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.

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.

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.

First Report on Intensity Bioassays for Pyrethroid Resistance in Anopheles culicifacies s.l in District Dindori of Madhya Pradesh State and Districts Kanker and Bastar of Chhattisgarh State, India.

Background: The major malaria vector in India is Anopheles culicifacies, and indoor residual spraying (IRS) and distribution of long-lasting insecticidal nets (LLINs) are the two main vector control measures in the national program. This species has shown resistance to dichlorodiphenyltrichloroethane (DDT), malathion, and synthetic pyrethroids (SP). The study was carried out in three districts, that is, Dindori of Madhya Pradesh and Kanker and Bastar from Chhattisgarh state to know the range of resistance phenotypes and to assess the strength of resistance in An. culicifacies. Methods: An. culicifacies collected from the field was tested to determine the susceptibility status to the discriminating concentration (DC) of different insecticides, that is, DDT 4.0%, malathion 5.0%, alphacypermethrin 0.05%, and deltamethrin 0.05% following the World Health Organization (WHO) procedures. Further, intensity bioassays of the resistant An. culicifacies to 1X discriminating concentration (DC) of alphacypermethrin and deltamethrin were conducted by exposing 5X and 10X concentrations of 1X DC. Results are interpreted as per the WHO criterion. Results: The overall result of susceptibility status in An. culicifacies in districts Dindori, Kanker, and Bastar revealed confirmed resistance to DDT, malathion, alphacypermethrin, and deltamethrin registering mortality of 15% (10-20%), 70% (65-75%), 78.6% (77-82.5%), and 87% (84.8-91.3%), respectively. Further, in district Dindori and Baster, the intensity bioassay test at 5X DC of alphacypermethrin and deltamethrin revealed 99% and 100%, respectively, while in district Kanker, the species registered moderate resistance with 92.5% and 95% mortality, respectively, in 5X DC of alphacypermethrin and deltamethrin. However, in 10X DC, the An. culicifacies was susceptible to both pyrethroids (100%) in district Kanker. Conclusion: The results of the intensity bioassay tests with SP-resistant An. culicifacies suggested no change of insecticide is required in the ongoing intervention. However, regular monitoring of insecticide susceptibility and intensity bioassays in malaria vectors in view of continued use of these interventions may increase resistance and for implementing effective vector management strategies.

Genetic diversity and expression profile of Plasmodium falciparum Pf34 gene supports its immunogenicity.

PURPOSE OF THE STUDY: Genetic variation is one of the major obstacles in the development of effective vaccines. A multivalent malaria vaccine is required to increase efficacy and confer long term protection. In this context, we analysed the genetic diversity, expression profile, and immune response against Pf34. METHODS: Phylogenetic analysis was carried out using Pf34 orthologues sequences of various Plasmodium species. Genetic diversity was analysed by PCR amplification and Sanger dideoxy sequencing of Pf34 gene from Plasmodium falciparum positive human blood samples. The expression level of Pf34 gene was studied during erythrocytic stage by real time qPCR at four-hour interval, and immune response against synthetic peptides of Pf34 (P1 and P2) was analysed using ELISA. RESULTS: Phylogenetic analysis revealed the conserved nature of Pf34 gene. Genetic diversity analysis showed that majority (92%) of Plasmodium falciparum isolates in available database bore wild type Pf34 gene (Hd = 0.160 ± 0.030, π = 0.00021), including the present study (89.3%). The P. falciparum specific amino acid repeats (NNDK, NNDLK, and NNNNNN) in the B cell epitope regions were conserved. Furthermore, Pf34 gene is expressed throughout the erythrocytic cycle and comparatively high expression was observed in early ring and schizont stage. High IgG response was observed against both the peptides P1 and P2 of Pf34 containing asparagine NNNNNN and NNDLK repeat respectively. CONCLUSION: The limited genetic diversity, presence of conserved amino acid repeats within B cell epitope and high IgG response suggests that Pf34 may be a potential vaccine candidate for malaria. However, further validation studies are required.

Diversity and expression of Plasmodium falciparum var gene in severe and mild malaria cases from Central India.

