Malaria Elimination Interventions Research Articles

Extension of efficacy range for targeted malaria-elimination interventions due to spillover effects.

Malaria-elimination interventions aim to extinguish hotspots and prevent transmission to nearby areas. Here, we re-analyzed a cluster-randomized trial of reactive, focal interventions (chemoprevention using artemether-lumefantrine and/or indoor residual spraying with pirimiphos-methyl) delivered within 500 m of confirmed malaria index cases in Namibia to measure direct effects (among intervention recipients within 500 m) and spillover effects (among non-intervention recipients within 3 km) on incidence, prevalence and seroprevalence. There was no or weak evidence of direct effects, but the sample size of intervention recipients was small, limiting statistical power. There was the strongest evidence of spillover effects of combined chemoprevention and indoor residual spraying. Among non-recipients within 1 km of index cases, the combined intervention reduced malaria incidence by 43% (95% confidence interval, 20-59%). In analyses among non-recipients within 3 km of interventions, the combined intervention reduced infection prevalence by 79% (6-95%) and seroprevalence, which captures recent infections and has higher statistical power, by 34% (20-45%). Accounting for spillover effects increased the cost-effectiveness of the combined intervention by 42%. Targeting hotspots with combined chemoprevention and vector-control interventions can indirectly benefit non-recipients up to 3 km away.

Community perspective and healthcare assessment in malaria endemic states of India: a cross-sectional study protocol

IntroductionIndia’s contribution to the malaria burden was highest in South-East Asia Region in 2021, accounting for 79% of the estimated malaria cases and 83% of malaria-related deaths. Intensified Malaria Control...

Statistical design and analysis of controlled human malaria infection trials

BackgroundMalaria is a potentially life-threatening disease caused by Plasmodium protozoa transmitted by infected Anopheles mosquitoes. Controlled human malaria infection (CHMI) trials are used to assess the efficacy of interventions for malaria elimination. The operating characteristics of statistical methods for assessing the ability of interventions to protect individuals from malaria is uncertain in small CHMI studies. This paper presents simulation studies comparing the performance of a variety of statistical methods for assessing efficacy of intervention in CHMI trials.MethodsTwo types of CHMI designs were investigated: the commonly used single high-dose design (SHD) and the repeated low-dose design (RLD), motivated by simian immunodeficiency virus (SIV) challenge studies. In the context of SHD, the primary efficacy endpoint is typically time to infection. Using a continuous time survival model, five statistical tests for assessing the extent to which an intervention confers partial or full protection under single dose CHMI designs were evaluated. For RLD, the primary efficacy endpoint is typically the binary infection status after a specific number of challenges. A discrete time survival model was used to study the characteristics of RLD versus SHD challenge studies.ResultsIn a SHD study with the continuous time survival model, log-rank test and t-test are the most powerful and provide more interpretable results than Wilcoxon rank-sum tests and Lachenbruch tests, while the likelihood ratio test is uniformly most powerful but requires knowledge of the underlying probability model. In the discrete time survival model setting, SHDs are more powerful for assessing the efficacy of an intervention to prevent infection than RLDs. However, additional information can be inferred from RLD challenge designs, particularly using a likelihood ratio test.ConclusionsDifferent statistical methods can be used to analyze controlled human malaria infection (CHMI) experiments, and the choice of method depends on the specific characteristics of the experiment, such as the sample size allocation between the control and intervention groups, and the nature of the intervention. The simulation results provide guidance for the trade off in statistical power when choosing between different statistical methods and study designs.

Progress towards malaria elimination in the Greater Mekong Subregion: perspectives from the World Health Organization

