Effect of routine seasonal malaria chemoprevention on malaria trends in children under 5 years in Dangassa, Mali.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is a new strategy to prevent malaria in children under 5 years old. It has been recommended by the World Health Organization since 2012 in malaria-endemic areas with seasonal transmission. This study aimed to assess the changes in malaria indicators through two consecutive years of SMC routine implementation in children under 5 years old in Dangassa, where malaria is endemic with a long and high transmission season. METHODS: From 2012 to 2016, a cohort study was conducted in Dangassa village. The study team based in the village followed all malaria clinical cases in children under 5 years old at the community health centre. During the study, SMC was routinely implemented in collaboration with the National Malaria Control Programme. The Cox regression model was used in order to compare malaria risk during the study. RESULTS: The Cox regression model showed a significant reduction in malaria clinical incidence, both in 2015 (HR = 0.27 (0.18-0.40), 95% CI) and in 2016 (HR = 0.23 (0.15-0.35), 95% CI) of SMC implementation compared to October 2013. Gametocyte and fever prevalence was lower between September and October during SMC implementation (2015 and 2016) compared to the same period before SMC implementation (2013-2014). A slight increase of malaria incidence was observed in December at the end of SMC implementation. CONCLUSION: SMC has significantly reduced both malaria incidence and gametocyte prevalence and improved haemoglobin levels in children under 5 years old after 2 years of routine implementation.

Effect of a fifth round of seasonal malaria chemoprevention in children aged 5-14 years in Dangassa, an area of long transmission in Mali.

Despite a significant reduction in the burden of malaria in children under five years-old, the efficient implementation of seasonal malaria chemoprevention (SMC) at large scale remains a major concern in areas with long malaria transmission. Low coverage rate in the unattainable areas during the rainy season, a shift in the risk of malaria to older children and the rebound in malaria incidence after stopping drug administration are mainly reported in these areas. These gaps represent a major challenge in the efficient implementation of SMC measures. An open randomized study was conducted to assess the effect of a fifth additional round to current regime of SMC in older children living in Dangassa, a rural malaria endemic area. Poisson regression Model was used to estimate the reduction in malaria incidence in the intervention group compared to the control group including age groups (5-9 and 10-14 years) and the use of long-lasting insecticidal nets (LLINs; Yes or No) with a threshold at 5%. Overall, a downward trend in participation rate was observed from August (94.3%) to November (87.2%). In November (round 4), the risk of malaria incidence was similar in both groups (IRR = 0.66, 95%CI [0.35-1.22]). In December (round 5), a decrease of 51% in malaria incidence was observed in intervention group compared to control group adjusted for age groups and the use of LLINs (IRR = 0.49, 95%CI [0.26-0.94]), of which 17% of reduction is attributable to the 5th round in the intervention group. An additional fifth round of SMC resulted in a significant reduction of malaria incidence in the intervention group. The number of SMC rounds could be adapted to the local condition of malaria transmission.

Sickle cell trait protects against Plasmodium falciparum infection.

Although sickle cell trait protects against severe disease due to Plasmodium falciparum, it has not been clear whether sickle trait also protects against asymptomatic infection (parasitemia). To address this question, the authors identified 171 persistently smear-negative children and 450 asymptomatic persistently smear-positive children in Bancoumana, Mali (June 1996 to June 1998). They then followed both groups for 2 years using a cohort-based strategy. Among the 171 children with persistently negative smears, the median time for conversion to smear-positive was longer for children with sickle trait than for children without (274 vs. 108 days, P < 0.001; Cox hazard ratio = 0.56, 95% confidence interval: 0.33, 0.96; P = 0.036). Similar differences were found in the median times to reinfection after spontaneous clearance without treatment (365 days vs. 184 days; P = 0.01). Alternatively, among the 450 asymptomatic children with persistently positive smears, the median time for conversion to smear-negative (spontaneous clearance) was shorter for children with sickle trait than for children without (190 vs. 365 days; P = 0.02). These protective effects of sickle trait against asymptomatic P. falciparum infection under conditions of natural transmission were demonstrable using a cohort-based approach but not when the same data were examined using a cross-sectional approach.

The West Africa ICEMR Partnerships for Guiding Policy to Improve the Malaria Prevention and Control.

