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.

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.

Molecular surveillance of anti-malarial drug resistance genes in Plasmodium falciparum isolates in Odisha, India.

BACKGROUND: Despite significant progress in eliminating malaria from the state of Odisha, India, the disease is still considered endemic. Artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been introduced since 2010 as first-line treatment for uncomplicated Plasmodium falciparum malaria. This study aimed to investigate the prevalence of mutations associated with resistance to chloroquine (CQ), sulfadoxine-pyrimethamine (SP), and artesunate (ART) in P. falciparum parasites circulating in the state. METHODS: A total of 239 isolates of P. falciparum mono infection were collected during July 2018-November 2020 from the four different geographical regions of the state. Genomic DNA was extracted from 200 µL of venous blood and amplified using nested polymerase chain reaction. Mutations on gene associated with CQ (Pfcrt and Pfmdr1) were assessed by PCR amplification and restriction fragment length polymorphism, artemisinin (Pfk13) gene by DNA sequencing and SP (Pfdhfr and Pfdhps) genes by allele-specific polymerase chain reaction (AsPCR). RESULTS: The point mutation in Pfcrt (K76T) was detected 2.1%, in Pfmdr1 (N86Y) 3.4%, and no mutations were found in Pfkelch13 propeller domain. Prevalence of Pfdhfr, Pfdhps and Pfhdfr-Pfdhps (two locus) gene mutations were 50.43%, 47.05% and 49.79% respectively. The single, double, triple and quadruple point mutations in Pfdhfr gene was 11.2%, 8.2%, 17.2% and 3.4% while, in Pfdhps gene was 10.9%,19.5%, 9.5% and 2.7% respectively. Of the total 13 haplotypes found in Pfdhfr, 8 were detected for the first time in the state and of the total 26 haplotypes found in Pfdhps, 7 were detected for the fisrt time in the state. The linked quintuple mutation Pfdhfr (N51I-C59R-S108N)-Pfdhps (A437G-K540E) responsible for clinical failure (RIII level of resistance) of SP resistance and A16V-S108T mutation in Pfdhfr responsible for cycloguanil was absent. CONCLUSION: The study has demonstrated a low prevalence of CQ resistance alleles in the study area. Despite the absence of the Pfkelch13 mutations, high prevalence of Pfdhfr and Pfdhps point mutations undermine the efficacy of SP partner drug, thereby threatening the P. falciparum malaria treatment policy. Therefore, continuous molecular and in vivo monitoring of ACT efficacy is warranted in Odisha.

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.

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.

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.

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.

Molecular epidemiology of Orientia tsutsugamushi from outbreak regions, Madhya Pradesh, central India.

Scrub typhus is a seriously neglected life threatening disease in Asia and the islands of the Pacific and Indian oceans. The causative agent is Orientia tsutsugamushi, an obligate intra-cytosolic bacterium transmitted to vertebrate animals such as human or rodent by larval trombiculid mites (chiggers). Here, we conducted an outbreak investigation in Madhya Pradesh state in central India after sudden upsurge in scrub typhus cases and mortality in humans. Sixty-five live traps were placed for capturing the rodents. The captured rodent species were identified and the samples were subjected to nested PCR targeting 56kDa TSA gene. Analysis revealed for the first-time predominant circulation of Karp genotype in this region. The vector species involved in transmission is Leptotrobidium deliense. In conclusion, we reported the circulation of Karp strain in outbreak regions of Madhya Pradesh and suggest that public health monitoring and surveillance needs to be improved. Studies on antigenic diversity, association of strains with clinical spectrum and pathogenicity in the local setup will be essential for development of region-specific diagnostics and vaccines.

An integrated virtual screening and drug repurposing strategy for the discovery of new antimalarial drugs against Plasmodium falciparum phosphatidylinositol 3-kinase.

The emergence and spread of drug resistance in Plasmodium falciparum, the parasite causing the most severe form of human malaria, is a major threat to malaria control and elimination programs around the globe. With P. falciparum having evolved widespread resistance against a number of previously widely used drugs, currently, artemisinin (ART) and its derivatives are the cornerstones of first-line treatments of uncomplicated malaria. However, growing incidences of ART failure reflect the spread of ART-resistant P. falciparum strains. Despite current efforts to understand the primary cause of ART resistance due to mutations in the Kelch 13 gene (PfK13), the mechanism underlying ART resistance is still not completely unclear and no feasible strategies to counteract the causes and thereby restoring the efficiency of ART have been developed. We use a polypharmacology approach to identify potential drugs that can be used for the novel purpose (target). Of note, we have designed a multimodal stratagem to identify approved drugs with a potential antimalarial activity using computational drug reprofiling. Our investigations suggest that oxetacaine, simvastatin, repaglinide, aclidinium, propafenone, and lovastatin could be repurposed for malaria control and prevention.

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.

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.

Significance of training, monitoring and assessment of malaria workers in achieving malaria elimination goal of Malaria Elimination Demonstration Project.

