Malaria Elimination Research Articles

Mapping malaria transmission foci in Northeast Thailand from 2011 to 2021: approaching elimination in a hypoendemic area

BackgroundThailand is approaching local elimination of malaria in the eastern provinces. It has successfully reduced the number of cases over the past decade, but there are persistent transmission hot spots in and around forests. This study aimed to use data from the malaria surveillance system to describe the spatiotemporal trends of malaria in Northeast Thailand and fine-scale patterns in locally transmitted cases between 2011 and 2021.MethodsCase data was stratified based on likely location of infection and parasite species. Annual Parasite Index per 1000 population (API) was calculated for different categories. Time series decomposition was performed to identify trends and seasonal patterns. Statistically significant clusters of high (hot spots) and low (cold spots) API were identified using the Getis-Ord Gi* statistic. The stability of those hot spots and the absolute change in the proportion of API density from baseline were compared by case type.ResultsThe total number of confirmed cases experienced a non-linear decline by 96.6%, from 1061 in 2011 to 36 in 2021. There has been a decline in both Plasmodium vivax and Plasmodium falciparum case numbers, with only four confirmed P. falciparum cases over the last two years—a 98.89% drop from 180 in 2011. API was generally higher in Si Sa Ket province, which had peaks every 2–3 years. There was a large outbreak in Ubon Ratchathani in 2014–2016 which had a high proportion of P. falciparum reported. The proportion of cases classified increased over the study period, and the proportion of cases classed as indigenous to the village of residence increased from 0.2% to 33.3%. There were stable hot spots of indigenous and imported cases in the south of Si Sa Ket and southeast of Ubon Ratchathani. Plasmodium vivax hot spots were observed into recent years, while those of P. falciparum decreased to zero in Ubon in 2020 and emerged in the eastern part in 2021, the same year that P. falciparum hot spots in Si Sa Ket reached zero.ConclusionsThere has been a large, non-linear decline in the number of malaria cases reported and an increasing proportion of cases are classed as indigenous to the patient’s village of residence. Stable hot spots of ongoing transmission in the forested border areas were identified, with transmission likely persisting because of remote location and high-risk forest-going behaviours. Future efforts should include cross-border collaboration and continued targeting of high-risk behaviours to reduce the risk of imported cases seeding local transmission.

Evaluation of the International Task Force for Disease Eradication: A Review of Past Deliberations.

The International Task Force for Disease Eradication (ITFDE) was formed at The Carter Center in 1988. Its primary purpose is to review activities and provide recommendations related to programs focused on eradication. The ITFDE also considers opportunities for disease elimination and improved control. Over the last two decades, the ITFDE has held 33 meetings, discussed 22 diseases, and made 244 recommendations. This report aims to analyze the patterns in recommendations made by the ITFDE between 2001 and 2022 and assess the ITFDE's role, impacts, and successes in advancing elimination and eradication efforts for selected diseases. Using a thematic analysis, recommendation categories were crafted, followed by a scoping review to determine evidence of implementation for each recommendation. Categories of recommendations included research (24%), leadership (20%), medical (17%), advocacy (11%), collaboration (13%), development (8%), and financial (8%). We determined that 123 (50.4%) ITFDE recommendations were implemented in some form. Notably, the ITFDE has helped raise the profile of neglected tropical diseases. Four salient outcomes include 1) the identification of the potential eradicability of lymphatic filariasis (1993), 2) the recognition of the critical need for improved treatments of human African trypanosomiasis (2002), 3) a recommendation for the elimination of lymphatic filariasis and malaria from Hispaniola (2006), and 4) recommendations for effective and safe ways to avoid disruption of elimination and eradication programs during the COVID-19 pandemic (2020). This review of the ITFDE will help to devise new approaches to monitor its impact in the future.

Malaria situation and elimination in Africa with specific focus on Zimbabwe: a systematic review

Malaria situation and elimination in Africa with specific focus on Zimbabwe: a systematic review

Spatiotemporal analysis of within-country imported malaria in Brazilian municipalities, 2004-2022.