The Mali National Malaria Control Program (NMCP) recently established a phased set of goals for eliminating malaria in Mali by 2030. Over the past decade, the scale-up of NMCP-led malaria control interventions has led to considerable progress, as evidenced by multiple malariometric indicators. The West Africa International Center of Excellence in Malaria Research (WA-ICEMR) is a multidisciplinary research program that works closely with the NMCP and its partners to address critical research needs for malaria control. This coordinated effort includes assessing the effectiveness of control interventions based on key malaria research topics, including immune status, parasite genetic diversity, insecticide and drug resistance, diagnostic accuracy, malaria vector populations and biting behaviors, and vectorial capacity. Several signature accomplishments of the WA-ICEMR include identifying changing malaria age demographic profiles, testing innovative approaches to improve control strategies, and providing regular reporting on drug and insecticide resistance status. The NMCP and WA-ICEMR partnership between the WA-ICEMR and the NMCP offers a comprehensive research platform that informs the design and implementation of malaria prevention and control research programs. These efforts build local expertise and capacity for the next generation of malaria researchers and guide local policy, which is crucial in sustaining efforts toward eliminating malaria in West Africa.

A Decade of Progress Accelerating Malaria Control in Mali: Evidence from the West Africa International Center of Excellence for Malaria Research.

This article highlights over a decade of signature achievements by the West Africa International Centers for Excellence in Malaria Research (WA-ICEMR) and its partners toward guiding malaria prevention and control strategies. Since 2010, the WA-ICEMR has performed longitudinal studies to monitor and assess malaria control interventions with respect to space-time patterns, vector transmission indicators, and drug resistance markers. These activities were facilitated and supported by the Mali National Malaria Control Program. Research activities included large-scale active and passive surveillance and expanded coverage of universal long-lasting insecticide-treated bed nets and seasonal malaria chemoprevention (SMC). The findings revealed substantial declines in malaria occurrence after the scale-up of control interventions in WA-ICEMR study sites. WA-ICEMR studies showed that SMC using sulfadoxine-pyrimethamine plus amodiaquine was highly effective in preventing malaria among children under 5 years of age. An alternative SMC regimen (dihydroartemisinin plus piperaquine) was shown to be potentially more effective and provided advantages for acceptability and compliance over the standard SMC regimen. Other findings discussed in this article include higher observed multiplicity of infection rates for malaria in historically high-endemic areas, continued antimalarial drug sensitivity to Plasmodium falciparum, high outdoor malaria transmission rates, and increased insecticide resistance over the past decade. The progress achieved by the WA-ICEMR and its partners highlights the critical need for maintaining current malaria control interventions while developing novel strategies to disrupt malaria transmission. Enhanced evaluation of these strategies through research partnerships is particularly needed in the wake of reported artemisinin resistance in Southeast Asia and East Africa.

Factors Associated with Intermittent Preventive Treatment of Malaria During Pregnancy in Mali.

Intermittent preventive treatment in pregnancy (IPTp) with 3 or more doses of sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organization to prevent malaria in pregnant women living in high-risk areas. According to the 2015 malaria indicator survey in Mali, malaria prevalence is 34.6%. The high risk of malaria among pregnant women and children led the Malian government to provide free SP during antenatal clinics visits. The Malian National Program of Malaria Control recommends at least 3 doses during pregnancy. The proportion of pregnant women taking 3 or more doses of IPTp-SP (IPTp 3+) still remains low. In Mali, only 36.7% of pregnant women with a live birth in the past 2 yr received IPTp 3+. To investigate the factors associated with this low coverage, we carried out a secondary data analysis using the database of the Mali 2015 Malaria Indicator Survey. Multiple logistic regression was used to analyze these factors among 2,382 interviewed women. Taking less than 3 doses was higher among women below 20 yr (adjusted odds ratio [AOR] = 1.43, 95% confidence interval [CI, 1.03; 1.98]); however, media accessibility (listening to radio) (AOR = 0.71, 95% CI [0.53-0.95]) and residing in Segou (AOR = 0.56, 95% CI [0.35-0.90]) seem to favor the opposite after adjusting the potential confusion. Residence, educational level, and wealth index were not statistically associated with taking 3 doses of IPTp-SP. This study identifies that women less than 20 yr of age were significantly associated with taking lower than 3 doses of IPTp-SP.