Malaria remains a global health challenge, disproportionately affecting vulnerable communities. Despite substantial progress, the emergence of anti-malarial drug resistance poses a constant threat. The Greater Mekong Subregion (GMS), which includes Cambodia, China’s Yunnan province, Lao People's Democratic Republic, Myanmar, Thailand, and Viet Nam has been the epicentre for the emergence of resistance to successive generations of anti-malarial therapies. From the perspective of the World Health Organization (WHO), this article considers the collaborative efforts in the GMS, to contain Plasmodium falciparum artemisinin partial resistance and multi-drug resistance and to advance malaria elimination. The emergence of artemisinin partial resistance in the GMS necessitated urgent action and regional collaboration resulting in the Strategy for Malaria Elimination in the Greater Mekong Subregion (2015–2030), advocating for accelerated malaria elimination interventions tailored to country needs, co-ordinated and supported by the WHO Mekong malaria elimination programme. The strategy has delivered substantial reductions in malaria across all GMS countries, with a 77% reduction in malaria cases and a 97% reduction in malaria deaths across the GMS between 2012 and 2022. Notably, China was certified malaria-free by WHO in 2021. Countries' ownership and accountability have been pivotal, with each GMS country outlining its priorities in strategic and annual work plans. The development of strong networks for anti-malarial drug resistance surveillance and epidemiological surveillance was essential. Harmonization of policies and guidelines enhanced collaboration, ensuring that activities were driven by evidence. Challenges persist, particularly in Myanmar, where security concerns have limited recent progress, though an intensification and acceleration plan aims to regain momentum. Barriers to implementation can slow progress and continuing innovation is needed. Accessing mobile and migrant populations is key to addressing remaining transmission foci, requiring effective cross-border collaboration. In conclusion, the GMS has made significant progress towards malaria elimination, particularly in the east where several countries are close to P. falciparum elimination. New and persisting challenges require sustained efforts and continued close collaboration. The GMS countries have repeatedly risen to every obstacle presented, and now is the time to re-double efforts and achieve the 2030 goal of malaria elimination for the region.

Determination of the Prevalence of Different Brands of Fixed Dose Artemether/Lumefantrine Tablets Sold in Pharmacies in Uganda

Substandard, counterfeit and falsified antimalarial agents are a big challenge to effective malaria elimination interventions mainly in developing countries. In low-and middle-income countries (LMICs), the quality of antimalarial agents inclusive of AL is affected by several factors including insufficient regulation porous borders and limited funds. This study therefore focused evaluation of quality of different brands of fixed dose artemether/ lumefantrine tablets sold in Ugandan Pharmacies. This was an experimental study conducted using AL tablets obtained from different pharmacies in the different cities of Uganda purchased using mystery shopper method. The samples were screened for quality using visual inspection, assessed different physical quality parameters like weight variation, friability, disintegration and dissolution and content assay tests were also done both for the brands from the pharmacies and their correspondent LTR. The assay test was done using HPLC technique USP method. The samples were considered substandard if the API content was outside 90-110% range of the label claim. Data was analysed using descriptive statistics and presented as means with standard deviations and frequencies. 400 AL samples were collected from the different Pharmacies in the different cities and the corresponding LTRs in the strengths of 20/120, 60/360 and 80/480 with commonest brands Lumartem, Lumaren and Artefan. The presence of A/L brands that are unregistered and the total assay failure of the brands of 18% for the AL tablets purchased causes alarm. Keywords: Artemether lumefantrine, quality, tablets, prevalence

Determination of Concentration of Active Pharmaceutical Ingredients in Different Brands of Artemether/Lumefantrine Tablets Sold in the Pharmacies in Uganda

Substandard, counterfeit and falsified antimalarial agents are a big challenge to effective malaria elimination interventions mainly in developing countries. In low-and middle-income countries (LMICs), the quality of antimalarial agents inclusive of AL is affected by several factors including insufficient regulation porous borders and limited funds. This study therefore focused evaluation of quality of different brands of fixed dose artemether/ lumefantrine tablets sold in Ugandan Pharmacies. This was an experimental study conducted using AL tablets obtained from different pharmacies in the different cities of Uganda purchased using mystery shopper method. The samples were screened for quality using visual inspection, assessed different physical quality parameters like weight variation, friability, disintegration and dissolution and content assay tests were also done both for the brands from the pharmacies and their correspondent LTR. The assay test was done using HPLC technique USP method. The samples were considered substandard if the API content was outside 90-110% range of the label claim. Data was analysed using descriptive statistics and presented as means with standard deviations and frequencies. Out of the 16 brands in the study, 14 brands (88%) passed the artemether assay and two brands failed at 89.8% and 110.2% of declared artemether content. For Lumefantrine assay, out of the 16 brands in the study, 14 brands (88%) passed the Lumefantrine assay except two brands (12%). The presence of A/L brands that are unregistered and the total assay failure of the brands of 18% for the AL tablets purchased causes alarm and the total assay failure of the brands of 18% for the AL tablets purchased calls for NDA to intensify on its operations to find out the conformity of the pharmacies to selling only registered medicines. Keywords: Artemether Lumefantrine, Quality, Tablets

