Transmission-blocking vaccines that interrupt malaria transmission from humans to mosquitoes are being tested in early clinical trials. The activity of such a vaccine is commonly evaluated using ...membrane-feeding assays. Understanding the field efficacy of such a vaccine requires knowledge of how heavily infected wild, naturally blood-fed mosquitoes are, as this indicates how difficult it will be to block transmission. Here we use data on naturally infected mosquitoes collected in Burkina Faso to translate the laboratory-estimated activity into an estimated activity in the field. A transmission dynamics model is then utilised to predict a transmission-blocking vaccine's public health impact alongside existing interventions. The model suggests that school-aged children are an attractive population to target for vaccination. Benefits of vaccination are distributed across the population, averting the greatest number of cases in younger children. Utilising a transmission-blocking vaccine alongside existing interventions could have a substantial impact against malaria.
In Mali, some children were treated by community health workers, using a rapid diagnostic test (RDT) to confirm Plasmodium falciparum parasitaemia. The following passively detected outcomes were ...included in this study: 1) incidence of malaria hospital admissions or deaths from malaria (as a combined outcome), defined as hospital admission for malaria combined with a positive blood slide or rapid diagnostic test, or deaths for which malaria was listed as the primary diagnosis; and 2) uncomplicated clinical malaria episodes, defined as history of fever or measured axillary temperature ≥37.5 °C combined with a positive RDT. At the end of each rainy season, the prevalence of P. falciparum infection was determined amongst randomly selected study children at cross-sectional surveys (target sample size of 2,000 per country, 1,000 per randomisation group in each country). The presence of molecular markers of resistance of P. falciparum to SP and AQ was determined amongst all study children who carried P. falciparum infection at the end-of-season surveys and from 50 school-age children with P. falciparum infection at the same time point.
There is an urgent need for high throughput, affordable methods of detecting pathogens inside insect vectors to facilitate surveillance. Near-infrared spectroscopy (NIRS) has shown promise to detect ...arbovirus and malaria in the laboratory but has not been evaluated in field conditions. Here we investigate the ability of NIRS to identify Plasmodium falciparum in Anopheles coluzzii mosquitoes. NIRS models trained on laboratory-reared mosquitoes infected with wild malaria parasites can detect the parasite in comparable mosquitoes with moderate accuracy though fails to detect oocysts or sporozoites in naturally infected field caught mosquitoes. Models trained on field mosquitoes were unable to predict the infection status of other field mosquitoes. Restricting analyses to mosquitoes of uninfectious and highly-infectious status did improve predictions suggesting sensitivity and specificity may be better in mosquitoes with higher numbers of parasites. Detection of infection appears restricted to homogenous groups of mosquitoes diminishing NIRS utility for detecting malaria within mosquitoes.
In Burkina Faso, malaria remains the overall leading cause of morbidity and mortality accounting for 35.12% of consultations, 40.83% of hospitalizations and 37.5% of deaths. Genotyping of malaria ...parasite populations remains an important tool to determine the types and number of parasite clones in an infection. The present study aimed to evaluate the merozoite surface protein 1 (msp1) and merozoite surface protein 2 (msp2) genetic diversity and allele frequencies in Bobo-Dioulasso, Burkina Faso.
Dried blood spots (DBS) were collected at baseline from patients with uncomplicated malaria in urban health centers in Bobo-Dioulasso. Parasite DNA was extracted using chelex-100 and species were identified using nested PCR. Plamodium falciparum msp1 and msp2 genes were amplified by nested polymerase chain reaction (PCR) and PCR products were analyzed by electrophoresis on a 2.5% agarose gel. Alleles were categorized according to their molecular weight.
A total of 228 blood samples were analyzed out of which 227 (99.9%) were confirmed as P. falciparum-positive and one sample classified as mixed infection for P. malaria and P. falciparum. In msp1, the K1 allelic family was predominant with 77.4% (162/209) followed respectively by the MAD20 allelic family with 41.3% and R033 allelic family with 36%. In msp2, the 3D7 allelic family was the most frequently detected with 93.1 % compared to FC27 with 41.3%. Twenty-one different alleles were observed in msp1 with 9 alleles for K1, 8 alleles for MAD20 and 4 alleles for R033. In msp2, 25 individual alleles were detected with 10 alleles for FC27 and 15 alleles for 3D7. The mean multiplicity of falciparum infection was 1.95 with respectively 1.8 (1.76-1.83) and 2.1 (2.03-2.16) for msp1 and msp2 (P = 0.01).
Our study showed high genetic diversity and allelic frequencies of msp1 and msp2 in Plasmodium falciparum isolates from symptomatic malaria patients in Bobo-Dioulasso.
