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This study has investigated the impact of temperature and rainfall on the transmission dynamics of malaria using an age-structured population model, with a class of pregnant women. The equilibrium solutions have been analyzed, and numerical simulations carried out. The results show that there are significantly high rates of malaria infections for the temperature and rainfall ranging between (23.53 °C - 39.80 °C) and (14.82 mm - 38.44 mm) respectively. The results have shown that, the most affected populations are children up to five years old and pregnant women, and that decreasing the rate of transplacental transmission increases the number of children born free of malaria infections. Therefore, this work recommends human individuals to be aware of the variations of temperature, rainfall, and their corresponding ranges at which malaria transmission occurs most, so that they can take precautions. [ABSTRACT FROM AUTHOR]

The primary control methods for the African malaria mosquito, Anopheles gambiae , are based on insecticidal interventions. Emerging resistance to these compounds is therefore of major concern to malaria control programs. The organophosphate (OP), pirimiphos-methyl, is a relatively new chemical in the vector control armory but is now widely used in indoor-residual spray campaigns. While generally effective, phenotypic resistance has developed in some areas in malaria vectors. Here, we used a population genomic approach to identify novel mechanisms of resistance to pirimiphos-methyl in A. gambiae s.l mosquitoes. In multiple populations, we found large and repeated signals of selection at a locus containing a cluster of detoxification enzymes, some of whose orthologs are known to confer resistance to OPs in Culex pipiens. Close examination revealed a pair of alpha-esterases, Coeae1f and Coeae2f , and a complex and diverse pattern of haplotypes under selection in A. gambiae, A. coluzzii and A. arabiensis. As in C. pipiens , copy number variants have arisen at this locus. We used diplotype clustering to examine whether these signals arise from parallel evolution or adaptive introgression. Using whole-genome sequenced phenotyped samples, we found that in West Africa, a copy number variant in A. gambiae is associated with resistance to pirimiphos-methyl. Overall, we demonstrate a striking example of contemporary parallel evolution which has important implications for malaria control programs. [ABSTRACT FROM AUTHOR]

The cGMP-dependent protein kinase (PKG) is the sole cGMP sensor in malaria parasites, acting as an essential signalling hub to govern key developmental processes throughout the parasite life cycle. Despite the importance of PKG in the clinically relevant asexual blood stages, many aspects of malarial PKG regulation, including the importance of phosphorylation, remain poorly understood. Here we use genetic and biochemical approaches to show that reduced cGMP binding to cyclic nucleotide binding domain B does not affect in vitro kinase activity but prevents parasite egress. Similarly, we show that phosphorylation of a key threonine residue (T695) in the activation loop is dispensable for kinase activity in vitro but is essential for in vivo PKG function, with loss of T695 phosphorylation leading to aberrant phosphorylation events across the parasite proteome and changes to the substrate specificity of PKG. Our findings indicate that Plasmodium PKG is uniquely regulated to transduce signals crucial for malaria parasite development. Author summary: Despite all efforts to control and eradicate malaria, the disease still poses a huge burden on human health. Almost half of the world's population lives in high malaria transmission areas with over half a million deaths occurring annually due to the disease, which is caused by a single-celled parasite called Plasmodium. Replication of the parasite inside red blood cells is responsible for all the clinical manifestations of the disease. At the end of each replicative cycle, parasites rupture the red blood cell in a process known as egress in order to invade new red blood cells. Previous studies have shown that an essential kinase termed PKG is a master regulator of egress. However, many aspects of PKG regulation are still unknown. In this work we examined the importance of phosphorylation on PKG function by replacing wild type PKG with mutant forms refractory to phosphorylation. We found that phosphorylation in a specific region of the protein is essential for parasite survival. Excitingly though, phosphorylation is not essential for kinase activity, as has been shown for mammalian PKG proteins but regulates its substrate specificity. Our results suggest that Plasmodium PKG is uniquely regulated compared to its mammalian counterparts, to facilitate parasite proliferation. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) has recommended two vaccines for malaria prevention, but neither vaccine meets the desired efficacy and durability for an optimal malaria vaccine. However, there are multiple next-generation vaccines in clinical testing that aim to provide higher efficacy, decrease vaccine delivery demands, and improve cost effectiveness. Computational biology plays a crucial role in informing the design of these vaccines, with techniques such as mRNA-lipid nanoparticle technology offering advantages such as quick manufacturing and safety for infants and pregnant women. The article also discusses the strategy of combining existing vaccines with additional antigens to improve efficacy and the potential of transmission-blocking vaccines. Overall, next-generation vaccines are seen as crucial in achieving malaria elimination goals and improving child health in endemic areas. [Extracted from the article]

Background: The Zanzibar archipelago of Tanzania has become a low-transmission area for Plasmodium falciparum. Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania and continued local transmission. Methods: To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282 P. falciparum isolates collected across Zanzibar and in Bagamoyo district on the coastal mainland from 2016 to 2018. Results: Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to the rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within shehias, suggests ongoing low-level local transmission. We also identified highly related parasites across shehias that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes. Conclusions: Our data support importation as a main source of genetic diversity and contribution to the parasite population in Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive to malaria reemergence due to susceptible hosts and competent vectors. Funding: This research was funded by the National Institutes of Health, grants R01AI121558, R01AI137395, R01AI155730, F30AI143172, and K24AI134990. Funding was also contributed from the Swedish Research Council, Erling-Persson Family Foundation, and the Yang Fund. RV acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 program supported by the European Union. RV also acknowledges funding by Community Jameel. [ABSTRACT FROM AUTHOR]

Background: Malaria risk maps are crucial for controlling and eliminating malaria by identifying areas of varying transmission risk. In the Greater Mekong Subregion, these maps guide interventions and resource allocation. This article focuses on analysing changes in malaria transmission and developing fine-scale risk maps using five years of routine surveillance data in Laos (2017–2021). The study employed data from 1160 geolocated health facilities in Laos, along with high-resolution environmental data. Methods: A Bayesian geostatistical framework incorporating population data and treatment-seeking propensity was developed. The models incorporated static and dynamic factors and accounted for spatial heterogeneity. Results: Results showed a significant decline in malaria cases in Laos over the five-year period and a shift in transmission patterns. While the north became malaria-free, the south experienced ongoing transmission with sporadic outbreaks. Conclusion: The risk maps provided insights into changing transmission patterns and supported risk stratification. These risk maps are valuable tools for malaria control in Laos, aiding resource allocation, identifying intervention gaps, and raising public awareness. The study enhances understanding of malaria transmission dynamics and facilitates evidence-based decision-making for targeted interventions in high-risk areas. [ABSTRACT FROM AUTHOR]

Background: Malaria remains a significant public health challenge in Sub-Saharan Africa (SSA), particularly affecting under-five (UN5) children. Despite global efforts to control the disease, its prevalence in high-risk African countries continues to be alarming, with records of substantial morbidity and mortality rates. Understanding the association of multiple childhood, maternal, and household factors with malaria prevalence, especially among vulnerable young populations, is crucial for effective intervention strategies. Objective: This study examines the prevalence of malaria among UN5 children in selected high-risk SSA countries and analyzes its association with various childhood, maternal, and household factors. Methods: Data from the Malaria Indicator Surveys (MIS) spanning from 2010 to 2023 were analyzed. A weighted sample of 35,624 UN5 children from seven countries in sub-Saharan Africa (SSA) known for high malaria prevalence was considered in the analyses. Descriptive statistics and modified Poisson regression analysis were used to assess the association of multiple factors with malaria prevalence. Stata version 15 software was used in analyzing the data and statistical significance was set at a 5% significance level. Results: The overall pooled prevalence of malaria among the studied population was 26.2%, with substantial country-specific variations observed. In terms of child factors, a child's age was significantly associated with malaria prevalence (APR = 1.010, 95% CI: 1.007–1.012). Children of mothers with higher education levels (APR for higher education = 0.586, 95% CI: 0.425–0.806) and Fansidar uptake during pregnancy (APR = 0.731, 95% CI: 0.666–0.802) were associated with lower malaria risk. Children from middle-wealth (APR = 0.783, 95% CI: 0.706–0.869) and rich (APR = 0.499, 95% CI: 0.426–0.584) households had considerably lower malaria prevalence compared to those from poor households. Additionally, rural residency was associated with a higher risk of malaria compared to urban residency (APR = 1.545, 95% CI: 1.255–1.903). Conclusion: The study highlights a notable malaria prevalence among under-five (UN5) children in high-risk SSA countries, influenced significantly by factors such as maternal education, Fansidar uptake during pregnancy, socioeconomic status, and residency. These findings underscore the importance of targeted malaria prevention strategies that address these key determinants to effectively reduce the malaria burden in this vulnerable population. [ABSTRACT FROM AUTHOR]