Access and use of interventions to prevent and treat malaria among pregnant women in Kenya and Mali: a qualitative study.

BACKGROUND: Coverage of malaria in pregnancy interventions in sub-Saharan Africa is suboptimal. We undertook a systematic examination of the operational, socio-economic and cultural constraints to pregnant women's access to intermittent preventive treatment (IPTp), long-lasting insecticide-treated nets (LLINs) and case management in Kenya and Mali to provide empirical evidence for strategies to improve coverage. METHODS: Focus group discussions (FGDs) were held as part of a programme of research to explore the delivery, access and use of interventions to control malaria in pregnancy. FGDs were held with four sub-groups: non-pregnant women of child bearing age (aged 15-49 years), pregnant women or mothers of children aged <1 year, adolescent women, and men. Content analysis was used to develop themes and sub-themes from the data. RESULTS: Women and men's perceptions of the benefits of antenatal care were generally positive; motivation among women consisted of maintaining a healthy pregnancy, disease prevention in mother and foetus, checking the position of the baby in preparation for delivery, and ensuring admission to a facility in case of complications. Barriers to accessing care related to the quality of the health provider-client interaction, perceived health provider skills and malpractice, drug availability, and cost of services. Pregnant women perceived themselves and their babies at particular risk from malaria, and valued diagnosis and treatment from a health professional, but cost of treatment at health facilities drove women to use herbal remedies or drugs bought from shops. Women lacked information on the safety, efficacy and side effects of antimalarial use in pregnancy. CONCLUSION: Women in these settings appreciated the benefits of antenatal care and yet health services in both countries are losing women to follow-up due to factors that can be improved with greater political will. Antenatal services need to be patient-centred, free-of-charge or highly affordable and accountable to the women they serve.

A qualitative health systems effectiveness analysis of the prevention of malaria in pregnancy with intermittent preventive treatment and insecticide treated nets in Mali.

INTRODUCTION: Delivery of intermittent preventive treatment with sulphadoxine-pyrimethamine to pregnant women (IPTp-SP) through antenatal clinic (ANC) in Mali is low, and whilst ANC delivery of insecticide treated nets (ITNs) is higher, coverage is still below national and international targets. The aim of this study was to explain quantitative data from a related study which identified ineffective processes in the delivery of these interventions in one district in Mali. METHODS: In-depth interviews were conducted with health workers at the national, regional, district and health facility levels on their perceptions of reasons for the ineffective processes identified in the quantitative study, and their reported practices. Themes were coded for each ineffective process, and within these a health systems lens was used. Content analysis was used for emergent themes within this framework. MindMaps were used to display the findings. RESULTS: Intervention specific factors for the ineffective delivery of IPTp-SP included misunderstanding of the upper limit of the gestational age at which SP could be given and side effects of SP. Incorrect practices had been recommended in training and supervision of health workers. Pregnant women who were ill on attendance at ANC were not consistently managed across health facilities. The most common reason for not offering women an ITN on their first ANC visit was if they were from outside the health facility catchment area. Broader health systems issues influencing the effectiveness of delivery of each of these interventions were also identified. CONCLUSION: In this setting, intervention-specific factors resulted in the ineffective delivery of IPTp-SP. These relate to complex policy guidelines, lack of guidance on how to implement the guidelines, and the institutionalising of practices that undermine the national guidelines. Interventions may be implemented and show real gains in the shorter-term whilst waiting for broader health systems issues to be addressed.

Prevention of malaria in pregnancy with intermittent preventive treatment and insecticide treated nets in Mali: a quantitative health systems effectiveness analysis.

