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Despite significant progress since the 2000s, malaria remains in Africa a major health problem for families who, in the absence of medical coverage, have to manage all the health problems occurring among household members. For economic reasons, the practice of self-medication is important, facilitated by a very active informal drug market. Thus, understanding the malaria burden in sub-Saharan Africa requires a dual approach combining quantitative measures estimating the extent of observed phenomena, and a qualitative ethnographic approach to better understand households’ management of these health issues. This chapter describes fifteen years of interdisciplinary research incorporating medical anthropological and social epidemiological approaches to explore ways of managing malaria in families and access to medicines outside the control of medical facilities. This was a collaborative research project, first conducted in parallel and then jointly as part of a European programme concerning pharmaceutical markets and Artemisinin-based combination therapies. Analyses and findings presented in this chapter based on surveys in Senegal and Benin highlight the impact that such a combined approach may have in improving the adaptation of malaria control strategies to people’s life contexts.

Background There are no data on the burden of malaria in pregnancy (MiP) in Laos, where malaria still remains prevalent in the south. Methods Two cross-sectional surveys were conducted in 2014 to assess the prevalence of MiP in Vapi District, Salavan Province, southern Laos: the first consisted of screening 204 pregnant women during pregnancies [mean (95 % CI) gestational age: 23 (22–25) weeks] living in 30 randomly selected villages in Vapi District; the second was conducted among 331 pregnant women, who delivered during the study period in Vapi and Toumlane District Hospitals and in Salavan Provincial Hospital. Peripheral and placental malaria was detected using rapid diagnostic tests (RDT), thick blood smears (TBS) and real-time quantitative polymerase chain reactions (RT-qPCR). Factors associated with low birth weight (LBW) and maternal anaemia were assessed. Results In the villages, 12/204 women (5.9 %; 95 % CI 3.1–10.0) were infected with malaria as determined by RT-qPCR: 11 were Plasmodium vivax infections and 1 was mixed Plasmodium vivax/Plasmodium falciparum infection, among which 9 were sub-microscopic (as not detected by TBS). History of malaria during current pregnancy tended to be associated with a higher risk of MiP (aIRR 3.05; 95 % CI 0.94–9.88). At delivery, two Plasmodium falciparum sub-microscopic infections (one peripheral and one placental) were detected (4.5 %; 0.6–15.5) in Vapi District. In both surveys, all infected women stated they had slept under a bed net the night before the survey, and 86 % went to the forest for food-finding 1 week before the survey in median. The majority of infections (94 %) were asymptomatic and half of them were associated with anaemia. Overall, 24 % of women had LBW newborns. Factors associated with a higher risk of LBW were tobacco use (aIRR 2.43; 95 % CI 1.64–3.60) and pre-term delivery (aIRR 3.17; 95 % CI 2.19–4.57). Factors associated with a higher risk of maternal anaemia were no iron supplementation during pregnancy, Lao Theung ethnicity and place of living. Conclusions The prevalence of MiP in this population was noticeable. Most infections were asymptomatic and sub-microscopic vivax malaria, which raises the question of reliability of recommended national strategies for the screening and prevention of MiP in Laos. Electronic supplementary material The online version of this article (doi:10.1186/s12936-016-1492-2) contains supplementary material, which is available to authorized users.

Different domains of a novel full-length var gene (termed 732var) isolated from a placenta of a malaria-infected woman were expressed in Escherichia coli as recombinant proteins and analysed biochemically and immunologically. Two of these, the Duffy binding-like (DBL)-3gamma domain and the cysteine-rich interdomain region (CIDR)-1alpha were able to bind chondroitin sulfate A and CD36, respectively. The DBL-3gamma domain was investigated in a previous study and confirmed here to exhibit anti-disease characteristics related to pregnancy-associated malaria. Mothers with high anti-DBL-3gamma antibody levels were protected from placental infection. The novel finding in this study is that babies born to mothers carrying anti-CIDR-1alpha antibodies had a delayed time to the first infection.

In African growing cities, vector-borne diseases (such as malaria and dengue) contribute to a large burden of childhood morbidity and mortality. During the peak of transmission, environmental factors can have an influence on those fevers, apart from the individual and household characteristics. A household survey conducted in 2008 in Dakar was completed by a community questionnaire on environmental threats that could be factored into multilevel analyses. Using a randomized sample of 7,300 children from 3,000 households dispatched within 50 neighborhoods, a three-level modeling process is presented. Rates of recent fever varied substantially from one neighborhood to another, ranging between 10 and 37 %. Findings indicate that the onset of fever is influenced by factors from all three hierarchical levels, with neighborhood factors playing a relatively lower role than the other two. Among the environmental factors, the effect of environmental sanitation is particularly interesting.

