: 36 FGDs and 63 IKIs with 419 respondents were conducted in nine blocks of district Mandla. Overall, 97% to 100% of beneficiaries associated MEDP with regularity and prompt service delivery, availability of diagnostics and drugs, friendly behaviour, good coordination, and community mobilization to enhance treatment-seeking behaviour. CONCLUSIONS: The study's findings highlighted the importance of building and maintaining the community's participation and promoting the demand for optimal utilization of healthcare services inside the village to promptly achieve the malaria elimination goal.

Significance of nested PCR testing for the detection of low-density malaria infection amongst febrile patients from the Malaria Elimination Demonstration Project in Mandla, Madhya Pradesh, India.

BACKGROUND: Low-density malaria infections (LDMI) are defined as infections that are missed by the rapid diagnostic test (RDT) and/or microscopy which can lead to continued transmission and poses a challenge in malaria elimination efforts. This study was conducted to investigate the prevalence of LDMI in febrile cases using species-specific nested Polymerase Chain Reaction (PCR) tests in the Malaria Elimination Demonstration Project, where routine diagnosis was conducted using RDT. METHODS: Every 10th fever case from a cross-sectional community based fever surveillance was tested with RDT, microscopy and nested PCR. Parasite DNA was isolated from the filter paper using Chelex based method. Molecular diagnosis by nested PCR was performed targeting 18SrRNA gene for Plasmodium species. RESULTS: The prevalence of malaria was 2.50% (436/17405) diagnosed by PCR, 1.13% (196/17405) by RDT, and 0.68% (118/ 17,405) by microscopy. Amongst 17,405 febrile samples, the prevalence of LDMI was 1.51% (263/17405) (95% CI 1.33-1.70), which were missed by conventional methods. Logistic regression analysis revealed that illness during summer season [OR = 1.90 (p < 0.05)] and cases screened within three days of febrile illness [OR = 5.27 (p < 0.001)] were the statistically significant predictors of LDMI. CONCLUSION: The prevalence of malaria among febrile cases using PCR was 2.50% (436/17405) as compared to 1.13% (196/17405) by RDT. Higher number of the LDMI cases were found in subjects with ≤ 3 days mean duration of reported fever, which was statistically significant (p < 0.001). This observation suggests that an early detection of malaria with a more sensitive diagnostic method or repeat testing of the all negative cases may be useful for curtailing malaria transmission. Therefore, malaria elimination programme would benefit from using more sensitive and specific diagnostic methods, such as PCR.

Clinical safety and pharmacokinetic evaluation of aqueous extract of Cocculus hirsutus, an anti-viral phytopharmacetical drug as a potential for the treatment of dengue and COVID-19.

Background and aim: Dengue a worldwide concern for public health has no effective vaccine or drug available for its prevention or treatment. There are billions of people who are at risk of contracting the dengue virus (DENV) infections with only anti-mosquito strategies to combat this disease. Based on the reports, particularly in vitro studies and small animal studies showing anti-viral activity of aqueous extract of Cocculus hirsutus (AQCH), studies were conducted on AQCH tablets as a potential for the treatment of dengue and COVID-19 infections. The current study was part of the research on AQCH tablet formulation and was aimed to evaluate safety and pharmacokinetics in healthy human subjects. Materials and methods: Sixty healthy adult human subjects were divided into 5 groups (cohorts: I to V; n = 12 per cohort) and randomized in the ratio of 3:1 to receive active treatment or placebo in a blinded manner. Five doses 100 mg, 200 mg, 400 mg, 600 mg and 800 mg tablets were administered three times daily at an interval of 8 h for days 01-09 under fasting conditions and a single dose in morning on day 10. Safety assessment was based on monitoring the occurrence, pattern, intensity, and severity of adverse events during study period. Blood samples were collected for measurement of the bio-active marker Sinococuline concentrations by a validated LC-MS/MS method followed by pharmacokinetic evaluation. Results and conclusion: The test formulation was well tolerated in all cohorts. Sinococuline peak plasma concentration (Cmax) and total exposure of plasma concentration (AUC) demonstrated linearity up to 600 mg and saturation kinetics at 800 mg dose. There was no difference observed in elimination half-life for all the cohorts, suggesting absence of saturation in rate of elimination. Dose accumulation was observed and steady state was achieved within 3 days. The information on human pharmacokinetics of AQCH tablets would assist in further dose optimization with defined pharmacokinetic-pharmacodynamic relationship.