Human mobility has challenged malaria elimination efforts and remains difficult to routinely track. In Brazil, administrative records from the Ministry of Health allow monitoring of mobility locally and internationally. Although most imported malaria cases are between municipalities in Brazil, detailed knowledge of patterns of mobility is limited. Here, we address this gap by quantifying and describing patterns of malaria-infected individuals across the Amazon. We used network analysis, spatial clustering, and linear models to quantify and characterize the movement of malaria cases in Brazil between 2004 and 2022. We identified sources and sinks of malaria within and between states. We found that between-state movement of cases has become proportionally more important than within-state, that source clusters persisted longer than sink clusters, that movement of cases into sinks was seasonal while movement out of sources was not, and that importation is an impediment for subnational elimination in many municipalities. We elucidate the vast travel networks of malaria infected individuals that characterize the Amazon region. Uncovering patterns of malaria case mobility is vital for effective microstratification within Brazil. Our results have implications for intervention stratification across Brazil in line with the country's goal of malaria elimination by 2035.

Unravelling heterogeneous malaria transmission dynamics in the Peruvian Amazon: insights from a cross-sectional survey

BackgroundMalaria remains a global health challenge, particularly in Peru's Loreto region. Despite ongoing efforts, high infection rates and asymptomatic cases perpetuate transmission. The Peruvian Ministry of Health’s “Zero Malaria Plan” targets elimination. This novel study combines microscopic, molecular, and serological techniques to assess transmission intensity, identify epidemiological risk factors, and characterize species-specific patterns across villages. The findings aim to inform targeted interventions and support broader malaria elimination efforts in line with the Zero Malaria Plan initiative.MethodsA cross-sectional malaria survey was conducted in the Zungarococha community, comprising the villages Llanchama (LL), Ninarumi (NI), Puerto Almendra (PA), and Zungarococha (ZG), using microscopic, molecular, and serological techniques to evaluate malaria transmission intensity. Statistical analysis, including multivariate-adjusted analysis, seroprevalence curves, and spatial clustering analysis, were performed to assess malaria prevalence, exposure, and risk factors.ResultsThe survey revealed a high prevalence of asymptomatic infections (6% by microscopy and 18% by PCR), indicating that molecular methods are more sensitive for detecting asymptomatic infections. Seroprevalence varied significantly between villages, reflecting the heterogeneous malaria transmission dynamics. Multivariate analysis identified age, village, and limited bed net use as significant risk factors for malaria infection and species-specific exposure. Seroprevalence curves demonstrated community-specific patterns, with Llanchama and Puerto Almendra showing the highest seroconversion rates for both Plasmodium species.ConclusionsThe study highlights the diverse nature of malaria transmission in the Loreto region, particularly nothing the pronounced heterogeneity as transmission rates decline, especially in residual malaria scenarios. The use of molecular and serological techniques enhances the detection of current infections and past exposure, aiding in the identification of epidemiological risk factors. These findings underscore the importance of using molecular and serological tools to characterize malaria transmission patterns in low-endemic areas, which is crucial for planning and implementing targeted interventions and elimination strategies. This is particularly relevant for initiatives like the Zero Malaria Plan in the Peruvian Amazon.

Genomic surveillance of malaria parasites in an indigenous community in the Peruvian Amazon

Hard-to-reach communities represent Peru's main challenge for malaria elimination, but information about transmission in these areas is scarce. Here, we assessed Plasmodium vivax (Pv) and P. falciparum (Pf) transmission dynamics, resistance markers, and Pf hrp2/3 deletions in Nueva Jerusalén (NJ), a remote, indigenous community in the Peruvian Amazon with high population mobility. We collected samples from November 2019 to May 2020 by active (ACD) and passive case detection (PCD) in NJ. Parasites were identified with microscopy and PCR. Then, we analyzed a representative set of positive-PCR samples (Pv = 68, Pf = 58) using highly-multiplexed deep sequencing assays (AmpliSeq) and compared NJ parasites with ones from other remote Peruvian areas using population genetics indexes. The ACD intervention did not reduce malaria cases in the short term, and persistent malaria transmission was observed (at least one Pv infection was detected in 96% of the study days). In Nueva Jerusalen, the Pv population had modest genetic diversity (He = 0.27). Pf population had lower diversity (He = 0.08) and presented temporal clustering, one of these clusters linked to an outbreak in February 2020. Moreover, Pv and Pf parasites from NJ exhibited variable levels of differentiation (Pv Fst = 0.07–0.52 and Pf Fst = 0.11–0.58) with parasites from other remote areas. No artemisin resistance mutations but chloroquine (57%) and sulfadoxine-pyrimethamine (35–67%) were detected in NJ's Pf parasites. Moreover, pfhrp2/3 gene deletions were common (32–50% of parasites with one or both genes deleted). The persistent Pv transmission and the detection of a Pf outbreak with parasites genetically distinct from the local ones highlight the need for tailored interventions focusing on mobility patterns and imported infections in remote areas to eliminate malaria in the Peruvian Amazon.

