Malaria Elimination Research Articles

Implementation of reactive case detection strategy recommendations towards malaria elimination in the Shai Osudoku district of Ghana

Implementation of reactive case detection strategy recommendations towards malaria elimination in the Shai Osudoku district of Ghana

Assessment of the quality of malaria surveillance and laboratory services for diagnosis in three districts of Gujarat state, India

ObjectivesSurveillance is the backbone for the control of malaria and its elimination. In the state of Gujarat, situated in the western region of India, some of the districts reported a high annual blood examination rate (ABER) for malaria. Therefore, a study was conducted to identify the underlying reasons for the increase in the ABER for malaria.MethodsPlanned investigations were carried out in three of the state districts, scrutinizing records of malaria forms and other epidemiological data collected during health worker surveillance, assessment of laboratory services, and rapid fever surveys.ResultsThe rate of fever ranged from 8 to 57% in the primary health centers that were surveyed. Analysis of epidemiological data revealed that malaria parasite positivity was more from passive than active surveillance. Increased ABER was accounted for by multiple factors, including blood slides collected during the mass survey and contact smears, which were included in the ABER and not mentioned separately. Blood slides prepared for the migrant population were included in the ABER, but the migrant population was not counted while calculating the ABER.ConclusionThe ABER in villages surveyed varied from 1.6 to 78%, which is mainly due to indiscriminate preparation of blood slides, i.e., without fever symptoms. Addressing the key gaps identified in data recording may aid in channeling the limited resources efficiently, thereby progressing toward malaria elimination. Adequate surveillance activities, along with systematic data recording, will enable timely, informed decision-making for the effective allocation of resources, ultimately supporting malaria elimination efforts in the state.

Eliminating malaria transmission requires targeting immature and mature gametocytes through lipoidal uptake of antimalarials.

Novel antimalarial compounds targeting both the pathogenic and transmissible stages of the human malaria parasite, Plasmodium falciparum, would greatly benefit malaria elimination strategies. However, most compounds affecting asexual blood stage parasites show severely reduced activity against gametocytes. The impact of this activity loss on a compound's transmission-blocking activity is unclear. Here, we report the systematic evaluation of the activity loss against gametocytes and investigate the confounding factors contributing to this. A threshold for acceptable activity loss between asexual blood stage parasites and gametocytes was defined, with near-equipotent compounds required to prevent continued gametocyte maturation and onward transmission. Target abundance is not predictive of gametocytocidal activity, but instead, lipoidal uptake is the main barrier of dual activity and is influenced by distinct physicochemical properties. This study provides guidelines for the required profiles of potential dual-active antimalarial agents and facilitates the development of effective transmission-blocking compounds.

Plasmodium vivax antigen candidate prediction improves with the addition of Plasmodium falciparum data.

Intensive malaria control and elimination efforts have led to substantial reductions in malaria incidence over the past two decades. However, the reduction in Plasmodium falciparum malaria cases has led to a species shift in some geographic areas, with P. vivax predominating in many areas outside of Africa. Despite its wide geographic distribution, P. vivax vaccine development has lagged far behind that for P. falciparum, in part due to the inability to cultivate P. vivax in vitro, hindering traditional approaches for antigen identification. In a prior study, we have used a positive-unlabeled random forest (PURF) machine learning approach to identify P. falciparum antigens based on features of known antigens for consideration in vaccine development efforts. Here we integrate systems data from P. falciparum (the better-studied species) to improve PURF models to predict potential P. vivax vaccine antigen candidates. We further show that inclusion of known antigens from the other species is critical for model performance, but the inclusion of only the unlabeled proteins from the other species can result in misdirection of the model toward predictors of species classification, rather than antigen identification. Beyond malaria, incorporating antigens from a closely related species may aid in vaccine development for emerging pathogens having few or no known antigens.