Urban malaria is considered a major public health problem in Africa. The malaria vector is well adapted in urban settings and autochthonous malaria has increased. Antimalarial treatments prescribed presumptively or after rapid diagnostic tests are also highly used in urban settings. Furthermore, health care strategies for urban malaria must comply with heterogeneous neighbourhood ecosystems where health-related risks and opportunities are spatially varied. This article aims to assess the capacity of the urban living environment to mitigate or increase individual or household vulnerabilities that influence the use of health services. The data are drawn from a survey on urban malaria conducted between 2008 and 2009. The study sample was selected using a twostage randomized sampling. The questionnaire survey covered 2952 households that reported a case of fever episode in children below 10 years during the month before the survey. Self-medication is a widespread practice for children, particularly among the poorest households in Dakar. For rich households, self-medication for children is more a transitional practice enabling families to avoid opportunity costs related to visits to health facilities. For the poorest, it is a forced choice and often the only treatment option. However, the poor that live in well-equipped neighbourhoods inhabited by wealthy residents tend to behave as their rich neighbours. They grasp the opportunities provided by the area and adjust their behaviours accordingly. Though health care for children is strongly influenced by household socio-economic characteristics, neighbourhood resources (facilities and social networks) will promote health care among the poorest and reduce access inequalities. Without being a key factor, the neighbourhood of residence—when it provides resources— may be of some help to overcome the financial hurdle. Findings suggest that the neighbourhood (local setting) is a relevant scale for health programmes in African cities.

Studies with animal models have suggested the possibility of interactions between parasites during concurrent infections and have raised the question of a similar phenomenon in humans. The present survey was undertaken to assess the impact of urinary schistosomiasis on the susceptibility of children to malaria. It was carried out in Senegal between September 2001 and March 2002 among 523 children 3-15 years of age. We tested the association between Plasmodium falciparum densities and the load of Schistosoma haematobium egg excretion using a linear mixed model because data were not independent. After controlling for age, sex, and season, we showed that children lightly infected with S. haematobium (1-9 eggs/10 mL of urine) had lower P. falciparum densities than those not infected (beta = -0.34, 95% confidence interval = -0.85, -0.10), suggesting a negative interaction between both parasites.

Objectives: The risk of malaria infection is increased during pregnancy, and many countries recommend chloroquine prophylaxis in pregnant women, despite Plasmodium falciparum chloroquine resistance. Chloroquine resistance is associated with the pfcrt gene K76T mutation. The aim of this study was to compare the prevalence rate of pfcrt T76 mutation in P. falciparum isolates from infected pregnant and non-pregnant individuals from Senegal. Methods: The study was conducted in the rural maternity hospital of Thiadiaye, Senegal, where malaria is seasonal. Sixty-nine P. falciparum isolates from infected women were collected at delivery. These women were part of a cohort study; they were followed from their first antenatal visit and advised to take chloroquine prophylaxis. For each woman, the earliest P. falciparum-infected blood sample was also used. A control group of 49 non-pregnant individuals with asymptomatic P. falciparum infection was enrolled. Results: During pregnancy, prevalence of T76 mutant parasites was higher than in the 49 non-pregnant controls (P < 0.001). Among pregnant women, this rate was highest at delivery (P 5 0.06), and tended to be higher in women who had taken chloroquine prophylaxis, as assessed in urine samples (P 5 0.08). Conclusions: Chloroquine prophylaxis is responsible for increased drug consumption and increased drug pressure that may lead to the selection of drug-resistant parasites. This is the first report showing that P. falciparum-infected pregnant women harbour pfcrt T76 mutant parasites more often than nonpregnant individuals, and that the prevalence of this mutation is higher at term than earlier during pregnancy.

BACKGROUND: In African rural settings, medically certified information on causes of death is largely lacking. The authors applied the verbal autopsy to identify causes of death before 15 years old in a rural area of Senegal where a demographic surveillance system is operating. METHODS: Between 1989 and 2000, a postmortem interview was conducted using a standardized questionnaire which was independently reviewed by two physicians who assigned the probable underlying cause of death. Discordant diagnoses were discussed by a panel of physicians. Causes of death were grouped into a few categories; cause-specific mortality rates and fractions were generated. RESULTS: Between 1989 and 1997, all-cause mortality fluctuated. Diarrhoeal diseases, malaria and acute respiratory infections explained between 30% and 70% of the mortality before 10 years of age. In children 1-9 years old, malaria death rate increased between 1989 and 1994 and thereafter did not change. The 1998-2000 years were marked by a peak in mortality, attributed to a meningitis outbreak in children more than one year old paralleled by an increase in death rate from fever of unknown origin, diarrhoeal diseases, and acute respiratory infections in children under 5 years. CONCLUSIONS: Verbal autopsy provided useful information on the mortality structure responsible for the 1998-2000 peak in mortality. It underlined that, outside outbreak situations, malaria was a leading cause of death for 1-9 year old children and that diarrhoea, acute respiratory infections, or fever from unknown origin accounted for up to 50% of the deaths among the children under 5 years.

Despite the importance of both environment and behaviour in vector-borne disease epidemiology, these factors are unable to explain alone the distribution of cases in a community and the diversity of clinical presentations, suggesting the involvement of more individual factors such as age, sex, immunity or genetic background. The existence of a genetic factor involved in the susceptibility/resistance to a disease can be suspected by the demonstration of a familial aggregation of cases or by the stability over time of infectious status (infected vs. uninfected; mean level of parasite density (PD), etc.). These familial resemblances can be explained by shared environment, family habits and behaviours (use of bed nets, field activities, etc.). In this preliminary study, we essentially investigated the influence of environment and behaviour on Plasmodium falciparum infection levels and reported the effects of these factors on the existence of familial resemblances. Our results are consistent with the existence of familial resemblances for both the level of P. falciparum infection and the qualitative infection status (QIS) (infected vs. uninfected) that seem to be more related to shared behaviour and environment than to a genetic factor. However, although familial resemblances decreased significantly when adjusted for shared behaviour and environment, this decrease is around 12% for the variability between families, against only 4.5% of that within families. Furthermore, we also demonstrated that the QIS is remarkably stable over time. Both these results are consistent with the hypothesis of the existence of a strong and complex individual factor involved in the control of infection status.

