Malaria Journal最新文献

The clinical development of novel vaccines, injectable therapeutics, and oral chemoprevention drugs has the potential to deliver significant advancements in the prevention of Plasmodium falciparum malaria. These innovations could support regions in accelerating malaria control, transforming existing intervention packages by supplementing interventions with imperfect effectiveness or offering an entirely new tool. However, to layer new medical tools as part of an existing programme, malaria researchers must come to an agreement on the gaps that currently limit the effectiveness of medical interventions for moderate to low transmission settings. In this perspective, three crucial gaps that may prevent new therapeutics from being used to their fullest extent are presented. First, do burden reduction outcomes, which are typically monitored in studies of new medical products, sufficiently capture the broader goal of accelerating malaria control? Layering novel malaria products requires monitoring health outcomes that reflect the novel product's targeted stage of the parasite life cycle, in addition to all-infection and prevalence-based outcomes. Second, what public health outcome does a novel medical prevention tool provide that existing malaria interventions cannot fully deliver? Novel medical tools should be developed not just for an incremental improvement in preventive efficacy over an existing product, but also to meet a gap in protection. Specifically, this means designing products with components that target parts of the parasite life cycle beyond the scope of existing therapeutics, and better addressing populations and settings not well covered by existing tools. Finally, when do the population-level benefits of a multi-tool prevention programme justify the individual-level outcomes from receiving multiple interventions? An individual-level perspective should be key for exploring when and how layering a novel prevention intervention can accelerate efforts towards P. falciparum malaria control.

Background: The current study sought to re-evaluate malaria prevalence, susceptibility to artemisinin-based combination therapy (ACT), transmission patterns and the presence of malaria vectors in the Kikuyu area of the Kenyan Central highlands, a non-traditional/low risk malaria transmission zone where there have been anecdotal reports of emerging malaria infections.

Methods: Sampling of adult mosquitoes was done indoors, while larvae were sampled outdoors in June 2019. The malaria clinical study was an open label non-randomized clinical trial where the efficacy of one ACT drug, was evaluated in two health facilities. Microscopy was used at the facility while nested 18 s rRNA subunit gene PCR amplification and MSP-1 and MSP-2 family alleles genotyping was done in the laboratory. Anti-malarial resistance gene markers Pfk13 and Pfmdr1 were profiled.

Results: Anopheles funestus mosquitoes were the predominant vectors at 76.35% of all larvae collections (N = 148). Only two non-blood fed, parasites negative adult mosquitoes were collected from houses sampled. Parasitological analysis of the 838 patients screened resulted in 41 positives whose treatment outcome was 100% Adequate Clinical and Parasitological Response (ACPR). From the 35 positive samples genotyped, 29 (82.9%) were polyclonal. The overall mean MOI was 2.8 (95% CI 2.36-3.35). The MOI for msp-1 and msp-2 genes, was 2.02 (95% CI 0.72-2.27) and 2.9 (95% CI 2.22-3.55), and parasite strains range of 1-3 and 1-7, respectively. Polyclonal variation in the two genes was at 76.4% and 70.3%, respectively. The Pfk13 gene revealed no single nucleotide polymorphisms (SNP) associated with suspected artemisinin resistance nor was there any pfmdr1 N86 mutant allele detected.

Conclusion: The Plasmodium infections positivity rate observed in the study site was very low but significant. A proportion of participants who tested positive did not report recent history of travel. This observation together with the finding of competent known vectors can probably suggest that several of the cases could have been acquired and transmitted locally. The observed genetic diversity and polyclonal variations was on the contrary and suggest that these are imported cases. This however does not rule out a likely changing malaria transmission scenario in this zone, thus the need for further investigations.

Background: Emodepside is an anthelmintic used in veterinary medicine that is currently under investigation in human clinical trials for the treatment of soil-transmitted helminths and possibly Onchocerca volvulus. Emodepside targets the calcium-activated voltage-gated potassium slowpoke 1 (SLO-1) channels of presynaptic nerves of pharynx and body wall muscle cells of nematodes leading to paralysis, reduced locomotion and egg laying, starvation, and death. Emodepside also has activity against Drosophila melanogaster SLO-1 channels. Orthologous SLO-1 genes are present in Anopheles gambiae and Aedes aegypti, suggesting that emodepside may have activity against mosquitoes.

