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The hypothesis that tumor necrosis factor (TNF) aggravates malaria in children is supported by observations that TNF polymorphisms and high TNF levels have been associated with cerebral malaria. Nevertheless, severe malaria was not associated with polymorphisms located at positions -308A and -238A in the TNF alpha gene promoter or with a high TNF level in plasma in children from Bamako, Mali.

We report the results of an in vivo antimalarial efficacy study with chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) conducted between 2003 and 2004 in Koumantou, southern Mali. A total of 244 children were included in the study; 210 children were followed-up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescence from re-infection. Global failure proportions at Day 14, without taking into account re-infections, were 44.2% (95% CI 34.9-53.5%) in the CQ group and 2.0% (95% CI 0.0-4.8%) in the SP group. PCR-adjusted failure proportions at Day 28 were even higher in the CQ group (90.5% (95/105), 95% CI 84.8-96.2%) and relatively low in the SP group (7.0% (7/100), 95% CI 1.9-12.1%). These results show that CQ is no longer efficacious in Koumantou. The use of SP in monotherapy is likely to compromise its efficacy. We recommend the use of artemisinin-based combination therapy as first-line treatment for uncomplicated Plasmodium falciparum malaria in Koumantou.

Background: Despite a broadening consensus about the effectiveness of intermittent preventive treatment (IPTp) in preventing the adverse outcomes of malaria during pregnancy, policy change to IPTp was initially limited to East Africa. In West Africa, where the policy change process for the prevention of malaria during pregnancy started much later, IPTp has been taken up swiftly., Objective: To describe the factors that contributed to the rapid adoption of policies to prevent malaria during pregnancy in West Africa., Results and Conclusion: Several factors appear to have accelerated the process: (1) recognition of the extent of the problem of malaria during pregnancy and its adverse consequences; (2) a clear, evidence-based program strategy strongly articulated by an important multilateral organization (World Health Organization); (3) subregionally generated evidence to support the proposed strategy; (4) a subregional forum for dissemination of data and discussion regarding the proposed policy changes; (5) widespread availability of the proposed intervention drug (sulfadoxine-pyrimethamine); (6) technical support from reputable and respected institutions in drafting new policies and planning for implementation; (7) donor support for pilot experiences in integrating proposed policy change into a package of preventive services; and (8) financial support for scaling up the proposed interventions.

Available facts on morbidity and mortality due to PEV diseases for children under 5 years come from routine facts in Bamako District. The Present study through population investigation proposed to evaluate indicators. It was about a transversal investigation realised about 1014 children less than 5 year living in Bamako (on October 2000). The selection of children has been made by boring after stratification of the district based on socio-economic level and stabilization of population of different sectors. According to study, the global incidence rate of target patients of PEV is about 4.93% +- 1.33%. These rate were about 4.14% +- 1.22% for measles which is the 1st cause of morbidity among target patients of PEV, 0.69% +- 0.50% for whooping cough, 0.903% +- 0.19 for poliomyelitis and 0% for neo natal tetanus. For tuberculosis of which evolution have been appreciated trough counting of antituberculosis clinic register (DAT) during 10 years (1990-1999), its tendency was increasing. The death rate registered during investigation was related to measles with an estimated rate of 4.93% +- 4.31%. Results analysis, global incidence of PEV target patients was in decrease at Bamako district. At vaccinated patients against measles (64.3%) and whooping cough (57.14%) is in favour for an investigation about effective vaccinal.

Background: Schistosoma haematobium infection causes severe urinary disease and considerable mortality. The factors that determine disease progression from mild to severe stages are not fully understood., Methods: Here we describe a cross-sectional epidemiological study of kidney and bladder diseases in 2 Dogon populations with different exposure to S. haematobium infection., Results: Early and high exposure resulted in more-severe disease, especially among young subjects, without clear evidence of a more-rapid development of immunity. Nevertheless, 50%-60% of subjects of all age classes in both villages showed no evidence of disease. Kidney and bladder disease peaked biphasically among young subjects and adults >25 years old. The first peak corresponded with infections of maximum intensity, whereas the second peak occurred among adults with infections of very low intensity. Kidney disease was correlated with circulating anodic antigen concentration in serum, whereas bladder disease was correlated with egg count and eosinophil cationic protein concentration in urine. Kidney and bladder disease did not correlate. Severe kidney disease was more frequent in certain families., Conclusions: The frequency of urinary disease is increased by infections acquired early during life, is regulated by strong clinical immunity in certain subjects, and may be dependent on hereditary factors. Kidney and bladder disease may involve different mechanisms of pathogenesis, which may differ between children and adults.

Background: The pathogenic mechanisms of cerebral malaria (CM) are unclear but are thought to involve cytokine-mediated inflammation enhanced by parasite sequestration in the brain microcirculation. The role that interferon (IFN)-gamma could play that would enhance inflammation but also reduce parasitemia is unclear., Methods: Plasma IFN-gamma concentrations were measured by enzyme-linked immunosorbent assay in 96 children with CM and 40 children with uncomplicated malaria (UM) who had been recruited from Gabriel Toure Hospital (Bamako, Mali). We investigated the relationship between IFN- gamma concentrations and disease by nonparametric analysis. Polymorphisms in IFNG were characterized by restriction enzyme analysis or size-determination electrophoresis. Associations between polymorphisms and CM were evaluated by the family-based association test on 240 families., Results: During episodes of malaria, IFN-gamma concentrations were lower in children with CM than in children with UM (P = .007). IFNG-183T (P = .009) and IFNG-183G/T (P = .013) were found to be less frequent than expected in children with CM. A trend toward association was also observed between IFNG(CA)14/(CA)14 (P = .073) and CM. The IFNG-183G/T and IFNG(CA)14/(CA)14 genotypes were more frequent in children with UM than in children with CM (odds ratio, 0.30 and 0.34, respectively)., Conclusions: The low plasma IFN- gamma concentrations in children with CM and the associations between a reduced risk of CM and (1) the IFNG-183T allele (which increases gene transcription) and (2) the IFNG-183G/T genotype are consistent with the concept that IFN-gamma protects against CM.

Objectives: To assess insecticide-treated nets (ITNs) use, other malaria prevention measures, knowledge of malaria and diffusion of information about ITNs by the National Malaria Control Programme (NMCP) in Mali., Design: A descriptive cross-sectional study., Setting: Four villages in Mopti region, Mali that had participated in the Mopti Regional Malaria Control Program (MRMCP) ITN Education Programme five years prior., Participants: Three hundred thirty nine randomly-selected households. Within each household, mothers of children one to nine years of age were interviewed regarding knowledge of malaria and prevention practices., Results: Overall, 11% of households used ITNs, with 97% of these in two villages. Ninety eight percent of households used bednets, 22% used insecticide sprays and 39% used mosquito coils. Significant predictors of ITNs use were: head of household literacy, larger family size, Bambara ethnicity, hearing about the NMCP and hearing about ITNs from health agents. Reasons why ITNs were not used included not knowing anything about ITNs, cost and not having net impregnation services readily available in the village. Levels of knowledge concerning malaria disease, transmission and prevention varied amongst the four villages. ITN households had significantly higher levels of knowledge about malaria and its prevention., Conclusion: Five years after the implementation of the MRMCP, ITNs use was low and diffusion of malaria prevention information was unequal among villages. Future efforts in improving the programme must recognise these differences in knowledge and ITNs utilisation and make village-specific changes that are acceptable for each village.