The consequences of pregnancy-associated malaria on a child's health have been poorly investigated. Malarial infection of the placenta seems to result in a higher susceptibility of children to the parasite during their first year of life. In 1993-1995, the authors investigated the role of antibodies in variable surface antigens (VSA) specific to chondroitin sulfate A (CSA)-binding parasites to assess the parasitologic status of the child. Flow cytometry was used to measure levels of antibodies to VSA from CSA-selected and -unselected parasite lines in the cord blood of 79 newborns in Ebolowa, Cameroon. These newborns were subsequently followed up for 2 years to determine the date of first occurrence of blood parasites and mean parasite density during follow-up. Maternally transmitted antibodies to VSA expressed by CSA-binding parasites, but not antibodies to any other specificity, were negatively related to time of first appearance of Plasmodium falciparum in a child's blood and were positively related to mean parasite density during the first 2 years of life. If maternal infection is thought to be the main mechanism influencing susceptibility of the newborn to malaria, antibodies to VSA may better denote maternal malaria infection during almost the entire pregnancy as opposed to placental blood smear reflecting infection during the last few months of pregnancy.

Sequestration of the mature Plasmodium falciparum forms complicates detection, quantification and molecular analysis of human infections. Whether the circulating parasites represent all or only a subset of co-infecting genotypes is unclear. We have investigated this issue and compared placenta and peripheral blood msp1 and msp2 genotypes in 58 women delivering with an ICT-positive placenta in Guediawaye, Senegal. Most placenta (91%) and blood samples (98%) were multiply infected. Multiplicity of infection was positively correlated in both tissues. However, the placental and circulating genotype profiles differed markedly. Only 10% of matched peripheral blood/placenta samples had identical genotypes, whereas 74% had only partially concordant genotypes, with some alleles detected in both tissues, together with additional allele(s) detected in one tissue only. Eight women (14%) had totally discordant placental and peripheral blood genotypes. Thus, in the vast majority of cases, some sequestered genotypes remain hidden, undetected in the peripheral circulation, indicating that analysis of peripheral parasites generates a partial picture of a P. falciparum infection.

Parasitic infections are associated with high morbidity and mortality in developing countries. Several studies focused on the influence of helminth infections on malaria but the nature of the biological interaction is under debate. Our objective was to undertake a study to explore the influence of the measure of excreted egg load caused by Schistosoma haematobium on Plasmodium falciparum parasite densities. Ten measures of malaria parasite density and two measures of schistosomiasis egg urinary excretion over a 2-year follow-up period on 178 Senegalese children were considered. A linear mixed-effect model was developed to take data dependence into account. This work showed that children with a light S. haematobium infection (1-9 eggs/mL of urine) presented lower P. falciparum parasite densities than children not infected by S. haematobium (P < 0.04). Possible changes caused by parasite coinfections should be considered in the anti-helminth treatment of children and in malaria vaccination development.

The interpretation of Western blot patterns according to differing seropositivity criteria represents a major obstacle to determining the seroprevalence of human T-cell lymphotropic virus (HTLV)-1 especially in tropical Africa and Melanesia where a high percentage of Western blots exhibit an indeterminate pattern. This study reviewed HTLV-1 seroprevalence in different ethnic groups and geographic areas of Cameroon by using stringent Western blot criteria and compared the epidemiologic determinants of HTLV-1 prevalence with those of HTLV-1-indeterminate patterns. HTLV-1 prevalence averaged 1.1% among 3783 rural residents of Cameroon. This rate was higher among females (1.5%) and Pygmies (2.0%) and increased with age. 1.6% of the population clustered in tropical forests of southern Cameroon demonstrated a unique HTLV-1 Gag-indeterminate Western blot profile showing strong reactivities to p19 p26 p28 p32 p36 and pr 53 but lacking p24 and env reactivity. Unlike HTLV-1 the seroprevalence of this pattern did not increase with age or differ by sex. Such a Western blot profile is considered to reflect a viral or parasitic factor endemic in tropical rain forest areas rather than an HTLV-1-related viral infection.