INTRODUCTION: The objectives of the study were to evaluate the health system effectiveness of ANC for the delivery of a dose of IPTp and an ITN to women attending ANC during eligible gestation, and to identify the predictors of systems effectiveness. METHODS: A cross sectional study was undertaken in 10 health facilities including structured non-participant observations of the ANC process for 780 pregnant women followed by exit interviews. The proportion of pregnant women receiving a dose of IPTp-SP and an ITN was assessed. Predictors of each ineffective intermediate process were identified using multivariable logistic regression. RESULTS: Overall, 0% and 24.5% of pregnant women of eligible gestation on the first visit to ANC received a dose of IPTp-SP by DOT at the district and community levels respectively. Ineffective intermediate processes were 'given IPTp-SP at the ANC' 63.9% and 74.0% (95% CI 62.0, 83.3), and 'given IPTp-SP by DOT' 0% and 34.3% (95% CI 10.5, 69.8), at district and community levels, respectively. Delivery of ITNs was effective where they were in stock; however stock-outs were a problem. Predictors of receiving IPTp-SP at the district level were 4 to 6 months gestation, not reporting symptoms of malaria at ANC visit and the amount of money spent during the visit. At the community level, the predictors were 4 to 6 months gestation, maternal education below primary level, routine ANC visit (not for an illness), palpation of the abdomen, and expenditure of money in ANC. CONCLUSION: In Segou District, the delivery of IPTp-SP was ineffective; whilst ITN delivery was effective if ITNs were in stock. Predictors of receiving IPTp-SP at the district and community levels included gestational age, the amount of expenditure during the ANC visit and no illness.

[Evaluation of the quality of prescription and dispensing of artemisinin-based therapeutic combinations in the Bamako District, Mali]. / Evaluation de la Qualite de la Prescription et de la Dispensation des Combinaisons Therapeutiques a Base D'Artemisinine (CTA) dans le District de Bamako, Mali.

The increasingly increasing resistance of the parasites of malaria to chloroquine pushed all the African countries almost to adopt the ACTs like treatment of first intention of uncomplicated malaria. However, correct use of the ACTs proves to be imperative to guarantee their effectiveness and to even delay the spread resistant parasites to these molecules. Thus, we have conducted this study in order to assess the quality of the prescription and the dispensation of ACTs in randomly selected health centers across Bamako. Our study was a cross-sectional study conducted between April and July 2008 with interview of patients received in clinic for malaria, a questionnaire was administered to physicians and other health workers who give prescription of antimalarials, and pharmacists and other people working in pharmacy or drugs deposit. In total, 52 prescribers, 72 dispensers and 92 patients were included. Our study has shown that the ACT constituted the treatment of first choice of malaria within prescribers (75%) and dispensers (78.8%). However, 57.61% of the prescriptions against malaria did not contain any ACTs. The ACTs recommended by the National Malaria Program (NMCP) were known by 59.7% of dispensers and 73.1% of prescribers. The majority of the prescribers (71.15%) and of the dispensers (84.72%) were favorable to the NMCP's recommendations. Many patients (41.30%) did not understand at all the dose of the prescribed ACTs. Almost all of the prescription containing ACT was a generic drug prescribed (97.72%; n = 44). The prices of the ACTs varied between 140 and 3,380 FCFA with an average of 750 FCFA. According to prescribers and dispensers, the ACT constitutes their first choice (75% of prescribers and 78.8% of the dispensers). However, 57.61% of the prescriptions against malaria did not contain any ACTs. The majority of prescribers (71.15%) and dispensers (84.72%) were favorable to the NMCP's recommendations of malaria treatment in Mali. The average cost of prescriptions containing ACT was 750 FCFA with the extreme ones going from 140 to 3,680 FCFA.

A randomized controlled phase 2 trial of the blood stage AMA1-C1/Alhydrogel malaria vaccine in children in Mali.

A double blind, randomized, controlled Phase 2 clinical trial was conducted to assess the safety, immunogenicity, and biologic impact of the vaccine candidate Apical Membrane Antigen 1-Combination 1 (AMA1-C1), adjuvanted with Alhydrogel. Participants were healthy children 2-3 years old living in or near the village of Bancoumana, Mali. A total of 300 children received either the study vaccine or the comparator. No impact of vaccination was seen on the primary endpoint, the frequency of parasitemia measured as episodes >3000/microL/day at risk. There was a negative impact of vaccination on the hemoglobin level during clinical malaria, and mean incidence of hemoglobin <8.5 g/dL, in the direction of lower hemoglobin in the children who received AMA1-C1, although these differences were not significant after correction for multiple tests. These differences were not seen in the second year of transmission.

Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.

BACKGROUND: The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria. METHODOLOGY/PRINCIPAL FINDINGS: A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively. CONCLUSION/SIGNIFICANCE: The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.