BACKGROUND: The Malaria Elimination Demonstration Project (MEDP) maintained a workforce of 235 Village Malaria Workers (VMWs) and 25 Malaria Field Coordinators (MFCs) to conduct disease surveillance, case management, IEC/BCC activities, capacity building, and monitoring of vector control activities in 1233 villages of Mandla, a high malaria endemic district of Madhya Pradesh in central India. METHODS: The induction training was conducted for 3 days on malaria diagnosis, treatment, prevention, and ethics. All trainings were assessed using a pre and post-training assessment questionnaire, with 70% marks as qualifying threshold. The questionnaire was divided into three thematic areas viz. general knowledge related to malaria (KAP), diagnosis and treatment (DXRX), and vector control (PVC). RESULTS: In 2017, the project trained 330 candidates, followed by 243 and 247 candidates in 2018 and 2019, respectively. 94.3% candidates passed after a single training session. Almost all (95%) candidates showed improvement in knowledge after the training with 4% showing no effect and 1% showing deterioration. Progressive improvement in scores of 2017 cohort was seen along with significant improvement in performance of candidates in 2019 after the introduction of systematic monitoring and 'shadowing' training exercises. CONCLUSION: The project has successfully demonstrated the value of recruitment of workers from the study area, outcome of training, and performance evaluation of field staff in malaria elimination programme. This careful strategy of recruitment and training resulted in a work-force that was capable of independently conducting surveillance, case management, vector control, and Information Education Communication/Behaviour Change Communication (IEC/BCC). The learnings of this study, including the training modules and monitoring processes, can be used to train the health delivery staff for achieving national goal for malaria elimination by 2030. Similar training and monitoring programmes could also be used for other public health delivery programmes.

Spatial and temporal village-level prevalence of Plasmodium infection and associated risk factors in two districts of Meghalaya, India.

BACKGROUND: Despite declining incidence over the past decade, malaria remains an important health burden in India. This study aimed to assess the village-level temporal patterns of Plasmodium infection in two districts of the north-eastern state of Meghalaya and evaluate risk factors that might explain these patterns. METHODS: Primary Health Centre passive malaria case data from 2014 to 2018 were analysed to characterize village-specific annual incidence and temporal trends. Active malaria case detection was undertaken in 2018 and 2019 to detect Plasmodium infections using PCR. A questionnaire collected socio-demographic, environmental, and behavioural data, and households were spatially mapped via GPS. Adult mosquitoes were sampled at a subset of subjects' houses, and Anopheles were identified by PCR and sequencing. Risk factors for Plasmodium infection were evaluated using bivariate and multivariate logistic regression analysis, and spatial cluster analysis was undertaken. RESULTS: The annual malaria incidence from PHC-based passive surveillance datasets in 2014-2018 was heterogenous but declining across villages in both districts. Active surveillance in 2018 enrolled 1468 individuals from 468 households (West Jaintia Hills) and 1274 individuals from 359 households (West Khasi Hills). Plasmodium falciparum prevalence per 100 people varied from 0 to 4.1% in the nine villages of West Jaintia Hills, and from 0 to 10.6% in the 12 villages of West Khasi Hills. Significant clustering of P. falciparum infections [observed = 11, expected = 2.15, Relative Risk (RR) = 12.65; p < 0.001] was observed in West Khasi Hills. A total of 13 Anopheles species were found at 53 houses in five villages, with Anopheles jeyporiensis being the most abundant. Risk of infection increased with presence of mosquitoes and electricity in the households [Odds Ratio (OR) = 1.19 and 1.11], respectively. Households with reported animals had reduced infection risk (OR = 0.91). CONCLUSION: Malaria incidence during 2014-2018 declined in all study villages covered by the passive surveillance data, a period that includes the first widespread insecticide-treated net campaign. The survey data from 2018 revealed a significant association between Plasmodium infection and certain household characteristics. Since species of Plasmodium-competent mosquito vectors continue to be abundant, malaria resurgence remains a threat, and control efforts should continue.

Socio-economic determinants of malaria in tribal dominated Mandla district enrolled in Malaria Elimination Demonstration Project in Madhya Pradesh.

BACKGROUND: Malaria is known as a disease of poverty because of its dominance in poverty-stricken areas. Madhya Pradesh state in central India is one of the most vulnerable states for malaria morbidity and mortality. Socio-economic, environmental and demographic factors present challenges in malaria control and elimination. As part of the Malaria Elimination Demonstration Project in the tribal district of Mandla in Madhya Pradesh, this study was undertaken to assess the role of different social-economic factors contributing to malaria incidence. METHODS: The study was conducted in the 1233 villages of district Mandla, where 87% population resides in rural areas. The data was collected using the android based mobile application-SOCH for a period of 2 years (September 2017 to August 2019). A wealth index was computed along with analysis of the socio-economic characteristics of houses with malaria cases. Variables with significant variation in malaria cases were used in logistic regression. RESULTS: More than 70% of houses in Mandla are Kuccha (made of thatched roof or mud), 20% do not have any toilet facilities, and only 11% had an annual income of more than 50,000 INR, which converts to about $700 per year. Households with younger heads, male heads, more number of family members were more likely to have malaria cases. Kuccha construction, improper water supply, low household income houses were also more likely to have a malaria case and the odds doubled in houses with no toilet facilities. CONCLUSION: Based on the results of the study, it has been found that there is an association between the odds of having malaria cases and different household variables such as age, gender, number of members, number of rooms, caste, type of house, toilet facilities, water supply, cattle sheds, agricultural land, income, and vector control interventions. Therefore, a better understanding of the association of various risk factors that influence the incidence of malaria is required to design and/or deploy effective policies and strategies for malaria elimination. The results of this study suggest that appropriate economic and environmental interventions even in low-income and poverty-stricken tribal areas could have huge impact on the success of the national malaria elimination goals.

