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Background: Thanks to the scale up of malaria control interventions, the malaria burden in Senegal has decreased substantially to the point that the National Malaria Control Programme plans to achieve malaria elimination by 2030. To guide such efforts, measuring and monitoring parasite population evolution and anti-malarial drugs resistance is extremely important. Information on the prevalence of parasite mutations related to drug resistance can provide a first signal of emergence, introduction and selection that can help with refining drug interventions. The aim of this study was to analyse the prevalence of anti-malarial drug resistance-associated markers before and after the implementation of artemisinin-based combination therapy (ACT) from 2005 to 2014 in Dielmo, a model site for malaria intervention studies in Senegal. Methods: Samples from both malaria patients and Plasmodium falciparum asymptomatic carriers were analysed with high resolution melting (HRM) technique to genotype P. falciparum chloroquine resistance transporter (Pfcrt) gene haplotypes and multidrug-resistant protein 1 (Pfmdr1) gene at codons N86 and Y184. Results: Among the 539 samples analysed, 474, 486, and 511 were successfully genotyped for Pfmdr1 N86, Y184, and Pfcrt, respectively. The prevalence of drug resistance markers was high, particularly during the malaria upsurges. Following the scale-up in bed net distribution, only the mutant (86F-like) variant of Pfmdr1 86 was present while during the malaria upsurges the predominance of two types 86Y-86N (43%) and 86F-like (56%) were observed. Most infections (87%) carried the wild type Y-allele at Pfmdr1 184 during the period of nets scale-up while during the malaria upsurges only 16% of infections had wild type and 79% of infections had mixed (mutant/wild) type. The frequency of the mixed genotypes SVMNT-like_CVMNK and SVMNT-like_CVIET within Pfcrt gene was particularly low during bednet scale up. Their frequency increased significantly (P < 0.001) during the malaria upsurges. Conclusion: This data demonstrated the effect of multiple interventions on the dynamics of drug resistance-associated mutations in the main malaria parasite P. falciparum in an endemic village in Senegal. Monitoring drug resistance markers should be conducted periodically to detect threats of emergence or resurgence that could compromise the efficacy of anti-malarial drugs. [ABSTRACT FROM AUTHOR]

Introduction: Asymptomatic carriage of P. falciparum is frequent in areas endemic for malaria and individual diagnosis of clinical malaria attacks is still difficult. We investigated the impact of changes in malaria endemicity on the diagnostic criteria for malaria attacks in an area of seasonal malaria transmission. Methods: We analyzed the longitudinal data collected over 20 years from a daily survey of all inhabitants of Ndiop, a rural community in central Senegal, in a logistic regression model to investigate the relationship between the level of Plasmodium falciparum parasitemia and the risk of fever, with the aim of determining the best parasitemia thresholds for attributing to malaria a fever episode. Results: A total of 34,136 observations recorded from July 1993 to December 2013 from 850 individuals aged from 1 day to 87 years were included. P. falciparum asymptomatic carriage declined from 36% to 1% between 1993 and 2013. A total of 9,819 fever episodes were associated with a positive blood film for P. falciparum. Using age-dependent parasitemia thresholds for attributing to malaria a fever episode, we recorded 6,006 malaria attacks during the study period. Parasitemia thresholds seemed to be lower during the low-to-zero transmission season and tended to decrease with changes in control policies. The number of clinical malaria attacks was overestimated for all age groups throughout the study when all fever episodes associated with P. falciparum parasitemia were defined as malaria attacks. Conclusion: Pyrogenic thresholds are particularly sensitive to changes in malaria epidemiology and are therefore an interesting tool to accurately assess the burden of malaria in the context of declining transmission. [ABSTRACT FROM AUTHOR]

Background: Urban malaria is now considered a major emerging health problem in Africa and urban insecticide resistance may represent a serious threat to the ambitious programme of further scaling-up coverage with long-lasting insecticide-treated bed nets and indoor residual spray. This study evaluates the levels and mechanisms of insecticide resistance in Anopheles gambiae populations in 44 urban areas of Dakar in a longitudinal entomological surveillance study. Methods: Adult mosquitoes sampled by night-landing catches at 44 sites across Dakar from 2007 to 2010 were genotyped to assess the frequency and distribution of resistance alleles. In addition World Health Organization susceptibility tests to six insecticides were performed on F0 adults issuing from immature stages of An. gambiae s.l. sampled in August 2010, 2011 and 2012 in three sites of Dakar: Pikine, Thiaroye and Almadies and repeated in 2012 with three of the insecticides after PBO exposure to test for mechanisms of oxydase resistance. Species, molecular forms and the presence of kdr and ace-1 mutations were assessed by polymerase chain reaction. Results: High frequencies of the kdr-e allele, ranging from 35 to 100 %, were found in Anopheles arabiensis at all 44 sites. The insecticide susceptibility tests indicated sensitivity to bendiocarb in Almadies in 2010 and 2011 and in Yarakh between 2010 and 2012 and sensitivity to fenitrothion in Almadies in 2010. The mortality rate of EE genotype mosquitoes was lower and that of SS mosquitoes was higher than that of SE mosquitoes, while the mortality rate of the SW genotype was slightly higher than that of the SE genotype. Pyperonyl butoxide (PBO) had a significant effect on mortality in Pikine (OR = 1.4, 95 % CI = 1.3–1.5, with mortality of 42–55 % after exposure and 11–17 % without PBO) and Yarakh (OR = 1.6, 95 % CI = 1.4–1.7, with mortality of 68–81 % after exposure and 23–37 % without), but not in Almadies (OR = 1.0, 95 % CI = 0.9–1.1). Conclusion: A high prevalence of kdr-e in West Africa was demonstrated, and knock-down resistance mechanisms predominate although some oxidases mechanisms (cytochrome P450 monooxygenases) also occur. In view of the increased use of insecticides and the proposed role of the kdr gene in the susceptibility of Anopheles to Plasmodium, this finding will significantly affect the success of vector control programmes. [ABSTRACT FROM AUTHOR]

