Search

Abstract 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 varATS 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 varATS qPCR. Although the prevalence of asymptomatic P. falciparum infections was higher in school-age children (5–14 years: 42.0%) compared to 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 varATS qPCR only (13.7 parasites/µL; 95% CI 11.4–16.3) (p

Summary: Background: Despite significant progress in malaria control over the past twenty years, malaria remains a leading cause of child morbidity and mortality in Tropical Africa. As most patients do not consult any health facility much uncertainty persists about the true burden of the disease and the range of individual differences in susceptibility to malaria. Methods: Over a 25-years period, from 1990 to 2015, the inhabitants of Dielmo village, Senegal, an area of intense malaria transmission, have been monitored daily for their presence in the village and the occurrence of diseases. In case of fever thick blood films were systematically examined through microscopy for malaria parasites and patients received prompt diagnosis and treatment. Findings: We analysed data collected in 111 children and young adults monitored for at least 10 years (mean 17.3 years, maximum 25 years) enrolled either at birth (95 persons) or during the two first years of life. A total of 11,599 episodes of fever were documented, including 5268 malaria attacks. The maximum number of malaria attacks in a single person was 112. Three other persons suffered one hundred or more malaria attacks during follow-up. The minimum number of malaria attacks in a single person was 11. The mean numbers of malaria attacks in children reaching their 4th, 7th, and 10th birthdays were 23.0, 37.7, and 43.6 attacks since birth, respectively. Sixteen children (14.4%) suffered ten or more malaria attacks each year at ages 1–3 years, and six children (5.4%) each year at age 4–6 years. Interpretation: Long-term close monitoring shows that in highly endemic areas the malaria burden is higher than expected. Susceptibility to the disease may vary up to 10-fold, and for most children childhood is an endless history of malaria fever episodes. No other parasitic, bacterial or viral infection in human populations has such an impact on health. Funding: The Pasteur Institutes of Dakar and Paris, the Institut de Recherche pour le Développement, and the French Ministry of Cooperation provided funding.

In sub-Saharan Africa, despite the implementation of multiple control interventions, the prevalence of malaria infection and clinical cases remains high. The primary tool for vector control against malaria in this region is the use of long-lasting insecticide-treated nets (LLINs) combined or not with indoor residual spraying (IRS) to achieve a synergistic effect in protection. The objective of this study was to assess the effectiveness of LLINs, with or without IRS, protected against Plasmodium falciparum infection and uncomplicated clinical cases (UCC) of malaria in Benin. A case-control study was conducted, encompassing all age groups, in the urban area of Djougou and the rural area of Cobly. A cross-sectional survey was conducted that included 2080 individuals in the urban area and 2770 individuals in the rural area. In the urban area, sleeping under LLINs did not confer significant protection against malaria infection and UCC when compared to no intervention. However, certain neighbourhoods benefited from a notable reduction in infection rates ranging from 65% to 85%. In the rural area, the use of LLINs alone, IRS alone, or their combination did not provide additional protection compared to no intervention. IRS alone and LLINs combined with IRS provided 61% and 65% protection against malaria infection, respectively, compared to LLINs alone. The effectiveness of IRS alone and LLINs combined with IRS against UCC was 52% and 54%, respectively, when compared to LLINs alone. In both urban and rural areas, the use of LLINs alone, IRS alone, and their combination did not demonstrate significant individual protection against malaria infection and clinical cases when compared to no intervention. In the conditions of this study, LLINs combined or not with IRS are not effective enough to eliminate malaria. In addition to the interventions, this study identified factors associated with malaria in Benin as housing design, neglected social groups like gender-marginalised individuals and adolescents, and socio-economic conditions acting as barriers to effective malaria prevention. Addressing these factors is crucial in order to facilitate malaria elimination efforts in sub-Saharan Africa.

Arboviruses have been shown to circulate in Madagascar, including West Nile, dengue, and chikungunya viruses, though the extent of their circulation remains poorly documented. We estimated the seroprevalence of these three arboviruses in Madagascar and determined risk factors associated with seropositivity. Serum samples obtained from 1680 individuals surrounding the Sentinel Health Centers network in all regions of the country were analyzed using ELISA and hemagglutination inhibition assays for dengue, chikungunya, and West Nile viruses IgG antibodies, and multivariate logistic regression models were run. Overall, 6.5% [IC 95% 3.2–9.9] were seropositive for dengue virus, predominantly of Dengue serotype 1, 13.7% [IC 95% 6.5–20.9] for chikungunya virus, and 12.7% [IC 95% 9.0–16.5] for West Nile virus. There was no association with age, showing that dengue and chikungunya viruses were likely recently introduced. Eastern and Northern parts were more affected by dengue and chikungunya viruses, while West Nile virus seemed to circulate in all parts of the country. Dengue and chikungunya seropositivity were notably associated with high levels of vegetation, as well as frequent work in the forest, and West Nile seropositivity with the presence of cultivated areas, as well as standard of living. This analysis gives a new insight into arboviruses circulation and transmission patterns in Madagascar.

Abstract 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.

