2022 |
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Journal Articles |
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Matthew Cairns, Amadou Barry, Issaka Zongo, Issaka Sagara, Serge R. Yerbanga, Modibo Diarra, Charles Zoungrana, Djibrilla Issiaka, Abdoul Aziz Sienou, Amadou Tapily, Koualy Sanogo, Mahamadou Kaya, Seydou Traore, Kalifa Diarra, Hama Yalcouye, Youssoufa Sidibe, Alassane Haro, Ismaila Thera, Paul Snell, Jane Grant, Halidou Tinto, Paul Milligan, Daniel Chandramohan, Brian Greenwood, Alassane Dicko, Jean Bosco Ouedraogo The duration of protection against clinical malaria provided by the combination of seasonal RTS,S/AS01E vaccination and seasonal malaria chemoprevention versus either intervention given alone Journal Article In: BMC Medicine, vol. 20, iss. 1, pp. 352, 2022, ISSN: 1741-7015. Abstract | BibTeX | Tags: Malaria, Malaria vaccination, Plasmodium falciparum, RTS, S/AS01E, seasonal malaria chemoprevention | Links: @article{Cairns2022, BACKGROUND A recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01E 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/AS01E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01E 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/AS01E 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/AS01E 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. | |||
2021 |
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Journal Articles |
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![]() | Mphatso Dennis Phiri, Matthew Cairns, Issaka Zongo, Frederic Nikiema, Modibo Diarra, Rakiswendé Serge Yerbanga, Amadou Barry, Amadou Tapily, Samba Coumare, Ismaila Thera, Irene Kuepfer, Paul Milligan, Halidou Tinto, Alassane Dicko, Jean Bosco Ouédraogo, Brian Greenwood, Daniel Chandramohan, Issaka Sagara The duration of protection from azithromycin against malaria, acute respiratory, gastrointestinal, and skin infections when given alongside seasonal malaria chemoprevention: Secondary analyses of data from a clinical trial in houndé, Burkina Faso, and bougouni, Mali Journal Article In: Clin. Infect. Dis., vol. 73, no. 7, pp. e2379–e2386, 2021, ISSN: 1537-6591 1058-4838, (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. PMID: 33417683 PMCID: PMC8492219). Abstract | BibTeX | Tags: Antimalarials/therapeutic use, Azithromycin, Azithromycin/therapeutic use, Burkina Faso/epidemiology, Chemoprevention, Child, child mortality, Drug Combinations, duration of protection, Humans, Infant, Malaria/drug therapy/epidemiology/prevention & control, Mali/epidemiology, Preschool, Sahel, seasonal malaria chemoprevention, Seasons | Links: @article{Phiri2021-oy, BACKGROUND: Mass drug administration (MDA) with azithromycin (AZ) is being considered as a strategy to promote child survival in sub-Saharan Africa, but the mechanism by which AZ reduces mortality is unclear. To better understand the nature and extent of protection provided by AZ, we explored the profile of protection by time since administration, using data from a household-randomized, placebo-controlled trial in Burkina Faso and Mali. METHODS: Between 2014 and 2016, 30 977 children aged 3-59 months received seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine and either AZ or placebo monthly, on 4 occasions each year. Poisson regression with gamma-distributed random effects, accounting for the household randomization and within-individual clustering of illness episodes, was used to compare incidence of prespecified outcomes between SMC+AZ versus SMC+placebo groups in fixed time strata post-treatment. The likelihood ratio test was used to assess evidence for a time-treatment group interaction. RESULTS: Relative to SMC+placebo, there was no evidence of protection from SMC+AZ against hospital admissions and deaths. Additional protection from SMC+AZ against malaria was confined to the first 2 weeks post-administration (protective efficacy (PE): 24.2% [95% CI: 17.8%, 30.1%]). Gastroenteritis and pneumonia were reduced by 29.9% [21.7; 37.3%], and 34.3% [14.9; 49.3%], respectively, in the first 2 weeks postadministration. Protection against nonmalaria fevers with a skin condition persisted up to 28 days: PE: 46.3% [35.1; 55.6%]. CONCLUSIONS: The benefits of AZ-MDA are broad-ranging but short-lived. To maximize impact, timing of AZ-MDA must address the challenge of targeting asynchronous morbidity and mortality peaks from different causes. | ||