Monitoring of the Village Malaria Workers to conduct activities of Malaria Elimination Demonstration Project in Mandla, Madhya Pradesh.

BACKGROUND: The capacity of the field staff to conduct activities related to disease surveillance, case management, and vector control has been one of the key components for successfully achieving malaria elimination. India has committed to eliminate malaria by 2030, and it has placed significance on monitoring and evaluation at the district level as one of the key strategies in its national framework. To support and guide the country's malaria elimination objectives, the Malaria Elimination Demonstration Project was conducted in the tribal district of Mandla, Madhya Pradesh. Robust monitoring of human resources received special attention to help the national programme formulate a strategy to plug the gaps in its supply chain and monitoring and evaluation systems. METHODS: A monitoring tool was developed to test the capabilities of field workers to conduct activities related to malaria elimination work. Between November 2018 to February 2021, twenty-five Malaria Field Coordinators (MFCs) of the project utilized this tool everyday during the supervisory visits for their respective Village Malaria Workers (VMWs). The data was analysed and the scores were tested for variations against different blocks, educational status, duration of monitoring, and post-training scores. RESULTS: During the study period, the VMWs were monitored a total of 8974 times using the monitoring tool. Each VMW was supervised an average of 1.8 times each month. The critical monitoring indicators scored well in all seven quarters of the study as monitored by the MFCs. Monitoring by MFCs remained stable at 97.3% in all quarters. Contrary to expectations, the study observed longer diagnosis to treatment initiation time in urban areas of the district. CONCLUSION: This study demonstrated the significance of a robust monitoring tool as an instrument to determine the capacity of the field workers in conducting surveillance, case management, and vector control related work for the malaria elimination programme. Similar tools can be replicated not only for malaria elimination, but other public health interventions as well.

Assessment of frontline health workers in providing services for malaria elimination in the tribal district of Mandla, Madhya Pradesh.

Background: The Accredited Social Health Activists (ASHAs) and Auxiliary Nurse Midwives (ANMs) are the frontline health staff that provide essential health care services, including diagnosis and treatment of malaria. To support India's malaria-free goal by 2030, a project known as the Malaria Elimination Demonstration Project (MEDP) in the tribal district of Mandla was initiated. This study assessed the capabilities of ASHAs and ANMs of Mandla district to diagnose and treat malaria. Methods: A cross-sectional study was conducted in the 71 sub-centers and their villages where at least one positive malaria case was diagnosed in 2019. Pre-designed and validated tools were used to assess the knowledge, attitude, and practices of ASHAs and ANMs. Analysis was performed using descriptive statistics and multivariate logistic regressions. Results: Malaria is the fifth priority of the ASHAs and ANMs of Mandla district. Good level of knowledge regarding malaria etiology, diagnosis, and prevention was found, but the ability to treat a malaria case as per the national drug policy was below expectations. Frequent and prolonged stockouts of drugs and diagnostics were found. Logistic regressions revealed better capacity of ANMs to dispense correct treatment as compared to the ASHAs. Improvement was seen in the ASHAs ability to interpret rapid diagnostic test (RDT) results following trainings by MEDP Mandla. Conclusion: There is a need to increase the capabilities of the frontline health staff of Mandla for malaria diagnosis and treatment. Continuous trainings and a robust supply chain management system is required to equip the ASHAs and ANMs to effectively deliver malaria diagnosis and treatment services.

Cocculus hirsutus-Derived Phytopharmaceutical Drug Has Potent Anti-dengue Activity.