Benchmarking and Optimization of Methods for the Detection of Identity-By-Descent in High-Recombining Plasmodium falciparum Genomes.

Genomic surveillance is crucial for identifying at-risk populations for targeted malaria control and elimination. Identity-by-descent (IBD) is increasingly being used in Plasmodium population genomics to estimate genetic relatedness, effective population size (N e ), population structure, and signals of positive selection. Despite its potential, a thorough evaluation of IBD segment detection tools for species with high recombination rates, such as P. falciparum, remains absent. Here, we perform comprehensive benchmarking of IBD callers - probabilistic (hmmIBD, isoRelate), identity-by-state-based (hap-IBD, phased IBD) and others (Refined IBD) - using population genetic simulations tailored for high recombination, and IBD quality metrics at both the IBD segment level and the IBD-based downstream inference level. Our results demonstrate that low marker density per genetic unit, related to high recombination relative to mutation, significantly compromises the accuracy of detected IBD segments. In genomes with high recombination rates resembling P. falciparum, most IBD callers exhibit high false negative rates for shorter IBD segments, which can be partially mitigated through optimization of IBD caller parameters, especially those related to marker density. Notably, IBD detected with optimized parameters allows for more accurate capture of selection signals and population structure; IBD-based N e inference is very sensitive to IBD detection errors, with IBD called from hmmIBD uniquely providing less biased estimates of N e in this context. Validation with empirical data from the MalariaGEN Pf 7 database, representing different transmission settings, corroborates these findings. We conclude that context-specific evaluation and parameter optimization are essential for accurate IBD detection in high-recombining species and recommend hmmIBD for quality-sensitive analysis, such as estimation of N e in these species. Our optimization and high-level benchmarking methods not only improve IBD segment detection in high-recombining genomes but also enhance overall genomic analysis, paving the way for more accurate genomic surveillance and targeted intervention strategies for malaria.

Asymptomatic malaria and predictors among migrant farmworkers East Shewa zone Oromia Ethiopia

Asymptomatic malaria can impact existing malaria control and elimination efforts around the world, particularly in Africa, where the majority of malaria cases and death occurs. This is a cross-sectional study aimed to determine the prevalence and predictors of asymptomatic malaria among migrant farmworkers from June to July 2020 in the Upper Awash Agro-industry, East Shewa zone, Oromia Regional State, Ethiopia. A total of 254 migrant farmworkers without signs and symptoms of malaria were enrolled. Data on socio-demographic characteristics and malaria prevention practices were obtained through a structured questionnaire. Venous blood samples were collected and diagnosed using microscopy, rapid diagnostic tests, and polymerase chain reaction (PCR). Data were coded, entered, and analyzed using SPSS version-21 statistical software. Multivariable logistic regression was used to assess associated factors. A p < 0.05 was considered statistically significant. The overall prevalence of asymptomatic malaria among farmworkers in this study was 5.1% [95% CI 1.6, 6.7]. The proportions of Plasmodium falciparum was 90.0% (9/10) while it was 10.0% (1/10) for Plasmodium vivax. Out of the microscopy and/or RDT-confirmed malaria cases, (n = 9; 100%) were confirmed to be P. falciparum by nested PCR, while (n = 3/122; 2.46%) were found to be P. falciparum among 50% negative cases with the microscopy and/or RDT. The gametocyte stage was detected in 40% of microscopically positive cases out of which 44.4% belongs to P. falciparum. Home area/origin of migrant laborers [AOR = 6.08, (95% CI 1.08, 34.66)], family history of malaria [AOR = 8.15, (95% CI 1.43, 46.44)], and outdoor sleeping [AOR = 10.14, (95% CI 1.15, 89.14)] were significantly associated with asymptomatic malaria. In conclusion, asymptomatic malaria was detected among farmworkers in the study area and it was significantly associated with outdoor sleeping, home area, and family history of malaria. Prevention tools and control strategies, particularly focusing on migrant farmworkers, should be considered to support the ongoing malaria control and elimination effort in Ethiopia.