Jumantik Education: Strategy Toward Malaria Elimination in the Resettlement Area of Osi Island, West Seram Regency

The Covid-19 pandemic, which has been global for 3 years, tends to have a domino effect in various aspects, such as individuals, groups, and countries. One of the causes of decreased immune system in the host is due to comorbid diseases suffered by the host (patients). Those at risk of Covid-19 may also be at risk of infectious diseases caused by viruses, parasites, and bacteria. In a pandemic situation like Covid-19, health behavior change education with a risk communication approach needs to be implemented in preventing, treating, and rehabilitating environmental stages of worm infection risk in the community of Osi Island hamlet. This education aims to increase public knowledge of potential health risks and threats. Thus, they can determine appropriate steps and actions to protect themselves from these issues. The method used is education with the project-based learning model, which combines lecture, discussion, and field practice methods. The target group is high school students of PGRI Pelita Jaya Seram Western Part. The achieved results are that the JUMANTIK cadres know about malaria-free health (cognitive), can collect trash (containers) from yards (psychomotor), do not allow stagnant water (affective), can drain water storage containers inside and around the house (psychomotor), can make simple mosquito traps using recycled materials, can sleep under mosquito nets (psychomotor), can observe larvae and pupae (psychomotor). Kyewords: Jumantik education, malaria elimination, Osi Island

Temporal genomics in Southern Zambia shows rising prevalence of Plasmodium falciparum mutations linked to delayed clearance after artemisinin-lumefantrine treatment

The emergence of antimalarial drug resistance is an impediment to malaria control and elimination in Africa. Analysis of temporal trends in molecular markers of resistance is critical to inform policy makers and guide malaria treatment guidelines. In a low and seasonal transmission region of southern Zambia, we successfully genotyped 85.5% (389/455) of Plasmodium falciparum samples collected between 2013 and 2018 from 8 spatially clustered health centres using molecular inversion probes (MIPs) targeting key drug resistance genes. Aside from one sample from 2016 carrying K13 622I, no other World Health Organization-validated or candidate artemisinin partial resistance (ART-R) mutations were observed. However, in the more recent years (2016–2017) five novel K13-propeller-domain mutations, C532S, A578S, Q613E, D680N and G718S were identified at low prevalence. Moreover, 13% (CI, 9.6–17.2) of isolates had the AP2MU 160N mutation, which has been associated with delayed clearance following artemisinin combination therapy in Africa. This mutation increased in prevalence between 2015 and 2018 and bears a genomic signature of selection. During this time period, there was an increase in the MDR1 NFD haplotype that is associated with reduced susceptibility to lumefantrine. Sulfadoxine-pyrimethamine polymorphisms were near fixation. While validated ART-R mutations are rare, a mutation associated with slow parasite clearance in Africa appears to be under selection in southern Zambia.

Genetic diversity of Plasmodium vivax population in northeast Myanmar assessed by amplicon sequencing of PvMSP1 and PvMSP3α

This study aimed to assess the baseline genetic diversity of the Plasmodium vivax population in an endemic area of northeast Myanmar at the onset of the malaria elimination campaign in the Greater Mekong Subregion. We genotyped 125 P. vivax clinical samples at two merozoite surface protein loci, PvMSP1 and PvMSP3α, by amplicon deep sequencing. Our study revealed that the parasite population in this region was highly diverse, identifying 60 PvMSP1 and 98 PvMSP3α haplotypes, with haplotype diversity of 0.929 and 0.944, respectively. Remarkably, 97.6% (122/125) of the patients harbored multiclonal infections with a mean multiplicity of infection of 4.18, indicating a relatively high transmission intensity. Neutrality tests and network analysis suggested a recent parasite population expansion, consistent with the concurrent malaria outbreak in the region. These findings underscore the existence of a highly diverse P. vivax population at the China-Myanmar border, highlighting the need for effective malaria control strategies to achieve the goal of regional malaria elimination.

Emerging public health strategies in malaria control: innovations and implications.

Malaria remains a significant global health challenge, particularly in regions with limited resources and tropical climates. Despite extensive efforts, the disease continues to cause significant morbidity and mortality, with ~229 million cases and 409000 deaths reported in 2020. However, recent years have seen promising advancements in public health strategies aimed at malaria control and elimination. Technological advancements have played a crucial role in improving malaria control efforts. Genomic surveillance techniques enable the monitoring of malaria parasite populations, aiding in the detection of drug resistance and informing targeted interventions. Additionally, innovative diagnostic technologies, such as rapid diagnostic tests (RDTs) and molecular assays, have enhanced the speed and accuracy of malaria diagnosis, facilitated prompt treatment and reduced transmission. These tools are instrumental in achieving the WHO goals of reducing malaria cases and deaths by at least 90% by 2030. Novel vector control methods offer innovative approaches to reduce malaria transmission. Insecticide-treated nets (ITNs) and indoor residual spraying (IRS) remain foundational strategies, with advancements including the development of next-generation insecticides and long-lasting insecticidal nets (LLINs). Furthermore, genetic modification of mosquitoes, such as gene drive technology, holds promise for reducing mosquito populations and interrupting malaria transmission. These vector control innovations complement other strategies, contributing to comprehensive malaria control efforts aimed at achieving sustainable disease reduction and eventual elimination.

