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Substantial reductions in malaria have been reported in several African countries after distribution of insecticide-treated bednets and the use of artemisinin-based combination therapies (ACTs). Our aim was to assess the effect of these policies on malaria morbidity, mosquito populations, and asymptomatic infections in a west African rural population. We did a longitudinal study of inhabitants of Dielmo village, Senegal, between January, 2007, and December, 2010. We monitored the inhabitants for fever during this period and we treated malaria attacks with artesunate plus amodiaquine. In July, 2008, we offered longlasting insecticide (deltamethrin)-treated nets (LLINs) to all villagers. We did monthly night collections of mosquitoes during the whole study period, and we assessed asymptomatic carriage from cross-sectional surveys. Our statistical analyses were by negative binomial regression, logistic regression, and binomial or Fisher exact test. There were 464 clinical malaria attacks attributable to Plasmodium falciparum during 17 858 person-months of follow-up. The incidence density of malaria attacks averaged 5·45 (95% CI 4·90–6·05) per 100 person-months between January, 2007, and July, 2008, before the distribution of LLINs. Incidence density decreased to 0·41 (0·29–0·55) between August, 2008, and August, 2010, but increased back to 4·57 (3·54–5·82) between September and December, 2010—ie, 27–30 months after the distribution of LLINs. The rebound of malaria attacks were highest in adults and children aged 10 years or older: 45 (63%) of 71 malaria attacks recorded in 2010 compared with 126 (33%) of 384 in 2007 and 2008 (p<0·0001). 37% of Anopheles gambiae mosquitoes were resistant to deltamethrin in 2010, and the prevalence of the Leu1014Phe kdr resistance mutation increased from 8% in 2007 to 48% in 2010 (p=0·0009). Increasing pyrethroid resistance of A gambiae and increasing susceptibility of older children and adults, probably due to decreasing immunity, caused the rebound and age shift of malaria morbidity. Strategies to address the problem of insecticide resistance and to mitigate its effects must be urgently defined and implemented. Institut de Recherche pour le Développement and the Pasteur Institute of Dakar.

Plasmodium ovale and Plasmodium malariae have long been reported to be widely distributed in tropical Africa and in other major malaria-endemic areas of the world. However, little is known about the burden caused by these two malaria species. We did a longitudinal study of the inhabitants of Dielmo village, Senegal, between June, 1990, and December, 2010. We monitored the inhabitants for fever during this period and performed quarterly measurements of parasitemia. We analyzed parasitological and clinical data in a random-effect logistic regression model to investigate the relationship between the level of parasitemia and the risk of fever and to establish diagnostic criteria for P. ovale and P. malariae clinical attacks. The prevalence of P. ovale and P. malariae infections in asymptomatic individuals were high during the first years of the project but decreased after 2004 and almost disappeared in 2010 in relation to changes in malaria control policies. The average incidence densities of P. ovale and P. malariae clinical attacks were 0.053 and 0.093 attacks per person per year in children <15 years and 0.024 and 0.009 attacks per person per year in adults ≥ 15 years, respectively. These two malaria species represented together 5.9% of the malaria burden. P. ovale and P. malariae were a common cause of morbidity in Dielmo villagers until the recent dramatic decrease of malaria that followed the introduction of new malaria control policies. P. ovale and P. malariae may constitute an important cause of morbidity in many areas of tropical Africa.

The saliva of haematophagous arthropods contains an array of anti-haemostatic, anti-inflammatory and immunomodulatory molecules that contribute to the success of the blood meal. The saliva of haematophagous arthropods is also involved in the transmission and the establishment of pathogens in the host and in allergic responses. This survey provides a comprehensive overview of the pharmacological activity and immunogenic properties of the main salivary proteins characterised in various haematophagous arthropod species. The potential biological and epidemiological applications of these immunogenic salivary molecules will be discussed with an emphasis on their use as biomarkers of exposure to haematophagous arthropod bites or vaccine candidates that are liable to improve host protection against vector-borne diseases.