Drugs resistance and new strategies of prevention against Malaria: An ongoing battle.

From ancient times until 21st century, Malaria has remained a fatal disease. It causes death in many poor and developing countries. Excluding vector control, Antimalarial drugs are the most reliable and effective weapon to tackle this severe disease. The emergence of antimalarial drug resistance in Plasmodium spp. becomes a barrier in Malaria elimination program as there has been no effective antimalarial vaccine till today. Apart from artemisinin, most of the antimalarial drugs have become resistant against malaria at present. Although, reduced efficacy of artemisinin-based combination therapy (ACT) has also been reported from southeast regions of Asia. Mutation of some genes within the parasite play a vital role in this drug resistance. Therefore, malaria is still a prime threat to human death and an unsolved problem. Newly emerging approaches like, vaccine development, plants based antimalarial drugs, nanoparticles, next generation antimalarial drugs should be taken & supported. In addition to that, public awareness is much needed for understanding the fatality of the disease and for encouraging self-protection and early treatment.

Molecular detection of sub-microscopic infections and Plasmodium falciparum histidine-rich protein-2 and 3 gene deletions in pre-elimination settings of South Africa

South Africa’s efforts toward eliminating malaria have positioned the country in the pre-elimination stage. Imported and sub-microscopic cases still contribute to the persistence of malaria in regions of low transmission as identified in this study where diagnostics is built largely on the use of Rapid Diagnostic Test (RDT). However, the presence of Pfhrp2/3 gene deletion is known to interfere with the accuracy of diagnosis with the use of RDT. Malaria elimination and detection of Pfhrp2/3 gene deletion in the pre-elimination setting requires accurate molecular surveillance. With the core objective of this study being the determination of the presence sub-microscopic malaria cases and deleted Pfhrp2/3 gene markers, a total of 354 samples were collected from five districts of KwaZulu Natal, South Africa. These samples were prepared for molecular analysis using primers and PCR conditions specific for amplification of 18S rRNA and msp-1gene. Positive amplicons were analysed for the presence of Pfhrp2/3 and flanking genes, along with Sanger sequencing and phylogenetic studies. Out of 354 samples collected 339 were tested negative with PfHRP2 based RDTs. Of these Pfhrp2 and Pfhrp3 gene deletions were confirmed in 94.7% (18/19) and 100% (19/19) respectively. High migration rate (75%) among the study participants was noted and phylogenetic analysis of sequenced isolates showed close evolutionary relatedness with India, United Kingdom, Iran, and Myanmar and China isolates. Molecular-based test is recommended as an essential surveillance tool for malaria management programs as the target focuses on elimination.

Plasmodium vivax genomic surveillance in the Peruvian Amazon with Pv AmpliSeq assay.