We conducted a national human serologic study of a hantavirus detected in Madagascar rodents using a commercial kit and a new ELISA targeting the virus. Our results suggest a conservative estimate of 2.7% (46/1,680) IgG seroprevalence. A second single-district study using the new ELISA revealed a higher prevalence (7.2%; 10/139).

Le risque de décès, d’aggravation d’une maladie ou d’endettement dans ses suites, dépend des dispositifs et moyens disponibles et accessibles à la population pour y faire face. Ainsi, la vulnérabilité liée au paludisme dépend des contextes socio-économique et géoclimatique qui déterminent le risque de transmission, des comportements individuels ou collectifs, et des moyens des ménages pour faire face à la maladie, la prendre en charge ou la prévenir.La présente étude vise à identifier les déterminants de la vulnérabilité liée au paludisme de la population de Madagascar, en analysant le contexte et les comportements de prévention et de recours aux soins médicaux en cas de fièvre. Une étude quantitative sur 4 043 personnes de 803 ménages a été combinée à une étude qualitative reposant sur une soixantaine d’entretiens, dans deux districts, Ankazobe (Hautes Terres) et Brickaville (côte est), où le risque de paludisme et les contextes psycho-sociaux différaient. Les données ont été collectées en 2014 dans le cadre d’une thèse et d’une étude pluridisciplinaire, multicentrique et internationale (projet PALEVALUT), pour laquelle un questionnaire et des guides d’entretien ont été développés, standardisés et validés.À Brickaville, les conditions bioclimatiques (chaudes et humides) sont plus favorables au développement des moustiques vecteurs du paludisme qu’à Ankazobe. La survenue de fièvre, la connaissance d’une personne décédée du paludisme, la perception de la dangerosité de cette maladie, la citation de fausses croyances à son sujet, l’utilisation de moustiquaires, le recours à un professionnel de santé et à un test sanguin pour son diagnostic, et le paiement de frais pour le déplacement vers une structure de santé ou pour obtenir des soins en cas de fièvre, y étaient significativement plus fréquents. En revanche, l’exposition à l’éducation pour la santé, la compréhension du paludisme, le recours aux agents communautaires et la prise d’une combinaison thérapeutique à base d’artémisinine en cas de prise d’antipaludique, y étaient significativement moins fréquents qu’à Ankazobe.Ainsi, à Brickaville où la prévalence du paludisme était la plus élevée, certaines connaissances, attitudes et pratiques, associées à la prévention ou au traitement étaient plus fréquentes alors que d’autres, notamment en matière thérapeutique, étaient plus souvent inappropriées. L’écosystème, la disponibilité, l’accessibilité et la nature des lieux de recours, l’exposition à l’éducation pour la santé, les pratiques médicales des soignants et des patients, différaient significativement dans ces sites distants de moins de 300 km ou entre des sous-populations d’un même site. Ces déterminants de la vulnérabilité liée au paludisme, multidimensionnels et complexes, sont présentés et discutés ici sur les plans quantitatifs et qualitatifs.

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.

Background: The reduction of global malaria burden over the past 15 years is much attributed to the expansion of mass distribution campaigns (MDCs) of long-lasting insecticidal nets (LLIN). In Madagascar, two LLIN MDCs were implemented and one district also benefited from a community-based continuous distribution (CB-CD). Malaria incidence dropped but eventually rebounded after a decade. Methods: Data from a sentinel surveillance network over the 2009–2015 period was analyzed. Alerts were defined as weekly number of malaria cases exceeding the 90th percentile value for three consecutive weeks. Statistical analyses assessed the temporal relationship between LLIN MDCs and (i) number of malaria cases and (ii) malaria alerts detected, and (iii) the effect of a combination of MDCs and a CB-CD in Toamasina District. Findings: Analyses showed an increase of 13.6 points and 21.4 points in the percentile value of weekly malaria cases during the second and the third year following the MDC of LLINs respectively. The percentage of alert-free sentinel sites was 98.2% during the first year after LLIN MDC, 56.7% during the second year and 31.5% during the third year. The number of weekly malaria cases decreased by 14% during the CB-CD in Toamasina District. In contrast, sites without continuous distribution had a 12% increase of malaria cases. Interpretation: These findings support the malaria-preventive effectiveness of MDCs in Madagascar but highlight their limited duration when not followed by continuous distribution. The resulting policy implications are crucial to sustain reductions in malaria burden in high transmission settings. Keywords: Malaria, Madagascar, LLINs effectiveness, Sentinel surveillance