Background: Insecticide-treated nets (ITNs) reduce malaria morbidity and mortality, but use is limited. A barrier to ITN use may be lack of knowledge regarding malaria transmission and prevention. This study is a controlled trial comparing ITN use and malaria knowledge levels between households in Piron, Mali, undertaken in 2003., Methods: Households received net impregnation services either with or without antecedent education. The main outcome measure was ITN use, defined as impregnation of at least one of the household's existing bednets with insecticide during the study. Knowledge about malaria and prevention practices was assessed pre- and post- educational intervention. Results were analysed by household and by individual., Results: Forty-nine percent (34/70) of households who received the educational component impregnated their nets in comparison to 35% (22/62) of households who did not (OR = 1.6 CI = 0.8-3.3, P = 0.19). In individual analysis, ITN use was significantly greater in participants who had received the educational intervention (48%) vs. individuals who did not (33%, OR = 1.9, P = 0.012). Knowledge levels about malaria significantly increased for each individual pre- versus post- educational intervention (average change score = 2.13, standard deviation = 1.97, t = -17.78, P < 0.001), although there was no difference found between educational (change score = 2.14) and control groups (change score = 2.12)., Conclusion: It is possible to educate individuals about malaria and to implement net impregnation services with limited resources. Greater accessibility to net-impregnation services is necessary but not sufficient to increase ITN use.

Background: In order to detect potential disease clusters where a putative source cannot be specified, classical procedures scan the geographical area with circular windows through a specified grid imposed to the map. However, the choice of the windows' shapes, sizes and centers is critical and different choices may not provide exactly the same results. The aim of our work was to use an Oblique Decision Tree model (ODT) which provides potential clusters without pre-specifying shapes, sizes or centers. For this purpose, we have developed an ODT-algorithm to find an oblique partition of the space defined by the geographic coordinates., Methods: ODT is based on the classification and regression tree (CART). As CART finds out rectangular partitions of the covariate space, ODT provides oblique partitions maximizing the interclass variance of the independent variable. Since it is a NP-Hard problem in RN, classical ODT-algorithms use evolutionary procedures or heuristics. We have developed an optimal ODT-algorithm in R2, based on the directions defined by each couple of point locations. This partition provided potential clusters which can be tested with Monte-Carlo inference. We applied the ODT-model to a dataset in order to identify potential high risk clusters of malaria in a village in Western Africa during the dry season. The ODT results were compared with those of the Kulldorff' s SaTScan., Results: The ODT procedure provided four classes of risk of infection. In the first high risk class 60%, 95% confidence interval (CI95%) [52.22-67.55], of the children was infected. Monte-Carlo inference showed that the spatial pattern issued from the ODT-model was significant (p < 0.0001). Satscan results yielded one significant cluster where the risk of disease was high with an infectious rate of 54.21%, CI95% [47.51-60.75]. Obviously, his center was located within the first high risk ODT class. Both procedures provided similar results identifying a high risk cluster in the western part of the village where a mosquito breeding point was located., Conclusion: ODT-models improve the classical scanning procedures by detecting potential disease clusters independently of any specification of the shapes, sizes or centers of the clusters.

Millions of humans are exposed to schistosome infections, which cause severe kidney and liver disease and 280,000 deaths annually. Th2-mediated immunity is critical to human defenses against this pathogen and susceptibility to infection is controlled by a major genetic locus that includes IL4, IL5, and IL13 genes. These observations led us to evaluate whether certain polymorphisms in IL4, IL5, or IL13 determine schistosome infection. The study was performed in two Dogon villages where Schistosoma haematobium is endemic. Schistosome infections were evaluated by counting eggs and measuring worm Ags in urine. Genetic polymorphisms were determined by restriction enzyme analysis or by primer extension and denaturing high-performance liquid chromatography analysis. Associations were tested using family-based association tests and logistical regression analysis. The alleles IL13-1055C (p = 0.05) and IL13-591A (p = 0.01) are shown, by family-based association test, to be preferentially transmitted to children with the 10% highest infections. A logistic regression analysis that included IL13-1055 G/G, G/T and T/T genotypes, age, gender, and village of residency, applied to the whole study population, showed that subjects bearing the IL13-1055T/T genotype were on average much less infected than individuals with other genotypes. Previous studies on asthma indicated that the IL13-1055T allele increased gene transcription, which is in agreement with the fact that this cytokine enhances resistance to infection by schistosome in humans.

The main goal of this work was to study the parasitic infections during AIDS diarrhoea. A longitudinal study was carried out from October 2000 to November 2001 in the Hepato-Gastro-Enterology department of Gabriel Toure Hospital and in the Department of Epidemiology and Parasitic infections of Faculty of Medicine, Pharmacy and Odonto-stomatology of Bamako (Mali), concerning HIV positive patients suffering from diarrhoea. Detecting microbes in stools has been done through direct microscopic examination and according to procedures of Henricksen Poblenz Baerman, Kato Katz and the PCR. Among the 70 patients involved, the sex-ratio was 53%, the average age was 35 +/- 8.4 years. Fever weight loss, skin affections and digestive mycosis were often associated. Opportunistic infections have been relatively frequent with Cryptosporidium parvum with 20%, Isospora belli with 8.5% and Microsporidium with 11.5% of cases. Other non-opportunistic microbes were found. Death within the first two weeks seems more important in case of infection by Cryptosporidium parvum. The frequency and the danger of those opportunistic infections require their efficient diagnosis and care management.

We compared malaria indicators among sympatric groups to study human heterogeneities in the response to Plasmodium falciparum malaria infection. Four cross-sectional surveys and two longitudinal surveys in two sympatric ethnic groups (Dogon and Fulani) in Mali were carried out from 1998 to 2000. Spleen and parasite rates were evaluated during the cross-sectional surveys and disease incidence was assessed during longitudinal surveys. In spite of similar sociocultural factors and entomologic inoculation rates between ethnic groups, the Fulani had a significantly higher spleen enlargement rate, lower parasite rate, and were less affected by the disease than the Dogon group, whose frequency of hemoglobin C was higher than that recorded among the Fulani group. The Fulani group had significantly higher levels of IgG and IgE against crude malaria antigen than the Dogon group, suggesting a role of anti-malaria antibodies in the immune protection seen in this group.