Plasmodium vivax is the most predominant malaria species in Latin America, constituting 71.5% of malaria cases in 2021. With several countries aiming for malaria elimination, it is crucial to prioritize effectiveness of national control programs by optimizing the utilization of available resources and strategically implementing necessary changes. To support this, there is a need for innovative approaches such as genomic surveillance tools that can investigate changes in transmission intensity, imported cases and sources of reintroduction, and can detect molecular markers associated with drug resistance. Here, we apply a modified highly-multiplexed deep sequencing assay: Pv AmpliSeq v2 Peru. The tool targets a newly developed 41-SNP Peru barcode for parasite population analysis within Peru, the 33-SNP vivaxGEN-geo panel for country-level classification, and 11 putative drug resistance genes. It was applied to 230 samples from the Peruvian Amazon (2007-2020), generating baseline surveillance data. We observed a heterogenous P. vivax population with high diversity and gene flow in peri-urban areas of Maynas province (Loreto region) with a temporal drift using all SNPs detected by the assay (nSNP = 2909). In comparison, in an indigenous isolated area, the parasite population was genetically differentiated (FST = 0.07-0.09) with moderate diversity and high relatedness between isolates in the community. In a remote border community, a clonal P. vivax cluster was identified, with distinct haplotypes in drug resistant genes and ama1, more similar to Brazilian isolates, likely representing an introduction of P. vivax from Brazil at that time. To test its applicability for Latin America, we evaluated the SNP Peru barcode in P. vivax genomes from the region and demonstrated the capacity to capture local population clustering at within-country level. Together this data shows that P. vivax transmission is heterogeneous in different settings within the Peruvian Amazon. Genetic analysis is a key component for regional malaria control, offering valuable insights that should be incorporated into routine surveillance.

Examining geographical inequalities for malaria outcomes and spending on malaria in 40 malaria-endemic countries, 2010–2020

BackgroundWhile substantial gains have been made in the fight against malaria over the past 20 years, malaria morbidity and mortality are marked by inequality. The equitable elimination of malaria within countries will be determined in part by greater spending on malaria interventions, and how those investments are allocated. This study aims to identify potential drivers of malaria outcome inequality and to demonstrate how spending through different mechanisms might lead to greater health equity.MethodsUsing the Gini index, subnational estimates of malaria incidence and mortality rates from 2010 to 2020 were used to quantify the degree of inequality in malaria burden within countries with incidence rates above 5000 cases per 100,000 people in 2020. Estimates of Gini indices represent within-country distributions of disease burden, with high values corresponding to inequitable distributions of malaria burden within a country. Time series analyses were used to quantify associations of malaria inequality with malaria spending, controlling for country socioeconomic and population characteristics.ResultsBetween 2010 and 2020, varying levels of inequality in malaria burden within malaria-endemic countries was found. In 2020, values of the Gini index ranged from 0.06 to 0.73 for incidence, 0.07 to 0.73 for mortality, and 0.00 to 0.36 for case fatality. Greater total malaria spending, spending on health systems strengthening for malaria, healthcare access and quality, and national malaria incidence were associated with reductions in malaria outcomes inequality within countries. In addition, government expenditure on malaria, aggregated government and donor spending on treatment, and maternal educational attainment were also associated with changes in malaria outcome inequality among countries with the greatest malaria burden.ConclusionsThe findings from this study suggest that prioritizing health systems strengthening in malaria spending and malaria spending in general especially from governments will help to reduce inequality of the malaria burden within countries. Given heterogeneity in outcomes in countries currently fighting to control malaria, and the challenges in increasing both domestic and international funding allocated to control and eliminate malaria, the efficient targeting of limited resources is critical to attain global malaria eradication goals.

Assessing LLIN distribution implementation using evidence-informed intervention core elements: a qualitative study in a resource-constrained setting