Abstract
Background
Widespread artemisinin resistance in Africa could be catastrophic when drawing parallels with the failure of chloroquine in the 1970s and 1980s. This article explores the role of ...anti-malarial market characteristics in the emergence and spread of arteminisin resistance in African countries, drawing on perspectives from Burkina Faso.
Methods
Data were collected through in-depth interviews and focus group discussions. A representative sample of national policy makers, regulators, public and private sector wholesalers, retailers, clinicians, nurses, and community members were purposively sampled. Additional information was also sought via review of policy publications and grey literature on anti-malarial policies and deployment practices in Burkina Faso.
Results
Thirty seven in-depth interviews and 6 focus group discussions were conducted. The study reveals that the current operational mode of anti-malarial drug markets in Burkina Faso promotes arteminisin resistance emergence and spread. The factors are mainly related to the artemisinin-based combination therapy (ACT) supply chain, to ACT quality, ACT prescription monitoring and to ACT access and misuse by patients.
Conclusion
Study findings highlight the urgent requirement to reform current characteristics of the anti-malarial drug market in order to delay the emergence and spread of artemisinin resistance in Burkina Faso. Four recommendations for public policy emerged during data analysis: (1) Address the suboptimal prescription of anti-malarial drugs, (2) Apply laws that prohibit the sale of anti-malarials without prescription, (3) Restrict the availability of street drugs, (4) Sensitize the population on the value of compliance regarding correct acquisition and intake of anti-malarials. Funding systems for anti-malarial drugs in terms of availability and accessibility must also be stabilized.
Background A recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01.sub.E malaria vaccine (primary series and two seasonal ...boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria. Methods In order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01.sub.E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01.sub.E with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01.sub.E alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes. Results The overall protective efficacy from RTS,S/AS01.sub.E over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2-3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks. Conclusions The efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems. Trial registration The RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218 Keywords: Malaria, Plasmodium falciparum, Seasonal malaria chemoprevention, Malaria vaccination, RTS,S/AS01.sub.E
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•A year-long analysis of malaria parasite transmission in highly endemic areas was undertaken.•The oocyst load in mosquitoes was higher than expected (average 10 ...oocysts/mosquitoes).•Using a transmission model we found the number of oocysts per infectious blood meal.•This number (single-feed infection load) varied with season from three to 24 oocysts.•Malaria prevalence in humans can be used to approximate the single-feed infection load.
The population dynamics of human to mosquito malaria transmission in the field has important implications for the genetics, epidemiology and control of malaria. The number of oocysts in oocyst-positive mosquitoes developing from a single, naturally acquired infectious blood meal (herein referred to as a single-feed infection load) greatly influences the efficacy of transmission blocking interventions but still remains poorly documented. During a year-long analysis of malaria parasite transmission in Burkina Faso we caught and dissected wild malaria vectors to assess Plasmodium oocyst prevalence and load (the number of oocysts counted in mosquitoes with detectable oocysts) and the prevalence of salivary gland sporozoites. This was compared with malaria endemicity in the human population, assessed in cross-sectional surveys. Data were analysed using a novel transmission mathematical model to estimate the per bite transmission probability and the average single-feed infection load for each location. The observed oocyst load and the estimated single-feed infection load in naturally infected mosquitoes were substantially higher than previous estimates (means ranging from 3.2 to 24.5 according to seasons and locations) and indicate a strong positive association between the single-feed infection load and parasite prevalence in humans. This work suggests that highly infected mosquitoes are not rare in the field and might have a greater influence on the epidemiology and genetics of the parasite, and on the efficacy of novel transmission blocking interventions.
Malaria remains a leading cause of morbidity and mortality in Burkina Faso, which utilizes artemether-lumefantrine as the principal therapy to treat uncomplicated malaria and seasonal malaria ...chemoprevention with monthly sulfadoxine-pyrimethamine plus amodiaquine in children during the transmission season. Monitoring the activities of available antimalarial drugs is a high priority. We assessed the
susceptibility of
to 11 drugs in isolates from patients presenting with uncomplicated malaria in Bobo-Dioulasso in 2021 and 2022. IC
values were derived using a standard 72 h growth inhibition assay. Parasite DNA was sequenced to characterize known drug resistance-mediating polymorphisms. Isolates were generally susceptible, with IC
values in the low-nM range, to chloroquine (median IC
10 nM, IQR 7.9-24), monodesethylamodiaquine (22, 14-46) piperaquine (6.1, 3.6-9.2), pyronaridine (3.0, 1.3-5.5), quinine (50, 30-75), mefloquine (7.1, 3.7-10), lumefantrine (7.1, 4.5-12), dihydroartemisinin (3.7, 2.2-5.5), and atovaquone (0.2, 0.1-0.3) and mostly resistant to cycloguanil (850, 543-1,290) and pyrimethamine (33,200, 18,400-54,200), although a small number of outliers were seen. Considering genetic markers of resistance to aminoquinolines, most samples had wild-type PfCRT K76T (87%) and PfMDR1 N86Y (95%) sequences. For markers of resistance to antifolates, established PfDHFR and PfDHPS mutations were highly prevalent, the PfDHPS A613S mutation was seen in 19% of samples, and key markers of high-level resistance (PfDHFR I164L; PfDHPS K540E) were absent or rare (A581G). Mutations in the PfK13 propeller domain known to mediate artemisinin partial resistance were not detected. Overall, our results suggest excellent susceptibilities to drugs now used to treat malaria and moderate, but stable, resistance to antifolates used to prevent malaria.