Dengue is a serious public health concern worldwide, with ∼3 billion people at risk of contracting dengue virus (DENV) infections, with some suffering severe consequences of disease and leading to death. Currently, there is no broad use vaccine or drug available for the prevention or treatment of dengue, which leaves only anti-mosquito strategies to combat the dengue menace. The present study is an extension of our earlier study aimed at determining the in vitro and in vivo protective effects of a plant-derived phytopharmaceutical drug for the treatment of dengue. In our previous report, we had identified a methanolic extract of aerial parts of Cissampelos pareira to exhibit in vitro and in vivo anti-dengue activity against all the four DENV serotypes. The dried aerial parts of C. pareira supplied by local vendors were often found to be mixed with aerial parts of another plant of the same Menispermaceae family, Cocculus hirsutus, which shares common homology with C. pareira. In the current study, we have found C. hirsutus to have more potent anti-dengue activity as compared with C. pareira. The stem part of C. hirsutus was found to be more potent (∼25 times) than the aerial part (stem and leaf) irrespective of the extraction solvent used, viz., denatured spirit, hydro-alcohol (50:50), and aqueous. Moreover, the anti-dengue activity of stem extract in all the solvents was comparable. Hence, an aqueous extract of the stem of C. hirsutus (AQCH) was selected due to greater regulatory compliance. Five chemical markers, viz., Sinococuline, 20-Hydroxyecdysone, Makisterone-A, Magnoflorine, and Coniferyl alcohol, were identified in fingerprinting analysis. In a test of primary dengue infection in the AG129 mice model, AQCH extract at 25 mg/kg body weight exhibited protection when administered four and three times a day. The AQCH was also protective in the secondary DENV-infected AG129 mice model at 25 mg/kg/dose when administered four and three times a day. Additionally, the AQCH extract reduced serum viremia and small intestinal pathologies, viz., viral load, pro-inflammatory cytokines, and vascular leakage. Based on these findings, we have undertaken the potential preclinical development of C. hirsutus-based phytopharmaceutical, which could be studied further for its clinical development for treating dengue.

Learnings from two independent malaria elimination demonstration projects in India.

PROBLEM: India and sub-Saharan Africa contributes about 85% of the global malaria burden, and India is committed to eliminating malaria by 2030. APPROACH: Two novel initiatives-the Malaria Elimination Demonstration Project (MEDP) in Madhya Pradesh and Durgama Anchalare Malaria Nirakaran (DAMaN) in Odisha-were initiated independently to demonstrate that indigenous malaria can be eliminated in a short period of time. LOCAL SETTING: These initiatives focused on rural, tribal areas where there is a high malaria burden and complex epidemiology. RELEVANT CHANGES: The case management and vector control strategies used in these programmes were based on the national guidelines, with context-specific changes and introduction of accountability at management, operational, technical and financial levels. The MEDP achieved a 91% reduction in malaria cases and recorded zero transmission for 6 consecutive and a total of 9 mo. The DAMaN project brought about an 88% reduction in malaria cases. LESSONS LEARNED: Malaria elimination will require robust surveillance and case management, monitoring of vector control interventions, community-centric information education communication and behaviour change communication initiatives and management controls, as well as regular internal and external reviews.

Assessing community knowledge, attitude and practices to strengthen communication strategy for Malaria Elimination Demonstration Project in Mandla.

BACKGROUND: Changes in social, belief, and behavioural practices are essential for the success of any public health delivery programme. In the planning stages of the Malaria Elimination Demonstration Project (MEDP), priority was given to communication with a goal to develop capacity of health workers and to improve the knowledge, attitude and practices (KAP) of the people of Mandla. This paper describes the level of community knowledge on malaria, including its prevention, diagnosis, treatment-seeking behaviour, and the level of satisfaction with the services provided by the project. METHODS: A cross sectional survey was undertaken in 1233 villages of Mandla to study the KAP and self-assessed improvement in knowledge and satisfaction level of the community. The goal of the study was to understand whether there is need for strengthening communication strategy of MEDP for better impact. The survey was conducted amongst the head/eligible members of the 733 households located in the nine blocks of the district using clustered random sampling. RESULTS: Though four-fifths of the respondents were able to correlate the transmission of malaria with mosquitoes, misconceptions existed among them. The types of malaria were not known to everyone. Only 39% were aware of the Indoor Residual Spray (IRS) and 41% understood the value of Long-Lasting Insecticidal Nets (LLIN). Around 71% of subjects surveyed were aware of the proper diagnostic tests for malaria. A total of 87% of the respondents knew about the MEDP staff working in their respective villages. CONCLUSION: The study reported gaps in knowledge on malaria at community level. The self-assessment of the community revealed that the communication strategy established by MEDP in Mandla district has been useful to them as they are becoming better informed about the prevention and treatment aspects of disease. The lessons learned as revealed in the KAP survey will improve malaria elimination outcomes in a timely manner.