Assessment of ASHA for knowledge, diagnosis and treatment on malaria in Mandla district of Madhya Pradesh as part of the malaria elimination demonstration project.

BACKGROUND: The role of Accredited Social Health Activist (ASHA) in the health care delivery services at the periphery level is crucial for achieving disease prevention, control and elimination goals. The objective of the study was to assess the knowledge, attitude, practices, priorities and capability of ASHA related to malaria diagnosis and treatment as part of the Malaria Elimination Demonstration Project in 1233 villages of district Mandla, Madhya Pradesh. METHODS: A cross sectional study was conducted using a fully structured, pre-tested interview schedule during June and July 2017 (before the field operations of MEDP were started). Two hundred twenty (17%) of the total ASHAs were selected for the interview from the 9 developmental blocks of Mandla district. RESULTS: Knowledge, Attitude and Practices (KAP) study revealed that most ASHAs knew that mosquitoes are the main agent for spread of malaria (97.7%). They mostly used Rapid Diagnostic Test (RDT) for diagnosis (91.8%). The majority (87.3%) correctly identified negative RDT result while only 15% and 10.5%, respectively, identified Plasmodium vivax and Plasmodium falciparum positive cases correctly. Further analysis showed that 85% ASHAs used chloroquine, 44.5% used artemisinin-based combination therapy (ACT), and 55.5% used primaquine for treatment of malaria. It was also found that only 38.2% ASHA gave PQ for 14 days in cases of P. vivax. At the time of the interview, 19.1% ASHAs did not have any RDTs for diagnosis and 47.7% reported not having ACT for treatment of P. falciparum malaria. CONCLUSIONS: This study has revealed that ASHAs in the test district were not adequately trained or stocked for malaria parasite species identification and treatment, which are the major components of malaria elimination programme. This study has, therefore, revealed a need for training ASHAs on testing by RDT and proper treatment regimen for P. vivax and P. falciparum.

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.

Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in four malaria endemic states of India.

BACKGROUND: Malaria is a major public health problem in India and accounts for about 88% of malaria burden in South-East Asia. India alone accounted for 2% of total malaria cases globally. Anti-malarial drug resistance is one of the major problems for malaria control and elimination programme. Artemether-lumefantrine (AL) is the first-line treatment of uncomplicated Plasmodium falciparum in north eastern states of India since 2013 after confirming the resistance against sulfadoxine-pyrimethamine. In the present study, therapeutic efficacy of artemether-lumefantrine and k13 polymorphism was assessed in uncomplicated P. falciparum malaria. METHODS: This study was conducted at four community health centres located in Koraput district of Odisha, Bastar district of Chhattisgarh, Balaghat district of Madhya Pradesh and Gondia district of Maharashtra state. Patients with uncomplicated P. falciparum malaria were administered with fixed dose combination (6 doses) of artemether-lumefantrine for 3 days and clinical and parasitological response was recorded up to 28 days as per World Health Organization protocol. Nucleotide sequencing of msp1 and msp2 gene was performed to differentiate between recrudescence and reinfection. Amplification and sequencing of k13 propeller gene region covering codon 450-680 was also carried out to identify the polymorphism. RESULTS: A total 376 malaria patients who fulfilled the enrolment criteria as well as consented for the study were enrolled. Total 356 patients were followed up successfully up to 28 days. Overall, the adequate clinical and parasitological response was 98.9% and 99.4% with and without PCR correction respectively. No case of early treatment failure was observed. However, four cases (1.1%) of late parasitological failure were found from the Bastar district of Chhattisgarh. Genotyping of msp1 and msp2 confirmed 2 cases each of recrudescence and reinfection, respectively. Mutation analysis of k13 propeller gene showed one non-synonymous mutation Q613H in one isolate from Bastar. CONCLUSIONS: The study results showed that artemether-lumefantrine is highly effective in the treatment of uncomplicated P. falciparum malaria among all age groups. No functional mutation in k13 was found in the study area. The data from this study will be helpful in implementation of artemether-lumefantrine in case of treatment failure by artesunate plus sulfadoxine-pyrimethamine.

Digitisation and realtime sharing of unified surveillance tool and clinicopathological data for efficient management of disease outbreaks.

Existing chronic co-morbidities in a population affect the clinical outcome of infectious diseases. In order to devise better management strategies at community level, patients related clinicopathological as well as local health care infrastructure data is required. The use of digitised, unified, multilingual surveillance tool may facilitate real-time sharing of clinicopathological data and better service delivery to the affected communities. In this article, we discuss that how digital collection, collation and sharing of health-related data may improve planning and management of disease outbreaks.