Background: Well-built housing limits mosquito entry and can reduce malaria transmission. The association between community-level housing and malaria burden in Uganda was assessed using data from randomly selected households near 64 health facilities in 32 districts. Methods: Houses were classified as 'improved' (synthetic walls and roofs, eaves closed or absent) or 'less-improved' (all other construction). Associations between housing and parasitaemia were made using mixed effects logistic regression (individual-level) and multivariable fractional response logistic regression (community-level), and between housing and malaria incidence using multivariable Poisson regression. Results: Between November 2021 and March 2022, 4.893 children aged 2–10 years were enrolled from 3.518 houses; of these, 1.389 (39.5%) were classified as improved. Children living in improved houses had 58% lower odds (adjusted odds ratio = 0.42, 95% CI 0.33–0.53, p < 0.0001) of parasitaemia than children living in less-improved houses. Communities with > 67% of houses improved had a 63% lower parasite prevalence (adjusted prevalence ratio 0.37, 95% CI 0.19–0.70, p < 0.0021) and 60% lower malaria incidence (adjusted incidence rate ratio 0.40, 95% CI 0.36–0.44, p < 0.0001) compared to communities with < 39% of houses improved. Conclusions: Improved housing was strongly associated with lower malaria burden across a range of settings in Uganda and should be utilized for malaria control. [ABSTRACT FROM AUTHOR]

A large body of evidence suggests that low parasite carriage in Plasmodium falciparum asymptomatic infection is required for the maintenance of malaria immunity. However, the fact that treating such infections has little to no impact on subsequent clinical malaria is rarely noted. In this paper, we review data and argue that low-density parasite carriage in asymptomatic infection may not support host immune processes and that parasites are virtually under the host's immunological radar. We also discuss factors that may be constraining parasitemia in asymptomatic infections from reaching the threshold required to cause clinical symptoms. A thorough understanding of this infectious reservoir is essential for malaria control and eradication because asymptomatic infections contribute significantly to Plasmodium transmission. [ABSTRACT FROM AUTHOR]

Background: In Africa, the relationship between childhood nutritional status and malaria remains complex and difficult to interpret. Understanding it is important in the improvement of malaria control strategies. This study aimed to assess the influence of nutritional status on the occurrence of multiple malaria episodes in children aged 6 to 59 months between 2013 and 2017 living in the village of Dangassa, Mali. Methods: A community-based longitudinal study was conducted using cross-sectional surveys (CSSs) at the beginning (June) and end (November) of the malaria transmission season associated with passive case detection (PCD) at the Dangassa Community Health Centre. Children with asymptomatic malaria infection during cross-sectional surveys were selected and their malaria episodes followed by PCD. Malaria indicators in person-months were estimated using an ordinal-logistic model repeated on subjects during follow-up periods. Results: The incidence rate (IR) during the period of high transmission (June to October), for 1 episode and for 2 + episodes peaked in 2013 with 65 children (IR = 95.73 per 1000 person-months) and 24 cases (IR = 35.35 per 1000 person-months), respectively. As expected, the risk of multiple episodes occurring during the period of high transmission was 3.23 compared to the period of low transmission after adjusting for other model parameters (95% CI [2.45–4.26], p = 0.000). Children with anaemia were at high risk of having multiple episodes (OR = 1.6, 95% CI [1.12–2.30], p = 0.011). However, the risk of having 2 + episodes for anemic children was higher during the period of low transmission (RR = 1.67, 95% CI [1.15–2.42], p = 0.007) compared to the period of high transmission (RR = 1.58, 95% CI [1.09–2.29], p = 0.016). The trend indicated that anemic and underweight children were significantly associated with multiple malaria episodes during the period of low transmission (p < 0.001). Conclusion: Results show that multiple episodes of malaria are significantly related to the nutritional status (anaemia and underweight) of the child during the two transmission seasons and more pronounced during the dry season (period of low transmission). Further research including other malnutrition parameters will be needed to confirm these findings. [ABSTRACT FROM AUTHOR]

• The Pk GIA will be an essential selection tool for P. vivax vaccine development. • The error of the assay was evaluated with human anti- Pv DBPII antibodies. • Significant assay-to-assay variation was observed. • 95 % confidence interval of inhibition for a given number of PkGIA was determined. Recent data indicate increasing disease burden and importance of Plasmodium vivax (Pv) malaria. A robust assay will be essential for blood-stage Pv vaccine development. Results of the in vitro growth inhibition assay (GIA) with transgenic P. knowlesi (Pk) parasites expressing the Pv Duffy-binding protein region II (Pv DBPII) correlate with in vivo protection in the first Pv DBPII controlled human malaria infection (CHMI) trials, making the Pk GIA an ideal selection tool once the precision of the assay is defined. To determine the precision in percentage of inhibition in GIA (%GIA) and in GIA 50 (antibody concentration that gave 50 %GIA), ten GIAs with transgenic Pk parasites were conducted with four different anti- Pv DBPII human monoclonal antibodies (mAbs) at concentrations of 0.016 to 2 mg/mL, and three GIAs with eighty anti- Pv DBPII human polyclonal antibodies (pAbs) at 10 mg/mL. A significant assay-to-assay variation was observed, and the analysis revealed a standard deviation (SD) of 13.1 in the mAb and 5.94 in the pAb dataset for %GIA, with a LogGIA 50 SD of 0.299 (for mAbs). Moreover, the ninety-five percent confidence interval (95 %CI) for %GIA or GIA 50 in repeat assays was calculated in this investigation. The error range determined in this study will help researchers to compare Pk GIA results from different assays and studies appropriately, thus supporting the development of future blood-stage malaria vaccine candidates, specifically second-generation Pv DBPII-based formulations. [ABSTRACT FROM AUTHOR]

Background: Malaria remains a major global health problem although there was a remarkable achievement between 2000 and 2015. Malaria drug resistance, along with several other factors, presents a significant challenge to malaria control and elimination efforts. Numerous countries in sub-Saharan Africa have documented the presence of confirmed or potential markers of partial resistance against artemisinin, the drug of choice for the treatment of uncomplicated Plasmodium falciparum malaria. The World Health Organization (WHO) recommends regular surveillance of artemisinin therapeutic efficacy to inform policy decisions. Methods: This study aimed to evaluate the therapeutic efficacy of artemether-lumefantrine (AL), which is the first-line treatment for uncomplicated P. falciparum malaria in Ethiopia since 2004. Using a single-arm prospective evaluation design, the study assessed the clinical and parasitological responses of patients with uncomplicated P. falciparum malaria in Metehara Health Centre, central-east Ethiopia. Out of 2332 malaria suspects (1187 males, 1145 females) screened, 80 (50 males, 30 females) were enrolled, followed up for 28 days, and 73 (44 males, 29 females) completed the follow up. The study was conducted and data was analysed by employing the per-protocol and Kaplan–Meier analyses following the WHO Malaria Therapeutic Efficacy Evaluation Guidelines 2009. Results: The results indicated rapid parasite clearance and resolution of clinical symptoms, with all patients achieving complete recovery from asexual parasitaemia and fever by day (D) 3. The prevalence of gametocytes decreased from 6.3% on D0 to 2.5% on D2, D3, D7, and ultimately achieving complete clearance afterward. Conclusion: The overall cure rate for AL treatment was 100%, demonstrating its high efficacy in effectively eliminating malaria parasites in patients. No serious adverse events related to AL treatment were reported during the study, suggesting its safety and tolerability among the participants. These findings confirm that AL remains a highly efficacious treatment for uncomplicated P. falciparum malaria in the study site after 20 years of its introduction in Ethiopia. [ABSTRACT FROM AUTHOR]