T cell responses to leucoagglutinin, PPD, and seven Plasmodium falciparum blood stages antigens were investigated in 164 cord blood samples from Cameroonian neonates. In vitro T cell responses were measured by lymphocyte proliferation, and IL-2, IFN-gamma, and IL-4 release in the presence of crude schizont extract, purified Pf155/RESA protein, and synthetic peptides from Pf155/ RESA. Following culture in presence of leucoagglutinin or PPD, proliferation and cytokine production were very low, as compared to adults from the same area. Interestingly, following stimulation of cord blood lymphocytes by malaria antigens, the percentage of responders and the mean level of positive responses were of the same order than those observed in adults for IL-2 production, while proliferative and IL-4 responses were only marginally decreased. Conversely, IFN-gamma production was highly reduced, as compared to adults. Our results demonstrate that prenatal immune priming to malarial antigens is common in this area and that the fetal immune system is able to respond to antigenic stimuli, as cells proliferate and generate cytokines. As cord blood lymphocytes may be induced to differentiate into effector cells producing predominantly Th1 or Th2 cytokines, malaria during pregnancy might direct the functional capacity of fetal T cells to respond to further infection.

In human populations, the concomitance of various parasitic infections can induce modifications of the specific immune response to each pathogen and thus induce changes in their clinical expression. Several studies, however, have produced conflicting results. To study the hypothesis that there is an association between helminthiasis and the occurrence of severe malaria a prospective case-control study was carried out in a rural zone of Senegal where 105 presumptive severe malaria attacks were studied in 2001 and 2002. Following parasitological control the cases were divided into two groups: A (severe malaria) with severe symptoms and parasite density >5000 parasites/microl (n = 64) and B (other causes) with severe symptoms and negative or weak parasite density (n = 41). In group A the prevalence of Ascaris lumbricoides infection was higher in cases of severe malaria than in controls, odds ratio (OR) = 9.95 (95% CI 3.03-32.69). Similar but not significantly different results were observed between patients in group B and their controls, OR = 2.47 (95% CI 0.95-6.38).

To investigate the mechanisms underlying the increased susceptibility to malaria in pregnant women, we determined the level of malaria-specific immunity in primigravidae. Humoral and cellular in vitro responses to unpurified (a crude schizont extract and a gametocyte preparation) and purified (affinity-purified Pf155/ring-infected erythrocyte surface antigen [RESA]) Plasmodium falciparum proteins, an immunodominant 45/47-kilodalton antigen from Mycobacterium bovis, and leucoagglutinin were compared between 52 primigravidae and 52 nonpregnant women from a semirural area of Cameroon. In vitro cellular responses were investigated in terms of lymphocyte proliferation, as well as production of interleukin-2 (IL-2), interferon-gamma (IFN-γ), and IL-4. Cells from primigravidae exhibited a reduced proliferative response to schizont and gametocyte antigens, as well as to the M. bovis antigen. Conversely, the IL-2 response to Pf155/RESA was reduced. Interleukin-4 and IFN-γ production did not appear to be affected in primigravidae. Antibody levels were also similar between pregnant and nonpregnant women. Our results underline the importance of examining several parameters of T cell activation with different types of antigens for a correct evaluation of the ability of lymphocytes to respond to malaria.

T- and B-cell responses to the Plasmodium falciparum blood-stage antigen Pf155/RESA were investigated in 104 Cameroonian women, half of whom were pregnant. We used purified protein and six synthetic peptides representing T- and B-cell epitopes. In vitro T-cell responses were measured by proliferation and IL2, IFN-gamma, and IL4 release. B-cell responses were assessed by plasma antibodies. All peptides induced a cellular response in some individuals. A proliferative response was induced in 25% of the donors by Pf155/RESA, and in 7 to 11% by any peptide. Cytokine release occurred in 23 to 30% of the Pf155/RESA-stimulated cultures, and in 8 to 25% of the peptide-stimulated cultures. Overall, each peptide induced a cellular response (proliferation and/or cytokine release) in 44% of the donors. T-cells from 23% of the donors failed to respond to any peptide. Responding cells did not usually respond in all readouts, and proliferation and release of any of the three cytokines were not correlated. Similarly, antibody and T-cell responses were not related. Selected epitopes of Pf155/RESA, an important vaccine candidate, are well recognized in naturally exposed individuals and are able to activate T-cells to proliferate and to produce various lymphokines in numerous individuals from a malaria endemic area.

International audience; Introduction The objective of this study was to measure the rate of asymptomatic carriage of plasmodium in the Dakar region two years after the implementation of new strategies in clinical malaria management. Methodology Between October and December 2008, 2952 households selected in 50 sites of Dakar area, were visited for interviews and blood sampling. Giemsa-stained thick blood smears (TBS) were performed for microscopy in asymptomatic adult women and children aged 2 to 10 years. To ensure the quality of the microscopy, we performed a polymerase chain reaction (PCR) with real time qPCR in all positive TBS by microscopy and in a sample of negative TBS and filter paper blood spots. Results The analysis has concerned 2427 women and 2231 children. The mean age of the women was 35.6 years. The mean age of the children was 5.4 years. The parasite prevalence was 2.01% (49/2427) in women and 2.15% (48/2231) in children. Parasite prevalence varied from one study site to another, ranging from 0 to 7.41%. In multivariate analysis, reporting a malaria episode in 2008 was associated with plasmodium carriage (OR = 2.57, P = 0.002) in women; in children, a malaria episode (OR = 6.19, P