Abstract Background Plague is a life-threatening disease caused by the bacterium, Yersinia pestis. Madagascar is the leading country for human plague cases worldwide. Human plague is a serious disease, particularly in its septicaemic and pneumonic forms. We report a case of pneumonic plague co-infected by a MDR-Stenotrophomonas maltophilia. Case presentation A 24 year-old man originated from Soavinandriana, a plague focus, felt uneasy and developed high fever with chills. He started treatment by himself, by private medical care and by a traditional healer for nine days moving several times from place to place. His condition had deteriorated when he presented to a district hospital with a syndrome of dyspnea, bronchial rale and altered state of consciousness. Two days later, plague diagnosis, performed as a last resort, revealed a positive F1 antigen on rapid diagnostic test. Additional tests (pla PCR and plague serology) evidenced a Y. pestis infection. However, streptomycin treatment did not achieve a complete recovery as the course of disease was complicated by the presence of MDR-S. maltophilia in his lung. This opportunistic infection could have been favored by an immunosuppression due to Y. pestis pulmonary infection and probably been acquired during his stay at a District Hospital. He was treated with a combination of ciprofloxacin and gentamycin and recovered fully. Conclusions Pneumonic plague infection may promote another virulent or avirulent bacterial infection particularly when it is not initially suspected. However, coinfection is rarely described and its occurrence frequency is unknown. In middle or low resources areas, which is the case of most plague endemic countries, control and prevention of infections in health facilities is not optimal. Co-infection with an opportunistic pathogen agent, such as S. maltophilia, is a risk which must not be disregarded as demonstrated by this case report. When deciding of a national control strategy, it should be taken into account in the choice of the first line treatment.

Humoral immunity to Plasmodium falciparum is acquired after repeated infections, and can lead to clinical protection. This study aimed to evaluate how human-, parasite-, and environment-related determinants can modulate the dynamics of IgG responses to Plasmodium falciparum after an infection. Individuals (n = 68, average age = 8.2 years) with uncomplicated malaria were treated with ACT and followed up for 42 days. IgG responses to P. falciparum merozoite antigens (PfMSP1, PfMSP3, PfAMA1, PfGLURP-R0), to whole schizont extract (PfSchz), and to Anopheles gSG6-P1 and Aedes Nterm–34 kDa salivary peptides were measured. Regression analyses were used to identify factors that influence the dynamics of IgG response to P. falciparum antigen between D0 and D42, including demographic and biological factors and the level of exposure to mosquito bites. The dynamics of IgG response to P. falciparum differed according to the antigen. According to multivariate analysis, IgG responses to PfSchz and to PfGLURP-R0 appear to be affected by exposure to Aedes saliva and are associated with age, parasite density, and anti-Plasmodium pre-existing immune response at study inclusion. The present work shows that human exposure to Aedes saliva may contribute, in addition to other factors, to the regulation of anti-Plasmodium immune responses during a natural infection.

Abstract Background Tungiasis is highly prevalent in low- and middle-income countries but remains often under diagnosed and untreated eventually leading to chronic sequels. The objective of the study was to assess whether tungiasis-associated inflammation can be detected and quantified by high-resolution infrared thermography (HRIT) and whether after removal of the parasite inflammation resolves rapidly. Methods Patients with tungiasis were identified through active case finding. Clinical examination, staging, and thermal imaging as well as conventional photography were performed. In exemplary cases, the embedded sandfly was extracted and regression of inflammation was assessed by thermal imaging 4 days after extraction. Results The median perilesional temperature was significantly higher than the median temperature of the affected foot (rho = 0.480, p = 0.003). Median perilesional temperature measured by high-resolution infrared thermography was positively associated with the degree of pain (rho = 0.395, p

Abstract Background WHO developed a global strategy to eliminate hepatitis B by 2030 and set target to treat 80% of people with chronic hepatitis B virus (HBV) infection eligible for antiviral treatment. As a first step to achieve this goal, it is essential to conduct a situation analysis that is fundamental to designing national hepatitis plans. We therefore estimated the prevalence of chronic HBV infection, and described the existing infrastructure for HBV diagnosis in Madagascar. Methods We conducted a stratified multi-stage serosurvey of hepatitis B surface antigen (HBsAg) in adults aged ≥18 years using 28 sentinel surveillance sites located throughout the country. We obtained the list of facilities performing HBV testing from the Ministry of Health, and contacted the person responsible at each facility. Results A total of 1778 adults were recruited from the 28 study areas. The overall weighted seroprevalence of HBsAg was 6.9% (95% CI: 5.6–8.6). Populations with a low socio-economic status and those living in rural areas had a significantly higher seroprevalence of HBsAg. The ratio of facilities equipped to perform HBsAg tests per 100,000 inhabitants was 1.02 in the capital city of Antananarivo and 0.21 outside the capital. There were no facilities with the capacity to perform HBV DNA testing or transient elastography to measure liver fibrosis. There are only five hepatologists in Madagascar. Conclusion Madagascar has a high-intermediate level of endemicity for HBV infection with a severely limited capacity for its diagnosis and treatment. Higher HBsAg prevalence in rural or underprivileged populations underlines the importance of a public health approach to decentralize the management of chronic HBV carriers in Madagascar by using simple and low-cost diagnostic tools.

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.

[This corrects the article DOI: 10.1371/journal.pntd.0004827.].