Application of loop-mediated isothermal amplification combined with lateral flow assay visualization of Plasmodium falciparum kelch 13 C580Y mutation for artemisinin resistance detection in clinical samples

Resistance to the antimalarial drug artemisinin (ART) has emerged in Greater Mekong Subregion. The molecular marker predominantly used to identify ART resistance is the C580Y mutation in Pfkelch13 of Plasmodium falciparum. Rapid and accurate detection of ART resistance in the field is necessary to guide malaria containment and elimination interventions. Our study evaluates the PfC580Y by using the loop-mediated isothermal amplification and single nucleotide polymorphism analysis visualization using a lateral flow assay (LAMP-SNP-LFA) method for detecting ART resistance in clinical samples collected from Thailand between 2014 and 2019. The optimized incubation condition for the reaction was determined as 45 min at 56 °C, followed by visual detection of positive amplicons using LFA. The assay demonstrated high analytical sensitivity and specificity, with a limit of detection of 16.8 copies of C580Y plasmid/µL of and 100% accuracy for C580Y mutation detection. The PfC580Y LAMP-SNP-LFA method is faster and simpler than conventional polymerase chain reaction/DNA sequencing and has the potential to support antimalarial management policies, malaria control, and global elimination efforts.

KNOWLEDGE, ATTITUDES, AND PRACTICES TOWARD MALARIA AND ANTIMALARIAL MASS DRUG ADMINISTRATION AMONG HEADS OF HOUSEHOLDS IN VILLAGES ON GRANDE COMORE ISLAND, THE COMOROS.

Knowledge, attitudes, and practices (KAP) surveys on malaria and antimalarial mass drug administration (MDA) have not received much attention in the Union of the Comoros. This study is a household-based cross-sectional survey using a multi-stage sampling technique aiming at investigating KAP toward malaria and antimalarial MDA with artemisinin-piperaquine among heads of households on Grande Comore Island, the largest island of the Comoros. A predefined structured questionnaire containing socio-demographic characteristics and questions about malaria and antimalarial MDA was administered to 1,368 randomly selected heads of households from 10 malaria-endemic villages on Grande Comore Island. The results showed that 81.4% of the heads of households knew that malaria is a transmissible disease, 77.6% recognized mosquitoes as the vectors of malaria, and 70.8% recognized fever as one of the frequent symptoms of malaria; 40.8% of respondents remembered the name of the antimalarial drug used for MDA, and 62.1% remembered the color of the antimalarial tablets; and 65.1% chose to go to a public health center to seek treatment as their first option within 24 hr of the onset of initial malaria symptoms. This study found that most heads of households had a reasonable level of knowledge about malaria and antimalarial MDA. However, only 7.3% obtained full points on all knowledge-related questions. Misconceptions about malaria cause, transmission, diagnostic method, and antimalarial MDA exist in the community of Grande Comore Island. As the Comoros continues to put great efforts to go toward malaria elimination, the community's KAP on malaria and antimalarial MDA is crucial to guarantee the community's long-term adherence to malaria elimination interventions and could become key to guaranteeing malarial elimination in the Comoros. Therefore, there is a great need to improve malaria prevention awareness through strengthening malaria education and promoting behavioral change. Heads of households should be the core target of malaria education and behavioral change for malaria elimination.

Acceptability and perceived barriers to reactive focal mass drug administration in the context of a malaria elimination program in Magude district, Southern Mozambique: A qualitative study.

This study analysed acceptability and perceived barriers to reactive focal mass drug administration (rfMDA) among community members exposed to community engagement campaigns and malaria elimination interventions in Magude district, following mass drug administration (MDA) in the same district. The study used a formative qualitative study design, consisting of 56 semi-structured interviews with community members, including community leaders, household heads, women of reproductive age, members of the community and adolescents, 4 semi-structured interviews with community health workers, 9 semi-structured interviews with healthcare professionals; and 16 focus group discussions with the general adult population. Data were collected between June and September 2017. A content thematic analysis approach was used to analyse the data. The results of this study showed that rfMDA was accepted due to awareness about the intervention, experience of a previous similar programme, the MDA campaign, and due to favourable perceptions built on the believe that rfMDA would help to prevent, treat and eliminate malaria in the community. Perceived barriers to rfMDA include lack of access to accurate information, reluctance to take a pregnancy test, concern on drug adverse reactions, and reluctance to take antimalarial drugs without any symptom. In conclusion, the community found rfMDA acceptable for malaria intervention. But more community engagement is needed to foster community involvement and self-appropriation of the malaria programme elimination.