This study aimed to estimate the prevalence of asymptomatic and subpatent P. falciparum infections in the city of Bouaké, Central Côte d’Ivoire, to compare the performance of three tests, and to investigate potential P. falciparum histidine-rich protein 2 ( pfhrp2 ) gene deletions. A cross-sectional survey was conducted in nine neighborhoods in Bouaké in 2016. Matched light microscopy (LM), rapid diagnostic test (RDT), and quantitative PCR (qPCR) data were used to determine the prevalence of P. falciparum infection and compare the performance of the three diagnostic tests. Pfhrp2 / 3 deletions were genotyped by digital PCR. Among 2313 individuals, 97.2% were asymptomatic and 2.8% were symptomatic. P. falciparum prevalence among symptomatic individuals was 25.8%, 30.3%, and 40.9% by LM, RDT, and var ATS qPCR, respectively, and among asymptomatic individuals, it was 10.3%, 12.5%, and 34.9%. Asymptomatic infections comprised 96.4% of all malaria infections, with 58.2% detectable only by var ATS qPCR. Although the prevalence of asymptomatic P. falciparum infections was higher in school-age children (5–14 years: 42.0%) compared to < 5 years (17.3%) and ≥ 15 years (35.9%), subpatent infections were more likely in ≥ 15 years (70.4%) than in < 5 years (39.7%) and school-age children (41.2%). LM and RDTs were reliable only at parasite densities > 10,000 parasites/µL. Individuals who were positive according to all three tests had significantly greater parasite density (856.8 parasites/µL; 95% CI 707.3–1,038) than did those who were positive by var ATS qPCR only (13.7 parasites/µL; 95% CI 11.4–16.3) (p < 0.0001). No pfhrp2 deletions were observed. The high prevalence of asymptomatic and subpatent infections highlights the need for targeted strategies to reduce malaria in urban Côte d’Ivoire.

Malaria control efforts and elimination in Africa are being challenged by the development of resistance of parasites to antimalarial drugs and vectors to insecticides. We investigated whether the combination of long-lasting insecticidal mosquito nets (LLINs) with indoor residual spraying (IRS) or carbamate-treated plastic sheeting (CTPS) conferred enhanced protection against malaria and better management of pyrethroid-resistance in vectors than did LLINs alone. We did a cluster randomised controlled trial in 28 villages in southern Benin, west Africa. Inclusion criteria of the villages were moderate level of pyrethroid resistance in malaria vectors and minimum distance between villages of 2 km. We assessed four malaria vector control interventions: LLIN targeted coverage to pregnant women and children younger than 6 years (TLLIN, reference group), LLIN universal coverage of all sleeping units (ULLIN), TLLIN plus full coverage of carbamate-IRS applied every 8 months (TLLIN+IRS), and ULLIN plus full coverage of CTPS lined up to the upper part of the household walls (ULLIN+CTPS). The interventions were allocated to villages by a block randomisation on the basis of preliminary surveys and children of each village were randomly selected to participate with computer-generated numbers. The primary endpoint was the incidence density rate of Plasmodium falciparum clinical malaria in children younger than 6 years as was analysed by Poisson regression taking into account the effect of age and the sampling design with a generalised estimating equation approach. Clinical and parasitological information were obtained by active case detection of malaria episodes during 12 periods of 6 consecutive days scheduled at six weekly intervals and by cross-sectional surveys of asymptomatic plasmodial infections. Children or study investigators were not masked to study group. This study is registered with Current Controlled Trials, number ISRCTN07404145. Of 58 villages assessed, 28 were randomly assigned to intervention groups. 413–429 children were followed up in each intervention group for 18 months. The clinical incidence density of malaria was not reduced in the children from the ULLIN group (incidence density rate 0·95, 95% CI 0·67–1·36, p=0·79), nor in those from the TLLIN+IRS group (1·32, 0·90–1·93, p=0·15) or from the ULLIN+CTPS group (1·05, 0·75–1·48, p=0·77) compared with the reference group (TLLIN). The same trend was observed with the prevalence and parasite density of asymptomatic infections (non significant regression coefficients). No significant benefit for reducing malaria morbidity, infection, and transmission was reported when combining LLIN+IRS or LLIN+CTPS compared with a background of LLIN coverage. These findings are important for national malaria control programmes and should help the design of more cost-effective strategies for malaria control and elimination. Ministère Français des Affaires Etrangères et Européennes (FSP project 2006-22), Institut de Recherche pour le Développement, President's Malaria Initiative (PMI) of US Governement.