BACKGROUND:Rift Valley fever (RVF) is a vector-borne disease affecting ruminants and humans. Madagascar was heavily affected by RVF in 2008-2009, with evidence of a large and heterogeneous spread of the disease. The identification of at-risk environments is essential to optimize the available resources by targeting RVF surveillance in Madagascar. Herein, the objectives of our study were: (i) to identify the environmental factors and areas favorable to RVF transmission to both cattle and human and (ii) to identify human behaviors favoring human infections in Malagasy contexts. METHODOLOGY/PRINCIPAL FINDINGS:First, we characterized the environments of Malagasy communes using a Multiple Factor Analysis (MFA). Then, we analyzed cattle and human serological data collected at national level using Generalized Linear Mixed Models, with the individual serological status (cattle or human) as the response, and MFA factors, as well as other potential risk factors (cattle density, human behavior) as explanatory variables. Cattle and human seroprevalence rates were positively associated to humid environments (p

BACKGROUND:Although its incidence has been decreasing during the last decade, malaria is still a major public health issue in Madagascar. The use of Long Lasting Insecticidal Nets (LLIN) remains a key malaria control intervention strategy in Madagascar, however, it encounters some obstacles. The present study aimed to explore the local terminology related to malaria, information channels about malaria, attitude towards bed nets, and health care seeking practices in case of fever. This article presents novel qualitative findings about malaria. Until now, no such data has been published for Madagascar. METHODS:A comparative qualitative study was carried out at four sites in Madagascar, each differing by malaria epidemiology and socio-cultural background of the populations. Seventy-one semi-structured interviews were conducted with biomedical and traditional caregivers, and members of the local population. In addition, observations of the living conditions and the uses of bed net were conducted. RESULTS:Due to the differences between local and biomedical perspectives on malaria, official messages did not have the expected impact on population in terms of prevention and care seeking behaviors. Rather, most information retained about malaria was spread through informal information circulation channels. Most interviewees perceived malaria as a disease that is simple to treat. Tazomoka ("mosquito fever"), the Malagasy biomedical word for malaria, was not used by populations. Tazo ("fever") and tazomahery ("strong fever") were the terms more commonly used by members of the local population to refer to malaria related symptoms. According to local perceptions in all areas, tazo and tazomahery were not caused by mosquitos. Each of these symptoms required specific health recourse. The usual fever management strategies consisted of self-medication or recourse to traditional and biomedical caregivers. Usage of bed nets was intermittent and was not directly linked to protection against malaria in the eyes of most Malagasy people. CONCLUSIONS:This article highlights the conflicting understanding of malaria between local perceptions and the biomedical establishment in Madagascar. Local perceptions of malaria present a holistic vision of the disease that includes various social and cultural dimensions, rather than reflecting one universal understanding, as in the biomedical image. The consideration of this "holistic vision" and other socio-cultural aspects surrounding the understanding of malaria is essential in implementing successful control intervention strategies.

Mapping and anticipating risk is a major issue in the fight against malaria, a disease causing an estimated one million deaths each year. Approximately half the world’s population is at risk and it is of prime importance to evaluate the burden of malaria at the spatial as well as the temporal level. The role of the environment with regard to the determinants of transmission and burden of the disease are described followed by a discussion of special issues such as urban malaria, human population mapping and the detection of changes at the temporal scale. Risk maps at appropriate scales can provide valuable information for targeted control and the present review discusses the essentials of principles, methods, advantages and limitations of remote sensing along with a presentation of ecological, meteorological and climatologic data which rule the distribution of malaria. The panel of commonly used analytic methods is examined and the methodological limitations are highlighted. A review of the literature details the increasing interest in the use of remotely sensed data in the study of malaria, by mapping or modeling several malariometric indices such as prevalence, morbidity and mortality, which are discussed with reference to vector breeding, vector density and entomological inoculation rate, estimates of which constitute the foundation for understanding endemicity and epidemics.

The efficacy of malaria control and elimination on islands may depend on the intensity of new parasite inflow. On the Comoros archipelago, where falciparum malaria remains a major public health problem because of spread of drug resistance and insufficient malaria control, recent interventions for malaria elimination were planned on Moheli, 1 of 4 islands in the Comoros archipelago. To assess the relevance of such a local strategy, we performed a population genetics analysis by using multilocus microsatellite and resistance genotyping of Plasmodium falciparum sampled from each island of the archipelago. We found a contrasted population genetic structure explained by geographic isolation, human migration, malaria transmission, and drug selective pressure. Our findings suggest that malaria elimination interventions should be implemented simultaneously on the entire archipelago rather than restricted to 1 island and demonstrate the necessity for specific chemoresistance surveillance on each of the 4 Comorian islands.