Malaria elimination in Zanzibar: where next?

In 2018, Zanzibar developed a national malaria strategic plan IV (2018-2023) to guide elimination of malaria by 2023. We assessed progress in the implementation of malaria activities as part of the end-term review of the strategic plan. The review was done between August and October 2022 following the WHO guideline to assess progress made towards malaria elimination, effectiveness of the health systems in delivering malaria case management; and malaria financing. A desk review examined available malaria data, annual work plans and implementation reports for evidence of implemented malaria activities. This was complemented by field visits to selected health facilities and communities by external experts, and interviews with health management teams and inhabitants to authenticate desk review findings. A steady increase in the annual parasite incidence (API) was observed in Zanzibar, from 2.7 (2017) to 3.6 (2021) cases per 1,000 population with marked heterogeneity between areas. However, about 68% of the detected malaria cases were imported into Zanzibar. Malaria case follow-up and investigation increased from <70% in 2017 to 94% and 96% respectively, in 2021. The review noted a 3.7-fold increase of the health allocation in the country's budget, from 31.7 million USD (2017/18) to 117.3 million USD (2022/23) but malaria allocation remained low (<1%). The varying transmission levels in the islands suggest a need for strategic re-orientation of the elimination attempts from a national-wide to a sub-national agenda. We recommend increasing malaria allocation from the health budget to ensure sustainability of malaria elimination interventions.

Low genetic diversity of Plasmodium falciparum merozoite surface protein 1 and 2 and multiplicity of infections in western Ethiopia following effective malaria interventions

BackgroundGenetic diversity of malaria parasites can inform the intensity of transmission and poses a major threat to malaria control and elimination interventions. Characterization of the genetic diversity would provide essential information about the ongoing control efforts. This study aimed to explore allelic polymorphism of merozoite surface protein 1 (msp1) and merozoite surface protein 2 (msp2) to determine the genetic diversity and multiplicity of Plasmodium falciparum infections circulating in high and low transmission sites in western Ethiopia.MethodsParasite genomic DNA was extracted from a total of 225 dried blood spots collected from confirmed uncomplicated P. falciparum malaria-infected patients in western Ethiopia. Of these, 72.4% (163/225) and 27.6% (62/225) of the samples were collected in high and low transmission areas, respectively. Polymorphic msp1 and msp2 genes were used to explore the genetic diversity and multiplicity of falciparum malaria infections. Genotyping of msp1 was successful in 86.5% (141/163) and 88.7% (55/62) samples collected from high and low transmission areas, respectively. Genotyping of msp2 was carried out among 85.3% (139/163) and 96.8% (60/62) of the samples collected in high and low transmission sites, respectively. Plasmodium falciparum msp1 and msp2 genes were amplified by nested PCR and the PCR products were analysed by QIAxcel ScreenGel Software. A P-value of less or equal to 0.05 was considered significant.ResultsHigh prevalence of falciparum malaria was identified in children less than 15 years as compared with those ≥ 15 years old (AOR = 2.438, P = 0.005). The three allelic families of msp1 (K1, MAD20, and RO33) and the two allelic families of msp2 (FC27 and 3D7), were observed in samples collected in high and low transmission areas. However, MAD 20 and FC 27 alleles were the predominant allelic families in both settings. Plasmodium falciparum isolates circulating in western Ethiopia had low genetic diversity and mean MOI. No difference in mean MOI between high transmission sites (mean MOI 1.104) compared with low transmission area (mean MOI 1.08) (p > 0.05). The expected heterozygosity of msp1 was slightly higher in isolates collected from high transmission sites (He = 0.17) than in those isolates from low transmission (He = 0.12). However, the heterozygosity of msp2 was not different in both settings (Pfmsp2: 0.04 in high transmission; pfmsp2: 0.03 in low transmission).ConclusionPlasmodium falciparum from clinical malaria cases in western Ethiopia has low genetic diversity and multiplicity of infection irrespective of the intensity of transmission at the site of sampling. These may be signaling the effectiveness of malaria control strategies in Ethiopia; although further studies are required to determine how specific intervention strategies and other parameters that drive the pattern.