Methods: Both Anopheles dirus and Ae. aegypti were blood-fed emodepside across a range of concentrations (1-10,000 nM) and mosquito survival was monitored for 10 days. Co-feeding experiments were also performed with An. dirus blood fed ivermectin at the concentrations that kills 25% (LC₂₅) and 50% (LC₅₀) of mosquitoes with and without emodepside at clinical peak concentration in humans (C_max) and five times the C_max, and mosquito survival was monitored for 10 days.

Results: Emodepside had weak mosquito-lethal effects in An. dirus but none observed in Ae. aegypti at the concentrations evaluated. The An. dirus emodepside LC₅₀ was 4,623 [4,159-5,066] ng/ml which is > 100-fold greater than the peak concentrations seen in human. The ivermectin and emodepside co-feed experiment with An. dirus did not indicate any altered effect of ivermectin on mosquito survival when emodepside co-fed at human C_max or five times that of the human C_max.

Conclusions: Emodepside was not lethal to An. dirus at human-relevant concentrations and had no effect on Ae. aegypti survival. Thus, mass distribution of emodepside does not appear to be a potential tool for vector-borne disease control. Emodepside induced mortality in An. dirus does suggest that the SLO-1 channel could be a potential target for novel vector control and may warrant further investigation.

Background: Malaria is a disease deeply rooted in poverty. Malaria in pregnant women leads to severe complications, including low birth weight and neonatal mortality, which can adversely affect both mother and child. This study aimed to identify the factors associated with malaria in pregnancy among women attending antenatal care (ANC) clinics in three districts of the Ashanti Region, Ghana.

Methods: A cross-sectional study was conducted among 1215 pregnant women selected through multi-stage sampling. Data were collected using structured questionnaires and analysed using descriptive and inferential statistics, including regression analysis.

Results: The self-reported prevalence of at least one episode of malaria was 76.7% (95% CI [74.1-79.3%]). Age, education, marital status, income, and religion were significantly associated with the prevalence of malaria among pregnant women, with a p-value < 0.001. Pregnant women aged 17-25 years were 10.26 times more likely to have malaria compared to other age groups (aOR = 10.26, 95% CI [4.52-11.05], p = 0.000). Women with no formal education had higher odds of malaria, being 15.10 times more likely to have malaria compared to those with tertiary education (aOR = 15.10, 95% CI [7.32-16.78], p = 0.002). Women not using insecticide-treated bed nets (ITNs) were 20 times more likely to have malaria compared to those who used ITNs (aOR = 20.0, 95% CI [7.04-21.03], p = 0.000).

Conclusion: Age, education, marital status, income, religion and insecticide-treated bed net (ITN) use significantly influence malaria prevalence in pregnancy. To achieve SDG 3 (Good Health and Well-being), particularly Target 3.1 (reducing maternal mortality) and Target 3.3 (ending malaria), the Ghana Health Service and Ministry of Health should prioritize expanding ITN distribution, educational campaigns, and targeted support for vulnerable groups to reduce malaria prevalence during pregnancy and improve maternal health outcomes.

Background: Mosquitoes are important drivers of infectious diseases transmission, with Anopheles mosquitoes being responsible of malaria transmission. In Cambodia, where malaria is prevalent in forested regions, understanding the ecology of these vectors is crucial. This study aimed to investigate the abundance, distribution, seasonal patterns, biting behaviour of Anopheles mosquitoes, and prevalence of Plasmodium, in Mondulkiri province, Northeastern Cambodia.

Methods: Conducted in 9 sites, seven in forested and two in neighbouring villages, over one year, the collection of Anopheles mosquitoes was made hourly for a 72-h period every month, using a human-baited double net trap. Each mosquito was collected using a mouth-aspirator and identified morphologically, and screened for the presence of Plasmodium.

Results: Primary vectors, including Anopheles baimaii, Anopheles dirus, Anopheles maculatus, and Anopheles minimus, constituted 11.1% of all female mosquitoes, while 12 secondary vector species represented 29.4% of the overall collection. Anopheles species were more prevalent during the late rainy season (August to November), with year-round activity observed. Primary vectors were predominantly found in forest sites, while other vector species were found in both village and forest environments. Notably, primary vectors exhibited a preference for nocturnal biting, yet a significant proportion (19.2%) displayed daytime activity, highlighting a potential risk of daytime malaria transmission. Among 5,056 Anopheles specimens tested, only 36 Plasmodium spp.-infected samples were detected, mainly in forest sites (94%), and in specimens collected at night. This study provides essential insights into the ecology of Anopheles in Mondulkiri Forest.