Rapid detection of mutations in the suspected piperaquine resistance gene E415G-exo in Plasmodium falciparum exonuclease via AS‒PCR and RAA with CRISPR/Cas12a

Malaria remains a major public health concern. The rapid spread of resistance to antimalarial drugs is a major challenge for malaria eradication. Timely and accurate molecular monitoring based on practical detection methods is a critical step toward malaria control and elimination. In this study, two rapid detection techniques, allele-specific PCR (AS‒PCR) and recombinase-aided amplification (RAA) combined with CRISPR/Cas12a, were established, optimized and assessed to detect single nucleotide polymorphisms in the Plasmodium falciparum exonuclease (Pfexo) gene related to suspected piperaquine resistance. Moreover, phosphorothioate and artificial mismatches were introduced into the allele-specific primers for AS‒PCR, and crRNA-mismatched bases were introduced into the RAA‒CRISPR/Cas12a assay because crRNAs designed according to conventional rules fail to discriminate genotypes. As a result, the detection limits of the AS‒PCR and RAA‒CRISPR/Cas12a assays were 104 copies/μL and 103 copies/μL, respectively. The detection threshold for dried blood spots was 100‒150 parasites/μL, with no cross-reactivity against other genotypes. The average cost of AS‒PCR is approximately $1 per test and takes 2–3 h, whereas that of the RAA‒CRISPR/Cas12a system is approximately $7 per test and takes 1 h or less. Therefore, we provide more options for testing single nucleotide polymorphisms in the Pfexo gene, considering economic conditions and the availability of instruments, equipment, and reagents, which can contribute to the molecular monitoring of antimalarial resistance.

Assessing contextual factors influencing scale-up: a interactive approach involving stakeholders

Abstract Issue Pilot interventions are not always put into practice at scale. When they are, effectiveness is often highly reduced in the field due to contextual factors. To effectively implement a scale-up, stakeholders’ involvement is crucial. Curema is an international research evaluating an intervention aiming to reduce malaria transmission by distributing RDTs and treatments in mobile hard-to-reach populations. This intervention might be scaled-up in Brazil, Suriname, and French Guiana as a tool of national malaria programs for specific areas and populations. Description of the problem An interactive pre-planning assessment was conducted involving key stakeholders -implementers, decision-makers, and researchers - in working sessions, semi-structured interviews, and formal meetings. Mendelow’s Power/Interest Matrix was used to map stakeholders and a SWOT analysis was conducted using ExpandNet/WHO Framework to evaluate contextual factors and identify levers and obstacles influencing the scale-up. Results A total of 23 participants were involved. Health authorities had high power and generally high interest, while implementers and recipients had lower power and different interest levels. National engagement for WHO E2025 or E2030 enhanced scalability and represented a main opportunity in the three countries. Nevertheless, several regulatory and administrative aspects were identified as potential obstacles to be addressed to make scale-up realistic. Funding was also a major concern for sustainability. The need for regional cooperation was emphasized to achieve malaria elimination. Lessons Despite financial and regulatory challenges, a window of opportunity is open to scale-up Curema. Identifying and involving stakeholders in a pre-planning assessment and advocating for foster regional cooperation are crucial steps to support the scale-up. Stakeholder analysis should be refined during the scaling-up to capture further changes in factors that might influence the process. Key messages • Engagements with WHO represent windows of opportunity to enhance Curema scale-up. • Stakeholder involvement and regional cooperation are crucial for scaling up Curema in Brazil, French Guiana and Suriname.