Linking science and action to improve public health capacity for climate preparedness in lower- and middle-income countries

ABSTRACT By 2030, the direct adaptation costs to the health sector due to climate change are expected to cost between USD$2 to USD$4 billion a year. People in many low- and middle-income countries already suffer from several health challenges, such as malnutrition and a high occurrence of infectious diseases, challenges that will be intensified by climate change and variability. Furthermore, these countries often have health systems with a limited capacity to adapt to and prepare for future climate scenarios. As a result, many of the poorest and most vulnerable countries are likely to bear the brunt of health impacts resulting from climate change and variability. The Intergovernmental Panel on Climate Change identified health as the sector with the greatest potential to reduce the impacts of climate change in many lower- and middle-income countries if adaptation measures are taken. In this paper, we use case studies from a project funded by the United States Agency for International Development (USAID) to examine how to design programmes to reduce climate risks in the health sector. The USAID project called the Adaptation, Thought Leadership, and Assessment (ATLAS) Project and it assisted public health institutions in lower- and middle-income countries. Four specific cases are presented: in Mozambique, supporting the National Institute of Health of to launch a climate and health research observatory; in Ethiopia, working with the Ministry of Health to include climate and weather information into malaria early warning systems; in sub-Saharan Africa, improving our understanding of the relationship between temperature and malaria to inform malaria elimination interventions; and working across all project countries (globally) to manage extreme heat to reduce impacts on human health and well-being. We analyze these four ATLAS Project case examples to identify lessons and opportunities for future decisions and investment in climate and health care system management and capacity building programmes. Key policy insights A user-driven participatory approach improves capacity-building efforts, especially around research for decision making. Identifying and attempting to overcome institutional barriers to work across the health and climate sectors is necessary early in the project design phase for cross-sectoral collaboration. Customized data analytics, such as climate forecasting and epidemiological surveillance, should be tailored to specific health risks. While work at the climate and health nexus is relatively new, there is an increasing number of programmes addressing this linkage. There is an opportunity to increase peer learning opportunities drawing on growing experience across countries.

Evaluation of the effect of targeted Mass Drug Administration and Reactive Case Detection on malaria transmission and elimination in Eastern Hararghe zone, Oromia, Ethiopia: a cluster randomized control trial

BackgroundReactive and proactive case detection measures are widely implemented by national malaria elimination programs globally. Ethiopia decided to include Reactive Case Detection (RCD) and targeted Mass Drug Administration (tMDA) approaches as part of their elimination strategy along with rigorous evaluation. The purpose of this study is to compare the impact of RCD and tMDA on malaria elimination over the 2-year study period, by looking at the annual parasite incidence before and after the intervention.MethodsThe study will be conducted in the East Hararghe zone of Ethiopia. Malaria transmission in the area is low to moderate. This study will deploy a community-based, three-arm, cluster-randomized control trial implemented over 2 years. Forty-eight clusters (16 clusters per arm) will be selected based on the annual number of confirmed malaria cases seen in the cluster. All clusters will receive the current standard of care in terms of malaria elimination interventions provided by the national malaria control program. In addition, following the identification of malaria parasite infection, individuals who reside within a 100-m radius of the index case will receive a diagnosis for malaria and treatment if positive in the RCD arm or presumptive treatment in the tMDA arm. The primary effectiveness endpoint will be measured at baseline and endline for each intervention arm and compared to the control arm using a difference in difference approach.DiscussionThis randomized controlled trial will provide evidence of the impact of the proposed intervention approaches for malaria elimination.Trial registrationClinicalTrials.gov NCT04241705. Registration date: January 27, 2020.

Does the roof type of a house influence the presence of adult Anopheles stephensi, urban malaria vector? - evidence from a few slum settings in Chennai, India.