Conclusions: The identification of primary and secondary vectors, their seasonal dynamics, and biting behaviour contribute to enhances our understanding of malaria transmission risks in these areas, guiding future strategies toward effective and context-specific control measures, while stressing the need for individual protection during daytime.

Background: Malaria is the parasitic disease with the highest global morbidity and mortality. According to estimates from the World Health Organization (WHO), there were around 249 million cases in 2022, with 3.4% occurring in Angola. The emergence and spread of drug-resistant Plasmodium falciparum have compromised anti-malarial efficacy and threatens malaria elimination campaigns using artemisinin-based combination therapy (ACT). Increased copy number (CNV) of the P. falciparum gene plasmepsin 2 (pfpm2) have been reported to confer parasite tolerance to piperaquine (PPQ) and the multidrug resistance-1 (pfmdr1), resistance to mefloquine (MEF) and decreased susceptibility to lumefantrine (LUM). PPQ, MEF and LUM are ACT partner drugs. Therefore, CNV detection is a useful tool to track ACT resistance risk. The potential for future treatment failure of artemisinin-based combinations (that include PPQ, LUM and AMQ), due to parasite resistance in the region, emphasizes the need for continued molecular surveillance.

Methods: One hundred and nine clinically derived samples were collected at Hospital Central Dr. António Agostinho Neto (HCL) in Lubango, Angola. qPCR targeting the small-subunit 18S rRNA gene was used to confirm P. falciparum infection. Copy number estimates were determined using a SYBR green-based quantitative PCR assay.

Results: Overall, this study revealed a low number of resistance CNVs present in the parasite population at Lubango, for the genes pfmdr1 and pfpm2. Of the 102 samples successfully analysed for pfpm2 10 (9.8%) carried increased CNV and 9/101 (8.9%) carried increased CNV of pfmdr1.

Conclusions: This study provides, for the first time, evidence for the presence of CNVs in the pfpm2 and pfmdr1 genes in P. falciparum isolates from southern Angola.

Background: In Myanmar, progress towards malaria elimination has stagnated in some areas requiring deployment of new tools and approaches to accelerate malaria elimination. While there is evidence that networks of community-based malaria workers and insecticide-treated nets (ITNs) can reduce malaria transmission in a variety of settings, evidence for the effectiveness of other interventions, such as topical repellents, is limited. Since malaria transmission in Myanmar occurs outdoors, mainly among forest-goers, this study tested the effectiveness of topical repellents in combination with supplemental ITN distribution and strengthened networks of malaria workers.

Methods: Thirty-eight villages in the Tanintharyi Region and Rakhine State were initially selected for the study based on malaria incidence in previous years. An additional 31 villages were included as comparison areas. The implementation of interventions began in March 2020 and continued through June 2021. Malaria cases were detected in all villages through surveillance at health facilities and a network of malaria workers. Data were analysed by interrupted time series. A nested case-control study was also conducted where forest-goers who tested positive for malaria by RDT were matched to up to three forest-goers who tested negative.

Results: A decrease in mean monthly incidence was observed in the intervention villages from 6.0 (95% CI 4.9-7.1) to 3.7 (95% CI 2.4-4.9) cases per 1000 people at risk before and after the interventions. For the comparison villages, the mean monthly incidence increased from 1.1 (95% CI 0.8-1.5) to 5.7 (95% CI 2.1-9.3) cases per 1000 people at risk. Malaria incidence was significantly lower following the implementation of the interventions (RR = 0.117; 95% CI 0.061-0.223; p < 0.001) in the intervention villages, whereas that of comparison villages was higher after the implementation of the interventions (RR = 3.558; 95% CI 0.311-40.750; p = 0.308). However, a significant trend for increasing malaria incidence after implementation was observed in the intervention villages (RR = 1.113; 95% CI 1.021-1.214, p = 0.015), suggesting a waning effect. The nested case-control analysis showed that the odds of topical repellent use were significantly lower among cases than controls (aOR: 0.063, 95% CI 0.013-0.313, p < 0.001).

Conclusion: The tailored intervention package for forest-goers helped reduce malaria incidence in Myanmar. Topical repellents may help to further reduce malaria transmission in elimination settings where high-risk populations such as forest-goers do not have easy access to routine health services or are less likely to use ITNs for malaria prevention.