![]() | Koudraogo Bienvenue Yaméogo, Rakiswendé Serge Yerbanga, Seydou Bienvenu Ouattara, Franck A Yao, Thierry Lef`evre, Issaka Zongo, Frederic Niki`ema, Yves Daniel Compaoré, Halidou Tinto, Daniel Chandramohan, Brian Greenwood, Adrien M G Belem, Anna Cohuet, Jean Bosco Ouédraogo Effect of seasonal malaria chemoprevention plus azithromycin on Plasmodium falciparum transmission: gametocyte infectivity and mosquito fitness Journal Article In: Malar. J., vol. 20, no. 1, pp. 326, 2021, ISSN: 1475-2875, (© 2021. The Author(s). PMID: 34315475 PMCID: PMC8314489). Abstract | BibTeX | Tags: Amodiaquine/administration & dosage, Animals, Antimalarials/administration & dosage, Chemoprevention, Child, Culicidae/physiology, Drug Combinations, Falciparum/prevention & control/transmission, Gametocytes, Genetic Fitness, Humans, Malaria, Plasmodium falciparum/physiology, Preschool, Pyrimethamine/administration & dosage, seasonal malaria chemoprevention, Seasons, Sulfadoxine/administration & dosage, Transmission | Links: @article{Yameogo2021-bb, BACKGROUND: Seasonal malaria chemoprevention (SMC) consists of administration of sulfadoxine-pyrimethamine (SP) + amodiaquine (AQ) at monthly intervals to children during the malaria transmission period. Whether the addition of azithromycin (AZ) to SMC could potentiate the benefit of the intervention was tested through a double-blind, randomized, placebo-controlled trial. The effect of SMC and the addition of AZ, on malaria transmission and on the life history traits of Anopheles gambiae mosquitoes have been investigated. METHODS: The study included 438 children randomly selected from among participants in the SMC + AZ trial and 198 children from the same area who did not receive chemoprevention. For each participant in the SMC + AZ trial, blood was collected 14 to 21 days post treatment, examined for the presence of malaria sexual and asexual stages and provided as a blood meal to An. gambiae females using a direct membrane-feeding assay. RESULTS: The SMC treatment, with or without AZ, significantly reduced the prevalence of asexual Plasmodium falciparum (LRT X(2)(2) = 69, P < 0.0001) and the gametocyte prevalence (LRT X(2)(2) = 54, P < 0.0001). In addition, the proportion of infectious feeds (LRT X(2)(2) = 61, P < 0.0001) and the prevalence of oocysts among exposed mosquitoes (LRT X(2)(2) = 22.8, P < 0.001) was reduced when mosquitoes were fed on blood from treated children compared to untreated controls. The addition of AZ to SPAQ was associated with an increased proportion of infectious feeds (LRT X(2)(1) = 5.2, P = 0.02), suggesting a significant effect of AZ on gametocyte infectivity. There was a slight negative effect of SPAQ and SPAQ + AZ on mosquito survival compared to mosquitoes fed with blood from control children (LRTX(2)(2) = 330, P < 0.0001). CONCLUSION: This study demonstrates that SMC may contribute to a reduction in human to mosquito transmission of P. falciparum, and the reduced mosquito longevity observed for females fed on treated blood may increase the benefit of this intervention in control of malaria. The addition of AZ to SPAQ in SMC appeared to enhance the infectivity of gametocytes providing further evidence that this combination is not an appropriate intervention. | ||
![]() | Mariken Wit, Matthew Cairns, Yves Daniel Compaoré, Issaka Sagara, Irene Kuepfer, Issaka Zongo, Amadou Barry, Modibo Diarra, Amadou Tapily, Samba Coumare, Ismaila Thera, Frederic Nikiema, R Serge Yerbanga, Rosemonde M Guissou, Halidou Tinto, Alassane Dicko, Daniel Chandramohan, Brian Greenwood, Jean Bosco Ouedraogo Nutritional status in young children prior to the malaria transmission season in Burkina Faso and Mali, and its impact on the incidence of clinical malaria Journal Article In: Malar. J., vol. 20, no. 1, pp. 274, 2021, ISSN: 1475-2875, (PMID: 34158054 PMCID: PMC8220741). Abstract | BibTeX | Tags: Acute malnutrition, Antimalarials/administration & dosage, Azithromycin/administration & dosage, Burkina Faso, Burkina Faso/epidemiology, Child, Chronic malnutrition, Female, Humans, Incidence, Infant, Malaria, Malaria/epidemiology/transmission, Male, Nutritional Status, Preschool, seasonal malaria chemoprevention, Seasons | Links: @article{De_Wit2021-yi, BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. |
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