Introduction: The national malaria programme of Cambodia targets the rapid elimination of all human malaria by 2025. As clinical cases decline to near-elimination levels, a key strategy is the rapid identification of malaria outbreaks triggering effective action to interrupt local transmission. We report a comprehensive, multipronged management approach in response to a 2022 Plasmodium falciparum outbreak in Kravanh district, western Cambodia. Methods: The provincial health department of Pursat in conjunction with the Center for Parasitology, Entomology and Malaria Control (CNM) identified villages where transmission was occurring using clinical records, and initiated various interventions, including the distribution of insecticide-treated bed nets, running awareness campaigns, and implementing fever screening with targeted drug administration. Health stations were set up at forest entry points, and later, targeted drug administrations with artesunate–pyronaridine (Pyramax) and intermittent preventive treatment for forest goers (IPTf) were implemented in specific village foci. Data related to adherence and adverse events from IPTf and TDA were collected. The coverage rates of interventions were calculated, and local malaria infections were monitored. Results: A total of 942 individuals were screened through active fever surveillance in villages where IPTf and TDA were conducted. The study demonstrated high coverage and adherence rates in the targeted villages, with 92% (553/600) coverage in round one and 65% (387/600) in round two. Adherence rate was 99% (551/553) in round one and 98% (377/387) in round two. The study found that forest goers preferred taking Pyramax over repeated testing consistent with the coverage rates: 92% in round one compared to 65% in round two. All individuals reachable through health stations or mobile teams reported complete IPTf uptake. No severe adverse events were reported. Only six individuals reported mild adverse events, such as loss of energy, fever, abdominal pain, diarrhoea, and muscle aches. Two individuals attributed their symptoms to heavy alcohol intake following prophylaxis. Conclusions: The targeted malaria outbreak response demonstrated high acceptability, safety, and feasibility of the selected interventions. Malaria transmission was rapidly controlled using the available community resources. This experience suggests the effectiveness of the programmatic response for future outbreaks. [ABSTRACT FROM AUTHOR]

Background: Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3–4 years, but the 2020–2021 campaign was altered because of COVID-19 restrictions so that the timing of delivery of new nets was different from the original plans made by the National Malaria Control Programme. Methods: A transmission dynamics modelling exercise was conducted to explore how the altered delivery of LLINs in 2020–2021 impacted malaria burden in Uganda. Data were available on the planned LLIN distribution schedule for 2020–2021, and the actual delivery. The transmission model was used to simulate 100 health sub-districts, and parameterized to match understanding of local mosquito bionomics, net use estimates, and seasonal patterns based on data collected in 2017–2019 during a cluster-randomized trial (LLINEUP). Two scenarios were compared; simulated LLIN distributions matching the actual delivery schedule, and a comparable scenario simulating LLIN distributions as originally planned. Model parameters were otherwise matched between simulations. Results: Approximately 70% of the study population received LLINs later than scheduled in 2020–2021, although some areas received LLINs earlier than planned. The model indicates that malaria incidence in 2020 was substantially higher in areas that received LLINs late. In some areas, early distribution of LLINs appeared less effective than the original distribution schedule, possibly due to attrition of LLINs prior to transmission peaks, and waning LLIN efficacy after distribution. On average, the model simulations predicted broadly similar overall mean malaria incidence in 2021 and 2022. After accounting for differences in cluster population size and LLIN distribution dates, no substantial increase in malaria burden was detected. Conclusions: The model results suggest that the disruptions in the 2020–2021 LLIN distribution campaign in Uganda did not substantially increase malaria burden in the study areas. [ABSTRACT FROM AUTHOR]

Background: Insecticide-treated nets (ITNs) are the backbone of anti-malarial vector control in Papua New Guinea (PNG). Over recent years the quality and performance of ITNs delivered to PNG decreased, which has likely contributed to the stagnation in the malaria control effort in the country. The present study reports results from the first 24 months of a durability study with the ITN product Yahe LN® in PNG. Methods: The durability study was conducted in four villages on the northern coast of PNG, in an area with high malaria parasite transmission, following WHO-recommended methodology adapted to the local scenario. A cohort of n = 500 individually identifiable Yahe® ITNs was distributed by the PNG National Malaria Control Programme from October to December 2021. Insecticidal efficacy of the ITNs was tested using cone bioassays with fully pyrethroid susceptible Anopheles farauti colony mosquitoes at baseline and at 6 months intervals, alongside evaluation of physical integrity and the proportion of ITNs lost to follow-up. A questionnaire was used to collect information on ITN end user behaviour, such as the frequency of use and washing. The observations from the durability study were augmented with simulated laboratory wash assays. Results: Gradual uptake and replacement of previous campaign nets by the communities was observed, such that at 6 months 45% of all newly distributed nets were in use in their designated households. Insecticidal efficacy of the Yahe® nets, expressed as the percent 24 h mortality in cone bioassays decreased from 91 to 45% within the first 6 months of distribution, even though > 90% of study nets had never been washed. Insecticidal efficacy decreased further to < 20% after 24 months. ITNs accumulated physical damage (holes) at a rate similar to previous studies, and 35% were classified as 'too torn' by proportional hole index after 24 months. ITNs were lost to follow-up such that 61% of cohort nets were still present after 24 months. Laboratory wash assays indicated a rapid reduction in insecticidal performance with each consecutive wash such that average 24 h mortality was below 20% after 10 washes. Conclusion: Yahe® ITNs are not performing as per label claim in an area with fully pyrethroid susceptible vectors, and should be investigated more comprehensively and in other settings for compliance with currently recommended durability and efficacy thresholds. The mass distribution of low quality ITN products with variable performance is one of the major ongoing challenges for global malaria control in the last decade. [ABSTRACT FROM AUTHOR]

Malaria continues to kill approximately 650 000 people each year. There is evidence that some second-generation insecticide-treated nets, which combine insecticide formulations with different modes of action, are protective against malaria while the nets are new; however, evidence for their impact over 3 years is scarce. In this study, we report the third-year results of a cluster-randomised controlled trial assessing the long-term effectiveness of dual-active ingredient long-lasting insecticidal nets (LLINs). This is a secondary analysis of a cluster-randomised controlled trial, carried out between May 23, 2019, and April 30, 2023, in southern Benin. Restricted randomisation was used to assign 60 clusters (villages or groups of villages with a minimum of 100 households) to the three study groups (1:1:1) to evaluate the efficacy of pyriproxyfen-pyrethroid LLINs and chlorfenapyr-pyrethroid LLINs compared with pyrethroid-only LLINs (reference) against malaria transmission. The study staff and communities were masked to the group allocation. The primary outcome was malaria incidence measured over the third year after LLIN distribution, in a cohort of children aged 6 months to 9 years at the time of enrolment, in the intention-to-treat population. Here, we present the data of the third year post-LLIN distribution. The trial was registered with ClinicalTrials.gov , NCT03931473. Study net use declined over the 3 years and was consistently lowest in the pyriproxyfen-pyrethroid LLIN group (at 36 months: 889 [39·4%] of 2257 participants vs 1278 [52·2%] of 2450 participants for the chlorfenapyr-pyrethroid LLIN group and 1400 [57·6%] of 2430 participants for the pyrethroid-only LLIN group). The cohort of children for the third year of follow-up (600 per group) were enrolled between April 9 and 30, 2022. Mean malaria incidence during the third year after distribution was 1·19 cases per child-year (95% CI 1·09–1·29) in the pyrethroid-only LLIN reference group, 1·21 cases per child-year (1·12–1·31) in the pyriproxyfen-pyrethroid LLIN group (hazard ratio [HR] 1·02, 95% CI 0·71–1·44; p=0·92), and 0·96 cases per child-year (0·88–1·05) in the chlorfenapyr-pyrethroid LLIN group (HR 0·80, 0·56–1·17; p=0·25). No adverse events related to study nets were reported by participants. During the third year, as was also observed during the first 2 years, the pyriproxyfen-pyrethroid LLIN group did not have superior protection against malaria cases compared with the standard LLIN group. In the third year, people living in the chlorfenapyr-pyrethroid LLIN group no longer benefited from greater protection against malaria cases and infections than those living in the pyrethroid-only LLIN group. This was probably influenced by lower study net use than previous years and the declining concentration of partner insecticides in the nets. UNITAID, The Global Fund. For the French translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Background: Accurate malaria diagnosis constitutes a challenging task, necessitating the need for the implementation of targeted and effective diagnostic tools. The purpose of the current study was to evaluate the effectiveness of two different molecular methodologies in terms of sensitivity for the detection of External Quality Assessment (EQA) Plasmodium samples. Methods: A total of 104 lyophilized blood samples from 14 different UK-NEQAS (National External Quality Assessment Site) (2016–2021) and eight WHO-NEQAS distributions (2017–2020) were analyzed. An in-house multiplex PCR protocol, followed by single target real-time PCR protocols for all five Plasmodium species, was implemented. Results: The multiplex PCR had a success rate of 10/16 and 20/28 for P. vivax and P. falciparum species, respectively. On the other hand, the respective results for real-time PCR had a success rate of 13/16 (P. vivax), 28/28 (P. falciparum), 5/8 (P. malariae), 8/10 (P. ovale), and 10/14 (P. knowlesi). Plasmodium falciparum samples displayed the highest sensitivity of detection, 0.02 parasites/μL. Plasmodium vivax samples displayed a 0.1 parasites/μL cutoff value, greater than the respective value for whole blood samples, while P. ovale species displayed a respective cutoff value of 0.05 parasites/μL. Due to the limited number of tested samples, data obtained for P. malariae and P. knowlesi species samples were inconclusive. Conclusions: Real-time PCR comprises a credible molecular methodology in terms of sensitivity assessment and detection of low parasitemia levels of Plasmodium sp. in EQA lyophilized blood samples. [ABSTRACT FROM AUTHOR]