Background: Malaria during pregnancy contributes to maternal anemia and low birth weight. In East Africa, several studies have demonstrated that intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) is more efficacious than weekly chloroquine (CQ) chemoprophylaxis in preventing these adverse consequences. To our knowledge, there are no published trials evaluating IPT in West Africa., Methods: We undertook a randomized controlled trial of weekly CQ chemoprophylaxis, 2-dose IPT with CQ, and 2-dose IPT with SP; 1163 women were enrolled., Results: In multivariate analyses, when compared with weekly CQ, IPT/SP was associated with a reduction in third-trimester anemia (adjusted odds ratio [AOR], 0.49; P<.001), placental parasitemia (AOR, 0.69; P=.04), and low birth weight (<2500 g) (AOR, 0.69; P=.04). The prevalence of placental infection remained unexpectedly high, even in the IPT/SP group (24.5%), possibly because of the intensity of seasonal transmission. There were no significant differences in stillbirths, spontaneous abortions, or neonatal deaths among the 3 groups., Conclusions: In Mali, IPT with SP appears more efficacious than weekly chloroquine chemoprophylaxis in preventing malaria during pregnancy. These data support World Health Organization recommendations to administer at least 2 doses of IPT during pregnancy. In intensely seasonal transmission settings in Mali, >2 doses may be required to prevent placental reinfection prior to delivery.

We compared the efficacy and safety of artemether versus Quinine in 67 children from 3 months to 15 years old hospitalised for severe and complicated in the pediatric service of Gabriel Touré's Hospital Children were randomised to receive artemether or quinine. Artemether was given at 3,2mg/kg in day 1 (two times) and 1; 6mg single dose from day 2 to day5) and quinine was administrated at 20mg/kg (attack dose) followed by 10mg/kg every 8 hours until oral drug administration (10 mg/kg every 8 hours). The treatment for artemether lasted 5 days while quinine treatment lasted 7 day. Thirty tree and 34 children received respectively artemether and quinine. Two groups were comparable with baseline characteristics. Cerebral malaria was most frequent in the two with no statistical difference. Seventy height percent in artemether group compared to 82,4% in quinine group. No statistical difference was found between groups regarding parameters such as : Parasitic clearance, thermal clearances, delay of exit of the coma, upsurge, tolerance, and mortality. Artemether is as efficacious and well safe as quinine for the treatment of sevese and complicated malaria.

Summary The aim of this work was to assess the attitude and practice of health staff about malaria. We undertook a cross sectional survey in the district hospital, two community health centers (CSCOM), one private doctor's cabinet and one private nurse's cabinet. We observed the doctors and the nurses during the visit of 261 patients. The most frequent presumption diagnosis was simple malaria without vomiting (53%). Among presumption diagnosis the high frequency of confirmed cases was malaria with vomiting (42%). In the health center, injectable quinine was the most prescribed drug (82%), followed by chloroquine (23%). The injectable quinine was more prescribed by nurses (85%) than doctors (15%) (p=10-6). At the time of follow-up, 98% of patients was cured clinically. Even though malaria was the first reason of visit (99,2%), only one out of ten practitioners checked up temperature of patients. Treatment administered dit not follow guidelines suggested by the national program for malaria control. We thus suggested the training of health staff as well as regular supervision of health centers.

Summary The aim of this work was to assess prevalence and clinic of schistosomiasis as well as the knowledge, attitude and practice (KAP) of populations living in the village of Molodo, a rice irrigated area of Mali. By cross sectional survey with a single passage, we enrolled 346 children aged of 7 to 14 years and 308 parents. The prevalence of Schistosoma haematobium and S. mansoni were respectively 72% and 68%. Micro-hematuria (Sy=86%; Sp=45%), urinary difficulty (Se=828% ; Sp=33%), high frequency of urine (Se=76% ; Sp=31%) and suspubians pain (Se=78% ; Sp=31%) associated with urinary schistosomiasis indicated that these symptoms could be relevant diagnosis signs. Similar observations could be considered as a good sign of diagnosis of intestinal schistosomiasis due to S. mansoni with abdominal pains (Se=75% ; Sp=36%), to have a fancy of stool (Se=75% ; Sp=32%), diarrhea (Se=71% ; Sp=32%), des conjunctival paleness (Se=85,% ; Sp=33%) et de spleen enlargement (Se=71% ; Sp=33%). The transmission patterns of schistosomiasis were not well known by populations, because only 15% of pupils and 38% of parents incriminated the canal and/or the 'fala" (the lake) as genitourinary bilharzias contamination source especially after bathing. The intestinal form was known by 11% of pupils and by 24% of parents. These results show that in spite of schistosomiasis endemic pattern, in this area, populations didn't know well this pathology.

Aims This study was carried up to assess the impact of mass chemotherapy with praziquantel on the prevalence and intensity of Schistosoma haematobium and Schistosoma mansoni in Office du Niger. Materials and Methods It was a cross sectional study with two passages about which we compared a test group of 7 villages (n=2342) treated in 1989 to a control group of 7 villages (n=2263). Results One year after mass chemotherapy, baseline prevalence rates of Schistoosma haematobium, Schistoaoma mansoni and those of the double infection decreased by 50%, 54% and 62,9% respectively. The geometric mean egg counts of Schistosma haematobium (GMECSh) was reduced by 66.6% and that of Schistosoma mansoni (GMECSm) by 43.4%. However, in spite of mass treatment, the overall prevalence rates of Schistosoma haematobium and mansoni were always higher than 20% in young people aged of 6-19 years. Conclusion These data show that in irrigated area, efficacy of praziquantel is strongly affected by age. This persistance of infection in population raises up several questions according to host immunity, parasite biology and praziquantel efficacy.

Summary Aims The coinfection of the VIH and the schistosomiasis is affections brought back in schistosomiasis endemic area. We valued the level of morbidity partner to the schistosomiasis in hospital yard to patients hospitalized without distinction of immunological statute of patients. Patients and Methods Our study was retrospective and prospective. We included all patients hospitalized to internal Medicine and infectious diseases carriers of schistosomiasis to the mucous rectal biopsy and parasitologic exam of stools and urines between January 1998 and July 2005. Results Twenty-four patients were included in the survey of which 15 of masculine sex (62,50%) and 9 of feminine sex (37,50%). The sex ratio (H/F) = 1,66. The most tainted professions were pupils, peasants and housewives. Ten patients had benefited from the VIH tracking (41,66%) and 6 patients were seropositive for the VIH (25%). Sixty fifteen percent of patients accommodated Schistosoma haematobium (18 cases), 20,83% Schistosoma mansoni (5 cases) and 1 patient had a mixed infection. It doesn't exist a statistically difference between the frequency of species met (p = 0,061) . The main motives of hospitalization were the fever (12,50%), the hepatomegaly and splenomegaly, the ascite, the abdominal pain associated to the diarrhea and the diarrhea associated to an anemic syndrome with 8,20% for each of these motives. The most frequent clinical symptomatology was diarrhea (12,50%). The underlying pathologies more associated were the opportunist infections of the VIH (8,30%) the cirrhosis (12,50%), a syndrome amoebic dysentery syndrome (8,30%), a hepatic granuloma (8,30%). In the group of patients HIV positive the symptomatology was made of chronic and /or of glair - bloody diarrhea. One alone patient with a rate of CD4 = 279/mm3 presented prurigos in bouquet on the right flank. All patients without immunological statute distinction answered favorably to the treatment by the praziquantel. Conclusion The schistosomiasis stays even frequent in hospital yard of Bamako. The best understanding of the interaction between HIV and schistosomiasis is a pledge of the success of struggle programs in endemic area of schistosomiasis and of VIH.