BACKGROUND: Plasmodium falciparum erythrocyte membrane protein is encoded by a highly variable multicopy var gene family known to play a key role in malaria pathogenicity. Therefore, we investigated sequence variation, expression profile and immune response of the Duffy binding-like domain (DBLα) region of the var gene. METHODS: Blood samples were collected from patients with cerebral, severe and mild malaria in Chhattisgarh, India, a region with endemic malaria. Polymerase chain reaction amplicons were cloned and sequenced to determine sequence variation. The expression level was analyzed targeting the upstream region of var gene using the Delta-Delta-Ct method. Immunoglobulin G (IgG) level was determined against the 6 synthetic peptides of the DBLα region. RESULTS: The study identified that group 1 and group 5 sequences (cysteine/position of limited variability (cys/PoLV) classification) along with cys2/cys4 and MFK*/REY motifs and short amino acid length were significantly associated with malaria severity. The specific PoLV (MFKS, LREA, PTNL) were restricted to cerebral malaria. The expression level of var group A was higher than var groups B and C, demonstrating its prognostic characteristic. All peptides showed high-quality IgG response, while VAR P5 appeared to be a good marker for severity. CONCLUSIONS: The present study illustrates the presence of specific sequences of DBLα tags involved in severe malaria that could be targeted in future interventions for malaria control and elimination.

First successful field evaluation of new, one-minute haemozoin-based malaria diagnostic device.

BACKGROUND: Early and accurate diagnosis of malaria is critical to the success of malaria elimination. However, the current mainstay of malaria diagnosis in the field, such as light microscopy and rapid diagnostic tests (RDTs), have limitations due to low parasite density or mutation in diagnostic markers. METHODS: We evaluated an inexpensive, robust, rapid, malaria diagnostic device, called Gazelle, that employs magneto-optical detection to identify haemozoin crystals (Hz) produced by all species of human malaria parasites in infected individuals. A beam of polarised light is passed through the lysed diluted blood sample under the influence of high (~.55T) and low magnetic fields. The difference in light transmission through the sample between the high and low magnetic fields indicates presence of Hz, suggesting possible malarial infection. A total of 300 febrile patients were screened at the malaria clinic of Indian Council of Medical Research-National Institute of Research in Tribal Health (ICMR-NIRTH), Jabalpur, India, from August 2018 to November 2018. Malaria diagnosis was done using four diagnostic methods: Gazelle, light microscopy, RDT, and malaria specific Polymerase Chain Reaction (PCR). Measures of diagnostic accuracy were compared. FINDINGS: Out of 300 febrile patients enroled and tested for the presence of malaria parasites, 262 patient samples were included in the final analysis. The sensitivity and specificity of Gazelle was 98% and 97% in comparison to light microscopy, 82% and 99% to PCR and 78% and 99% to RDT, respectively. The results of the four diagnostic methods were comparable and statistically no significant differences in sensitivity or specificity was observed between these methods. Enhanced diagnostic accuracy of Gazelle in malaria patients with no prior history of malaria treatment was observed in this study. INTERPRETATION: The diagnostic ability of Gazelle was comparable to light microscopy and better than RDTs even in low parasitemia and in presence of pfhrp2/3 deletion mutant parasites. Gazelle may be a novel valuable diagnostic tool in resource poor settings where (i) microscopy is not feasible and (ii) pfhrp2/3gene deleted parasite are present. Its speed, cost-efficiency, and alternative to lack of microscopists makes it an important adjunct in field settings. FUNDING: HemexDx, India.

What affects utilization of malaria control services? A qualitative approach to understanding community perception in highly malarious Gadchiroli district, Maharashtra, India.

National Vector Borne Disease Control Programme (NVBDCP) data have shown that nearly half of all malaria deaths in India occur in tribal-dominated areas. The present study took a qualitative approach to understanding community perceptions and practices related to malarial infection and anti-malarial programmes. Twelve focus group discussions and 26 in-depth interviews of Accredited Social Health Activists (ASHAs) were conducted in nine villages in the district of Gadchiroli, Maharashtra state in India in June 2016. A total of 161 village residents (94 males and 67 females) participated in the focus group discussions and 26 health workers participated in the in-depth interviews. Data were analysed using the content analysis approach. The findings revealed widespread misconceptions about malaria among village residents, and low use of preventive measures and anti-malarial services. Ignorance and treatment by unqualified traditional healers delay effective treatment seeking. Furthermore, failure to maintain drug compliance adds to the gravity of the problem. The study identified the social and behavioural factors affecting treatment uptake and use of treatment facilities in the study area. These should help the development of the behavioural change communication arm of any control strategy for malaria through improving community participation, so improving preventive practices and optimizing utilization of anti-malarial services.

Prevention and treatment of malaria in pregnancy: what do pregnant women and health care workers in East India know and do about it?