A population modification approach involves spreading genes/elements through the populations to make mosquitoes refractory to the parasite. Parasite refractoriness of mosquito vectors can be achieved by genetic manipulations of mosquito endogenous effectors and host factors or by introducing exogenous effectors into the mosquito genome. Gene-drive technology allows the spread and persistence of the desired genes/elements within targeted populations. The success of transgenic mosquitoes in spreading and maintaining desired genes/elements in the field relies on their performance compared with wild types. Field implementation of the transgenic applications is a phase-by-phase process that is subject to public acceptance and regulations. Malaria remains a persistent global public health challenge because of the limitations of current prevention tools. The use of transgenic mosquitoes incapable of transmitting malaria, in conjunction with existing methods, holds promise for achieving elimination of malaria and preventing its reintroduction. In this context, population modification involves the spread of engineered genetic elements through mosquito populations that render them incapable of malaria transmission. Significant progress has been made in this field over the past decade in revealing promising targets, optimizing genetic tools, and facilitating the transition from the laboratory to successful field deployments, which are subject to regulatory scrutiny. This review summarizes recent advances and ongoing challenges in 'curing' Anopheles vectors of the malaria parasite. [ABSTRACT FROM AUTHOR]

There has been significant progress in malaria control in the last 2 decades, with a decline in mortality and morbidity. However, these gains are jeopardised by insecticide resistance, which negatively impacts the core interventions, such as insecticide‐treated nets (ITN) and indoor residual spraying (IRS). While most malaria control and research efforts are still focused on Anopheles gambiae complex mosquitoes, Anopheles funestus remains an important vector in many countries and, in some cases, contributes to most of the local transmission. As countries move towards malaria elimination, it is important to ensure that all dominant vector species, including An. funestus, an important vector in some countries, are targeted. The objective of this review is to compile and discuss information related to A. funestus populations' resistance to insecticides and the mechanisms involved across Africa, emphasising the sibling species and their resistance profiles in relation to malaria elimination goals. Data on insecticide resistance in An. funestus malaria vectors in Africa were extracted from published studies. Online bibliographic databases, including Google Scholar and PubMed, were used to search for relevant studies. Articles published between 2000 and May 2023 reporting resistance of An. funestus to insecticides and associated mechanisms were included. Those reporting only bionomics were excluded. Spatial variation in species distribution and resistance to insecticides was recorded from 174 articles that met the selection criteria. It was found that An. funestus was increasingly resistant to the four classes of insecticides recommended by the World Health Organisation for malaria vector control; however, this varied by country. Insecticide resistance appears to reduce the effectiveness of vector control methods, particularly IRS and ITN. Biochemical resistance due to detoxification enzymes (P450s and glutathione‐S‐transferases [GSTs]) in An. funestus was widely recorded. However, An. funestus in Africa remains susceptible to other insecticide classes, such as organophosphates and neonicotinoids. This review highlights the increasing insecticide resistance of An. funestus mosquitoes, which are important malaria vectors in Africa, posing a significant challenge to malaria control efforts. While An. funestus has shown resistance to the recommended insecticide classes, notably pyrethroids and, in some cases, organochlorides and carbamates, it remains susceptible to other classes of insecticides such as organophosphates and neonicotinoids, providing potential alternative options for vector control strategies. The study underscores the need for targeted interventions that consider the population structure and geographical distribution of An. funestus, including its sibling species and their insecticide resistance profiles, to effectively achieve malaria elimination goals. [ABSTRACT FROM AUTHOR]

Ivermectin (IVM) has been proposed as a new tool for malaria control as it is toxic on vectors feeding on treated humans or cattle. Nevertheless, IVM may have a direct mosquitocidal effect when applied on bed nets or sprayed walls. The potential for IVM application as a new insecticide for long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) was tested in this proof-of-concept study in a laboratory and semi-field environment. Laboratory-reared, insecticide-susceptible Kisumu Anopheles gambiae were exposed to IVM on impregnated netting materials and sprayed plastered- and mud walls using cone bioassays. The results showed a direct mosquitocidal effect of IVM on this mosquito strain as all mosquitoes died by 24 h after exposure to IVM. The effect was slower on the IVM-sprayed walls compared to the treated nettings. Further work to evaluate possibility of IVM as a new insecticide formulation in LLINs and IRS will be required. [ABSTRACT FROM AUTHOR]

Malaria poses a global threat to human health, with millions of cases and thousands of deaths each year, mainly affecting developing countries in tropical and subtropical regions. Malaria's causative agent is Plasmodium species, generally transmitted in the hematophagous act of female Anopheles sp. mosquitoes. The main approaches to fighting malaria are eliminating the parasite through drug treatments and preventing transmission with vector control. However, vector and parasite resistance to current strategies set a challenge. In response to the loss of drug efficacy and the environmental impact of pesticides, the focus shifted to the search for biocompatible products that could be antimalarial. Plant derivatives have a millennial application in traditional medicine, including the treatment of malaria, and show toxic effects towards the parasite and the mosquito, aside from being accessible and affordable. Its disadvantage lies in the type of administration because green chemical compounds rapidly degrade. The nanoformulation of these compounds can improve bioavailability, solubility, and efficacy. Thus, the nanotechnology-based development of plant products represents a relevant tool in the fight against malaria. We aim to review the effects of nanoparticles synthesized with plant extracts on Anopheles and Plasmodium while outlining the nanotechnology green synthesis and current malaria prevention strategies. [ABSTRACT FROM AUTHOR]

Background: There is a need to identify different insecticide resistance profiles that represent circumscription–encapsulation of knowledge about malaria vectors' insecticide resistance to increase our understanding of malaria vectors' insecticide resistance dynamics. Methods: Data used in this study are part of the aggregation of over 20,000 mosquito collections done between 1957 and 2018. We applied two data preprocessing steps. We developed three clustering machine learning models based on the K-means algorithm with three selected datasets. The elbow method was used to fine-tune the hyperparameters. We used the silhouette score to assess the clustering results produced by each of the three models. The proposed framework incorporates continuous learning, allowing the machine learning models to learn continuously. Results: For the first model, the optimal number of clusters (profiles) k was 17. For the second model, we found four profiles. For the third model, the optimal number of profiles was 7. Discussion: We found that the insecticide resistance profiles have dynamic resistance levels with respect to the insecticide component, species component, location component, and time component. This profiling task provided knowledge about the evolution of malaria vectors' insecticide resistance in the African continent by encapsulating the information on the complex interaction between the different dimensions of malaria vectors' insecticide resistance into different profiles. Policy makers can use the knowledge about the different profiles found from the analysis of available insecticide resistance monitoring data (through profiling) by using our proposed approach to set up malaria vector control strategies that consider the locations, species present in those locations, and potentially efficient insecticides. [ABSTRACT FROM AUTHOR]