Background : Thanks to a considerable increase in funding, malaria control interventions (MCI) whose efficacy had been demonstrated by controlled trials have been largely scaled up during the last decade. Nevertheless, it was not systematically investigated whether this efficacy had been preserved once deployed on the field. Therefore, we sought the literature to assess the disparities between efficacy and effectiveness and the effort to measure the protective effectiveness (PE) of MCI. Methods : The PubMed database was searched for references with keywords related to malaria, to control interventions for prevention and to study designs that allow for the measure of the PE against parasitemia or against clinical outcomes. Results : Our search retrieved 1423 references, and 162 articles were included in the review. Publications were scarce before the year 2000 but dramatically increased afterwards. Bed nets was the MCI most studied (82.1%). The study design most used was a cross-sectional study (65.4%). Two thirds (67.3%) were conducted at the district level or below, and the majority (56.8%) included only children even if the MCI didn’t target only children. Not all studies demonstrated a significant PE from exposure to MCI: 60.6% of studies evaluating bed nets, 50.0% of those evaluating indoor residual spraying, and 4/8 showed an added PE of using both interventions as compared with one only; this proportion was 62.5% for intermittent preventive treatment of pregnant women, and 20.0% for domestic use of insecticides. Conclusions : This review identified numerous local findings of low, non-significant PE –or even the absence of a protective effect provided by these MCIs. The identification of such failures in the effectiveness of MCIs advocates for the investigation of the causes of the problem found. Ideal evaluations of the PE of MCIs should incorporate both a large representativeness and an evaluation of the PE stratified by subpopulations.

Background Although it is accepted that long-lasting insecticidal net (LLIN) use is an effective means to prevent malaria, children aged 5 to 15 years do not appear to be sufficiently protected in Madagascar; the malaria prevalence is highest in this age group. The purpose of this research is to summarize recent qualitative studies describing LLIN use among the Malagasy people with a focus on children aged 5–15 years. Methods Qualitative data from three studies on malaria conducted between 2012 and 2016 in 10 districts of Madagascar were analysed. These studies cover all malaria epidemiological profiles and 10 of the 18 existing ethnic groups in Madagascar. A thematic analysis was conducted on the collected data from semi-structured interviews, direct observation data, and informal interviews. Results A total of 192 semi-structured interviews were conducted. LLINs are generally perceived positively because they protect the health and well-being of users. However, regional representations of mosquito nets may contribute to LLIN lower use by children over 5 years of age including the association between married status and LLIN use, which leads to the refusal of unmarried young men to sleep under LLINs; the custom of covering the dead with a mosquito net, which leads to fear of LLIN use; and taboos governing sleeping spaces for siblings of opposite sexes, which leads to LLIN shortages in households. Children under 5 years of age are known to be the most vulnerable age group for acquiring malaria and, therefore, are prioritized for LLIN use when there are limited supplies in households. In contrast, children over 5 years of age, who are perceived to be at less risk for malaria, often sleep without LLINs. Conclusions Perceptions, social practices and regional beliefs regarding LLINs and vulnerability to malaria contribute to the nonuse of LLINs among children over 5 years of age in Madagascar. Modifying LLIN policies to account for these factors may increase LLIN use in this age group and reduce disease burden.

In areas where malaria epidemiology is spatially and temporally heterogeneous, human-mediated parasite importation can result in non-locally acquired clinical cases and outbreaks in low-transmission areas. Using mobility estimates derived from the mobile phone data and spatial malaria prevalence data, we identify travel routes relevant to malaria transmission in Madagascar. We find that the primary hubs of parasite importation are in a spatially connected area of the central highlands. Surprisingly, sources of these imported infections are not spatially clustered. We then related these source locations directly to clinical cases in the low-transmission area of the capital. We find that in the capital, a major sink, the primary sources of infection are along the more populated coastal areas, although these sources are seasonally variable. Our results have implications for targeting interventions at source locations to achieve local or national malaria control goals. Understanding the source of malaria outbreaks in low-transmission areas is important for controlling the disease. Here, the authors use mobile phone data to map malaria transmission in Madagascar, and are able to show that primary sources of infection in the capital city are found along populated coastal areas.