Immunity against schistosomes includes anti-infection immunity, which is mainly active against invading larvae in the skin, and anti-disease immunity, which controls abnormal fibrosis in tissues invaded by schistosome eggs. Anti-infection immunity is T-helper 2 (Th2) cell-dependent and is controlled by a major genetic locus that is located near the Th2 cytokine locus on chromosome 5q31-q33. Mutations in the gene encoding interleukin (IL)-13 that decrease or increase IL-13 production account, at least in part, for that genetic control. In contrast, protection against hepatic fibrosis is dependent on interferon (IFN)-gamma and is controlled by a major genetic locus that is located on 6q23, near the gene encoding the IFN-gamma receptor beta chain. Mutations that modulate IFN-gamma gene transcription are associated with different susceptibility to disease. These data indicate that IL-13 in the skin and IFN-gamma in the liver are key players in protective immunity against schistosomes. These roles relate to the high anti-fibrogenic activities of IFN-gamma and to the unique ability of IL-13 in Th2 priming in the skin and in the mobilization of eosinophils in tissues. The coexistence of strong IFN-gamma and IL-13-mediated immune responses in the same subject may involve the compartmentalization of the anti-schistosome immune response between the skin and the liver.

Background: DNA mutations resulting in the McCoy and Swain-Langley polymorphisms have been identified on complement receptor 1 (CR1)-a ligand for rosetting of Plasmodium falciparum-infected RBCs. The molecular identification of the Kna/Knb polymorphism was sought to develop a genotyping method for use in the study of the Knops blood group and malaria., Study Design and Methods: CR1 deletion constructs were used in inhibition studies of anti-Kna. PCR amplification of Exon 29 was followed by DNA sequencing. A PCR-RFLP was developed with NdeI, BsmI, and MfeI for the detection of Kna/Knb, McCa/McCb, and Sl1/Sl2, respectively. Knops phenotypes were determined with standard serologic techniques., Results: A total of 310 Malian persons were phenotyped for Kna with 200 (64%) Kn(a+) and 110 (36%) Kn(a-). Many of the Kn(a-) exhibited the Knops-null phenotype, that is, Helgeson. The Kna/b DNA polymorphism was identified as a V1561M mutation with allele frequencies of Kna (V1561) 0.9 and Knb (M1561) 0.1., Conclusion: The high frequency (18%) of Knb in West African persons suggests that it is not solely a Caucasian trait. Furthermore, because of the high incidence of heterozygosity as well as amorphs, accurate Knops typing of donors of African descent is best accomplished by a combination of molecular and serologic techniques.

This study was carried out in the village of Faladié, Mali located in the malaria-endemic Kati region, two years after routine use of chloroquine prophylaxis was discontinued in children 0 to 9 years old. The main purpose of this study was to assess changes in chloroquine resistance. Two cross-sectional surveys in association with WHO in vivo chloroquine sensitivity testing were conducted, i.e., one in September 2000 and one in December 2002. Findings in 2000 showed that 77.5% of mothers administered chloroquine prophylaxis to their children in compliance with physician orders. The plasmodic index was 62%. The overall level of parasitologic resistance (based on the 1996 WHO in vivo tests) was 80%. The overall therapeutic failure rate was 17.5%. Findings in 2002 demonstrated a plasmodic index of 28%, an overall parasitologic resistance rate of 45% (based on WHO in vivo tests), and an overall therapeutic failure rate of 15%. The diminution of resistance in 2002 may be due to the decrease of drugs pressure and to low exposure of individuals to mosquitoes at the end of transmission season. Althougt these data indicate a 44% drop in chloroquine resistance (P=0.0001), no increase in the clinical efficacy of chloroquine was observed (P=0.05). In view of these results we propose more emphasis on information campaigns to increase public awareness of the need for chemoprophylaxis only for pregnant women, on the promotion of the use of bednets and insecticide-impregnated materials, and on environmental management.

We carried out five cross sectional surveys between 1993 and 1994 to assess the epidemiology of malaria in the village of Bancoumana, located in the Sudanese savannah areas of Mali. Each survey included a collection of entomological, clinical, parasitological and immunological data. The study population involved 1600 children from six months to 9 years of age. The main vector was Anopheles gambiae s.l., man bite rate and entomological inoculation rate were maximum respectively in August (peak of the transmission season) and October (end of transmission season). Plasmodium. falciparum was the main parasite species observed. Spleen enlargement rate, parasite rate, gametocyte rate and parasite density varied significantly with age and season. The parasite rate, gametocyte rate and parasite density were significantly low in October 1994 compared with October 1993 while the entomologic parameter did not show any variation over the two years. This reduction of parasitologic index between 1993 and 1994 may be related to an increase of anti-malarial drug use in the population. Our results show that malaria is hyperendemic in the village of Bancoumana.

Vaccine development research is an important component of malaria control strategies. Thrombospondin related anonymous protein (TRAP) and the circumsporozoite (CS) protein are two antigens of sporozoite surface. Immune response to these two antigens may contribute to the development of anti-sporozoite vaccine. Recent studies suggest that antibodies anti-TRAP may partially block sporozoites penetration in hepatocyte, and thereby reducing malaria morbidity. We carried out a study to assess the seroprevalence of anti-TRAP and anti-CS antibodies and to identify a possible role of these antibodies on malaria morbidity in children 1-9 years old living in a rural hyperendemic village. We performed 5 cross sectional surveys and a longitudinal follow up in 1993 and 1994. During each cross sectional study, children were examined for fever and splenomegaly; all febrile children received thick film examination, and serologic analysis was performed in one third of these, randomly selected. The results show that the seroprevalence of anti-TRAP and anti-CS varied with age and season (p < 0.05). Association between the prevalence of anti-TRAP and splenomegaly was observed during two cross sectional surveys (June and October 1993). The presence of anti-TRAP antibody was associated with Plasmodium falciparum infection at the beginning of the transmission season (June 1993 and July 1994). A negative association between the level of anti-TRAP title and parasitemia was observed (March and October 1994). These findings suggest no clear evidence of the protective role of anti-TRAP antibodies in uncomplicated malaria, possibly due to the limited persistence of these antibodies under natural situations.