The study investigated the strategies for malaria control programmes and assessed the effects of inter-governmental collaboration on malaria control in Southwestern Nigeria. Primary data were collected through the administration of questionnaires and conduct of in-depth interviews. The study population of 404 comprised all categories of staff in the Malaria Control Unit of the Federal Ministry of Health, three states and six local Governments. A sample size of 388 respondents was selected for questionnaire administration using Taro Yemane sample size formula. Interviews were also conducted to complement the information collected through questionnaire administration. Data were analysed using percentages, simple linear regression, relative impact index and content analysis methods. The results revealed that free distribution of insecticide-treated nets (87.3%); intermittent preventive treatment during pregnancy (92.8%); indoor residual spraying (71.3%); larva source management (76.1%); diagnosis and treatment (81.6%); and advocacy, communication and social mobilisation (88.7%) were the key malaria control strategies adopted to control malaria in Southwestern Nigeria. Furthermore, the results established that inter-governmental collaboration had a significant effect on the malaria control programme (F =20.538 p < 0.05) with indications from qualitative outcomes. The study concluded that inter-governmental collaboration made a considerable level of impact on the malarial control programme in Southwestern Nigeria. [ABSTRACT FROM AUTHOR]

aimon Jada,2 Moses Tionga,2 Constantino Doggale Remijo Marcello,3 Deng Gai Dual War,3 Robert Colebunders4,51Ministry of Health, Vector Control Division, Kampala, Uganda; 2Amref Health Africa, Juba, South Sudan; 3Ministry of Health, National Malaria Control Program, Juba, South Sudan; 4Global Health Institute, University of Antwerp, Antwerp, Belgium; 5Department of Tropical Disease Pathology, Liverpool School of Tropical Medicine, Liverpool, UK Correspondence: Robert Colebunders, Email [email protected] Background: Mvolo in Western Equatoria of South Sudan has been a hotspot for Onchocerca volvulus transmission since the 1940s. In Mvolo onchocerciasis is a disease of public health importance, associated with onchocerciasis-associated epilepsy including nodding syndrome. Methods: We conducted an entomological study to map the breeding sites of blackflies (Simulium damnosum, sensu lato) on the river Naam, to allow the removal of vegetation from vector breeding sites, the "slash and clear". Three blackfly catching sites were established along the river. Focus group discussions were also conducted to assess the willingness of the communities to support the "slash and clear" intervention and the semi-annual distribution of ivermectin. Results: A total of 2466 female S. damnosum s.l. were caught in 14× 11h (06.00– 15.00) catches. The highest biting density of 4210.25 flies/month/h and monthly biting rate (MBR) of 11,482.25 bites/man/month were observed in November 2023. Biting density and MBR reduced to zero in the intervention site by April 2024. While the mean parity rate was 31% (CI: 0.2976± 0.9176). Two diurnal biting peaks were observed, one from 9:00– 10:00 (at the bridge site) and a prominent one from 14:00– 15:00 in the two catching sites in Mvolo. Along the river Naam, only one site was found productive for S. damnosum s.l.; and the larvae and adults were morphologically associated with the anthropophilic S. damnosum. The "slash and clear" intervention was implemented at Dogoyabolu along the river Naam. Communities expressed willingness to support a "slash and clear" intervention and the semi-annual distribution of ivermectin. Conclusion: S. damnosum active breeding was identified along the river Naam in a stretch of 3– 5 km close to human settlements. Highest blackfly biting density was 4210.25 flies/month/h, and two fly biting peaks were observed. A community "slash and clear" vector control was implemented, and will be prospectively monitored. [ABSTRACT FROM AUTHOR]

Background and Objective: Despite the significant burden of Plasmodium falciparum (Pf) malaria and the licensure of two vaccines for use in infants and young children that are partially effective in preventing clinical malaria caused by Pf, a highly effective vaccine against Pf infection is still lacking. Live attenuated vaccines using Pf sporozoites as the immunogen (PfSPZ Vaccines) hold promise for addressing this gap. Here we review the safety and efficacy of two of the most promising PfSPZ approaches: PfSPZ Vaccine (radiation attenuated PfSPZ) and PfSPZ-CVac (chemo-attenuated PfSPZ). Methods: We conducted a systematic review and meta-analysis by searching PubMed, EMBASE, SCOPUS, CENTRAL, and WOS until 22nd December 2021. We included randomized controlled trials (RCTs) of these two vaccine approaches that measured protection against parasitaemia following controlled human malaria infection (CHMI) in malaria-naive and malaria-exposed adults or following exposure to naturally transmitted Pf malaria in African adults and children (primary outcome) and that also measured the incidence of solicited and unsolicited adverse events as indicators of safety and tolerability after vaccination (secondary outcome). We included randomized controlled trials (RCTs) that measured the detected parasitaemia after vaccination (primary outcome) and the incidence of various solicited and unsolicited adverse events (secondary outcome). The quality of the included RCTs using the Cochrane ROB 1 tool and the quality of evidence using the GRADE system were evaluated. We pooled dichotomous data using the risk ratio (RR) for development of parasitemia in vaccinees relative to controls as a measure of vaccine efficacy (VE), including the corresponding confidence interval (CI). This study was registered with PROSPERO (CRD42022308057). Results: We included 19 RCTs. Pooled RR favoured PfSPZ Vaccine (RR: 0.65 with 95% CI [0.53, 0.79], P = 0.0001) and PfSPZ-table (RR: 0.42 with 95% CI [0.27, 0.67], P = 0.0002) for preventing parasitaemia, relative to normal saline placebo. Pooled RR showed no difference between PfSPZ Vaccine and the control in the occurrence of any solicited adverse event (RR: 1.00 with 95% CI [0.82, 1.23], P = 0.98), any local solicited adverse events (RR: 0.73 with 95% CI [0.49, 1.08], P = 0.11), any systemic solicited adverse events (RR: 0.94 with 95% CI [0.75, 1.17], P = 0.58), and any unsolicited adverse event (RR: 0.93 with 95% CI [0.78, 1.10], P = 0.37). Conclusion: PfSPZ and PfSPZ-CVacs showed comparable efficacy. Therefore, they can introduce a promising strategy for malaria prophylaxis, but more large-scale field trials are required to sustain efficacy and yield clinically applicable findings. [ABSTRACT FROM AUTHOR]

Introduction: Between 2000 and 2015, significant gains were recorded in reducing the global burden of malaria due to enhanced global collaboration and increased funding. However, progress has stagnated post‐2015, and the COVID‐19 pandemic seems to have reversed some of these gains, necessitating a critical reevaluation of interventions. This paper aims to analyze the setbacks and offer recommendations for advancement in malaria control and prevention in sub‐Saharan Africa. Methods: We conducted searches on Google Scholar, PubMed, and relevant organization websites to identify relevant studies on malaria control and prevention and associated challenges in sub‐Saharan Africa from 2015 to the present. Additionally, studies on individual sub‐Saharan African countries were reviewed to ensure comprehensiveness. Data from selected studies were extracted and analyzed using a narrative synthesis approach to offer a concise overview of the evidence. Findings: We observe that the halt in progress of malaria control in sub‐Saharan Africa has deep roots in socioeconomic, political, and environmental factors. These challenges are exacerbated by the population explosion in the region, low coverage of interventions due to funding deficits and incessant crises, and the degradation of the efficacy of existing malaria commodities. Conclusion: Sub‐Saharan Africa is at a crossroads in its fight against malaria. Promising new frontiers such as malaria vaccines, preventive monoclonal antibodies, new‐generation insecticide‐treated nets, and potentially artificial intelligence‐driven technologies offer hope in advancing malaria control and prevention in the region. Through commitment and collaboration, leveraging these opportunities can help surmount challenges and ultimately eliminate malaria in sub‐Saharan Africa. [ABSTRACT FROM AUTHOR]