Optimization of loop mediated isothermal amplification assay (LAMP) for detection of chloroquine resistance in P. vivax malaria

Chloroquine is still used as a first-line treatment for uncomplicated Plasmodium vivax malaria in India and resistance to this therapy can act as a major hurdle for malaria elimination. It is difficult to monitor drug-efficacy and drug resistance through in vivo and in vitro studies in case of Plasmodium vivax so analysis of molecular markers serves as an important tool to track resistance. Molecular methods that are currently in use for detecting single nucleotide polymorphisms in resistant genes including Polymerase chain reaction (PCR), Realtime-Polymerase chain reaction require highly sophisticated labs and are time consuming. So, with this background the study has been designed to optimize Loop Mediated Isothermal Amplification Assay to detect single nucleotide polymorphisms in chloroquine resistance gene of Plasmodium vivax in field settings. Eighty-eight Plasmodium vivax positive samples were collected. Pvmdr1 gene was amplified for all the samples and sequenced. Obtained sequences were analyzed for the presence of single nucleotide polymorphisms in the target gene. Further Loop Mediated Isothermal Amplification Assay primer sets were designed for the target mutants and the assay was optimized. Clinical as well as analytical sensitivity and specificity for the assay was calculated. Double mutants with variations at T958M and F1076L were detected in 100% of the Plasmodium vivax clinical isolates with haplotype M958 Y976 Y1028 L1076. Designed primers for Loop Mediated Isothermal Amplification Assay successfully detected both the mutants (T958M and F1076L) in 100% of the isolates and do not show cross-reactivity with other strains. So, the assay was 100% sensitive and specific for detecting single nucleotide polymorphisms in the target Pvmdr1 gene. Limit of detection was found to be 0.9 copies/µl and lowest DNA template concentration detected by designed assay was 1.5 ng/µL. Observed prevalence of single nucleotide polymorphisms in Pvmdr 1 gene is indicating a beginning of trend towards chloroquine resistance in Plasmodium vivax. The present study optimized LAMP for detecting single nucleotide polymorphisms in Plasmodium vivax cases in field settings, thus would help in finding significant hubs of emerging chloroquine drug resistance and ultimately helping in the management of suitable antimalarial drug policy.

A constant contact community-based epidemiological investigation (C3EI) as part of malaria elimination demonstration project, Mandla district, Madhya Pradesh, India

BackgroundIn India, an increase in malaria cases by 21% (223,961 cases) has been reported between 2022 and 2023. Madhya Pradesh ranks 10th in malaria burden, with Mandla district selected for the Malaria Elimination Demonstration Project (MEDP) to demonstrate the feasibility of malaria elimination in a hard-to-reach, tribal-dominated, and hilly forested district. A Constant Contact Community-based Epidemiological Investigation (C3EI) was undertaken by continuous engagement with the community for real-time data collection, mapping of malaria cases, identification of risk factors, and monitoring of intervention outcomes designed to drive effective strategies for malaria elimination.MethodsThe study mapped 1,143,126 individuals from 248,825 households in the year 2017 in Mandla district for constant contact surveillance. Fortnightly household visits were conducted to inquire about febrile episodes, with on-spot diagnosis and treatment. Data collection was done using the SOCH mobile application, and analysis using R.ResultsThe constant contact household surveillance revealed that out of 956,795 individuals, 230,780 (24.12%) unique individuals reported one or more febrile episodes, with a total of 322,577 febrile episodes and 490 malaria episodes (RDT positive). Males had a higher risk of malaria infection than females (OR = 2.62; p < 0.0001). The cumulative incidence of malaria was highest among children aged 5–15 years and pregnant women. Multiple episodes of malaria infections were more common in adults over 30 years. The incidence of malaria per 100,000 persons gradually declined from 26.13 in 2018 to 11.18 in 2020, with the highest incidence during the monsoon season.ConclusionThe C3EI presents a new strategy suitable for disease elimination programmes. Implementing C3EI-type longitudinal studies in elimination projects holds promise for generating data to expedite malaria elimination efforts because the unit of observation is a ‘household’. Such a comprehensive approach allows identification in the gaps in case management for prompt interventions at the household-level.

Assessing the role of the for-profit private healthcare sector in malaria elimination efforts in Bangladesh: a cross-sectional study of challenges and opportunities