Parasitological, malacological and anthropological studies were performed to assess the prevalence of Schistosoma haematobium and S. mansoni in schoolchildren living in the suburban area of Bamako. A total of 1017 schoolchildren aged 6-14 years were selected in two different areas between September 1997 and December 1999. In Djikoroni, the prevalence of S. haematobium and S. mansoni was 80.7% (339/420) and 22.8% (85/372) respectively. There was no significant difference of prevalence and intensity of infection with S. haematobium between schools, gender and age (p > 0.05), whereas, those of S. mansoni were higher in the vicinity of (+/- 100 m from) major sites where infected Biomphalaria pfeifferi were found (p < 0.001). In Niomirambougou, S. haematobium was prevalent in 46.7% (279/597) and S. mansoni in 28.2% (134/475). Boys and children aged 11-14 years were more infected (p < 0.001). Associated intestinal helminths (Hymenolepis nana, Necator americanus and Ascaris lumbricoides) were relatively scarce (prevalence < 1%). The prevalences of schistosome infected snails intermediate host were relatively high, 49.3% (100/203) in B. pfeifferi, 20.6% (88/138) in B. truncatus and 24.1% (7/29) in B. globosus. We recorded a total of 2514 water contacts about which 1130 in December and 1384 in January. Most of the children, 42.9% (1077/2511) were attracted to water bodies for bathing, swimming and playing, suggesting the lack of recreational facilities in these areas. Developing local control programmes in schools located in the vicinity of water bodies would contribute to break the parasite transmission cycle in Bamako.

The prevalence of urinary and intestinal schistosomiasis, the knowledge, attitude and practice (KAP) regarding the disease among both the children and their parents were investigated in Djikoroni para, a Suburban area of Bamako. The prevalence of Schistosoma haematobium and S. mansoni were respectively 69.8% and 8.7%. Compared with the girls, the boys were significantly more infected by S. haematobium (p = 5.10(-3)), but no difference between the sexes was observed for S. mansoni (p = 0.36). Interviews indicated that 88% of children and 91% of adults considered micro-haematuria as a pathology, but did not know anything about intestinal schistosomiasis. The low sensitivity of micro-haematuria (56.8%) and of the criterion "abdominal pains" (66.7%) indicated that they couldn't be relevant diagnosis signs. The symptoms and mode of transmission were generally well understood for S. haematobium but not for S. mansoni. The later parasite, its intermediate host and their interactions were unknown. The main man water contacts are bathing and playing in the Woyowayanko and in the Niger river. Inadequate perception of schistosomiasis contributes to maintain schistosomiasis at a high level of prevalence in Djikoroni.

Our main objective consists in evaluating the frequency of digestive signs and digestive opportunistic infections in AIDS patients with diarrhea. The prospective study occurred from January 1997 to July 1998 in Bamako hospitals. The patients underwent a clinical examination, blood and stools tests, and sometimes upper digestive endoscopy. Among 434 cases of AIDS, 426 patients (98%) had at least one digestive sign. The main digestive signs were diarrhea (80.1%), abdominal pains (62.2%), vomiting (47.2%) and dysphagea (36.6%). Isospora belli and Cryptosporidium parvum have been pointed up in respectively 9% and 16.3% of examined specimen. Echerichia coli was found in 8.6% of stool cultures and in 2.9% in the case of Salmonella Arizonae. Twenty cases of Kaposi's sarcoma were diagnosed and mycosis was found in 71.9% of patients. In conclusion, digestive change is a constant phenomenon in AIDS patients. Patients survival could be improved by early management, improvement of diagnosis and provisioning of medicines.

Epilepsy is a public health problem in Africa due to prevalence and social exclusion. We report a follow-up protocol for epileptic patients treated at home in rural areas of Mali. The objectives were: education for the patient, family, and village leaders in orders to achieve good compliance, uninterrupted supply of generic phenobarbitol, follow-up visits once a month for one year then every two months if good compliance with a country physician with delivery of phenobarbitol in sufficient quantity to reach the next visit, verification of correct drug dosage and use, supervision of treatment effect. After two years, the follow-up visits showed that 57.4% of the patients had been seizure free for at least 24 months (more than 4 monthly seizures before treatment). Rate of seizures decreased in 15.7% of the patients. Results were excellent with no seizures, clear physical, psychic and social improvement (work, married life, school attendance). Very few side effects were observed. There were no cases of poisoning. The management scheme is very cost effective: 1.5 USD per month per patient, including phenobarbitol and implementation. There is a need for anti-epilepsy programs in Africa which should be implemented on the local (rural medicalisation), national and international level ("Epilepsy out of the shadows" campaign).

A retrospective study was conducted on the epidemiological patterns and treatment of snakebites in the village of Bancoumana, 60 km south-west from Bamako. We analysed a total of 17 cases (8 males and 9 females). The distribution of snakebite cases by gender and by age showed that among subjects aged 5 to 20 years, boys were more exposed than girls (6 vs. 2), whereas, in those of 21 years and above, females were more frequently bitten than males (7 vs. 2) (p = 0.04). The treatment was mainly based on the use of anti-inflammatories and antibiotics, and sometimes of saline, glucose or anti-tetanic serum. Vitamin K was used in 7 cases and no patient was treated specifically. The success of therapy mostly depended on the shortness of delay between the snakebite occurring and patient referral to the health centre, and the low rate of envenomation. All the patients referred the same day they were bitten were cured, whereas three persons referred to the health centre at D3, D7 and D43 after bite died. The surveillance parameters were oedema, bleeding and vomiting.

This study sought to estimate the frequency of ocular complications in malaria and its prognostic value in Mali. A total of 140 children (aged 6 months to 9 years) with severe malaria (105 with cerebral malaria, 35 without neurological complications) were compared with 34 children with mild malaria and 82 children with nonmalarial fever. Ocular lesions were rare in the mild malaria group (5.8%). Retinal hemorrhages occurred in 11.8% of the children in the severe noncerebral malaria group. Cerebral malaria was associated with retinal hemorrhages (22.9%) and retinal edema (10.5%). No association was found between ocular signs such as retinal hemorrhages or retinal edema and mortality. Exudates, papilledema, and the presence of cottonwool spots were associated with an increased risk of death. Coma score and convulsions were significantly associated with death but not with ocular signs. The presence of retinal signs in a child in a malaria-endemic area may signal a case of severe malaria.

A 2-month study was carried out in Mali to evaluate an immunofluorescent-antibody test (IFAT) using monoclonal probes specific for Enterocytozoon bieneusi or Encephalitozoon intestinalis. Sixty-one human immunodeficiency virus (HIV)-seropositive adult patients and 71 immunocompetent children were enrolled. Microsporidia were detected in stools from 8 of 61 patients (13.1%) seropositive for HIV. A single species, E. bieneusi, was identified. All the children were negative for microsporidia. The sensitivity and specificity of IFAT were 100% compared with those of PCR, which was used as the "gold standard." Moreover, species identification by IFAT was more rapid and less expensive than that by PCR. These results show the suitability of IFAT for detection of microsporidia in developing countries.