The human landing catches is the gold standard method used to study the vectors of malaria and to estimate their aggressiveness. However, this method has raised safety concerns due to a possible increased risk of malaria or other mosquito-borne diseases among the mosquito collectors. The aim of this study was to evaluate the incidence of malaria attacks among mosquito collectors and to compare these results with those of non-collectors in a Senegalese village.From July 1990 to December 2011, a longitudinal malaria study involving mosquito collectors and non-collectors was performed in Dielmo village, Senegal. During the study period, 4 drugs were successively used to treat clinical malaria, and long-lasting insecticide-treated nets were offered to all villagers in July 2008. No malaria chemoprophylaxis was given to mosquito collectors. Incidence of uncomplicated clinical malaria and asymptomatic malaria infection were analyzed among these two groups while controlling for confounding factors associated with malaria risk in random effects negative binomial and logistic regression models, respectively.A total of 3,812 person-trimester observations of 199 adults at least 15 years of age were analyzed. Clinical malaria attacks accounted for 6.3% both in collectors and non-collectors, and asymptomatic malaria infections accounted for 21% and 20% in collectors and non-collectors, respectively. A non-significant lower risk of malaria was observed in the collector group in comparison with the non-collector group after adjusting for other risk factors of malaria and endemicity level (Clinical malaria: adjusted incidence rate ratio = 0.89; 95% confidence interval = 0.65-1.22; p= 0.47).Being a mosquito collector in Dielmo was not significantly associated with an increased risk of malaria both under holoendemic, mesoendemic and hypoendemic conditions of malaria epidemiology. This result supports the view that HLC, the most accurate method for evaluating malaria transmission, may be used without health concerns in Dielmo.

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.

The aim of this study in Curaça, Bahia, Northeast Brazil was to explore possible factors associated with the infestation of human dwellings by Triatoma brasiliensis or Triatoma pseudomaculata, two sylvatic triatomine species. We use multiple logistic regression analysis to show how structural features of the peridomiciliary area combine with the number of animals and sociological factors to allow infestation of some dwellings. It is suggested that T. brasiliensis is associated with human activities, while T. pseudomaculata is associated with vegetation and animals. Peridomiciliary farm animals are a strong risk factor for triatomine infestation.

Analysis of Plasmodium falciparum isolates collected before, during, and after a 1999 malaria epidemic in Djibouti shows that, despite a high prevalence of resistance to chloroquine, the epidemic cannot be attributed to a sudden increase in parasite drug resistance of local parasite populations.

Plasmodium falciparum malaria is usually transmitted by mosquitoes. We report 2 cases in France transmitted by other modes: occupational blood exposure and blood transfusion. Even where malaria is not endemic, it should be considered as a cause of unexplained acute fever.

Dengue is not well documented in Africa. In Cameroon, data are scarce, but dengue infection has been confirmed in humans. We conducted a study to document risk factors associated with anti-dengue virus Immunoglobulin G seropositivity in humans in three major towns in Cameroon.A cross sectional survey was conducted in Douala, Garoua and Yaounde, using a random cluster sampling design. Participants underwent a standardized interview and were blood sampled. Environmental and housing characteristics were recorded. Randomized houses were prospected to record all water containers, and immature stages of Aedes mosquitoes were collected. Sera were screened for anti-dengue virus IgG and IgM antibodies. Risk factors of seropositivity were tested using logistic regression methods with random effects. Anti-dengue IgG were found from 61.4% of sera in Douala (n = 699), 24.2% in Garoua (n = 728) and 9.8% in Yaounde (n = 603). IgM were found from 0.3% of Douala samples, 0.1% of Garoua samples and 0.0% of Yaounde samples. Seroneutralization on randomly selected IgG positive sera showed that 72% (n = 100) in Douala, 80% (n = 94) in Garoua and 77% (n = 66) in Yaounde had antibodies specific for dengue virus serotype 2 (DENV-2). Age, temporary house walls materials, having water-storage containers, old tires or toilets in the yard, having no TV, having no air conditioning and having travelled at least once outside the city were independently associated with anti-dengue IgG positivity in Douala. Age, having uncovered water containers, having no TV, not being born in Garoua and not breeding pigs were significant risk factors in Garoua. Recent history of malaria, having banana trees and stagnant water in the yard were independent risk factors in Yaounde.In this survey, most identified risk factors of dengue were related to housing conditions. Poverty and underdevelopment are central to the dengue epidemiology in Cameroon.

The mechanisms underlying the heterogeneity of clinical malaria remain largely unknown. We hypothesized that differential gene expression contributes to phenotypic variation of parasites which results in a specific interaction with the host, leading to different clinical features of malaria. In this study, we analyzed the transcriptomes of isolates obtained from asymptomatic carriers and patients with uncomplicated or cerebral malaria. We also investigated the transcriptomes of 3D7 clone and 3D7-Lib that expresses severe malaria associated-variant surface antigen. Our findings revealed a specific up-regulation of genes involved in pathogenesis, adhesion to host cell, and erythrocyte aggregation in parasites from patients with cerebral malaria and 3D7-Lib, compared to parasites from asymptomatic carriers and 3D7, respectively. However, we did not find any significant difference between the transcriptomes of parasites from cerebral malaria and uncomplicated malaria, suggesting similar transcriptomic pattern in these two parasite populations. The difference between isolates from asymptomatic children and cerebral malaria concerned genes coding for exported proteins, Maurer's cleft proteins, transcriptional factor proteins, proteins implicated in protein transport, as well as Plasmodium conserved and hypothetical proteins. Interestingly, UPs A1, A2, A3 and UPs B1 of var genes were predominantly found in cerebral malaria-associated isolates and those containing architectural domains of DC4, DC5, DC13 and their neighboring rif genes in 3D7-lib. Therefore, more investigations are needed to analyze the effective role of these genes during malaria infection to provide with new knowledge on malaria pathology. In addition, concomitant regulation of genes within the chromosomal neighborhood suggests a common mechanism of gene regulation in P. falciparum.