BACKGROUND: Limited qualitative research has been performed in India to investigate views and behaviours of pregnant women regarding malaria despite the threat of malaria-related adverse maternal and neonatal outcomes. To address this gap, a comprehensive study on malaria prevention and treatment attitudes, knowledge and behaviour among pregnant women in India was conducted. METHODS: Pregnant women and healthcare workers (HCWs), encompassing clinic-based providers, traditional birth attendants, and auxiliary nurse-midwives were enrolled for in-depth interviews (IDIs) at 7 hospital sites and nearby communities in Jharkhand and Chhattisgarh States. Questions addressed health concerns and attitudes, knowledge and practices regarding malaria prevention and treatment; probing covered modern and traditional approaches. Data were analyzed using a thematic approach. RESULTS: A total of 83 pregnant women and 119 HCWs participated in 202 IDIs, 90 in Jharkhand and 112 in Chhattisgarh. A majority of Jharkhand respondents, but only one-fourth in Chhattisgarh, named malaria among top health issues for pregnant women. Just over half of pregnant women were willing to try new prevention methods (especially insecticide-treated bed nets), although cost-related barriers to such methods were stressed. Most respondents voiced concerns about malaria treatment during pregnancy, mainly citing potential harm to the baby. Most knew that mosquitoes transmitted malaria, but a substantial minority, including among HCWs, described incorrect transmission modes. Most knew a proven prevention method (usually bed nets or coils); a few knew other methods. A minority of pregnant women, but most HCWs, knew about malaria treatment, although some HCWs described unproven treatments. Most respondents described use of modern prevention methods in their communities, typically bed nets, although probing revealed irregular use. Half (especially in Jharkhand and particularly HCWs) described use of traditional prevention approaches such as burning leaves and rubbing oils on the body; traditional remedies for malaria treatment were common, and varied by site and population. CONCLUSIONS: Understanding of malaria varied as a concern for pregnant women, continued use of unproven malaria prevention and treatment strategies was evident in this population in India. These results highlight the need to educate both pregnant women and HCWs about effective malaria methods to protect pregnant women and their babies from malaria.

Factors associated with treatment seeking for malaria in Madhya Pradesh, India.

OBJECTIVES: To determine household factors associated with treatment seeking for malaria. METHODS: The study was carried out in four districts of Madhya Pradesh with different malaria endemicity. A total of 1470 households were interviewed in which at least one member suffered from microscopically confirmed malaria in the 3 months preceding the survey. Socio-demographic, economic, cultural characteristics, their health beliefs, knowledge and practices regarding malaria and choice of treatment seeking were explored. RESULTS: A total of 764 households were from high-endemic and 706 from low-endemic areas. More than half of household heads were illiterate; most are farmers. Approximately 46% sought treatment for malaria from unqualified informal providers; 19% from qualified private health practitioners and 35% from government health providers. Analysis revealed that household's area of residence, education, occupation, ethnicity, use of preventive measures, economic status, knowledge and practices, distance and delayed treatment seeking was strongly associated with the type of healthcare providers selected. CONCLUSIONS: Demand for formal health services among the poor, illiterate, tribal population living in remote areas is low. Accessible and affordable health services and a sensitisation programme to increase the demand for formal providers are needed.

Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria from three highly malarious states in India.

BACKGROUND: Anti-malarial drug resistance continues to be a leading threat to malaria control efforts and calls for continued monitoring of waning efficacy of artemisinin-based combination therapy (ACT). Artesunate + sulfadoxine/pyrimethamine (AS + SP) is used for the treatment of uncomplicated Plasmodium falciparum malaria in India. However, resistance against AS + SP is emerged in northeastern states. Therefore, artemether-lumefantrine (AL) is the recommended first line treatment for falciparum malaria in north eastern states. This study investigates the therapeutic efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in three malaria-endemic states in India. The data generated through this study will benefit the immediate implementation of second-line ACT as and when required. METHODS: This was a one-arm prospective evaluation of clinical and parasitological responses for uncomplicated falciparum malaria using WHO protocol. Patients diagnosed with uncomplicated mono P. falciparum infection were administered six-dose regimen of AL over 3 days and subsequent follow-up was carried out up to 28 days. Molecular markers msp-1 and msp-2 were used to differentiate recrudescence and re-infection and K13 propeller gene was amplified and sequenced covering the codon 450-680. RESULTS: A total of 402 eligible patients were enrolled in the study from all four sites. Overall, adequate clinical and parasitological response (ACPR) was 98 % without PCR correction and 99 % with PCR correction. At three study sites, ACPR rates were 100 %, while at Bastar, cure rate was 92.5 % on day 28. No early treatment failure was found. The PCR-corrected endpoint finding confirmed that one late clinical failure (LCF) and two late parasitological failures (LPF) were recrudescences. The PCR corrected cure rate was 96.5 %. The mean fever clearance time was 27.2 h ± 8.2 (24-48 h) and the mean parasite clearance time was 30.1 h ± 11.0 (24-72 h). Additionally, no adverse event was recorded. Analysis of total 186 samples revealed a mutation in the k13 gene along with non-synonymous mutation at codon M579T in three (1.6 %) samples. CONCLUSION: AL is an efficacious drug for the treatment of uncomplicated falciparum malaria. However, regular monitoring of AL is required in view of malaria elimination initiatives, which will be largely dependent on therapeutic interventions, regular surveillance and targeted vector control.