Background Urban malaria can be a serious public health problem in Africa. Human-landing catches of mosquitoes, a standard entomological method to assess human exposure to malaria vector bites, can lack sensitivity in areas where exposure is low. A simple and highly sensitive tool could be a complementary indicator for evaluating malaria exposure in such epidemiological contexts. The human antibody response to the specific Anopheles gSG6-P1 salivary peptide have been described as an adequate tool biomarker for a reliable assessment of human exposure level to Anopheles bites. The aim of this study was to use this biomarker to evaluate the human exposure to Anopheles mosquito bites in urban settings of Dakar (Senegal), one of the largest cities in West Africa, where Anopheles biting rates and malaria transmission are supposed to be low. Methods One cross-sectional study concerning 1,010 (505 households) children (n = 505) and adults (n = 505) living in 16 districts of downtown Dakar and its suburbs was performed from October to December 2008. The IgG responses to gSG6-P1 peptide have been assessed and compared to entomological data obtained in or near the same district. Results Considerable individual variations in anti-gSG6-P1 IgG levels were observed between and within districts. In spite of this individual heterogeneity, the median level of specific IgG and the percentage of immune responders differed significantly between districts. A positive and significant association was observed between the exposure levels to Anopheles gambiae bites, estimated by classical entomological methods, and the median IgG levels or the percentage of immune responders measuring the contact between human populations and Anopheles mosquitoes. Interestingly, immunological parameters seemed to better discriminate the exposure level to Anopheles bites between different exposure groups of districts. Conclusions Specific human IgG responses to gSG6-P1 peptide biomarker represent, at the population and individual levels, a credible new alternative tool to assess accurately the heterogeneity of exposure level to Anopheles bites and malaria risk in low urban transmission areas. The development of such biomarker tool would be particularly relevant for mapping and monitoring malaria risk and for measuring the efficiency of vector control strategies in these specific settings.

Background To be effective, national malaria guidelines must be properly followed. This study evaluated nurses' practices in the management of uncomplicated malaria cases at a District Hospital. Its objective was to identify the reasons for discrepancies between official guidelines and usual practices. Methods This study took place at Oussouye hospital, south-western Senegal. Blood smears were available for biological diagnosis in patients aged more than five years while the Integrated Management of Childhood Illness recommended treating fevers presumptively in children under five. First line anti-malarial was Amodiaquine plus sulphadoxine-pyrimethamine (AQ+SP) bi-therapy. Hospital records of children under 13 years of age seen between 2004 and 2005 were reviewed. Results Among children treated with anti-malarials, 74% (2, 063/2, 789) received AQ+SP. However, only 22% (406/1, 879) of febrile children and 19% (429/2, 198) of children diagnosed with malaria got a blood smear. Moreover, an anti-malarial was prescribed for 80% (377/474) of children with a negative blood smear. Conclusions The transition from chloroquine to AQ+SP was well followed. Nonetheless, blood smear use was very low and many over-prescriptions were reported. Reasons for discrepancies between guidelines and practices can be classified in three main categories: ambiguous guidelines, health system's dysfunctions and nurses' own considerations. Aside from the strengthening of the public health system, in order to guarantee practices complying with guidelines, training content should be more adapted to nurses' own considerations.

This anthropological study, conducted in Cotonou, Benin between 2005 and 2007, investigates the informal pharmaceuticals market. It was carried out through a long-term participant observation of informal vendors and semi-directive and unstructured interviews. A classification of products sold in the informal market was developed. The fact that a high percentage of them come from Anglophone countries near Benin (Nigeria and Ghana) led to a comparison of the sources of pharmaceutical supply in these three countries as well as their current legislation regarding pharmaceutical distribution. Our study results highlight a new understanding of the phenomenon of the informal market. Nigeria and Ghana rely on a liberal pharmaceutical distribution system with little intervention from public authorities. Conversely, the government maintains considerable influence over pharmaceutical distribution in Benin. Hence, the differences between these three countries in terms of variety of supply sources and flexibility of access to drugs are understood through an investigation of Benin’s informal market. Therefore, it appears that beyond issues concerning the quality of the pharmaceuticals, this phenomenon illustrates a kind of liberalization of pharmaceutical distribution and the ensuing public health issues.

Background The introduction of new anti-malarial treatment that is effective, but more expensive, raises questions about whether the high level of effectiveness observed in clinical trials can be found in a context of family use. The objective of this study was to determine the factors related to adherence, when using the amodiaquine/sulphadoxine-pyrimethamine (AQ/SP) association, a transitory strategy before ACT implementation in Senegal. Methods The study was conducted in five rural dispensaries. Children, between two and 10 years of age, who presented mild malaria were recruited at the time of the consultation and were prescribed AQ/SP. The child's primary caretaker was questioned at home on D3 about treatment compliance and factors that could have influenced his or her adherence to treatment. A logistic regression model was used for the analyses. Results The study sample included 289 children. The adherence rate was 64.7%. Two risks factors for non-adherence were identified: the children's age (8–10 years) (ORa = 3.07 [1.49–6.29]; p = 0.004); and the profession of the head of household (retailer/employee versus farmer) (ORa = 2.71 [1.34–5.48]; p = 0.006). Previously seeking care (ORa = 0.28 [0.105–0.736], p=0.001] satisfaction with received information (ORa = 0.45 [0.24–0.84]; p = 0.013), and the quality of history taking (ORa = 0.38 [0.21–0.69]; p = 0.001) were significantly associated with good compliance. Conclusion The results of the study show the importance of information and communication between caregivers and health center staff. The experience gained from this therapeutic transition emphasizes the importance of information given to the patients at the time of the consultation and drug delivery in order to improve drug use and thus prevent the emergence of rapid drug resistance.