BackgroundThe National Malaria Elimination Programme implements the mass LLIN Distribution Campaigns in Ghana. Implementation science promotes the systematic study of social contexts, individual experiences, real-world environments, partnerships, and stakeholder consultations regarding the implementation of evidence-informed interventions. In this paper, we assess the core elements of the mass LLIN distribution campaign in a resource constrained setting to learn best implementation practices. Three core domains were assessed through the application of Galbraith’s taxonomy (i.e., implementation, content, and pedagogy) for evidence-informed intervention implementation.MethodsSix districts in two regions (Eastern and Volta) in Ghana participated in this study. Fourteen Focus Group Discussions (FGDs) were conducted across these communities. Eligible participants were purposively sampled considering age, occupation, gender, and care giving for children under 5 years and household head roles. All audio-recorded FGDs were transcribed verbatim, data was assessed and coded through deductive and inductive processes. NVivo software version 13 was used for the coding process. Themes were refined, legitimized, and the most compelling extracts selected to produce the results.ResultsSixty-nine (69) caregivers of children under 5 years and sixty (60) household heads participated in the FGDs. All caregivers were females (69), whilst household heads included more males (41). Core elements identified under implementation domain of the LLIN distribution campaign in Ghana include the registration and distribution processes, preceded by engagement with traditional authorities and continuous involvement of community health volunteers during implementation. For pedagogy domain, core elements include delivery of intervention through outreaches, illustrations, demonstrations, and the use of multiple communication channels. Core elements realized within the content domain include information on effective malaria prevention, and provision of information to enhance their self-efficacy. Yet, participants noted gaps (e.g., misuse) in the desired behavioural outcome of LLIN use and a heavy campaign focus on women.Conclusion and recommendationsAlthough the implementation of the mass LLIN distribution campaigns exhibit components of core elements of evidence informed interventions (implementation, content and pedagogy), it has not achieved its desired behavioural change intentions (i.e. continuous LLIN use). Future campaigns may consider use of continuous innovative pedagogical approaches at the community level and lessons learnt from this study to strengthen the implementation process of evidence-based health interventions. There is also the need for standardization of core elements to identify the number of core elements required within each domain to achieve efficacy.Ethical approvalEthical clearance was obtained from the Ghana Health Service Ethics Review Committee (GHS-ERC: 002/06/21) before the commencement of all data collection.

Efficacy and safety of chloroquine plus primaquine for the treatment of Plasmodium vivax malaria in Hamusit site, Northwestern Ethiopia

BackgroundPlasmodium vivax malaria is still an important public health problem in Ethiopia. Unlike Plasmodium falciparum, P. vivax has a dormant liver stage (hypnozoite) that can be a risk of recurrent vivax malaria unless treated by radical cure with primaquine. Drug resistance to chloroquine is threatening malaria control and elimination efforts. This study assessed the therapeutic efficacy and safety of chloroquine plus 14 days of primaquine on P. vivax infection based on parasitological, clinical, and haematological parameters.MethodsA single-arm in vivo prospective therapeutic efficacy study was conducted to assess the clinical and parasitological response to the first-line treatment of P. vivax in Ethiopia, chloroquine plus 14 days low dose of (0.25 mg/kg/day) primaquine between December 2022 and March 2023 at Hamusit Health Centre using the standard World Health Organization (WHO) protocol. A total of 100 study participants with P. vivax mono-infection who were over 6 months old were enrolled and monitored for adequate clinical and parasitological responses for 42 days. The WHO double-entry Excel sheet and SPSS v.25 software were used for Kaplan–Meier survival analysis, and a paired t-test was used for analysis of haemoglobin improvements between follow up days.ResultsA total of 100 patients were enrolled among those, 96% cases were rural residents, 93% had previous malaria exposure, and predominant age group was 5–15 years (61%). 92.6% (95% CI 85.1–96.4%) of enrolled patients were adequate clinical and parasitological response, and 7.4% (95% CI 3.6–14.9%) recurrences were observed among treated patients. The fever and parasite clearance rate on day 3 were 98% and 94%, respectively. The baseline haemoglobin levels improved significantly compared to those days 14 and 42 (p < 0.001). No serious adverse event was observed during the study period.ConclusionsIn this study, co-administration of chloroquine with primaquine was efficacious and well-tolerated with fast resolution of fever and high parasites clearance rate. However, the 7.4% failure is reported is alarming that warrant further monitoring of the therapeutic efficacy study of P. vivax.

Identification of Southeast Asian Anopheles mosquito species using MALDI-TOF mass spectrometry.