Detection of Mixed Infections with Plasmodium spp. by PCR, India, 2014.

In 8 malaria-endemic states in India, mixed Plasmodium spp. infections were detected by PCR in 17.4% (265/1,521) of blood samples that microscopy had shown to contain only P. falciparum. The quality of microscopy must be improved because use of PCR for detection of malaria parasites is limited in rural areas.

Socio-economic & household risk factors of malaria in tribal areas of Madhya Pradesh, central India.

BACKGROUND & OBJECTIVES: Malaria is a major public health problem in many States of the country, particularly, in Madhya Pradesh where both Plasmodium vivax and P. falciparum are endemic. Although many studies have been conducted to investigate risk factors for malaria, but only a few have examined household and socio-economic risk factors. The present study was, therefore, undertaken to explore the relationship of different socio-demographic, socio-economic and behavioural risk factors with malaria prevalence in tribal areas of Madhya Pradesh, India. METHODS: This study was undertaken in all 62 villages of Bargi Primary Health Centre from May 2005 to June 2008. These villages comprised 7117 households with an average family size of five members. Fortnightly fever surveys were conducted in all villages to assess prevalence of malaria infection in the community. The distinct univariate and multivariate logistic regression models were fitted on the data set. RESULTS: The important socio-demographic risk factors like age of household head, social group, occupation and family size; socio-economic factors like type of walls of house, place of drinking water source, irrigated land, cash crop; and behavioural variables like place of sleeping, use of bed nets, etc. were found significantly associated with malaria in univariate analyses. In multivariate analyses only social groups, family size, type of walls of house, and place of sleeping had strong significant association with prevalence of malaria. INTERPRETATION & CONCLUSIONS: The study shows that in tribal areas where people are living in poor quality of houses with no proper use of preventive measures, malaria is firmly established. We conclude that community based interventions which bring improvement in standard of living, access to healthcare facilities and health awareness, will have a significant impact on malaria prevention in these areas.

Association between wood cooking fuel and maternal hypertension at delivery in central East India.

OBJECTIVE: Smoke from burning of biomass fuels has been linked with adverse pregnancy outcomes and hypertension among nonpregnant subjects; association with hypertension during pregnancy has not been well studied. We evaluated whether the use of wood cooking fuel increases the risk of maternal hypertension at delivery compared to gas which burns with less smoke. METHODS: Information on fuel use and blood pressure was available for analysis from a cross-sectional survey of 1369 pregnant women recruited at delivery in India. RESULTS: Compared to gas users, women using wood as fuel had on average lower mean arterial pressure (adjusted effect size - 2.0 mmHg; 95% CI: -3.77, -0.31) and diastolic blood pressure (adjusted effect size -1.96 mmHg; 95% CI: -3.60, -0.30) at delivery. Risk of hypertension (systolic >139 mmHg or diastolic >89 mmHg) was 14.6% for wood users compared to 19.6% for gas users although this did not reach significance after adjustment, using propensity score techniques, for factors that make wood and gas users distinct (adjusted prevalence ratio 0.76; 95% CI: 0.49, 1.17). CONCLUSIONS: Combustion products from the burning of biomass fuels are similar to those released with tobacco smoking, which has been linked with a reduced risk for preeclampsia. The direction of our findings suggests the possibility of a similar effect for biomass cook smoke. Whether clean cooking interventions being promoted by international advocacy organizations will impact hypertension in pregnancy warrants further analysis as hypertension remains a leading cause of maternal death worldwide and cooking with biomass fuels is widespread.