Arterolane-piperaquine-mefloquine versus arterolane-piperaquine and artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a single-centre, open-label, randomised, non-inferiority trial.

BACKGROUND: Triple antimalarial combination therapies combine potent and rapidly cleared artemisinins or related synthetic ozonides, such as arterolane, with two, more slowly eliminated partner drugs to reduce the risk of resistance. We aimed to assess the safety, tolerability, and efficacy of arterolane-piperaquine-mefloquine versus arterolane-piperaquine and artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Kenyan children. METHODS: In this single-centre, open-label, randomised, non-inferiority trial done in Kilifi County Hospital, Kilifi, coastal Kenya, children with uncomplicated Plasmodium falciparum malaria were recruited. Eligible patients were aged 2-12 years and had an asexual parasitaemia of 5000-250 000 parasites per µL. The exclusion criteria included the presence of an acute illness other than malaria, the inability to tolerate oral medications, treatment with an artemisinin derivative in the previous 7 days, a known hypersensitivity or contraindication to any of the study drugs, and a QT interval corrected for heart rate (QTc interval) longer than 450 ms. Patients were randomly assigned (1:1:1), by use of blocks of six, nine, and 12, and opaque, sealed, and sequentially numbered envelopes, to receive either arterolane-piperaquine, arterolane-piperaquine-mefloquine, or artemether-lumefantrine. Laboratory staff, but not the patients, the patients' parents or caregivers, clinical or medical officers, nurses, or trial statistician, were masked to the intervention groups. For 3 days, oral artemether-lumefantrine was administered twice daily (target dose 5-24 mg/kg of bodyweight of artemether and 29-144 mg/kg of bodyweight of lumefantrine), and oral arterolane-piperaquine (arterolane dose 4 mg/kg of bodyweight; piperaquine dose 20 mg/kg of bodyweight) and oral arterolane-piperaquine-mefloquine (mefloquine dose 8 mg/kg of bodyweight) were administered once daily. All patients received 0·25 mg/kg of bodyweight of oral primaquine at hour 24. All patients were admitted to Kilifi County Hospital for at least 3 consecutive days and followed up at day 7 and, thereafter, weekly for up to 42 days. The primary endpoint was 42-day PCR-corrected efficacy, defined as the absence of treatment failure in the first 42 days post-treatment, of arterolane-piperaquine-mefloquine versus artemether-lumefantrine, and, along with safety, was analysed in the intention-to-treat population, which comprised all patients who received at least one dose of a study drug. The 42-day PCR-corrected efficacy of arterolane-piperaquine-mefloquine versus arterolane-piperaquine was an important secondary endpoint and was also analysed in the intention-to-treat population. The non-inferiority margin for the risk difference between treatments was -7%. The study is registered in ClinicalTrials.gov, NCT03452475, and is completed. FINDINGS: Between March 7, 2018, and May 2, 2019, 533 children with P falciparum were screened, of whom 217 were randomly assigned to receive either arterolane-piperaquine (n=73), arterolane-piperaquine-mefloquine (n=72), or artemether-lumefantrine (n=72) and comprised the intention-to-treat population. The 42-day PCR-corrected efficacy after treatment with arterolane-piperaquine-mefloquine (100%, 95% CI 95-100; 72/72) was non-inferior to that after treatment with artemether-lumefantrine (96%, 95% CI 88-99; 69/72; risk difference 4%, 95% CI 0-9; p=0·25). The 42-day PCR-corrected efficacy of arterolane-piperaquine-mefloquine was non-inferior to that of arterolane-piperaquine (100%, 95% CI 95-100; 73/73; risk difference 0%). Vomiting rates in the first hour post-drug administration were significantly higher in patients treated with arterolane-piperaquine (5%, 95% CI 2-9; ten of 203 drug administrations; p=0·0013) or arterolane-piperaquine-mefloquine (5%, 3-9; 11 of 209 drug administrations; p=0·0006) than in patients treated with artemether-lumefantrine (1%, 0-2; three of 415 drug administrations). Upper respiratory tract complaints (n=26 for artemether-lumefantrine; n=19 for arterolane-piperaquine-mefloquine; n=23 for arterolane-piperaquine), headache (n=13; n=4; n=5), and abdominal pain (n=7; n=5; n=5) were the most frequently reported adverse events. There were no deaths. INTERPRETATION: This study shows that arterolane-piperaquine-mefloquine is an efficacious and safe treatment for uncomplicated falciparum malaria in children and could potentially be used to prevent or delay the emergence of antimalarial resistance. FUNDING: UK Department for International Development, The Wellcome Trust, The Bill & Melinda Gates Foundation, Sun Pharmaceutical Industries.