BACKGROUND: 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. METHODS AND FINDINGS: 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

We describe clinical and parasitologic features of in vivo and in vitro Plasmodium falciparum resistance to quinine in a nonimmune traveler who returned to France from Senegal in 2007 with severe imported malaria. Clinical quinine failure was associated with a 50% inhibitory concentration of 829 nmol/L. Increased vigilance is required during treatment follow-up.

BACKGROUND: Tungiasis, a parasitic skin disease caused by the female sand flea Tunga penetrans, is a prevalent condition in impoverished communities in the tropics. In this setting, the ectoparasitosis is associated with important morbidity. It causes disfigurement and mutilation of the feet. Feasible and effective treatment is not available. So far prevention is the only means to control tungiasis-associated morbidity. METHODOLOGY: In two villages in Central Madagascar, we assessed the efficacy of the availability of closed shoes and the twice-daily application of a plant-based repellent active against sand fleas (Zanzarin) in comparison to a control group without intervention. The study population was randomized into three groups: shoe group, repellent group and control group and monitored for ten weeks. The intensity of infestation, the attack rate and the severity of tungiasis-associated morbidity were assessed every two weeks. FINDINGS: In the repellent group, the median attack rate became zero already after two weeks. The intensity of the infestation decreased constantly during the observation period and tungiasis-associated morbidity was lowered to an insignificant level. In the shoe group, only a marginal decrease in the intensity of infestation and in the attack rate was observed. At week 10, the intensity of infestation, the attack rate and the severity score for acute tungiasis remained significantly higher in the shoe group than in the repellent group. Per protocol analysis showed that the protective effect of shoes was closely related to the regularity with which shoes were worn. CONCLUSIONS: Although shoes were requested by the villagers and wearing shoes was encouraged by the investigators at the beginning of the study, the availability of shoes only marginally influenced the attack rate of female sand fleas. The twice-daily application of a plant-based repellent active against sand fleas reduced the attack to zero and lowered tungiasis-associated morbidity to an insignificant level.

BACKGROUND: In tropical Africa, where malaria is highly endemic, low grade infections are asymptomatic and the diagnosis of clinical malaria is usually based on parasite density. Here we investigate how changes in malaria control and endemicity modify diagnostic criteria of Plasmodium falciparum attacks. METHODS AND FINDINGS: Parasitological and clinical data from the population of Dielmo, Senegal, monitored during 20 years, are analyzed in a random-effect logistic regression model to investigate the relationship between the level of parasitemia and risk of fever. Between 1990 and 2010, P. falciparum prevalence in asymptomatic persons declined from 85% to 1% in children 0-3 years and from 34% to 2% in adults ≥50 years. Thresholds levels of parasitemia for attributing fever episodes to malaria decreased by steps in relation to control policies. Using baseline threshold during following periods underestimated P. falciparum attacks by 9.8-20.2% in children and 18.9-40.2% in adults. Considering all fever episodes associated with malaria parasites as clinical attacks overestimated P. falciparum attacks by 42.2-68.5% in children and 45.9-211.7% in adults. CONCLUSIONS: Malaria control modifies in all age-groups the threshold levels of parasitemia to be used for the assessment of malaria morbidity and to guide therapeutic decisions. Even under declining levels of malaria endemicity, the parasite density method must remain the reference method for distinguishing malaria from other causes of fever and assessing trends in the burden of malaria.

INTRODUCTION: High malaria transmission heterogeneity in an urban environment is basically due to the complex distribution of Anopheles larval habitats, sources of vectors. Understanding 1) the meteorological and ecological factors associated with differential larvae spatio-temporal distribution and 2) the vectors dynamic, both may lead to improving malaria control measures with remote sensing and high resolution data as key components. In this study a robust operational methodology for entomological malaria predictive risk maps in urban settings is developed. METHODS: The Tele-epidemiology approach, i.e., 1) intensive ground measurements (Anopheles larval habitats and Human Biting Rate, or HBR), 2) selection of the most appropriate satellite data (for mapping and extracting environmental and meteorological information), and 3) use of statistical models taking into account the spatio-temporal data variability has been applied in Dakar, Senegal. RESULTS: First step was to detect all water bodies in Dakar. Secondly, environmental and meteorological conditions in the vicinity of water bodies favoring the presence of Anopheles gambiae s.l. larvae were added. Then relationship between the predicted larval production and the field measured HBR was identified, in order to generate An. gambiae s.l. HBR high resolution maps (daily, 10-m pixel in space). DISCUSSION AND CONCLUSION: A robust operational methodology for dynamic entomological malaria predictive risk maps in an urban setting includes spatio-temporal variability of An. gambiae s.l. larval habitats and An. gambiae s.l. HBR. The resulting risk maps are first examples of high resolution products which can be included in an operational warning and targeting system for the implementation of vector control measures.