Background Although there are many methods available for measuring compliance, there is no formal gold standard. Different techniques used to measure compliance were compared among children treated by the anti-malarial amodiaquine/sulphadoxine-pyrimethamine (AQ/SP) combination therapy, in use in Senegal between 2004 and 2006. Methods The study was carried out in 2004, in five health centres located in the Thies region (Senegal). Children who had AQ/SP prescribed for three and one day respectively at the health centre were recruited. The day following the theoretical last intake of AQ, venous blood, and urine samples were collected for anti-malarial drugs dosage. Caregivers and children above five years were interviewed concerning children's drug intake. Results Among the children, 64.7% adhered to 80% of the prescribed dose and only 37.7% were strict full adherent to the prescription. There was 72.7% agreement between self-reported data and blood drug dosage for amodiaquine treatment. Concerning SP, results found that blood dosages were 91.4% concordant with urine tests and 90% with self-reported data based on questionnaires. Conclusion Self-reported data could provide useful quantitative information on drug intake and administration. Under strict methodological conditions this method, easy to implement, can be used to describe patients' behaviors and their use of new anti-malarial treatment. Self-reported data is a major tool for assessing compliance in resource poor countries. Blood and urine drug dosages provide qualitative results that confirm any drug intake. Urine assays for SP could be useful to obtain public health data, for example on chemoprophylaxis among pregnant women.

Increased Plasmodium falciparum resistance to chloroquine has prompted national malaria programs to develop new policies in several African countries. Less than a year after the introduction of amodiaquine/sulfadoxine-pyrimethamine (AQ/SP) as first-line treatment in Senegal, we examined adherence rates to therapy and its efficacy among children. The study was conducted in five dispensaries in rural Senegal. Children aged 2-10 years with a presumptive diagnosis of malaria were prescribed AQ/SP. Thick blood film analyses were carried out on days 0, 3, 7, 14 and 28. Blood and urine samples were collected on day 3 for drug level measurements. The principal caregivers were questioned on treatment adherence. Among the 289 recruited children, 144 had a parasitemia >2500/microl. The results demonstrated markedly good efficacy for the treatment, as no detectable parasitemia was observed on day 28 for 97.9% of the children. However, we noticed that 35.3% of children did not comply with the recommended doses and 62.3% did not exactly adhere to the drug schedule. Despite the good efficacy of the drugs, adherence to the therapeutic scheme was poor. Strategies to promote patient adherence would improve drug performance and thus might help to prevent the rapid emergence of drug resistance.

The deployment of Artemisinin-based Combination Therapy for treating uncomplicated malaria poses problems in the patient compliance to these new treatments. The aim of our study was to investigate the relationship between compliance to 3 days treatment with Artesunate plus Amodiaquine (AS + AQ) and the Mono-Desethyl-Amodiaquine (MDA) blood concentration on the fourth day. A reference scale of mean MDA blood concentrations was constructed in 40 healthy adults. Each concentration corresponded to the MDA level on day 3 in a subject having one of the seven compliance degrees defined by the number and sequence of drug intakes from day 0 to day 2: one single dose on day 0, day 1 or day 2; two single doses separated by 24 h, on day 0 and day 1 or on day 1 and day 2; two single doses separated by 48 h, on day 0 and day 2; three single doses, on day 0, day 1 and day 2. MDA was assayed in whole blood samples by HPLC. Non-parametric Mann and Whitney U tests were used for the comparison of two means. Our results demonstrated no clear relationship between the mean MDA blood concentrations on day 3 and compliance degrees, according to neither the number nor the sequence of doses taken. In particular, even though the differences were not significant, the mean concentration after three doses, expected to be the maximum, was unexpectedly lower than after two doses, on day 0 and day 1 or on day 1 and day 2. The high inter-individual variability of MDA concentrations attributed to the different rates of hepatic metabolism of each individual appears to have a greater effect on MDA levels than the number or timing of doses. Therefore, it seems that the role of a MDA blood assay is limited in use to discerning if none or one or more doses have been taken. A MDA assay do not allow to measure the compliance degree of one patient to AS + AQ association. Presently, interview and pill count following treatment seem to be the only tools available that may permit differentiation between degrees of compliance.