A comprehensive mobile application tool for disease surveillance, workforce management and supply chain management for Malaria Elimination Demonstration Project.

BACKGROUND: Health care technologies are now offering accountability, quality, robustness, and accuracy in disease surveillance and health care delivery programmes. With the advent of mobile hand-held devices, these technologies have become more accessible and adaptable for use by field staff working in remote areas. The Malaria Elimination Demonstration Project started collection of data and conduct of routine operations using paper-based reporting systems. Observing the need for a robust and quality digital mobile application, a comprehensive mobile application tool was developed that allowed the project to conduct disease surveillance, workforce management and supply chain management. METHODS: In June 2017, the project conceptualized a comprehensive mobile application tool in the local language (Hindi) for disease surveillance, human resources management, and supply chain management. The tool is also available in English. Solution for Community Health-workers (SOCH) mobile app is an android native application developed using android SDK and web-based tool using MVC.net framework. Construction of the application started in November 2017 and rolled out its pilot in April 2018, followed by pan-district roll out in July 2018. The application uses self-validation tools to ensure high level of data quality and integrity. RESULTS: The software is available in android based hand-held devices and web-screens with built-in data analytical capabilities. Using SOCH, the project has now successfully digitized its routine surveillance, attendance, tour plans, supply chain management components. The project has documented a reduction in 91% indigenous cases in the district, 60% improvement in stock accountability, and 99.6% accuracy in data collected through the mobile application. CONCLUSION: SOCH is an excellent and user-friendly tool, which can be customized for any public health management programme. The system ensures accountability and data robustness, which is needed for malaria elimination efforts throughout the country. The mobile application can be adapted for English or any other Indian or international language for use for malaria or any other disease surveillance and control programme. Another expansion feature of this mobile application is incorporation of indicators for Indoor Residual Spraying (IRS), Long-Lasting Insecticidal Nets (LLINs), and minor engineering by the residents of community under surveillance. The authors believe that it would be highly desirable and appropriate for an international organization, such as the World Health Organization (WHO), to conduct an independent comparison of all available mobile e-surveillance tools, so that a high-performing and globally suitable system can be selected for use in malaria elimination programmes. The Foundation of Disease Elimination and Controlof India has decided to make the SOCH mobile application available to anyone who would like to use it for disease surveillance and health care programmes.

A model for malaria elimination based on learnings from the Malaria Elimination Demonstration Project, Mandla district, Madhya Pradesh.