BackgroundAmong 13 endemic districts, the Chittagong Hill Tracts bear more than 90% of Bangladesh’s malaria burden. Despite the private sector’s prominence in rural healthcare, its role in malaria management remains underutilized. This study aimed to strategize leveraging the for-profit private sector, such as diagnostic and treatment centers, to bolster national malaria surveillance and control, advancing Bangladesh toward malaria elimination by 2030.MethodsThis mixed-method study commenced with a questionnaire-based cross-sectional survey followed by selected focused group discussions (FGDs) among the participants. Three FGDs were held with the for-profit service providers so that further insights and qualitative viewpoints of them can be utilized in situation analysis. Based on the endemicity and strategic priorities, a comprehensive mapping of private for-profit facilities from the regions comprising 15 sub-districts across 8 chosen districts (7 malaria endemic districts and the rest non-endemic districts) was created. For the non-endemic zone, the sub-districts were selected based on their proximity to an area with high malaria transmission.ResultsAmong the 104 representative participants, majority were male (n = 92, 88.5%), had a diploma in their respective fields (n = 53, 51%) and were involved either in laboratory work (n = 49, 47.1%) or as owners/managers of health centers (n = 41, 39.4%). The selected health facilities were close to the corresponding Upazila Health Complexes (mean distance 2.8 km), but were distantly located from the designated district hospitals (mean distance 48.9 km). The main sources of RDT kits (62.3%) and anti-malarial drugs (63.2%) were local wholesale markets. A large share of the corresponding facilities neither provided malaria treatment services (81.7%) nor worked with the NMEP (93.3%).ConclusionsThis study highlights challenges and recommendations for engaging private for-profit health facilities in Bangladesh’s malaria elimination efforts. The identified challenges include low-quality RDTs, staff shortages, and inadequate capacity building. Recommendations emphasize effective training, stakeholder interaction, and enhanced oversight for successful malaria control efforts.

DISTRIBUTION OF PLASMODIUM FALCIPARUM CHLOROQUINE RESISTANCE TRANSPORTER (PFCRT) AND PLASMODIUM FALCIPARUM MULTIDRUG RESISTANCE 1(PFMDR-1) GENES IN ILORIN NORTH-CENTRAL NIGERIA

Globally, malaria is a peculiar health challenge particularly in continent of Africa. The ease of developing resistance to anti-malaria drugs by Plasmodium falciparum is a serious impediment towards programs aim at control and elimination of malaria. Consequently, drug efficacy surveillance is desirable to institute adequate and effective treatment policies. In this study, distribution of these genes in Plasmodium falciparum isolates in Ilorin metropolis were investigated. One hundred and three samples collected randomly from 5 hospitals in Ilorin metropolis. The samples were amplified at codon 76 and 86 for Pfcrt and Pfmdr-1 respectively using PCR / Restricted Fragment Length Polymorphism (RFLP). The most prevalent alleles were drug susceptible alleles in the study area (K76 and N86) with 31% and 40% respectively, while drug resistance alleles (86Y) have 13% and the least prevalence 2% was the mixed alleles K76T. UITH has the highest number of susceptible alleles followed by CSC 38% and 46% for K76 and N86 respectively. There are significant differences in the distribution of these alleles and the study sites (P&lt; 0.05). The prevalence of resistance alleles in the area is a welcome development that can be employed for possibility of re-introduction of CQ for the treatment of malaria in the study area which will serve as an advantage over expensive ACT due to fact that it is safe cheap and readily affordable.

Ecological change increases malaria risk in the Brazilian Amazon

Ecological change in the Brazilian Amazon is closely linked to human mobility and health. Mining, agriculture, logging, and other activities alter highly diverse ecological and demographic contexts and subsequent exposure to diseases such as malaria. Studies that have attempted to quantify the impact of deforestation on malaria in the Brazilian Amazon have produced conflicting results. However, they varied in methodology and data sources. Most importantly, all studies used annual data, neglecting the subannual seasonal dynamics of malaria. Here, we fill the knowledge gap on the subannual relationship between ecological change in the Brazilian Amazon and malaria transmission. Using the highest spatiotemporal resolution available, we estimated the effect of deforestation on malaria cases between 2003 and 2022 using a stratified Bayesian spatiotemporal hierarchical zero-inflated Poisson model fitted with the Integrated Nested Laplace Approximation. The model was also stratified by state. We found that a 1% increase in 1-mo lagged deforestation increased malaria cases in a given month and municipality by 6.3% [95% credible interval (Crl): 6.2, 6.5%]. Based on an interaction term included in the model, the effect of deforestation on malaria was even larger in areas with higher forest cover. We found that the coefficients for deforestation and mobility were highly variable when stratified by state. Our results provide detailed evidence that, on average, deforestation increases malaria transmission, but that the relationship is not spatiotemporally uniform. These results have implications for stratifying malaria control interventions based on ecological dynamics to help Brazil achieve its goal of malaria elimination by 2035.