BackgroundDistribution of long-lasting insecticidal bed nets (LLINs) is one of the main control strategies for malaria. Improving malaria prevention programmes requires understanding usage patterns in households receiving LLINs, but there are limits to what standard cross-sectional surveys of self-reported LLIN use can provide. This study was designed to assess the performance of an accelerometer-based approach for measuring a range of LLIN use behaviours as a proof of concept for more granular LLIN-use monitoring over longer time periods.MethodsThis study was carried out under controlled conditions from May to July 2018 in Liverpool, UK. A single accelerometer was affixed to the side panel of an LLIN and participants carried out five LLIN use behaviours: (1) unfurling a net; (2) entering an unfurled net; (3) lying still as if sleeping; (4) exiting from under a net; and, (5) folding up a net. The randomForest package in R, a supervised non-linear classification algorithm, was used to train models on 20-s epochs of tagged accelerometer data. Models were compared in a validation dataset using overall accuracy, sensitivity and specificity, receiver operating curves and the area under the curve (AUC).ResultsThe five-category model had overall accuracy of 82.9% in the validation dataset, a sensitivity of 0.681 for entering a net, 0.632 for exiting, 0.733 for net down, and 0.800 for net up. A simplified four-category model, combining entering/exiting a net into one category had accuracy of 94.8%, and increased sensitivity for net down (0.756) and net up (0.829). A further simplified three-category model, identifying sleeping, net up, and a combined net down/enter/exit category had accuracy of 96.2% (483/502), with an AUC of 0.997 for net down and 0.987 for net up. Models for detecting entering/exiting by adults were significantly more accurate than for children (87.8% vs 70.0%; p

Background: Nigeria is facing a severe malaria crisis, accounting for a significant proportion of global cases and deaths of malaria. This study aimed to investigate the differences between female-headed households (FHHs) and male-headed households (MHHs) and their impact on malaria risk among children under five (U5) in Nigeria. Methods: Data from the 2021 Nigeria Malaria Indicator Survey (NMIS) were used for this cross-sectional study. A representative sample of 10,988 households was analysed, with key variables subjected to frequency calculations, descriptive statistics, and bivariate analyses using t-tests and chi-square analyses to compare the differences between FHHs and MHHs. Results: Among all participants, 92.1% (N = 10,126) reported residing in male-headed households, while 7.8% (N = 862) reported living in female-headed households. MHHs were significantly more likely to own insecticide-treated bed nets (ITNs) than FHHs (64.7% vs. 53.6%, P < 0.001). U5 children in MHHs had a greater likelihood of sleeping under a bed net the night before the survey than U5 children in FHHs (35.3% vs. 30.0%, P < 0.05). The prevalence of fever in the previous two weeks among U5 children was similar in MHHs and FHHs (35.4% vs. 31.4%), and the testing rates for malaria among U5 children who experienced febrile episodes were higher in MHHs than FHHs (22.4% vs. 15.4%, P < 0.05). Although not statistically significant, FHHs exhibited a higher percentage of U5 children testing positive for malaria compared to MHHs (87.8% vs. 78.9%). On the other hand, FHHs had higher education levels, overall wealth index scores, and a larger presence in urban areas compared to MHHs (P < 0.001). Moreover, FHHs reported higher adherence to malaria prevention awareness (P < 0.001). Conclusion: In Nigeria, FHHs enjoy relatively better socioeconomic conditions and stronger awareness of malaria prevention compared to their male-headed counterparts. Contrary to expectations, FHHs are at an increased risk of malaria in children under 5 years old. This phenomenon is associated with entrenched gender inequality and the challenges women face in accessing critical assets. As women in FHHs bear the responsibility of income generation while caring for their children, it is crucial to prioritize interventions that address malaria management in FHHs to reduce both malaria incidence and mortality rates. [ABSTRACT FROM AUTHOR]

Background: Mosquitoes of the Anopheles gambiae complex are one of the major vectors of malaria in sub-Saharan Africa. Their ability to transmit this disease of major public health importance is dependent on their abundance, biting behaviour, susceptibility and their ability to survive long enough to transmit malaria parasites. A deeper understanding of this behaviour can be exploited for improving vector surveillance and malaria control. Findings: Adult mosquitoes emerge from aquatic habitats at dusk. After a 24 h teneral period, in which the cuticle hardens and the adult matures, they may disperse at random and search upwind for a mate or to feed. Mating generally takes place at dusk in swarms that form over species-specific 'markers'. Well-nourished females may mate before blood-feeding, but the reverse is true for poorly-nourished insects. Females are monogamous and only mate once whilst males, that only feed on nectar, swarm nightly and can potentially mate up to four times. Females are able to locate hosts by following their carbon dioxide and odour gradients. When in close proximity to the host, visual cues, temperature and relative humidity are also used. Most blood-feeding occurs at night, indoors, with mosquitoes entering houses mainly through gaps between the roof and the walls. With the exception of the first feed, females are gonotrophically concordant and a blood meal gives rise to a complete egg batch. Egg development takes two or three days depending on temperature. Gravid females leave their resting sites at dusk. They are attracted by water gradients and volatile chemicals that provide a suitable aquatic habitat in which to lay their eggs. Conclusion: Whilst traditional interventions, using insecticides, target mosquitoes indoors, additional protection can be achieved using spatial repellents outdoors, attractant traps or house modifications to prevent mosquito entry. Future research on the variability of species-specific behaviour, movement of mosquitoes across the landscape, the importance of light and vision, reproductive barriers to gene flow, male mosquito behaviour and evolutionary changes in mosquito behaviour could lead to an improvement in malaria surveillance and better methods of control reducing the current over-reliance on the indoor application of insecticides. [ABSTRACT FROM AUTHOR]

Background: Plasmodium vivax represents the most geographically widespread human malaria parasite affecting civilian and military populations in endemic areas. Targeting the pre-erythrocytic (PE) stage of the parasite life cycle is especially appealing for developing P. vivax vaccines as it would prevent disease and transmission. Here, naturally acquired immunity to a panel of P. vivax PE antigens was explored, which may facilitate vaccine development and lead to a better understanding of naturally acquired PE immunity. Methods: Twelve P. vivax PE antigens orthologous to a panel of P. falciparum antigens previously identified as highly immunogenic in protected subjects after immunization with radiation attenuated sporozoites (RAS) were used for evaluation of humoral and cellular immunity by ELISA and IFN-γ ELISpot. Samples from P. vivax infected individuals (n = 76) from a low endemic malaria region in the Peruvian Amazon Basin were used. Results: In those clinical samples, all PE antigens evaluated showed positive IgG antibody reactivity with a variable prevalence of 58–99% in recently P. vivax diagnosed patients. The magnitude of the IgG antibody response against PE antigens was lower compared with blood stage antigens MSP1 and DBP-II, although antibody levels persisted better for PE antigens (average decrease of 6% for PE antigens and 43% for MSP1, p < 0.05). Higher IgG antibodies was associated with one or more previous malaria episodes only for blood stage antigens (p < 0.001). High IgG responders across PE and blood stage antigens showed significantly lower parasitaemia compared to low IgG responders (median 1,921 vs 4,663 par/µl, p < 0.05). In a subgroup of volunteers (n = 17),positive IFN-γ T cell response by ELISPOT was observed in 35% vs 9–35% against blood stage MSP1 and PE antigens, respectively, but no correlation with IgG responses. Conclusions: These results demonstrate clear humoral and T cell responses against P. vivax PE antigens in individuals naturally infected with P. vivax. These data identify novel attractive PE antigens suitable for use in the potential development and selection of new malaria vaccine candidates which can be used as a part of malaria prevention strategies in civilian and military populations living in P. vivax endemic areas. [ABSTRACT FROM AUTHOR]

Yellow Fever (YF) is an acute viral hemorrhagic disease. Uganda is located within the Africa YF belt. Between 2019 and 2022, the Ugandan Health Authorities reported at least one outbreak of YF annually with an estimated 892 suspected cases, on average per year. The persistent recurrence of this disease raises significant concerns about the efficacy of current response strategies and prevention approaches. YF has been recognized as a One Health issue due to its interrelatedness with the animal and environmental domains. Monkeys have been recognized as the virus primary reservoir. The YF virus is transmitted through bites of infected Aedes or Haemagogus species mosquitoes between monkeys and humans. Human activities, monkey health, and environmental health issues (e.g., climate change and land use) impact YF incidence in Uganda. Additionally, disease control programs for other tropical diseases, such as mosquitoes control programs for malaria, impact YF incidence. This review adopts the One Health approach to highlight the limitations in the existing segmented YF control and prevention strategies in Uganda, including the limited health sector surveillance, the geographically localized outbreak response efforts, the lack of a comprehensive vaccination program, the limited collaboration and communication among relevant national and international agencies, and the inadequate vector control practices. Through a One Health approach, we propose establishing a YF elimination taskforce. This taskforce would oversee coordination of YF elimination initiatives, including implementing a comprehensive surveillance system, conducting mass YF vaccination campaigns, integrating mosquito management strategies, and enhancing risk communication. It is anticipated that adopting the One Health approach will reduce the risk of YF incidence and outbreaks. [ABSTRACT FROM AUTHOR]