BACKGROUND: Malaria Elimination Demonstration Project (MEDP) was started as a Public-Private-Partnership between the Indian Council of Medical Research through National Institute of Research in Tribal Health, Govt. of Madhya Pradesh and Foundation of Disease Elimination and Control of India, which is a Corporate Social Responsibility (CSR) initiative of the Sun Pharmaceutical Industries Limited. The project's goal was to demonstrate that malaria can be eliminated from a high malaria endemic district along with prevention of re-establishment of malaria and to develop a model for malaria elimination using the lessons learned and knowledge acquired from the demonstration project. METHODS: The project employed tested protocols of robust surveillance, case management, vector control, and capacity building through continuous evaluation and training.  The model was developed using the learnings from the operational plan, surveillance and case management, monitoring and feedback, entomological investigations and vector control, IEC and capacity building, supply chain management, mobile application (SOCH), and independent reviews of MEDP. RESULTS: The MEDP has been operational since April 2017 with field operations from August 2017, and has observed: (1) reduction in indigenous cases of malaria by about 91 %; (2) need for training and capacity building of field staff for diagnosis and treatment of malaria; (3) need for improvement insecticide spraying and for distribution and usage of bed-nets; (4) need for robust surveillance system that captures and documents information on febrile cases, RDT positive individuals, and treatments provided; (5) need for effective supervision of field staff based on advance tour plan; (6) accountability and controls from the highest level to field workers; and (7) need for context-specific IEC. CONCLUSIONS: Malaria elimination is a high-priority public health goal of the Indian Government with a committed deadline of 2030. In order to achieve this goal, built-in systems of accountability, ownership, effective management, operational, technical, and financial controls will be crucial components for malaria elimination in India. This manuscript presents a model for malaria elimination with district as an operational unit, which may be considered for malaria elimination in India and other countries with similar geography, topography, climate, endemicity, health infrastructure, and socio-economic characteristics.

Improvement of Indoor Residual Spraying and Long-Lasting Insecticidal Net services through structured monitoring and supervision as part of the Malaria Elimination Demonstration Project in Mandla, Madhya Pradesh.

BACKGROUND: The Government of Madhya Pradesh employed Indoor Residual Spraying (IRS) with alpha-cypermethrin synthetic pyrethroids in sub-centres with Annual Parasite Incidence (API) from 2 to 4.99. In sub-centres with API more than 5, Long-Lasting Insecticidal Nets (LLINs) were distributed. At the request of the State Government, the Malaria Elimination Demonstration Project (MEDP) staff observed and provided support to both IRS and LLINs campaigns. In the year 2017, the study team monitored only the IRS campaigns, however, in the year 2018, the supportive supervision was provided to the IRS campaign teams along with post-distribution monitoring of the LLINs. METHODS: The study was carried out during IRS spraying using a pre-tested, closed-ended monitoring checklist which consisted of two parts- observations of spraying team and observation of sprayed houses. For LLINs, a sample of the households that received the bed nets was taken for the study. For IRS, the spraying teams were monitored for quality and technique for a total of 159 times in 2017 and 183 times in the year 2018, respectively. For post spraying observations, a total of 1261 and 1791 households were observed in the years 2017 and 2018, respectively. The use of LLINs was observed in 5 % of the households in 2018 and 2020, which is about 2,000 houses in each survey where each house received about 2.5 LLINs per household. The results of surveys were compared to assess impact of supportive supervision and monitoring. RESULTS: Significant improvement was noted after supportive supervision in year 2018 in various aspects of spraying. Preparedness of spraying, such as advance information to villagers, presence of equipment and records improved by up to 70 %. The methodology of spraying preparation improved from 50 to 90 %, spraying technique improved from 54 to 80 %, and proper use equipment during spraying improved from 51 to 92 %. After eight months post distribution of the LLINs in 2019, improvement was seen in regular usage of LLINs by 28 %. It was found that on-spot demonstrations during distribution and carrying of LLINs when sleeping outside homes increased by 56 %. Results of IEC campaigns revealed the reduction in adverse effects by 64 % and increase in awareness by 97 %. CONCLUSIONS: Effective supervision improved the quality of IRS and usage of LLINs in the study area. Based on these results, continued training and monitoring of staff that is deployed to spraying houses and distribute bed nets was suggested. The study also revealed that proper IEC/BCC drives help increase community acceptance of vector control measures and their rational usage.