Background In Thailand, South Africa and Zanzibar, a decrease in malaria morbidity was observed following the introduction of artemisinin-based combination therapy (ACT). In Senegal, therapeutic trials supervised the in vivo efficacy of artesunate plus amodiaquine from 1999 to 2005 at the M'lomp village dispensary. The trends in malaria morbidity in this village were evaluated from 2000 to 2002. Methods Each year, between July and December inclusive, fevers treated with antimalarials and slide-proven, uncomplicated malaria cases were collected from dispensary health records. Data were also collected in 1998, just prior to ACT introduction. Pearson's chi square tests and Student tests were used to compare two percentages or two means respectively (α = 0.05). Results Between 1998 and 2002, the total number of fevers treated with antimalarials and their repetitiveness progressively decreased: From 2824 to 945 fevers and from 17.6% to 9.7% (RR1998–2002 = 0.55; [0.44–0.69]; p < 0.0001) respectively. Considering uncomplicated malaria cases only, a decrease was observed in their total number between 2001 and 2002, from 953 to 570 cases. The incidence rate and repetitiveness also decreased. The incidence rate fell from 46.1% in 2001 to 37.5% in 2002 (p < 0.0001) and the repetitiveness decreased from 13.0% in 2000 to 6.6% in 2002 (RR2000–2002 = 0.51; [0.35–0.72]; p = 0.0001). Conclusion The percentage of uncomplicated malaria cases treated with ACT increased, from 18.9% in 2000 to 64.0% in 2002, making it tempting to conclude an impact on malaria morbidity. Nonetheless, the decline in incidence rate of uncomplicated malaria was slight and a lower recorded rainfall was reported in 2002 which could also explain this decline. The context in which ACT is introduced affects the impact on malaria morbidity. In M'lomp, in contrast to studies in Thailand, South Africa and Zanzibar, ACT coverage of malaria cases was low and no vector control measure was deployed. Moreover, the malaria transmission level is higher. In sub-Saharan countries, in order to optimize the impact on malaria morbidity, ACT deployment must be supported, on the one hand, by a strengthening of public health system to ensure a high ACT coverage and, on the other hand, by others measures, such vector control measures.

Malarial infection during pregnancy leads to placental infection, a known risk factor for low birth weight. Whether the stage of pregnancy at infection has a differential influence on these effects is not clearly known, but may be of importance for prevention strategies, including intermittent preventive treatment of pregnant women. Malaria infection during early (before 20 weeks), middle (20-28 weeks), or late (after 28 weeks) pregnancy was evaluated by logistic regression and receiver operating characteristics analysis in relation to placental infection in pregnant Senegalese women. Plasmodium falciparum infections during late pregnancy are strongly related to placental infection, as well as those that occur in middle pregnancy. Knowledge of parasitological events over the entire duration of pregnancy permits a highly accurate prediction of placental infection. Not only malaria infections during late pregnancy increase the likelihood of placental infection. The current policy of intermittent preventive treatment of pregnant women, which implies an initial antimalarial cure after 20 weeks of pregnancy, will not avoid early infections. An earlier initiation of malaria prevention might improve its efficacy. (c) 2006 Elsevier B.V. All rights reserved.

Naturally acquired immunity to Plasmodium falciparum is related to immune system that changes during normal development and ageing. The effects of repeated infections during the early life on the maturation of the immune system are still unknown. Elucidation of these effects is of considerable interest given that malaria originates high mortality, especially during the first years of life. We conducted a cohort study to identify naturally acquired immune responses to P. falciparum. Cellular responses of Cameroonian neonates from birth to 36 months of age were evaluated every 6 months by cell proliferation and cytokines (IFN-gamma, IL-2 and IL-4) production after in vitro culture in the presence of schizont extract and Pf155/RESA peptides. Data were analyzed by a multiple correspondence analysis (MCA) exhibiting three main findings. Firstly, the lack of time-dependant evolution of specific immune pathways recruitment in the response to a given antigen, no antigen inducing a specific mode of response at a given time-point. Secondly, most of the data variability was expressed by IFN-gamma and IL-4 productions, and the major variation of the immune response with age involved this change in IFN-gamma production. Thirdly, the age-related immune response evolution is characterized by the acquisition of the capacity to mount a IFN-gamma response, a transient phase during which children produce a high IL-4 response, and the fast vanishing of the dominance of the IL-2 response. These results suggest that P. falciparum specific immune responses are first oriented towards a Th2-type of response, and later switch to Th1-type of response. (c) 2006 Elsevier B.V. All rights reserved.

Pregnancy-associated malaria is characterized by Plasmodium falciparum adherence to chondroitin sulfate A (CSA) in placenta, through a particular variant surface antigen (VSA). VSA(CSA)-specific IgG are involved in protection against placental malaria. In order to assess the relationship between VSA(CSA)-specific antibody responses and parity as well as protection against placental malaria, the occurrence of P. falciparum infection was assessed in 306 pregnant women from a low malaria transmission area of Senegal. Anti-VSA(CSA) antibodies against three placental parasite isolates were measured by flow cytometry, at enrollment and delivery. Placental infection prevalence rates were highest in primigravidae, but no clear decreasing trend was observed from the second pregnancy onwards. Anti-VSA(CSA) antibody prevalence rates increased with parity. Both anti-VSA(CSA) antibody prevalence rates and levels increased during pregnancy only in women infected with P. falciparum. Although a single or a very limited number of P. falciparum infections were able to induce an anti-VSA(CSA) antibody response, the level or the quality of this response did not appear to confer protection against placental malaria infection. (c) 2006 Elsevier B.V. All rights reserved.

Plasmodium falciparum msp-1 and msp-2 genes were quantified by fragment analysis in matched placental, peripheral, and cord blood samples. In the three compartments, the multiplicity of infection values were similar, and parasite populations only partially overlapped, as reported. However, identical alleles represented 80 to 95% of the overall parasite populations of each compartment, demonstrating much more homogenous parasite populations than previously thought.