In an urban setting, it is a difficult task to collect adult Anopheles stephensi, unlike the immature stages, due to various reasons. A longitudinal study was undertaken from January 2016 to April 2017, with CDC light traps to collect adult Anopheles stephensi and other mosquito species in houses located in a few slums of Chennai, India. A total of 203 trap collections were made indoors from human dwellings having different roof types, as well as outdoors. Three to four trap collections were made at night (18:00 to 06:00 h) once a week. Overall, Culex quinquefasciatus (64%) was the predominant mosquito species captured, followed by An. stephensi (24%). In 98 of the 203 trap collections (48.3%), at least one female An. stephensi was trapped. In all, 224 female An. stephensi were trapped, of which the majority were collected during monsoon and winter seasons. Compared to outdoors, 10% more An. stephensi, the majority of them unfed, were collected indoors, with relatively more contribution coming from asbestos-roofed houses (71.4%), followed by thatched-roof houses (47.3%). Overall, 2.2% positivity for Plasmodium vivax was detected in An. stephensi through Circumsporozoite-ELISA. Binary logistic regression model indicated that season (winter and monsoon), asbestos-roofed dwelling, lesser number of rooms in a house, and more members in a family were significant predictor variables for the odds of trapping an An. stephensi. The study brought out significant factors associated with the presence of An. stephensi in urban slums setting in Chennai, where malaria is declining. The findings would help in devising targeted, effective vector control interventions for malaria elimination in urban settings.

Malaria Trigram: improving the visualization of recurrence data for malaria elimination

BackgroundAlthough considerable success in reducing the incidence of malaria has been achieved in Brazil in recent years, an increase in the proportion of cases caused by the harder-to-eliminate Plasmodium vivax parasite can be noted. Recurrences in P. vivax malaria cases are due to new mosquito-bite infections, drug resistance or especially from relapses arising from hypnozoites. As such, new innovative surveillance strategies are needed. The aim of this study was to develop an infographic visualization tool to improve individual-level malaria surveillance focused on malaria elimination in the Brazilian Amazon.MethodsAction Research methodology was employed to deal with the complex malaria surveillance problem in the Amazon region. Iterative cycles were used, totalling four cycles with a formal validation of an operational version of the Malaria Trigram tool at the end of the process. Further probabilistic data linkage was carried out so that information on the same patients could be linked, allowing for follow-up analysis since the official system was not planned in such way that includes this purpose.ResultsAn infographic user interface was developed for the Malaria Trigram that incorporates all the visual and descriptive power of the Trigram concept. It is a multidimensional and interactive historical representation of malaria cases per patient over time and provides visual input to decision-makers on recurrences of malaria.ConclusionsThe Malaria Trigram is aimed to help public health professionals and policy makers to recognise and analyse different types of patterns in malaria events, including recurrences and reinfections, based on the current Brazilian health surveillance system, the SIVEP-Malária system, with no additional primary data collection or change in the current process. By using the Malaria Trigram, it is possible to plan and coordinate interventions for malaria elimination that are integrated with other parallel actions in the Brazilian Amazon region, such as vector control management, effective drug and vaccine deployment strategies.

Investigating differences in village-level heterogeneity of malaria infection and household risk factors in Papua New Guinea

Malaria risk is highly heterogeneous. Understanding village and household-level spatial heterogeneity of malaria risk can support a transition to spatially targeted interventions for malaria elimination. This analysis uses data from cross-sectional prevalence surveys conducted in 2014 and 2016 in two villages (Megiar and Mirap) in Papua New Guinea. Generalised additive modelling was used to characterise spatial heterogeneity of malaria risk and investigate the contribution of individual, household and environmental-level risk factors. Following a period of declining malaria prevalence, the prevalence of P. falciparum increased from 11.4 to 19.1% in Megiar and 12.3 to 28.3% in Mirap between 2014 and 2016, with focal hotspots observed in these villages in 2014 and expanding in 2016. Prevalence of P. vivax was similar in both years (20.6% and 18.3% in Megiar, 22.1% and 23.4% in Mirap) and spatial risk heterogeneity was less apparent compared to P. falciparum. Within-village hotspots varied by Plasmodium species across time and between villages. In Megiar, the adjusted odds ratio (AOR) of infection could be partially explained by household factors that increase risk of vector exposure, such as collecting outdoor surface water as a main source of water. In Mirap, increased AOR overlapped with proximity to densely vegetated areas of the village. The identification of household and environmental factors associated with increased spatial risk may serve as useful indicators of transmission hotspots and inform the development of tailored approaches for malaria control.