Background: Members of the Anopheles gambiae complex are major malaria vectors in sub-Saharan Africa. Their larval stages inhabit a variety of aquatic habitats in which, under natural circumstances, they are preyed upon by different taxa of aquatic macroinvertebrate predators. Understanding the potential impact of predators on malaria vector larval population dynamics is important for enabling integrated local mosquito control programmes with a stronger emphasis on biocontrol approaches. This study experimentally evaluated the predation efficacy and foraging strategy of three common aquatic macroinvertebrate predators of An. gambiae, diving beetles (Coleoptera), backswimmers (Hemiptera), and dragonfly nymphs (Odonata) in a semi-field system in South-Eastern Tanzania.

Methods: An array of alternating small and large basins used as aquatic habitats was created in two compartments of a semi-field system and filled with well water. Field-collected adult diving beetles, backswimmers or dragonfly nymphs were randomly assigned to these habitats and Anopheles arabiensis larvae were added as prey in half of the habitats. The number of mosquito larvae consumed, predator mobility across habitats and mortality were recorded at 24, 48 and 72 h.

Results: The presence of An. gambiae larvae in habitats significantly increased the survival of backswimmer and dragonfly nymphs, which are not mobile. In contrast, diving beetles survived well under any initial condition by preferentially flying away from habitats without prey to nearby larger habitats with prey. The larval predation rates of predacious diving beetle, backswimmer and dragonfly nymphs were stable over time at a mean of 3.2, 7.0 and 9.6 larvae consumed each day.

Conclusion: This study demonstrates that aquatic macroinvertebrate predators display adaptive foraging behaviour in response to prey presence and aquatic habitat size. It also confirms the ability of these predators to significantly reduce An. gambiae larval densities in aquatic habitats, thus their potential for consideration as additional biocontrol tools for mosquito population reduction.

Background: The Highlands of Papua New Guinea are non-endemic for malaria compared to the rest of the country. This study aimed to explore the local transmission of malaria in the Highlands through a cross-sectional school survey coupled with reactive case detection.

Methods: Between July and November 2019, 5575 schoolchildren and 1048 household members were screened for malaria using Rapid Diagnostic Tests, subsequently validated by light microscopy. In addition, an analysis of malaria cases (2017 to 2019) was conducted across 33 health facilities within the catchment areas of the surveyed schools and households.

Results: Thirteen individuals were diagnosed with malaria: eleven with Plasmodium falciparum (five schoolchildren, six household members) and two with Plasmodium vivax (one student, one household member); all were aged ten years or older. Malaria prevalence was 0.09% [95% CI 0.03, 0.3] among schoolchildren and 1.7% [95% CI 0.3, 9.1] among household members. Eleven positive individuals (84%) reported recent travel, mainly to lower-altitude endemic areas. Long-Lasting Insecticidal Nets were used by 34.8% [95% CI 28.7, 40.8] of household members. The average annual malaria incidence in the catchment areas was 3.7 cases per 1000 [95% CI 2.6, 5.3] among the general population, while children under 15 years accounted for 19% [95% CI 14, 27] of the positive cases.

Conclusions: Local malaria transmission appears to be minimal in the surveyed Highlands areas. Strengthening surveillance-response system to control imported cases and stop local foci could support malaria elimination in PNG. However, effective operational triggers for reactive case finding remain to be determined.

Background: Malaria incidence in the Greater Mekong Subregion has been on the decline, and most remaining malaria risk in the region is concentrated among hard-to-reach populations, especially those with exposure to forested areas. New vector control tools focused on outdoor protection in forest settings are needed for these populations.

Methods: The delivery of a 'forest pack' containing a volatile pyrethroid spatial repellent (VPSR), a topical repellent, and pyrethroid treatment of clothing was evaluated in an operational study in Cambodia. Costs were collected using micro-costing approaches and the cost of distribution for the 'forest pack' was estimated using standard economic evaluation approaches and examined in sensitivity analyses.

Results: The cost per eligible person (the target population) per malaria season for the whole pack was estimated to be 138 USD, which was nearly entirely driven by the cost of the products.

Conclusions: Modifications to the 'forest pack' including adding a longer-lasting spatial repellent product or a reduced-cost topical repellent could significantly reduce the cost of pack distribution over the course of a malaria season.