Randomized Trial of Piperaquine with Sulfadoxine-Pyrimethamine or Dihydroartemisinin for Malaria Intermittent Preventive Treatment in Children

BACKGROUND: The long terminal half life of piperaquine makes it suitable for intermittent preventive treatment for malaria but no studies of its use for prevention have been done in Africa. We did a cluster randomized trial to determine whether piperaquine in combination with either dihydroartemisin (DHA) or sulfadoxine-pyrimethamine (SP) is as effective, and better tolerated, than SP plus amodiaquine (AQ), when used for intermittent preventive treatment in children delivered by community health workers in a rural area of Senegal. METHODS: Treatments were delivered to children 3-59 months of age in their homes once per month during the transmission season by community health workers. 33 health workers, each covering about 60 children, were randomized to deliver either SP+AQ, DHA+PQ or SP+PQ. Primary endpoints were the incidence of attacks of clinical malaria, and the incidence of adverse events. RESULTS: 1893 children were enrolled. Coverage of monthly rounds and compliance with daily doses was similar in all groups; 90% of children received at least 2 monthly doses. Piperaquine combinations were better tolerated than SP+AQ with a significantly lower risk of common, mild adverse events. 103 episodes of clinical malaria were recorded during the course of the trial. 68 children had malaria with parasitaemia >3000/microL, 29/671 (4.3%) in the SP+AQ group, compared with 22/604 (3.6%) in the DHA+PQ group (risk difference 0.47%, 95%CI -2.3%,+3.3%), and 17/618 (2.8%) in the SP+PQ group (risk difference 1.2%, 95%CI -1.3%,+3.6%). Prevalences of parasitaemia and the proportion of children carrying Pfdhfr and Pfdhps mutations associated with resistance to SP were very low in all groups at the end of the transmission season. CONCLUSIONS: Seasonal IPT with SP+PQ in children is highly effective and well tolerated; the combination of two long-acting drugs is likely to impede the emergence of resistant parasites. TRIAL REGISTRATION: ClinicalTrials.gov NCT00529620

Methods to collect Anopheles mosquitoes and evaluate malaria transmission: A comparative study in two villages in Senegal

<p>Abstract</p> <p>Background</p> <p>Various methods have been studied as replacement of human landing catches (HLC) for mosquito sampling in entomological studies on malaria transmission. Conflicting results have been obtained in comparing relative efficiency of alternative methods, according to the area, the species present and their density. The aim of this study was to compare the number and characteristics of mosquitoes sampled in two areas of Senegal by three different methods: HLC, light traps adjacent to an occupied bed net (LT/N), pyrethrum spray catches (PSC).</p> <p>Methods</p> <p>Collections were performed in two villages: Dielmo (Soudan savanna) and Bandafassi (Soudan Guinean savanna), two or three nights per month for a 4-5 months period during the maximal transmission season in 2001-2002. Species were identified and <it>Plasmodium </it>infection determined by ELISA. The specific composition, circumsporozoite protein rate and entomological inoculation rate were calculated.</p> <p>Results</p> <p>The diversity of mosquito species captured was maximal with LT/N, minimal with PSC. The mean number of anopheles captures each night was significantly different according to the method used and the species. PSC displayed a significantly lower anopheles density. HLC was the most efficient sampling method when <it>Anopheles gambiae </it>was the main vector (in Bandafassi); LT/N when it was <it>Anopheles funestus </it>(in Dielmo). A significant correlation was found between HLC and LT/M but correlation parameters were different according to the species. Circumsporozoite protein rates were not significantly different between methods or species. The entomological inoculation rate varied along with vector density and thus with methods and species.</p> <p>Conclusions</p> <p>The choice of sampling method influenced entomological data recorded. Therefore, the sampling technique has to be chosen according to the vector studied and the aim of the study. Only HLC must be considered as the reference method, but in some conditions LT/N can be used as an alternative method.</p

Resistance to DDT and Pyrethroids and Increased kdr Mutation Frequency in An. gambiae after the Implementation of Permethrin-Treated Nets in Senegal