Mosquito-borne diseases are major health problems worldwide. Serological responses to mosquito saliva proteins may be useful in estimating individual exposure to bites from mosquitoes transmitting these diseases. However, the relationships between the levels of these IgG responses and mosquito density as well as IgG response specificity at the genus and/or species level need to be clarified prior to develop new immunological markers to assess human/vector contact. To this end, a kinetic study of antibody levels against several mosquito salivary gland extracts from southeastern French individuals living in three areas with distinct ecological environments and, by implication, distinct Aedes caspius mosquito densities were compared using ELISA. A positive association was observed between the average levels of IgG responses against Ae. caspius salivary gland extracts and spatial Ae. caspius densities. Additionally, the average level of IgG responses increased significantly during the peak exposure to Ae. caspius at each site and returned to baseline four months later, suggesting short-lived IgG responses. The species-specificity of IgG antibody responses was determined by testing antibody responses to salivary gland extracts from Cx. pipiens, a mosquito that is present at these three sites at different density levels, and from two other Aedes species not present in the study area (Ae. aegypti and Ae. albopictus). The IgG responses observed against these mosquito salivary gland extracts contrasted with those observed against Ae. caspius salivary gland extracts, supporting the existence of species-specific serological responses. By considering different populations and densities of mosquitoes linked to environmental factors, this study shows, for the first time, that specific IgG antibody responses against Ae. caspius salivary gland extracts may be related to the seasonal and geographical variations in Ae. caspius density. Characterisation of such immunological-markers may allow the evaluation of the effectiveness of vector-control strategies or estimation of the risk of vector-borne disease transmission.

BACKGROUND:Buruli ulcer, the third mycobacterial disease after tuberculosis and leprosy, is caused by the environmental mycobacterium M. ulcerans. Various modes of transmission have been suspected for this disease, with no general consensus acceptance for any of them up to now. Since laboratory models demonstrated the ability of water bugs to transmit M. ulcerans, a particular attention is focused on the transmission of the bacilli by water bugs as hosts and vectors. However, it is only through detailed knowledge of the biodiversity and ecology of water bugs that the importance of this mode of transmission can be fully assessed. It is the objective of the work here to decipher the role of water bugs in M. ulcerans ecology and transmission, based on large-scale field studies. METHODOLOGY/PRINCIPAL FINDINGS:The distribution of M. ulcerans-hosting water bugs was monitored on previously unprecedented time and space scales: a total of 7,407 water bugs, belonging to large number of different families, were collected over one year, in Buruli ulcer endemic and non endemic areas in central Cameroon. This study demonstrated the presence of M. ulcerans in insect saliva. In addition, the field results provided a full picture of the ecology of transmission in terms of biodiversity and detailed specification of seasonal and regional dynamics, with large temporal heterogeneity in the insect tissue colonization rate and detection of M. ulcerans only in water bug tissues collected in Buruli ulcer endemic areas. CONCLUSION/SIGNIFICANCE:The large-scale detection of bacilli in saliva of biting water bugs gives enhanced weight to their role in M. ulcerans transmission. On practical grounds, beyond the ecological interest, the results concerning seasonal and regional dynamics can provide an efficient tool in the hands of sanitary authorities to monitor environmental risks associated with Buruli ulcer.

BackgroundStudies on human genetic factors associated with malaria have hitherto concentrated on their role in susceptibility to and protection from disease. In contrast, virtually no attention has been paid to the role of human genetics in eliciting the production of parasite transmission stages, the gametocytes, and thus enhancing the spread of disease.Methods and findingsWe analysed four longitudinal family-based cohort studies from Senegal and Thailand followed for 2-8 years and evaluated the relative impact of the human genetic and non-genetic factors on gametocyte production in infections of Plasmodium falciparum or P. vivax. Prevalence and density of gametocyte carriage were evaluated in asymptomatic and symptomatic infections by examination of Giemsa-stained blood smears and/or RT-PCR (for falciparum in one site). A significant human genetic contribution was found to be associated with gametocyte prevalence in asymptomatic P. falciparum infections. By contrast, there was no heritability associated with the production of gametocytes for P. falciparum or P. vivax symptomatic infections. Sickle cell mutation, HbS, was associated with increased gametocyte prevalence but its contribution was small.ConclusionsThe existence of a significant human genetic contribution to gametocyte prevalence in asymptomatic infections suggests that candidate gene and genome wide association approaches may be usefully applied to explore the underlying human genetics. Prospective epidemiological studies will provide an opportunity to generate novel and perhaps more epidemiologically pertinent gametocyte data with which similar analyses can be performed and the role of human genetics in parasite transmission ascertained.