An observational analysis of the impact of deltamethrin + piperonyl butoxide insecticide-treated nets on malaria case incidence and entomological indicators in Ebonyi State, Nigeria, 2017–2021

BackgroundIntense pyrethroid resistance threatens the effectiveness of the primary vector control intervention, insecticide-treated nets (ITNs), in Nigeria, the country with the largest malaria burden globally. In this study, the epidemiological and entomological impact of a new type of ITN (piperonyl-butoxide [PBO] ITNs) distributed in Ebonyi State were evaluated. The epidemiological impact was also compared to the impact of standard pyrethroid-only ITNs in Cross River State.MethodsA controlled interrupted time series analysis was conducted on monthly malaria incidence data collected at the health facility level, using a multilevel mixed-effects negative binomial model. Data were analysed two years before and after the PBO ITN campaign in Ebonyi State (December 2017 to November 2021). A pre-post analysis, with no comparison group, was used to assess the impact of PBO ITNs on human biting rates and indoor resting density in Ebonyi during the high transmission season immediately before and after the PBO ITN campaign.ResultsIn Ebonyi, PBO ITNs were associated with a 46.7% decrease (95%CI: -51.5, -40.8%; p < 0.001) in malaria case incidence in the 2 years after the PBO ITN distribution compared to a modelled scenario of no ITNs distributed, with a significant decrease from 269.6 predicted cases per 1000 population to 143.6. In Cross River, there was a significant 28.6% increase (95%CI: -10.4, 49.1%; p < 0.001) in malaria case incidence following the standard ITN distribution, with an increase from 71.2 predicted cases per 1000 population to 91.6. In Ebonyi, the human biting rate was 72% lower (IRR: 0.28; 95%CI 0.21, 0.39; p < 0.001) and indoor resting density was 73% lower (IRR: 0.27; 95%CI 0.21, 0.35; p < 0.001) after the PBO ITNs were distributed.ConclusionsThe epidemiological and entomological impact of the PBO ITNs underscore the impact of these ITNs in areas with confirmed pyrethroid resistance. These findings contribute to ongoing research on the impact of new types of ITNs in Nigeria, providing critical evidence for the Nigeria National Malaria Elimination Programme and other countries for future ITN procurement decisions as part of mass ITN campaign planning and malaria programming.

Epidemiologic trends and clinical outcomes of imported malaria in a tertiary care hospital, Bangkok, Thailand: A retrospective analysis (2013–2022)

BackgroundDespite a significant declined in malaria incidence in Thailand, the rising global travel has resulted in an increase of imported malaria cases, posing a threat to the goal of malaria elimination. This study aims to understand the epidemiological trends and clinical outcomes of imported malaria cases in Thailand. MethodsMedical records of all imported malaria cases admitted from 1st January 2013 to 31st December 2022 at the Hospital for Tropical Diseases, Thailand, were retrospectively examined. Demographic data, travel details, severity of illness, and clinical outcomes were described. Logistic regression was performed to identify factors associated with severe disease outcomes. ResultsIn total, 335 cases of imported malaria were identified, with 33 % classified as transnational malaria and 67 % as border malaria. Transnational malaria cases (79 % P. falciparum) were mostly acquired from Sub-Saharan Africa for business or visiting friends and relatives (VFRs). Border malaria cases (81 % P. vivax) involved unskilled labourers and were acquired from land-border countries. The proportion of imported malaria in business travelers increased from 13 % to 50 % over the ten years. Risk factors for severe imported malaria included male gender, age 40 and older, infection with P. falciparum, and acquired malaria from Africa. ConclusionsUnderstanding unique demographic and socioeconomic characteristics in both border and transnational cases is crucial for effective malaria prevention. The increasing imported malaria among business travelers highlight the need for targeted prevention in this high-risk group.

Towards malaria elimination: a case–control study to assess associated factors to malaria relapses in the extra-Amazon Region of Brazil from 2008 to 2019