Results from a malaria indicator survey highlight the importance of routine data capture in high-risk forest and farm transmission sites in Vietnam to tailor location-specific malaria elimination interventions.

In-line with the World Health Organization’s (WHO) Global Technical Strategy for Malaria (2016–2030), Vietnam is striving to eliminate malaria by 2030. Targeting appropriate interventions in high-risk populations such as forest and forest-fringe communities is a critical component of malaria elimination efforts in Vietnam. In 2016, a household-level malaria indicator survey was conducted in Phu Yen Province, Vietnam with the aim of assessing the knowledge, behaviors and associated risks of malaria infection among priority mobile and migrant populations (MMPs) working and sleeping in forests and on farms. A total of 4211 people were included in the survey, comprised of 1074 heads of households and 3137 associated household members. Of the 1074 head-of-household respondents, 472 slept in a forest, 92 slept on a farm, 132 slept in both forests and farms, and 378 slept at their villages within the last 12 months. Age, literacy, and occupation were significantly different among those who slept in a forest versus on a farm. Of 301 respondents who answered questions about malaria risk factors at sleeping sites, 35% were somewhat aware of malaria prevention practices, but only 4% could recall at least four malaria prevention messages. Among the same group of 301 respondents, only 29% used nets and only 11% used treated nets. Ownership and use of nets among forest-goers was significantly lower than those who slept on a farm or in their village. Huts without walls were significantly prominent forest sleeping site locations (POR = 10.3; 95% CI 4.67–22.7). All respondents who slept in a forest requested standby malaria drugs and one-third of them self-treated without blood testing. Results from this study highlight the importance of capturing relevant location-specific data among priority populations such as remote forest and farm going mobile and migrant populations in Vietnam. Data regarding behavioral practices, knowledge, preventative measures, and intervention coverage at remote-area transmission sites must be routinely captured to effectively monitor progress and refine targeted intervention strategies accordingly.

Malaria elimination in India requires additional surveillance mechanisms.

Malaria surveillance is weak in high malaria burden countries. Surveillance is considered as one of the core interventions for malaria elimination. Impressive reductions in malaria-associated morbidity and mortality have been achieved across the globe, but sustained efforts need to be bolstered up to achieve malaria elimination in endemic countries like India. Poor surveillance data become a hindrance in assessing the progress achieved towards malaria elimination and in channelizing focused interventions to the hotspots. A major obstacle in strengthening India's reporting systems is that the surveillance data are captured in a fragmented manner by multiple players, in silos, and is distributed across geographic regions. In addition, the data are not reported in near real-time. Furthermore, multiplicity of malaria data resources limits interoperability between them. Here, we deliberate on the acute need of updating India's surveillance systems from the use of aggregated data to near real-time case-based surveillance. This will help in identifying the drivers of malaria transmission in any locale and therefore will facilitate formulation of appropriate interventional responses rapidly.

A LAMP-SNP Assay Detecting C580Y Mutation in Pfkelch13 Gene from Clinically Dried Blood Spot Samples.

Artemisinin resistance (ART) has been confirmed in Greater Mekong Sub-region countries. Currently, C580Y mutation on Pfkelch13 gene is known as the molecular marker for the detection of ART. Rapid and accurate detection of ART in field study is essential to guide malaria containment and elimination interventions. A simple method for collection of malaria-infected blood is to spot the blood on filter paper and is fast and easy for transportation and storage in the field study. This study aims to evaluate LAMP-SNP assay for C580Y mutation detection by introducing an extra mismatched nucleotide at the 3’ end of the FIP primer. The LAMP-SNP assay was performed in a water bath held at a temperature of 56°C for 45 min. LAMP-SNP products were interpreted by both gel-electrophoresis and HNB-visualized changes in color. The method was then tested with 120 P. falciparum DNA from dried blood spot samples. In comparing the LAMP-SNP assay results with those from DNA sequencing of the clinical samples, the 2 results fully agreed to detect C580Y. The sensitivity and specificity of the LAMP-SNP assay showed 100%. There were no cross-reactions with other Plasmodium species and other Pfkelch13 mutations. The LAMP-SNP assay performed in this study was rapid, reliable, and useful in detecting artemisinin resistance in the field study.

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

BackgroundPlasmodium 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. MethodsBlood 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. ResultsThe 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. ConclusionsThe 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.