Introduction: The aim of this study was to evaluate the susceptibility to insecticides of An. gambiae mosquitoes sampled in Dielmo (Senegal), in 2010, 2 years after the implementation of Long Lasting Insecticide-treated Nets (LLINs) and to report the evolution of kdr mutation frequency from 2006 to 2010. Methods: WHO bioassay susceptibility tests to 6 insecticides were performed on adults F0, issuing from immature stages of An. gambiae s.l., sampled in August 2010. Species and molecular forms as well as the presence of L1014F and L1014S kd

Genetic Determination and Linkage Mapping of Plasmodium falciparum Malaria Related Traits in Senegal

Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10−4, Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved

Low and seasonal malaria transmission in the middle Senegal River basin: identification and characteristics of Anopheles vectors

<p>Abstract</p> <p>Background</p> <p>During the last decades two dams were constructed along the Senegal River. These intensified the practice of agriculture along the river valley basin. We conducted a study to assess malaria vector diversity, dynamics and malaria transmission in the area.</p> <p>Methods</p> <p>A cross-sectional entomological study was performed in September 2008 in 20 villages of the middle Senegal River valley to evaluate the variations of <it>Anopheles </it>density according to local environment. A longitudinal study was performed, from October 2008 to January 2010, in 5 selected villages, to study seasonal variations of malaria transmission.</p> <p>Results</p> <p>Among malaria vectors, 72.34% of specimens collected were <it>An. arabiensis</it>, 5.28% <it>An. gambiae </it>of the S molecular form, 3.26% M form, 12.90% <it>An. pharoensis</it>, 4.70% <it>An. ziemanni</it>, 1.48% <it>An. funestus </it>and 0.04% <it>An. wellcomei</it>. <it>Anopheles </it>density varied according to village location. It ranged from 0 to 21.4 <it>Anopheles</it>/room/day and was significantly correlated with the distance to the nearest ditch water but not to the river.</p> <p>Seasonal variations of <it>Anopheles </it>density and variety were observed with higher human biting rates during the rainy season (8.28 and 7.55 <it>Anopheles </it>bite/man/night in October 2008 and 2009 respectively). Transmission was low and limited to the rainy season (0.05 and 0.06 infected bite/man/night in October 2008 and 2009 respectively). During the rainy season, the endophagous rate was lower, the anthropophagic rate higher and L1014F kdr frequency higher.</p> <p>Conclusions</p> <p>Malaria vectors are present at low-moderate density in the middle Senegal River basin with <it>An. arabiensis </it>as the predominant species. Other potential vectors are <it>An. gambiae </it>M and S form and <it>An. funestus</it>. Nonetheless, malaria transmission was extremely low and seasonal.</p

Evidence for an Age-Dependent Pyrogenic Threshold of Plasmodium falciparum Parasitemia in Highly Endemic Populations

Abstract. The high prevalence of asymptomatic malaria infections and the nonspecific signs and symptoms of the disease make the individual diagnosis of clinical malaria uncertain in highly endemic areas. Longitudinal data oqtained during a four-month period from a daily survey of 200 permanent inhabitants (one month-83 years old) living in a holoendemic area were analyzed in a random-effects logistic regression model to investigate the relationship between the level of Plasrnodiuirz falciparurn parasitemia and risk of fever. It was not possible to build a model that describedl summarized correctly this relationship by a continuous function. Findings provide evidence for an age-dependent threshold effect of parasitemia on the occurrence of fever. The level of this threshold varied by 2.45 trophozoites per leukocyte, maximum at one year of age, to 0.5 trophozoites per leukocyte, minimum at 60 years of age. When the parasite density of a person crossed the threshold level corresponding to his or her age, the individual&apos;s risk of fever was multiplied by 44 (95%&apos;confidence interval = 13.6-144.8). The existence of this threshold effect allows parasite density to be used to distinguish malaria attacks from other causes of fever within an individual and should facilitate the accurate evaluation of the incidence of clinical malaria in highly endemic areas. Because of the high prevalence of asymptomatic malaria infections and the nonspecific signs and symptoms of the disease, the diagnosis of clinical malaria presents difficul