Malaria and malnutrition remain major problems in Sahel countries, especially in young children. The direct effect of malnutrition on malaria remains poorly understood, and may have important ...implications for malaria control. In this study, nutritional status and the association between malnutrition and subsequent incidence of symptomatic malaria were examined in children in Burkina Faso and Mali who received either azithromycin or placebo, alongside seasonal malaria chemoprevention.
Mid-upper arm circumference (MUAC) was measured in all 20,185 children who attended a screening visit prior to the malaria transmission season in 2015. Prior to the 2016 malaria season, weight, height and MUAC were measured among 4149 randomly selected children. Height-for-age, weight-for-age, weight-for-height, and MUAC-for-age were calculated as indicators of nutritional status. Malaria incidence was measured during the following rainy seasons. Multivariable random effects Poisson models were created for each nutritional indicator to study the effect of malnutrition on clinical malaria incidence for each country.
In both 2015 and 2016, nutritional status prior to the malaria season was poor. The most prevalent form of malnutrition in Burkina Faso was being underweight (30.5%; 95% CI 28.6-32.6), whereas in Mali stunting was most prevalent (27.5%; 95% CI 25.6-29.5). In 2016, clinical malaria incidence was 675 per 1000 person-years (95% CI 613-744) in Burkina Faso, and 1245 per 1000 person-years (95% CI 1152-1347) in Mali. There was some evidence that severe stunting was associated with lower incidence of malaria in Mali (RR 0.81; 95% CI 0.64-1.02; p = 0.08), but this association was not seen in Burkina Faso. Being moderately underweight tended to be associated with higher incidence of clinical malaria in Burkina Faso (RR 1.27; 95% CI 0.98-1.64; p = 0.07), while this was the case in Mali for moderate wasting (RR 1.27; 95% CI 0.98-1.64; p = 0.07). However, these associations were not observed in severely affected children, nor consistent between countries. MUAC-for-age was not associated with malaria risk.
Both malnutrition and malaria were common in the study areas, high despite high coverage of seasonal malaria chemoprevention and long-lasting insecticidal nets. However, no strong or consistent evidence was found for an association between any of the nutritional indicators and the subsequent incidence of clinical malaria.
The success of current control tools in combatting malaria vectors is well established. However, sustained residual transmission of Plasmodium parasites persists. Mass drug administration (MDA) to ...humans of the endectocide ivermectin for vector control is receiving increasing attention. However, vectors feeding upon animals escape this promising approach. Zoophagy of mosquitoes sustains both the vector population and endemic population of vector-borne pathogens. Therefore, only a strategy that will combine ivermectin MDAs targeted at humans and their peridomestic animals could be successful at controlling residual malaria transmission.
Burkinabé cattle have been treated with injectable therapeutic dose of ivermectin (0.2 mg/kg of body weight) to render blood meals toxic to field representative populations of Anopheles coluzzii carrying the kdr mutation. Direct skin-feeding assays were performed from 2 to 28 days after injection (DAI) and mosquitoes were followed for their survival, ability to become gravid and fecundity. Membrane feeding assays were further performed to test if an ivermectin blood meal taken at 28 DAI impacts gametocyte establishment and development in females fed with infectious blood.
The mosquitocidal effect of ivermectin is complete for 2 weeks after injection, whether 12 days cumulative mortalities were of 75 and 45 % the third and fourth weeks, respectively. The third week, a second ivermectin blood meal at sub-lethal concentrations further increased mortality to 100 %. Sub-lethal concentrations of ivermectin also significantly decreased egg production by surviving females, increasing further the detrimental effect of the drug on vector densities. Although females fitness was impaired by sub-lethal ivermectin blood meals, these did not diminish nor increase their susceptibility to infection.
This study demonstrates the potential of integrated MDA of ivermectin to both human and peridomestic cattle to target vector reservoirs of residual malaria transmission. Such integration lies in 'One-Health' efforts being implemented around the globe, and would be especially relevant in rural communities in Africa where humans are also at risk of common zoonotic diseases.
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