Malaria elimination in Southeast Asia remains a challenge, underscoring the importance of accurately identifying malaria mosquitoes to understand transmission dynamics and improve vector control. Traditional methods such as morphological identification require extensive training and cannot distinguish between sibling species, while molecular approaches are costly for extensive screening. Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) has emerged as a rapid and cost-effective tool for Anopheles species identification, yet its current use is limited to few specialized laboratories. This study aimed to develop and validate an online reference database for MALDI-TOF MS identification of Southeast Asian Anopheles species. The database, constructed using the in-house data analysis pipeline MSI2 (Sorbonne University), comprised 2046 head mass spectra from 209 specimens collected at the Thailand-Myanmar border. Molecular identification via COI and ITS2 DNA barcodes enabled the identification of 20 sensu stricto species and 5 sibling species complexes. The high quality of the mass spectra was demonstrated by a MSI2 median score (min-max) of 61.62 (15.94-77.55) for correct answers, using the best result of four technical replicates of a test panel. Applying an identification threshold of 45, 93.9% (201/214) of the specimens were identified, with 98.5% (198/201) consistency with the molecular taxonomic assignment. In conclusion, MALDI-TOF MS holds promise for malaria mosquito identification and can be scaled up for entomological surveillance in Southeast Asia. The free online sharing of our database on the MSI2 platform (https://msi.happy-dev.fr/) represents an important step towards the broader use of MALDI-TOF MS in malaria vector surveillance.

Malaria transmission blocking activity of Anopheles stephensi alanyl aminopeptidase N antigen formulated with MPL, CpG, and QS21 adjuvants.

Malaria, a preventive and treatable disease, is still responsible for annual deaths reported in most tropical regions, principally in sub-Saharan Africa. Subunit recombinant transmission-blocking vaccines (TBVs) have been proposed as promising vaccines to succeed in malaria elimination and eradication. Here, a provisional study was designed to assess the immunogenicity and functional activity of alanyl aminopeptidase N (APN1) of Anopheles stephensi, as a TBV candidate, administered with MPL, CpG, and QS21 adjuvants in the murine model. The mouse groups were immunized with recombinant APN1 (rAPN1) alone or formulated with CpG, MPL, QS-21, or a combination of adjuvants (CMQ), and the elicited immune responses were evaluated after the third immunization. The standard membrane feeding assay (SMFA) measured the functional activity of antibodies against bacterial-expressed APN1 protein in adjuvanted vaccine groups on transmission of P. falciparum (NF54) to An. stephensi mosquitoes. Evaluation of mice vaccinated with rAPN1 formulated with distinct adjuvants manifested a significant increase in the high-avidity level of anti-APN1 IgG and IgG subclasses; however, rAPN1 induced the highest level of high-avidity anti-APN1 IgG1, IgG2a, and IgG2b antibodies in the immunized vaccine group 5 (APN1/CMQ). In addition, vaccine group 5 (receiving APN1/CMQ), had still the highest level of anti-APN1 IgG antibodies relative to other immunized groups after six months, on day 180. The SMFA data indicates a trend towards higher transmission-reducing activity in groups 2 and 5, which received the antigen formulated with CpG or a combination of three adjuvants. The results have shown the capability of admixture to stimulate high-affinity and long-lasting antibodies against the target antigen to hinder Plasmodium parasite development in the mid-gut of An. stephensi. The attained results authenticated APN1/CMQ and APN1/CpG as a potent APN1-based TBV formulation which will be helpful in designing a vaccine in the future.

Malaria Severity in the Elimination Continuum: A Retrospective Cohort Study between Beitbridge and Lupane Districts in Zimbabwe, 2021-2023.

Malaria has created a resurgence crisis in Zimbabwe's elimination continuum, diverging from global commitment to malaria elimination by 2030. This retrospective cohort study aimed to determine the risk factors associated with severe malaria in the Beitbridge and Lupane districts. Multistage sampling was used to recruit 2414 individuals recorded in the District Health Information Software2 Tracker database. The study used IBM SPSS 29.0.2.0(20) for data analysis, and odds ratios (ORs) to estimate the relative risk (RR; 95% C.I; p < 0.05). The study revealed significant relative risks (p-value < 0.05) for individuals who had no Long-Lasting Insecticidal Nets (Beitbridge 47.4; Lupane 12.3), those who owned but used the LLINs (Beitbridge 24.9; Lupane 7.83), those who slept outdoors during the night (Beitbridge 84.4; Lupane 1.93), and adults (Beitbridge 0.18; Lupane 0.22) compared to the corresponding reference groups. Other factors showed varying RR: sex (Beitbridge 126.1), prompt treatment (Beitbridge 6.78), hosting visitor(s) (Lupane 6.19), and residence (Lupane 1.94) compared to the corresponding reference groups. Risk factor management needs to focus on increasing local awareness of malaria, universal LLINs coverage of indoor and outdoor sleeping spaces, community-based programs on proper and consistent LLIN usage, screening of visitors from malaria-endemic areas, comprehensive entomological activities, mixed malaria interventions in rural hotspots, and future research on local malaria transmission dynamics. While Zimbabwe has the potential to meet the global goal of malaria elimination, success depends on overcoming the risk factors to sustain the gains already made among malaria elimination districts.