Hypertension is one of the main risk factors of cardiovascular diseases. In Madagascar, studies on hypertension in urban and rural communities are scarce. The aim of this study was to determine the prevalence of hypertension and identify associated risk factors in adults living in a health and demographic system in Moramanga, Madagascar. The study included people aged 15 years old and above living in a health and demographic system in Moramanga. A household census was performed in 2012 to enumerate the population in 3 communities in Moramanga. In addition to the questionnaire used in the initial census, a standardized questionnaire and blood pressure were taken twice after 5 and 10 minutes of rest. In urban areas, heights and weights were also measured to calculate the body mass index. There were 3621 and 4010 participants respectively in rural and urban areas. Prevalence of hypertension in rural population was 27.0% (IC95% [25.6-28.5]) and 29.7% (IC95% [28.3-31.1]) in urban population. Among hypertensive subjects, 1.7% (17/979) and 5.3% (64/1191) were on antihypertensive treatment for at least 1 month before the survey in rural and urban population, respectively. In rural areas, increasing age (65 years and older vs 18-25 years OR = 11.81, IC95% [7.79-18.07]), giving more than 3 positive responses to the usual risks factors of hypertension (OR = 1.67, IC95% [1.14-2.42]) and singles in comparison with married people (OR = 1.61, IC95% [1.20-2.17]) were associated to hypertension in a logistic regression model. In urban areas, increasing age (65 years and older vs 18-25 years OR = 37.54, IC95% [24.81-57.92]), more than 3 positive responses to the usual risks of hypertension (OR = 3.47, IC95% [2.58-4.67]) and obesity (OR = 2.45, IC95% [1.56-3.87]) were found as risk factors. Hypertension is highly prevalent in rural areas although it is significantly less treated. As a result, a major epidemic of cardiovascular diseases is at risk in Madagascar's progressively aging society.

Background Madagascar has made significant progress in the fight against malaria. However, the number of malaria cases yearly increased since 2012. ITNs and IRS are key interventions for reducing malaria in Madagascar. Given the increasing number of cases and limited resources, understanding the cost-effectiveness of these strategies is essential for policy development and resource allocation. Methods Using a societal perspective, this study aims to estimate the cost of the National Malaria Control Program (NMCP) through the first national malaria strategic plan (implemented over the period 2009–2013) and to assess the cost-effectiveness of two individually implemented malaria control interventions (ITNs and IRS) in two districts, Ankazobe and Brickaville. The cost-effectiveness ratio (CER) of ITN intervention was then compared to the CER of IRS intervention to identify the most cost-effective intervention. The cost of the NMCP and the costs incurred in the implementation of each intervention at the district level were initially estimated. On the basis of two results, the CERs of ITN or IRS correspond to the total cost of ITN or IRS divided by the number of people protected or the number of disability-adjusted life years (DALYs) averted. A deterministic univariate sensitivity analysis was conducted to assess the robustness of the results with a discount rate of 2.5% (0–5%) (costs and DALYs) and a 95% CI (person protected). Results From 2009 to 2013, the NMCP cost USD 45.4 million (USD 43.5–47.5, r  = 0–5%) per year, equivalent to USD 2.0 per capita per year. IRS implementation costs were four times higher than those of ITNs. The CER of IRS per case protected (USD 295.1 [285.1-306.1], r  = 0–5%) was higher than the CER of ITNs (USD 48.6 [USD 46.0-51.5, r  = 0–5%] in Ankazobe and USD 26.5 [USD 24.8–28.4, r  = 0–5%] in Brickaville). The CERs per DALY averted of IRS was USD 427.6 [USD 413.0-546.3, r  = 0–5%] in Ankazobe and, for ITNs, it was USD 85.4 [USD 80.8–90.5, r  = 0–5%] in Ankazobe and USD 45.3 [USD 42.2–48.4, r  = 0–5%] in Brickaville. Compared to the country GDP per capita (USD PPP 1494.6 in 2013), ITN intervention was “highly cost-effective” while the CER for IRS interventions was sensitive to parameter variation (CI, 95% of persons protected), which ranges from highly cost-effective to only cost-effective (USD 291.5–2004, r  = 2.5%). Conclusion In the Malagasy context, IRS intervention cost more and was less effective than ITN intervention. Willingness to pay for IRS is questioned. A relevant budget impact analysis should be conducted before a potential extension of this intervention.