The present work describes the recognition of three synthetic polypeptides encompassing the N- and C-terminal regions of the transmembrane Exp-1 protein of the parasite Plasmodium falciparum by plasma and peripheral blood mononuclear cells from naturally exposed individuals living in African endemic areas. The three polypeptides comprise the sequences 23-105, 73-162 and 101-162, and overlap at the transmembrane domain (73-105). Thus, they permitted characterization of the immune response specific to the N- and C-terminal domains in an independent fashion. Two different populations were evaluated, one in the village of Safo in Mali and the other in the villages of Somnaway, Kabortenga and Toussouktenga in Burkina Faso. Antibodies to the sequence 73-162 of Pf Exp-1 were found in 70% of adult Mali donors and in all of the donors tested from Burkina Faso. Strikingly, the N-terminal fragment Pf Exp-1 23-105 was only weakly recognized by a few donors. Evaluation of the T-cell response indicated that the peptide Pf Exp-1 23-105 was more potent than Pf Exp-1 73-162 in inducing a proliferative response. A correlation between peptide-specific interferon-gamma and interleukin-6 production and proliferation to peptide Pf Exp-1 23-105 was observed. Further studies are needed to evaluate this molecule as a vaccine candidate.

In areas of intense malaria parasite transmission, preliminary studies of the rate of reinfection after curative therapy suggest that small sample size studies of vaccine efficacy are feasible. However, the effect of transmission rate, which may vary considerably between transmission seasons, on reinfection rate has not been assessed in areas of mesoendemicity with seasonal transmission. To address this question, the Plasmodium falciparum reinfection rate after curative therapy was measured in Sotuba, a Malian village with historically low transmission rates, as estimated by the entomological inoculation rate (EIR). The reinfection rate after curative Fansidar (sulfadoxine-pyrimethamine) treatment was 80.7% (88/109). The EIR during the 13-week study period (seasonal transmission) varied between 1 and 4.5 infected bites/person/month. The finding that reinfection rates were high despite low EIRs suggests that a low EIR may be sufficient to support small sample size vaccine efficacy trials in mesoendemic areas.

Objective: To assess the efficacy of phenobarbital treatment for epileptic patients in rural Mali., Methods: Epileptic patients were treated at home with phenobarbital at daily dosages ranging from 50 mg for children to 200 mg for adults and their condition was monitored. Advice was given to patients, their families, and the village authorities in order to achieve compliance. An uninterrupted supply of generic phenobarbital was provided and a rural physician made two follow-up visits to each village to ensure that the drug was taken in the correct doses. The physician gave information to the population, distributed the phenobarbital in sufficient quantities to cover the periods between visits, and monitored the patients' responses to treatment. During the first year the physician visited the patients every two months. The frequency of visits was subsequently reduced to once every four months., Findings: In the six months preceding treatment the average rate of seizures among patients exceeded four per month. After a year of treatment, 80.2% of the patients experienced no seizures for at least five months. A total of 15.7% of patients experienced a reduction in seizures. In many cases no further seizures occurred and there were improvements in physical health, mental health and social status. There were very few side-effects and no cases of poisoning were reported. The cost of treatment per patient per year was 7 US dollars for generic phenobarbital and 8.4 US dollars for logistics., Conclusion: Low doses of phenobarbital were very effective against epilepsy. However, there is an urgent need for programmes involving increased numbers of physicians in rural areas and, at the national level, for the inclusion of epilepsy treatment in the activities of health care facilities. Internationally, an epilepsy control programme providing free treatment should be developed.

Practice of multidrug therapy in leprosy (combination Dapsone + Rifampicine + Clofazimine) established since 1981, has significantly reduced the incidence of the disease. However, immunosuppression due to treatment of multi-drugs therapy induced adverse reactions with glucocorticoid and the change in host immune response due to the leprosy itself, might increase the risk of parasitic infections. To test this hypothesis, we carried out a case-control study at the "Institut Marchoux" in Bamako. Stool and urine samples from all patients included in the study were examined for parasites identification. In addition, we performed thick and thin blood film to identify malaria infection and skin biopsy (snip) to detect onchocerciasis. A total of 121 cases of leprosy and 219 controls aged 10-84 years old were included in the study from March 1999 to February 2000. Sixty two percent (n = 121) of cases were treated with glucocorticoid. The prevalence of infection due to Entamoeba coli and Entamoeba histolytica were higher in cases than in controls (p = 0.02). The prevalence of infection due to hookworms was higher in cases than in controls. There was no difference of the infections to the other intestinal parasites. Three cases of cryptosporidiosis and one case of isosporosis were observed in leprosy group vs none in the control group. There was no significant difference between cases and controls with regard to prevalence of Schistosoma haematobium, Trichomonas vaginalis and Onchocera volvulus. The prevalence of Plasmodium falciparum was 4.9% (6/121) in the leprosy case and 7.8% (17/219) in the control group. In conclusion, despite the corticotherapy and immunosuppression due to leprosy, there was no difference in prevalence of pathogenic parasites. Entomoeba coli, Entamoeba histolytica which have significantly higher prevalence among the cases were not pathogen therefore there was no higher risk of severe intestinal parasitosis among the cases of leprosy. Treatment with glycocorticoid in patients with leprosy did not suggest any impact on the prevalence of this parasitic infections. In addition, multidrug therapy did not show any effect on the carriage of Plasmodium falciparum.

Urinary bilharziasis is a parasitic infection responsible for vesical, urethral and renal lesions. The authors demonstrate the importance of ambulatory echography on a large scale and describe various echographic lesions. Vesical attacks occurred in 27% of the wall irregularity, 44% of the masses and polyps. Pyelic and urethral abnormalities occurred in 16.6% and 29.9% of cases respectively at the baseline in 1991. These prevalence rates decreased after seven years, in 1998. The authors discuss the utility of chemotherapy with praziquantel and the necessity of a periodical mass treatment in the areas with high bilharziasis endemicity in Mali.

The toxicity and the genotoxicity of antimalarial alkaloid rich extracts derived from two plants used in traditional medicine in Mali (Mitragyna inermis (Willd.) O. Kuntze Rubiaceae and Nauclea latifolia (Sm.) Rubiaceae) were evaluated on in vitro and in vivo systems. The results demonstrated that an alkaloid rich extract derived from M. inermis induced a strong inhibition of protein synthesis in mammalian cells but did not exhibit mutagenic or genotoxic activity. An alkaloid rich extract derived from N. latifolia could interact in vitro with DNA of bacteria and mammalian cells, leading to G2-M cell cycle arrest and heritable DNA-damage, as well as inducing in vivo single-strand breaks in liver, kidney and blood cells.