Background: The attractive targeted sugar bait (ATSB) is a novel malaria vector control tool designed to attract and kill mosquitoes using a sugar-based bait, laced with oral toxicant. Western Province, Zambia, was one of three countries selected for a series of phase III cluster randomized controlled trials of the Westham ATSB Sarabi version 1.2. The trial sites in Kenya, Mali, and Zambia were selected to represent a range of different ecologies and malaria transmission settings across sub-Saharan Africa. This case study describes the key characteristics of the ATSB Zambia trial site to allow for interpretation of the results relative to the Kenya and Mali sites. Methods: This study site characterization incorporates data from the trial baseline epidemiological and mosquito sugar feeding surveys conducted in 2021, as well as relevant literature on the study area. Results: Characterization of the trial site The trial site in Zambia was comprised of 70 trial-designed clusters in Kaoma, Nkeyema, and Luampa districts. Population settlements in the trial site were dispersed across a large geographic area with sparsely populated villages. The overall population density in the 70 study clusters was 65.7 people per square kilometre with a total site population of 122,023 people living in a geographic area that covered 1858 square kilometres. However, the study clusters were distributed over a total area of approximately 11,728 square kilometres. The region was tropical with intense and seasonal malaria transmission. An abundance of trees and other plants in the trial site were potential sources of sugar meals for malaria vectors. Fourteen Anopheles species were endemic in the site and Anopheles funestus was the dominant vector, likely accounting for around 95% of all Plasmodium falciparum malaria infections. Despite high coverage of indoor residual spraying and insecticide-treated nets, the baseline malaria prevalence during the peak malaria transmission season was 50% among people ages six months and older. Conclusion: Malaria transmission remains high in Western Province, Zambia, despite coverage with vector control tools. New strategies are needed to address the drivers of malaria transmission in this region and other malaria-endemic areas in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Introduction: Malaria is a vector-borne disease that initially manifests as fever, headache, and chills. The illness could progress to more severe conditions, including lethargy, impaired consciousness, convulsions, shortness of breath, blood in urine, jaundice, and haemorrhage if left untreated. The risk of contracting malaria is considerably heightened in specific occupational settings, particularly among forest rangers, following frequent exposure to natural habitats. Consequently, advancing the understanding of malaria and emphasising how specific occupational environments (including those of forest rangers) contribute to disease risk and management is imperative. Objective: The present study aims to determine the factors associated with malaria infection among forest rangers by systematically reviewing electronic articles from three databases (EBSCOhost, ScienceDirect, and ResearchGate). Methods: The current review was prepared based on the updated preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. First, three independent reviewers screened the titles and abstracts of the data collected. The information was then stored in Endnote20 based on the inclusion and exclusion criteria. The articles were critically appraised with the mixed methods appraisal tool (MMAT) to assess their quality. Result: A total of 103, 31, and 51 articles from EBSCOhost, ScienceDirect, and ResearchGate, respectively, were selected, resulting in 185 unique hits. Nevertheless, only 63 full-text publications were assessed following a rigorous selection screening, from which only five were included in the final review. The studies revealed that several factors contribute to malaria infection among forest rangers. The parameters were classified into sociodemographic, individual, and living condition-related. Conclusion: A better understanding of malaria progresses and identifying its potential risk factors is essential to impact worker well-being. The findings might be utilised to improve malaria infection prevention programme implementations, hence maximising their success. Pre-employment and regular health screenings could also aid in evaluating and identifying potential risks for malaria infection among forest rangers. [ABSTRACT FROM AUTHOR]

Background: Malaria elimination in Senegal requires accurate diagnosis of all Plasmodium species. Plasmodium falciparum is the most prevalent species in Senegal, although Plasmodium malariae, Plasmodium ovale, and recently Plasmodium vivax have also been reported. Nonetheless, most malaria control tools, such as Histidine Rich Protein 2 rapid diagnosis test (PfHRP2-RDT,) can only diagnose P. falciparum. Thus, PfHRP2-RDT misses non-falciparum species and P. falciparum infections that fall below the limit of detection. These limitations can be addressed using highly sensitive Next Generation Sequencing (NGS). This study assesses the burden of the four different Plasmodium species in western and eastern regions of Senegal using targeted PCR amplicon sequencing. Methods: Three thousand samples from symptomatic and asymptomatic individuals in 2021 from three sites in Senegal (Sessene, Diourbel region; Parcelles Assainies, Kaolack region; Gabou, Tambacounda region) were collected. All samples were tested using PfHRP2-RDT and photoinduced electron transfer polymerase chain reaction (PET-PCR), which detects all Plasmodium species. Targeted sequencing of the nuclear 18S rRNA and the mitochondrial cytochrome B genes was performed on PET-PCR positive samples. Results: Malaria prevalence by PfHRP2-RDT showed 9.4% (94/1000) and 0.2% (2/1000) in Diourbel (DBL) and Kaolack (KL), respectively. In Tambacounda (TAM) patients who had malaria symptoms and had a negative PfHRP2-RDT were enrolled. The PET-PCR had a positivity rate of 23.5% (295/1255) overall. The PET-PCR positivity rate was 37.6%, 12.3%, and 22.8% in Diourbel, Kaolack, and Tambacounda, respectively. Successful sequencing of 121/295 positive samples detected P. falciparum (93%), P. vivax (2.6%), P. malariae (4.4%), and P. ovale wallikeri (0.9%). Plasmodium vivax was co-identified with P. falciparum in thirteen samples. Sequencing also detected two PfHRP2-RDT-negative mono-infections of P. vivax in Tambacounda and Kaolack. Conclusion: The findings demonstrate the circulation of P. vivax in western and eastern Senegal, highlighting the need for improved malaria control strategies and accurate diagnostic tools to better understand the prevalence of non-falciparum species countrywide. [ABSTRACT FROM AUTHOR]

Background: Vector control using insecticides is a key prevention strategy against malaria. Unfortunately, insecticide resistance in mosquitoes threatens all progress in malaria control. In the perspective of managing this resistance, new insecticide formulations are being tested to improve the effectiveness of vector control tools. Methods: The efficacy and residual activity of Pirikool® 300 CS was evaluated in comparison with Actellic® 300 CS in experimental huts at the Tiassalé experimental station on three substrates including cement, wood and mud. The mortality, blood-feeding inhibition, exiting behaviour and deterrency of free-flying wild mosquitoes was evaluated. Cone bioassay tests with susceptible and resistant mosquito strains were conducted in the huts to determine residual efficacy. Results: A total of 20,505 mosquitoes of which 10,979 (53%) wild female Anopheles gambiae were collected for 112 nights. Residual efficacy obtained from monthly cone bioassay was higher than 80% with the susceptible, laboratory-maintained An. gambiae Kisumu strain, from the first to the tenth study period on all three types of treated substrate for both Actellic® 300CS and Pirikool® 300CS. This residual efficacy on the wild Tiassalé strain was over 80% until the 4th month of study on Pirikool® 300CS S treated substrates. Overall 24-h mortalities of wild free-flying An. gambiae sensu lato which entered in the experimental huts over the 8-months trial on Pirikool® 300CS treatment was 50.5%, 75.9% and 52.7%, respectively, on cement wall, wood wall and mud wall. The positive reference product Actellic® 300CS treatment induced mortalities of 42.0%, 51.8% and 41.8% on cement wall, wood wall and mud wall. Conclusion: Pirikool® 300CS has performed really well against resistant strains of An. gambiae using indoor residual spraying method in experimental huts. It could be an alternative product for indoor residual spraying in response to the vectors' resistance to insecticides. [ABSTRACT FROM AUTHOR]