BackgroundMalaria is an infectious disease caused by the Plasmodium species and is a global burden. When not treated correctly, it can reemerge as a relapse or recrudescence. Malaria relapse cases can contribute to maintaining active transmission chains and can influence the patient to develop severe malaria, potentially leading to hospitalization or death. The objective of this study is to estimate the number of malaria relapse cases in the extra-Amazon region of Brazil and to investigate the associated factors.MethodsThis is a case–control study that analyses malaria infections caused by Plasmodium vivax, as reported in Notifiable Diseases Information System (Sinan) for the Brazilian extra-Amazon region (an area not endemic for the disease) from 2008 to 2019. For the identification of relapse cases, deduplication record linkage processes in R software were used. Malaria relapses were defined as the case group, and new malaria infections were defined as the control group. Logistic regression models were used to assess associated factors.ResultsOf the 711 malaria relapses, 589 (82.8%) were first relapses. Most relapses (71.6%) occurred between 30 and 120 days after the previous infection. Malaria relapses are spread throughout the extra-Amazon region, with a higher concentration near big cities. Driver occupation was found to be a common risk factor compared to other occupations, along with asymptomatic individuals. Other associated factors were: being infected in the Brazilian Amazon region, having follow-ups for malaria relapses, and having parasite density of the previous infection higher than 10,000 parasites per mm3.ConclusionsThis study provides evidence that allows malaria health surveillance services to direct their efforts to monitor cases of malaria in the highest risk segments identified in this study, particularly in the period between 30 and 120 days after being infected and treated. Relapses were associated to driver occupation, absence of symptoms, infection in endemic areas of Brazil, being detected through active surveillance or routine follow-up actions, and with parasitaemia greater than 10,000 parasites per mm3 in the previous infection. Improving cases follow-up is essential for preventing relapses.

Insecticide Resistance and Target-Site Mutations kdr, N1575Y, and Ace-1 in Anopheles gambiae s.l. Populations in a Low-Malaria-Transmission Zone in the Sudanian Region of Senegal.

Background/Objectives: Significant progress in malaria control has been achieved through long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), raising hopes for malaria elimination. However, emerging insecticide resistance threatens these gains. This study assessed the susceptibility of Anopheles gambiae s.l. populations to public health insecticides, examined the frequencies of kdr, Ace-1, and N1575Y mutations, and explored their associations with phenotypic resistance in Dielmo and Ndiop, Senegal. Methods: Anopheles larvae collected between September and December 2022 were reared to adulthood. Adult mosquitoes were exposed to discriminating concentrations of various insecticides following WHO guidelines. Knockdown times (KDT50 and KDT95) for pyrethroids were calculated using the Probit model. RT-qPCR detected target-site mutations (kdr: L1014F and L1014S, Ace-1, N1575Y) and assessed correlations with phenotypic resistance. Species-specific PCR identified species within the An. gambiae complex. Results/Conclusions: The populations of Dielmo and Ndiop showed susceptibility to pirimiphos-methyl and bendiocarb, with no Ace-1 mutation detected. Resistance to DDT and pyrethroids was observed. The knockdown times indicated that alphacypermethrin and lambdacyhalothrin were more effective than permethrin and deltamethrin. The L1014F allele was widespread, while L1014S was absent in Ndiop and low in Dielmo. The N1575Y mutation occurred only in populations with L1014F. The L1014S mutation was significantly associated with resistance to lambdacyhalothrin in both villages and to deltamethrin in Ndiop.

Expanded roles of community health workers beyond malaria in the Asia-Pacific: A systematic review.

In the Greater Mekong Subregion (GMS), community health workers (CHWs) are a key component of malaria elimination strategies. As malaria declines, support for, and uptake of, malaria services may also subsequently decrease. Expanding their roles beyond malaria has been proposed to sustain the services. A systematic review was conducted to identify and characterize programmes with CHWs providing services in addition to those for malaria in the Asia Pacific. This review describes the expanded roles, identifies evidence of impact or success of the programmes, and explores strategies to ensure sustainability and factors for effective implementation to inform the design of malaria CHW programmes. Searches were conducted in 6 databases, for grey literature, and in bibliographies of retrieved articles. Data were extracted from 38 published articles, 12 programme reports, and 4 programme briefs and analysed using thematic coding and descriptive analysis. Twenty-nine programmes were identified with CHWs performing both malaria and non-malaria roles in the Asia Pacific. There was evidence of impact on malaria incidence in 4 of these, none on malaria mortality, and 4 on other diseases. Monitoring and evaluation mechanisms, multi-sectoral stakeholder collaborations, and adequate training and consistent supervision of CHWs were key to effective programme implementation. Integration of programmes into broader health services, ongoing political and funding support, and engagement with local communities were found to contribute to sustaining provision of health services by CHWs. Expanding CHW roles depends on programme management and strengthening linkages with local health systems. To sustain malaria CHW services, countries need adequate policies and financing, and sufficiently strong health systems to deliver basic health services that are adapted to the health needs of the community which means transitioning away from vertical disease programs. Further research should explore programmes that have not been captured in this review and address gaps in measuring malaria outcomes.