We studied child malaria treatment practices among mothers living in the District of Yanfolila in southern Mali. For sampling, we first chose five of 13 health areas with probability proportional to size. Then villages, compounds and mothers with at least one child aged 1-5 years were randomly chosen. We assessed the spleen size of one 1-5 year-old child of each mother, collected a thick blood film and recorded the body temperature of every child whose mother thought he/she was sick. 399 mothers in 28 villages were interviewed with a structured questionnaire divided into two parts. If the child had had soumaya (a term previously associated with uncomplicated malaria) during the past rainy season, we asked about signs and symptoms, health-seeking behaviour (who the mother consulted first) and treatment. If not, information about knowledge of the disease and treatment to be given was collected. 86% of the mothers interviewed stated that their child had been sick and almost half of them had had soumaya. All mothers named at least one sign by which they recognized the disease. Vomiting, fever and dark urine/yellow eyes/jaundice were the three most common signs mentioned. 75.8% managed their child's disease at home and used both traditional and modern treatment. The most common anti-malarial drug was chloroquine, often given at inappropriate dosage. The sensitivity and specificity of the mothers' diagnosis was poor, although this might be explained by the large percentage of children who had already been treated at the time of the interview. The results of our survey call for prompt educational action for the correct treatment of uncomplicated malaria/soumaya, particularly for mothers and possibly for shopkeepers. The high spleen rate (58.1%) among randomly selected children confirms that malaria is a common disease in this area. Improved case-management at home could only be beneficial.

The malaria hypothesis proposes a survival advantage for individuals with hemoglobin variants in areas of endemic Plasmodium falciparum malaria. Hemoglobin C (HbC) is a possible example in West Africa, where this hemoglobin has a centric distribution with high frequencies among certain populations including the Dogon ethnic group. To test whether HbC is associated with protection from malaria, we performed a case-control study in the Dogon of Bandiagara, Mali. HbC was present in 68 of 391 (17.4%) of uncomplicated malaria control cases, whereas it was detected in only 3 of 67 cases (4.5%) of severe malaria (odds ratio [OR], 0.22; P =. 01). Further, HbC was present in only 1 of 34 cases (2.9%) with cerebral manifestations, the most common presentation of severe malaria in this population (OR, 0.14; P =.03). Episodes of uncomplicated malaria and parasitemias (4800-205 050/microL) were identified in cases of homozygous HbC (HbCC), which indicates that P falciparum parasites are able to efficiently replicate within HbCC erythrocytes in vivo. These findings suggest that HbC does not protect against infection or uncomplicated malaria but can protect against severe malaria in the Dogon population of Bandiagara, Mali. The data also suggest that the protective effect associated with HbC may be greater than that of HbS in this population.

Complement receptor one (CR1) is a ligand for the rosetting of Plasmodium falciparum infected red cells with uninfected cells. Since CR1 exhibits three known polymorphisms, we studied European-Americans (n = 112) and African-Americans (n = 330) and Malians (n = 158) to determine if genetic differences existed in an area endemic for malaria that could offer a survival advantage. The frequencies of Knops blood group phenotypes McC(b+) and Sl(a-) were greatly increased in Africans vs Europeans. Although the frequency of McC(b+) was similar between Africans from the USA or Mali, the Sl(a-) phenotype was significantly higher in Mali (39% vs 65%, respectively). There was an increased frequency of the largest size (250 kD) of CR1 in Mali, but this did not differ significantly from the USA (P = 0.09). Both cohorts of Africans had higher expression of red cell CR1 than European-Americans but this showed little difference between the USA and Mali groups. Thus, the most important CR1 polymorphism relevant to rosetting of malaria infected cells appears to be the Knops blood group.

Temporal variations of blood parasite density were evaluated in a longitudinal study of young, asymptomatic men in a village with endemic malaria in Mali (West Africa). Our main intention was to challenge the value of a single measure of parasite density for the diagnosis of malaria, and to define the level of endemicity in any given area. Parasitaemia and body temperature were recorded three times a day in the wet season (in 39 subjects on 12 days) and in the dry season (in 41 subjects on 13 days). Two thousand nine hundred and fifty seven blood smears (98.5% of the expected number) were examined for malaria parasites. We often found 100-fold or greater variations in parasite density within a 6-hour period during individual follow-up. All infected subjects had frequent negative smears. Although fever was most likely to occur in subjects with a maximum parasite density exceeding 10000 parasites/mm3 (P = 0.009), there was no clear relationship between the timing of these two events. Examples of individual profiles for parasite density and fever are presented. These variations (probably due to a 'sequestration-release' mechanism, which remains to be elucidated) lead us to expect a substantial impact on measurements of endemicity when only a single sample is taken. In this study, the percentage of infected individuals varied between 28.9% and 57.9% during the dry season and between 27.5% and 70.7% during the wet season. The highest rates were observed at midday, and there were significant differences between days. Thus, high parasite density sometimes associated with fever can no longer be considered as the gold standard in the diagnosis of malaria. Other approaches, such as decision-making processes involving clinical, biological and ecological variables must be developed, especially in highly endemic areas where Plasmodium infection is the rule rather than the exception and the possible causes of fever are numerous.

Mitragyna inermis (De Willd.) O. Kuntze Rubiaceae, Nauclea latifolia (Sm.) Rubiaceae, Glinus oppositofolius (Linn) Molluginaceae and Trichilia roka (Forsk.) Chiv. Meliaceae were investigated for their in vitro antimalarial activity. Leaves, roots and stem barks were submitted to aqueous, hydromethano and chloroform extractions and antimalarial activity was evaluated by microscopic and flow cytometric analysis. The results present evidence that the alkaloids contained in chloroform extracts and ursolic acid, purified from the hydromethanol extract of M. inermis induced a significant decrease of parasite proliferation. However, aqueous extracts, traditionally used for medication did not show high antimalarial activity. Statistical comparison between microscopic and cytometric analysis demonstrated the validity of this new technique for the screening of active antimalarial compounds isolated from plants., (Copyright 2000 John Wiley & Sons, Ltd.)

The dynamics of reinfection by Schistosoma haematobium and Schistosoma mansoni after repeated treatment with praziquantel (40 mg/kg body weight, single dose) was studied in a cohort of schoolchildren living in an endemic area. A total of 214 urine and 220 stool samples were collected and examined at three different times, i.e., February 1989, July 1989 and February 1990. Mass chemotherapy was administered at the beginning of study (February 89). Treatment was repeated in children with positive tests at each subsequent sampling. Prevalence rates were 55.1 p. 100, 3.7 p. 100, and 35.0 p. 100 for Schistosoma haematobium and 62.7 p. 100, 46.3 p. 100 and 73.1 p. 100 for Schistosoma mansoni in February 1989, July 1989 and February 1990 respectively (p < 0.001). From July 1989 to February 1990, reinfection was observed in 84.5 p. 100 of children by Schistosoma haematobium versus 57.8 p. 100 by Schistosoma mansoni. The risk of reinfection by Schistosoma haematobium was higher in children between the ages of 7 and 10 years than in children between the ages of 11 and 15 years (p < 0.001), The incidence of intense Schistosoma haematobium egg excretion rose from 0 p. 100 in July 1989 to 6.0 p. 100 in February 1990. The incidence of intense Schistosoma mansoni excretion in February 1990 was 4.5 p. 100. The reinfection rate at 7 months was over 50 p. 100 for both parasite species despite repeated treatment. This finding demonstrates that additional measures such as proper sanitation and vector control are needed to control human schistosomiasis in irrigated rice paddies.