BACKGROUND: Chikungunya virus (CHIKV), an arbovirus, is responsible for a two-stage disabling disease, consisting of an acute febrile polyarthritis for the first 10 days, frequently followed by chronic rheumatisms, sometimes lasting for years. Up to now, the pathophysiology of the chronic stage has been elusive. Considering the existence of occasional peripheral vascular disorders and some unexpected seronegativity during the chronic stage of the disease, we hypothesized the role of cryoglobulins. METHODS: From April 2005 to May 2007, all travelers with suspected CHIKV infection were prospectively recorded in our hospital department. Demographic, clinical and laboratory findings (anti-CHIKV IgM and IgG, cryoglobulin) were registered at the first consultation or hospitalization and during follow-up. RESULTS: Among the 66 travelers with clinical suspicion of CHIKV infection, 51 presented anti-CHIKV IgM. There were 45 positive with the serological assay tested at room temperature, and six more, which first tested negative when sera were kept at 4 degrees C until analysis, became positive after a 2-hour incubation of the sera at 37 degrees C. Forty-eight of the 51 CHIKV-seropositive patients were screened for cryoglobulinemia; 94% were positive at least once during their follow-up. Over 90% of the CHIKV-infected patients had concomitant arthralgias and cryoglobulinemia. Cryoglobulin prevalence and level drop with time as patients recover, spontaneously or after short-term corticotherapy. In some patients cryoglobulins remained positive after 1 year. CONCLUSION: Prevalence of mixed cryoglobulinemia was high in CHIKV-infected travelers with long-lasting symptoms. No significant association between cryoglobulinemia and clinical manifestations could be evidenced. The exact prognostic value of cryoglobulin levels has yet to be determined. Responsibility of cryoglobulinemia was suspected in unexpected false negativity of serological assays at room temperature, leading us to recommend performing serology on pre-warmed sera.

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

BackgroundSurrogate markers of protective immunity to malaria in humans are needed to rationalize malaria vaccine discovery and development. In an effort to identify such markers, and thereby provide a clue to the complex equation malaria vaccine development is facing, we investigated the relationship between protection acquired through exposure in the field with naturally occurring immune responses (i.e., induced by the parasite) to molecules that are considered as valuable vaccine candidates.Methods and findingsWe analyzed, under comparative conditions, the antibody responses of each of six isotypes to five leading malaria vaccine candidates in relation to protection acquired by exposure to natural challenges in 217 of the 247 inhabitants of the African village of Dielmo, Senegal (96 children and 121 older adolescents and adults). The status of susceptibility or resistance to malaria was determined by active case detection performed daily by medical doctors over 6 y from a unique follow-up study of this village. Of the 30 immune responses measured, only one, antibodies of the IgG3 isotype directed to merozoite surface protein 3 (MSP3), was strongly associated with clinical protection against malaria in all age groups, i.e., independently of age. This immunological parameter had a higher statistical significance than the sickle cell trait, the strongest factor of protection known against Plasmodium falciparum. A single determination of antibody was significantly associated with the clinical outcome over six consecutive years in children submitted to massive natural parasite challenges by mosquitoes (over three parasite inoculations per week). Finally, the target epitopes of these antibodies were found to be fully conserved.ConclusionsSince anti-MSP3 IgG3 antibodies can naturally develop along with protection against P. falciparum infection in young children, our results provide the encouraging indication that these antibodies should be possible to elicit by vaccination early in life. Since these antibodies have been found to achieve parasite killing under in vitro and in vivo conditions, and since they can be readily elicited by immunisation in naïve volunteers, our immunoepidemiological findings support the further development of MSP3-based vaccine formulations.

BACKGROUND: Inadequate treatment practices with antimalarials are considered major contributors to Plasmodium falciparum resistance to chloroquine, pyrimethamine and sulfadoxine. The longitudinal survey conducted in Dielmo, a rural Senegalese community, offers a unique frame to explore the impact of strictly controlled and quantified antimalarial use for diagnosed malaria on drug resistance. METHODOLOGY/PRINCIPAL FINDINGS: We conducted on a yearly basis a retrospective survey over a ten-year period that included two successive treatment policies, namely quinine during 1990-1994, and chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) as first and second line treatments, respectively, during 1995-1999. Molecular beacon-based genotyping, gene sequencing and microsatellite analysis showed a low prevalence of Pfcrt and Pfdhfr-ts resistance alleles of Southeast Asian origin by the end of 1994 and their effective dissemination within one year of CQ and SP implementation. The Pfcrt resistant allele rose from 9% to 46% prevalence during the first year of CQ reintroduction, i.e., after a mean of 1.66 CQ treatment courses/person/year. The Pfdhfr-ts triple mutant rose from 0% to 20% by end 1996, after a mean of 0.35 SP treatment courses/person in a 16-month period. Both resistance alleles were observed at a younger age than all other alleles. Their spreading was associated with enhanced in vitro resistance and rapidly translated in an increased incidence of clinical malaria episodes during the early post-treatment period. CONCLUSION/SIGNIFICANCE: In such a highly endemic setting, selection of drug-resistant parasites took a single year after drug implementation, resulting in a rapid progression of the incidence of clinical malaria during the early post-treatment period. Controlled antimalarial use at the community level did not prevent dissemination of resistance haplotypes. This data pleads against reintroduction of CQ in places where resistant allele frequency has dropped to a very low level after CQ use has been discontinued, unless drastic measures are put in place to prevent selection and spreading of mutants during the post-treatment period.

We report 2 cases of Plasmodium falciparum malaria in southern France in a French woman and an American man of Togolese origin who reported no recent travel to malaria-endemic countries. Both infections occurred after a stay near Marseille, which raises the possibility of autochthonous transmission. Entomologic and genotypic investigations are described.