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...

Plasmodium vivax populations in the western Greater Mekong Subregion evaluated using a genetic barcode.

An improved understanding of the Plasmodium vivax populations in the Great Mekong Subregion (GMS) is needed to monitor the progress of malaria elimination. This study aimed to use a P. vivax single nucleotide polymorphism (SNP) barcode to evaluate the population dynamics and explore the gene flow among P. vivax parasite populations in the western GMS (China, Myanmar and Thailand). A total of 315 P. vivax patient samples collected in 2011 and 2018 from four regions of the western GMS were genotyped for 42 SNPs using the high-throughput MassARRAY SNP genotyping technology. Population genetic analysis was conducted to estimate the genetic diversity, effective population size, and population structure among the P. vivax populations. Overall, 291 samples were successfully genotyped at 39 SNPs. A significant difference was observed in the proportion of polyclonal infections among the five P. vivax populations (P = 0.0012, Pearson Chi-square test, χ2 = 18.1), with western Myanmar having the highest proportion (96.2%, 50/52) in 2018. Likewise, the average complexity of infection was also highest in western Myanmar (1.31) and lowest in northeast Myanmar (1.01) in 2018. The older samples from western China in 2011 had the highest pairwise nucleotide diversity (π, 0.388 ± 0.046), expected heterozygosity (He, 0.363 ± 0.02), and the largest effective population size. In comparison, in the neighboring northeast Myanmar, the more recent samples in 2018 showed the lowest values (π, 0.224 ± 0.036; He, 0.220 ± 0.026). Furthermore, the 2018 northeast Myanmar parasites showed high and moderate genetic differentiation from other populations with FST values of 0.162-0.252, whereas genetic differentiation among other populations was relatively low (FST ≤ 0.059). Principal component analysis, phylogeny, and STRUCTURE analysis showed that the P. vivax population in northeast Myanmar in 2018 substantially diverged from other populations. Although the 42 SNP barcode is a valuable tool for tracking parasite origins of worldwide parasite populations, a more extended barcode with additional SNPs is needed to distinguish the more related parasite populations in the western GMS.

Descriptive, Hospital-Based, 10-Year Study of Malaria Transmission in Goa, a Southwest Indian State in the Malaria Elimination Phase.

The South Asia International Center of Excellence for Malaria Research, an NIH-funded collaborative program, investigated the epidemiology of malaria in the Indian state of Goa through health facility-based data collected from the Goa Medical College and Hospital (GMC), the state's largest tertiary healthcare facility, between 2012 and 2021. Our study investigated region-specific spatial and temporal patterns of malaria transmission in Goa and the factors driving such patterns. Over the past decade, the number of malaria cases, inpatients, and deaths at the GMC decreased significantly after a peak in 2014-2015. However, the proportion of severe malaria cases increased over the study period. Also, a trend of decreasing average parasitemia and increasing average gametocyte density suggests a shift toward submicroscopic infections and an increase in transmission commitment characteristic of low-transmission regions. Although transmission occurred throughout the year, 75% of the cases occurred between June and December, overlapping with the monsoon (June-October), which featured rainfall above yearly average, minimal diurnal temperature variation, and high relative humidity. Sociodemographic factors also had a significant association with malaria cases, with cases being more frequent in the 15-50-year-old age group, men, construction workers, and people living in urban areas within the GMC catchment region. Our environmental model of malaria transmission projects almost negligible transmission at the beginning of 2025 (annual parasitic index: 0.0095, 95% CI: 0.0075-0.0114) if the current control measures continue undisrupted.