BACKGROUND During healthy pregnancy, T helper (Th) 1-type and inflammatory-type responses are down-regulated, and Th2-type and proinflammatory-type responses predominate. In Plasmodium falciparum-infected females, these responses induce enhanced production of tumor necrosis factor- alpha and interferon- gamma. METHODS To assess the respective implication of monocytes and T cells in this placental immunomodulation, we cocultured cells from delivering females living in an area where malaria is endemic. Monocytes and T cells from both peripheral and intervillous blood were crossed in in vitro cultures, to compare the proliferative response to several antigens. Moreover, monocyte cell-surface molecules were quantified by flow cytometry. RESULTS Coculture results confirmed placental immunomodulation and suggested that the most affected cells are not the intervillous monocytes, which are as able to present the antigen as the peripheral monocytes, but the intervillous T cells. Monocyte staining showed significant increases in human leukocyte antigen D-related, CD54, CD80, and CD86 surface markers in intervillous blood, compared with peripheral blood, which suggests a relative activation of monocytes in the placenta. CONCLUSION A state of T cell deactivation and monocyte activation is present at delivery. The T cell deactivation in reaction to purified protein derivative could be explained by the presence of local T cell immunoregulatory factors.

Some of the remarks made by M. Nacher about potential biases that may have occurred in our field study are interesting but I do not think that they call into question our results in such a radical way. In particular the arguments concerning the definition of severe malaria do not appear to be compatible with a negative association between severity of malaria and Ascaris infection as he suggests in his letter. Firstly repeated vomiting is indeed a recognized clinical criterion of severity of malaria according to the WHO definition. Secondly a significant proportion of these children presented not only with repeated vomiting but also with other unquestionable criteria of severity such as alterations in consciousness coma or convulsions which would bring our figures far beyond the 60% figure of ‘really severe malaria’ quoted by M. Nacher. Lastly an ideal situation would be to have a complete clinical parasitological and biological definition of the cases. This is very seldom possible particularly in a rural area of Senegal where the latest biological techniques are not available. We were therefore obliged to define severity on a clinical basis with the utmost rigour in the assessment of diagnostic criteria. Cases were identified by skilled nurses or physicians and systematically checked by parasitologists from the IRD (Institut de recherche pour le developpement) team who have had a long experience of malaria surveys in such rural settings. (excerpt)

An epidemiological study of human T-lymphotropic virus type 1 (HTLV-1) and syphilis has been carried out in a multiethnic community of seven neighboring villages located in eastern Gabon on 1240 subjects over 5 years old (82.7% of the population in this age range). Antibodies to HTLV-1 (anti-HTLV-1) were detected by ELISA with confirmation by Western Blot and antibodies to syphilis by Venereal Diseases Research Laboratory assay with confirmation by the Treponema pallidum hemaglutination assay. The prevalence rate of anti-HTLV-1 was 8.5% and increased from 3.7% in the 5 to 14 years age group to 23.8% in the over 60 years age group. Logistic regression showed that the positivity for anti-HTLV-1 was associated with age ethnic group and sex (higher prevalence in females). The seroprevalence rate of syphilis was 8.2%. Seropositivity for syphilis and HTLV-1 were related but age was a confounding variable in this relationship. This study showing a highly heterogeneous distribution of HTLV-1 in a geographically limited area suggests the role of environmental and behavioral factors in HTLV-1 transmission. (authors)

Helminthic infections concomitant with malaria are common in inter-tropical areas. A recent study showed that mice co-infected with Schistosoma mansoni and Plasmodium chabaudi develop higher P. chabaudi parasitaemia and had a higher mortality rate. This important observation deserved to be further investigated among human populations. Malaria attacks were recorded in 512 children aged 6–15 years living in Richard Toll (Northern Senegal) among whom 336 were infected by S. mansoni, and 175 were not. The incidence rate of malaria attacks was significantly higher among S. mansoni-infected individuals, particularly those carrying the highest worm loads, as compared to uninfected subjects (26.6% versus 16,4 %). In contrast, the rate of malaria attacks was lower, without reaching significance, in medium grade S. mansoni infections. Thus, infection by S. mansoni affects susceptibility to malaria, but this can vary according to the intensity of parasite load. The immunological mechanisms underlying this dual effect need to be further explored.

The prevalence of serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) was measured in a Gabonese community at high risk for HBV infection. Among 698 subjects 5 to 24 years old, the prevalence of HBsAg was 11.1% vs. 57.9% for anti-HBs and 7.2% for anti-HBc alone. The prevalence of HBeAg among HBsAg-positive subjects was 26.5% vs. 59.5% for anti-HBe. The prevalence of HBV DNA tested by a hybridization spot test was 2.1% in the overall population and 18.7% among HBsAg-positive subjects. HBV DNA was found in 15 of 21 HBeAg-positive subjects but in none of the subjects positive for anti-HBe or negative for both HBeAg and anti-HBe. HBV DNA was not detected in any HBsAg negative subjects. The prevalence of HBV DNA decreased with age. This low prevalence of HBV DNA contrasts with the high level of endemicity in the study population.