A door-to-door survey was conducted in 18 villages in Mali with a total of 5,243 inhabitants classified according to the endemicity of onchocerciasis. Each epileptic was matched with two controls. The survey protocol included the following steps in cases and controls: census taking, socioeconomic data, screening for epilepsy, clinical examination, laboratory testing to detect parasites in stools and urine, and snip-test. The crude prevalence of epilepsy was 13.35 per 1,000 (n = 70). Epidemiological study provided a number of valuable demographic insights concerning age at onset, type of seizure activity during seizure and personal and family medical history. A transverse study showed that the prevalence of epilepsy was not significantly higher (p = 9.09) in zones of high endemicity of onchocerciasis (16.1 per 1000) than in zones of low endemicity (10.8 per 1000). Case-control findings showed evidence of onchocerciasis in 22.4 p. 100 of epileptics and 21.7 p. 100 of controls (odds ratio = 1.02 IC 95 p. 100: 0.4-2.19, not significant). Various risk factors including genetic factors and low socio-economic status could explain the trend toward a higher incidence of epilepsy as well as higher morbidity rates in zones of high endemicity of onchocerciasis.

We have investigated whether naturally induced immunity to Plasmodium falciparum thrombospondin related adhesive protein contributes to protection against malaria in humans. We have carried out a case control study in children living in an endemic region of West Africa to reveal associations between PfTRAP seroprevalence and the risk of cerebral malaria. Sera collected from the case and control groups were analysed by ELISA to compare their serum reactivity against PfTRAP, the circumsporozoite protein and the merozoite surface protein 1. Children with uncomplicated malaria had a significantly higher PfTRAP seroprevalence when compared to children with cerebral malaria. The risk of developing cerebral malaria appeared to depend on the reciprocal relationship between sporozoite inoculation rates and humoral immunity against PfTRAP. Our results suggest that naturally induced humoral immunity against PfTRAP contributes to the development of protection against severe malaria. Experimentally induced immunity against TRAP in different rodent models has consistently proven to elicit a high degree of protection against malaria. This together with the functional properties of TRAP and data describing CD4 and CD8 epitopes for PfTRAP indicate that this molecule could increase the protective efficiency of available sporozoite malaria vaccines.

Epilepsy is a chronic, disabling disease. Its incidence in Mali is 15.6 cases per 1000 people which is four to five times higher than in the West. Kirikirimasien is the name of a local bambaran disease entity similar to epilepsy with respect to both manifestations and course. A field study in a rural, bambaran area was performed to ascertain the nosologic nature of kirikirimasien and determine whether it was comparable with epilepsy in the west. Interviews with patients, family, friends, and healers were carried out and analyzed using qualitative investigative techniques, results showed that diagnosis was established on the basis of symptoms as well as underlying etiology. Nosologic information from the descriptions was correlated with contextual data in order to better understand the nature of the disease. To some extent close attention to pathologic signs associated with this disease such as dreaming and running away, revealed the important sociocultural dimension of kirikirimasien. This dimension is further supported by circumlocutions to avoid pronouncing the name of this disease considered as socially unacceptable. In summary, the sociocultural implications of kirikirimasien are evident in both criteria used for diagnosis and language used to describe it.

Infectivity of gametocytemic volunteers living in Bancoumana, a village 60 km from Bamako, Mali, was determined by direct feeds of laboratory-reared Anopheles gambiae s. l. Gametocytemic adolescents (10-18 years old) were as infectious to mosquitoes as younger volunteers and appear to be a more suitable population for testing transmission-blocking efficacy as compared with adults (> 18 years old). To begin to validate the membrane-feeding assay, sera collected from these same volunteers were subjected to a standard membrane-feeding assay. The data suggest that areas with intense but seasonal transmission might be feasible sites for testing transmission-blocking vaccines because of the high gametocytemic rates, high mosquito infectivity rates, and lack of pre-existing humoral-mediated transmission-blocking activity. The differences observed between field-based direct mosquito feeds and laboratory-based membrane feeding assays suggests that caution be used in interpreting Phase I study results in which laboratory-based membrane-feeding assays are used as a surrogate for vaccine efficacy.

Inappropriate use of antimalarial drugs undermines therapeutic efficacy and promotes the emergence and spread of drug-resistant malaria. Strategies for improving compliance require accurate information about current practices. Here we describe Knowledge-Attitude-Practice surveys conducted among health providers and consumers in two Malian villages, one rural and one periurban. All sanctioned providers limited their first choices of antimalarial drug to those recommended by the national malaria control program and reported using correct dosing regimens. However, the majority of consumers in the two villages chose non-recommended treatments for malaria and reported suboptimal treatment regimens when they did use recommended drugs. Antimalarial drugs were also widely available from unsanctioned sources, often accompanied by erroneous advice on dosing regimens. This study demonstrates that even when the most peripheral health providers are well-trained in correct use of antimalarial drugs, additional measures directly targeting consumers will be required to improve drug use practices.

We have developed a typing system using natural sequence variation in the thrombospondin-related adhesive protein (TRAP) gene of Plasmodium falciparum. This method permits a haplotype to be assigned to any particular TRAP gene. We have applied this method to a hospital-based, case control-study in Mali. Previous sequence variation and conservation in TRAP has been confirmed. Particular TRAP haplotypes can be used as geographic hallmarks. Because of the high level of conflict between characters, we have examined the phylogenetic relationships between parasites using a network approach. Having received patient samples from urban and periurban areas of Bamako, the majority of haplotypes were closely related and distinct from TRAP sequences present in other continents. This suggests that the structure of TRAP can only tolerate a limited number of sequence variations to preserve its function but that this is sufficient to allow the parasite to evade the host's immune system until a long-lived immune response can be maintained. It may also reflect host genetics in that certain variants may escape the host immune response more efficiently than others. For vaccine design, sequences from the major regional variants may need to be considered in the production of effective subunit vaccines.

Although a protective effect against malaria has been demonstrated for several hemoglobin variants, no selective factor is established for the high incidence of HbC in regions of West Africa. Here we report a survey of hemoglobin profiles among children admitted with symptomatic and severe malaria to the Gabriel Touré Hospital in Bamako, Mali, where the frequency of the HbC gene is 8-10%. Children with AC and AA profiles presented with severe malaria at comparable rates, indicating lack of protection by the heterozygous state. Two admitted children, one of whom presented with cerebral malaria, were found to have SC profiles. No CC homozygotes were detected in the study cohort.