The field of infectious diseases saw numerous exciting advances in 2023. Trials of new antibiotics and treatment regimens sought to address rising rates of antimicrobial resistance. Other studies focused on the most appropriate use of currently available treatments, balancing the dual goals of providing effective treatment and impactful antimicrobial stewardship. Improvements in disease prevention were made through trials of both new vaccines and new chemoprophylaxis approaches. Concerning trends this year included increasing rates of invasive group A streptococcal infections, medical tourism-associated cases of fungal meningitis, and the return of locally acquired malaria to the United States. This review covers some of these notable trials and clinical developments in infectious diseases in the past year. [ABSTRACT FROM AUTHOR]

Background: Monitoring therapeutic efficacy is important to ensure the efficacy of artemisinin-based combination therapy (ACT) for malaria. The current first-line treatment for uncomplicated malaria recommended by the National Malaria Control Program in Niger is artemether–lumefantrine (AL). In 2020, an in vivo study was carried out to evaluate clinical and parasitological responses to AL as well as the molecular resistance to the drug in three sentinel sites: Agadez, Tessaoua and Gaya, in Niger. Methods: A multi-center, single-arm trial was conducted according to the 28-day World Health Organization (WHO) 2009 therapeutic efficacy study protocol. Children between 6 months and 15 years with confirmed uncomplicated Plasmodium falciparum infection and 1000–200,000 asexual parasites/μL of blood were enrolled and followed up for 28 days. Uncorrected and PCR-corrected efficacy results at day 28 were calculated, and molecular correction was performed by genotyping the msp1, msp2, and glurp genes. The pfk13, pfdhfr, pfdhps, pfcrt and pfmdr genes were analyzed by PCR and Sanger sequencing. The Kaplan–Meier curve assessed parasite clearance. Results: A total of 255 patients were enrolled in the study. The adequate clinical and parasitological response after PCR correction was 98.9% (95% CI 96.4–101.0%), 92.2% (85.0–98.5%) and 97.1% (93.1–101.0%) in Gaya, Tessaoua and Agadez, respectively. No adverse events were observed. Ten mutations (SNP) were found, including 7 synonyms (K248K, G690G, E691E, E612E, C469C, G496G, P718P) and 3 non-synonyms (N594K, R255K, V714S). Two mutations emerged: N594K and V714S. The R255K mutation detected in Southeast Asia was also detected. The pfdhpsK540E and pfdhfrI164L mutations associated with high levels of resistance are absent. There is a reversal of chloroquine resistance. Conclusion: The study findings indicate that AL is effective and well tolerated for the treatment of uncomplicated malaria in three sites in Niger. The emergence of a pfk13 mutation requires additional testing such as the Ring Stage Assay and CRISPR/Cas9 to confirm the role of these emerging mutations. Trial registration NCT05070520, October 7, 2021. [ABSTRACT FROM AUTHOR]

Background: The newly developed malaria vaccine called "R21/Matrix-M malaria vaccine" showed a high safety and efficacy level, and Ghana is the first country to approve this new vaccine. The present study aimed to evaluate the rate of vaccine hesitancy (VH) towards the newly developed malaria vaccine among parents who currently have children who are not eligible for the vaccine but may be eligible in the near future. Additionally, the study aimed to identify the factors that could potentially influence VH. Methods: A cross-sectional survey using both online-based questionnaires and face-to-face interviews was conducted in Ghana from June to August 2023. The survey specifically targeted parents of ineligible children for vaccination, including those aged less than 5 months or between 3 and 12 years. The Parent Attitudes about Childhood Vaccination (PACV) scale was used to assess parental VH. Results: A total of 765 people participated in this study. Their median age was 36.0 years with an interquartile range of 31.0–41.0 years, 67.7% were females, 41.8% completed their tertiary education, 63.3% were married, 81.6% worked in non-healthcare sectors, and 59.7% reported that their monthly income was insufficient. About one-third (34.5%) of the parents were hesitant to give their children the R21/Matrix-M malaria vaccine. The following predictors were associated with VH: working in the healthcare sector (adjusted odds ratio (AOR) = 0.50; 95% confidence interval (CI) 0.30–0.80; p = 0.005), having the other parent working in the healthcare sector (AOR = 0.54; 95% CI 0.30–0.94; p = 0.034), and not taking scheduled routine vaccinations (AOR = 1.90; 95% CI 1.27–2.84; p = 0.002). Conclusions: Addressing VH is crucial for optimizing R21/Matrix-M vaccine coverage in Ghana's malaria control strategy. By tackling VH issues, Ghana can effectively safeguard children's health in malaria-prone areas. [ABSTRACT FROM AUTHOR]

Artemisinin-based combination therapies (ACTs) represent one of the mainstays of malaria control. Despite evidence of the risk of ACTs resistant infections in resource-limited countries, studies on the rational use of ACTs to inform interventions and prevent their emergence and/or spread are limited. The aim of this study was designed to analyze practices toward ACTs use for treating the treatment of uncomplicated malaria (UM) in an urban community. Between November 2015 and April 2016, a cross-sectional and prospective study was conducted in the 6 health facilities and all pharmacies in the Douala 5e subdivision, Cameroon. Anonymous interviews including both open- and closed-ended questions were conducted with selected participants among drug prescribers, patients attending the health facilities, and customers visiting the pharmacies. Data analysis was performed using StataSE11 software (version 11 SE). A total of 41 prescribers were included in the study. All were aware of national treatment guidelines, but 37.7% reported not waiting for test results before prescribing an antimalarial drug, and the main reason being stock-outs at health facilities. Likewise, artemether+lumefantrine/AL (81%) and dihydroartemisinin+piperaquine (63.5%) were the most commonly used first- and second-line drugs respectively. Biological tests were requested in 99.2% (128/129) of patients in health facilities, 60.0% (74) were performed and 6.2% were rationally managed. Overall 266 (35%) of 760 customers purchased antimalarial drugs, of these, 261 (98.1%) agreed to participate and of these, 69.4% purchased antimalarial drugs without a prescription. ACTs accounted for 90.0% of antimalarials purchased from pharmacies, of which AL was the most commonly prescribed antimalarial drug (67.1%), and only 19.5% of patients were appropriately dispensed. The current data suggest a gap between the knowledge and practices of prescribers as well as patients and customers misconceptions regarding the use of ACTs in Douala 5e subdivision. Despite government efforts to increase public awareness regarding the use of ACTs as first-line treatment for UM, our findings point out a critical need for the development, implementation and scaling-up of control strategies and continuing health education for better use of ACTs (prescription and dispensing) in Cameroon. [ABSTRACT FROM AUTHOR]

Background: Universal coverage with insecticide-treated nets (ITNs) is important for malaria control and elimination. The emergence and intensification of insecticide resistance threatens progress made through the deployment of these interventions and has required the development of newer, more expensive ITN types. Understanding malaria prevention behaviour, including barriers and facilitators to net access and use, can support effective decision-making for the promotion and distribution of ITNs. Methods: In-depth interviews and focus group discussions were conducted in 3 to 4 villages per district, in 13 districts across Burkina Faso, Mozambique, Nigeria and Rwanda from 2019 to 2022. Interviews were conducted in the local language, translated and transcribed in English, French or Portuguese. Transcripts were coded and analysed using Nvivo and ATLAS.ti. Results: ITNs were obtained from mass distribution campaigns, antenatal care and immunization visits, and purchased on the private market in some locations. While there were divergent perspectives in whether the number of distributed nets were adequate, participants consistently expressed concerns of bias, discrimination, and a lack of transparency with the distribution process. ITNs were frequently used alongside other malaria prevention methods. The primary motivation for use was malaria prevention. While some participants reported using nets nightly throughout the year, other participants reported seasonal use, both due to the perceived higher density of mosquitoes and discomfort of sleeping under a net in the increased heat. Other barriers to consistent net use included activities that take place away from the home, sleeping patterns and arrangements, and sensitivity to the insecticides on the nets. Conclusions: ITNs remain an important malaria control intervention. To ensure adequate and increased net access, distribution campaigns should consider family structures, available sleeping spaces, and other bed sharing preferences when identifying the number of nets needed for distribution. In addition, campaigns should allow for multiple options for net distribution points and timing to accommodate households remote to health services. Continuous distribution channels and complimentary distribution through the private sector could help fill gaps in coverage. Solutions are needed for outdoor malaria transmission, including alternative designs for ITNs, and improving access to complementary personal protective measures. [ABSTRACT FROM AUTHOR]