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

Background We examined the potential sex-differential and non-specific effects of bacille Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP) and measles vaccine (MV) in a rural area of Senegal. Methods The 4133 children born in the area between 1996 and 1999 were included in the study. Vaccinations were provided at three health centres. Vaccine information was collected through 3-monthly home visits. The survival analysis compared the effects of BCG and DTP according to the following sequence of vaccinations: BCG-first, BCG+DTP1-first, or DTP1-first. We compared DTP and MV between 9 and 24 months of age, as 9 months is the minimum age for MV. Results At 12 months the vaccination coverage was 44%, 46% and 9%, respectively, for BCG, DTP1 and MV. Most children received BCG+DTP1-first and this combination was associated with a significantly lower mortality rate ratio (MRR) of 0.69 (0.53–0.89) compared with unvaccinated children. There was no benefit for children receiving BCG-first or DTP1-first. The female-male MRR was 0.79 (0.64–0.96) among unvaccinated children, but was significantly inversed with 1.45 (1.00–2.10) for children receiving DTP vaccination (test of homogeneity, p=0.006). Children who had received DTP simultaneously with MV or DTP after MV had significantly higher mortality (MRR=2.59 [1.32–5.07]) compared with children having MV-only as their most recent vaccination. After 9 months, the female-male MRR was 0.61 (0.31–1.19) for measles-vaccinated children but remained 1.54 (1.03–2.31) for DTP-vaccinated children who had not received MV (p=0.01). Conclusions The sequence of routine vaccinations is important for the overall impact on child survival and these vaccines are associated with sex-differential effects. [ABSTRACT FROM AUTHOR]

Summary: Background: A better understanding of the effect of malaria control interventions on vector and parasite populations, acquired immunity, and burden of the disease is needed to guide strategies to eliminate malaria from highly endemic areas. We monitored and analysed the changes in malaria epidemiology in a village community in Senegal, west Africa, over 22 years. Methods: Between 1990 and 2012, we did a prospective longitudinal study of the inhabitants of Dielmo, Senegal, to identify all episodes of fever and investigate the relation between malaria host, vector, and parasite. Our study included daily medical surveillance with systematic parasite detection in individuals with fever. We measured parasite prevalence four times a year with cross-sectional surveys. We monitored malaria transmission monthly with night collection of mosquitoes. Malaria treatment changed over the years, from quinine (1990–94), to chloroquine (1995–2003), amodiaquine plus sulfadoxine-pyrimethamine (2003–06), and finally artesunate plus amodiaquine (2006–12). Insecticide-treated nets (ITNs) were introduced in 2008. Findings: We monitored 776 villagers aged 0–101 years for 2 378 150 person-days of follow-up. Entomological inoculation rate ranged from 142·5 infected bites per person per year in 1990 to 482·6 in 2000, and 7·6 in 2012. Parasite prevalence in children declined from 87% in 1990 to 0·3 % in 2012. In adults, it declined from 58% to 0·3%. We recorded 23 546 fever episodes during the study, including 8243 clinical attacks caused by Plasmodium falciparum, 290 by Plasmodium malariae, and 219 by Plasmodium ovale. Three deaths were directly attributable to malaria, and two to severe adverse events of antimalarial drugs. The incidence of malaria attacks ranged from 1·50 attacks per person-year in 1990 to 2·63 in 2000, and to only 0·046 in 2012. The greatest changes were associated with the replacement of chloroquine and the introduction of ITNs. Interpretation: Malaria control policies combining prompt treatment of clinical attacks and deployment of ITNs can nearly eliminate parasite carriage and greatly reduce the burden of malaria in populations exposed to intense perennial malaria transmission. The choice of drugs seems crucial. Rapid decline of clinical immunity allows rapid detection and treatment of novel infections and thus has a key role in sustaining effectiveness of combining artemisinin-based combination therapy and ITNs despite increasing pyrethroid resistance. Funding: Pasteur Institutes of Dakar and Paris, Institut de Recherche pour le Développement, and French Ministry of Cooperation. [ABSTRACT FROM AUTHOR]

Background Programmes of pre-elimination of malaria have been implemented in Senegal since 2010, and the burden of malaria has decreased substantially. These changes in the epidemiology should be monitored with effective tools that allow changes in patterns of transmission to be monitored. In Dielmo and Ndiop, two villages of Senegal with different malaria endemicity, infections have been followed longitudinally for 20 years, during which time there have been several control interventions leading to substantial decreases of transmission. This study aimed to compare malaria antibody responses of the inhabitants of these two villages, between 2000 and 2010, using schizont crude extracts of a local strain of P. falciparum (Pf Sch07/03). Methods Sera collected from inhabitants of the two villages (141 from Dielmo and 79 from Ndiop in 2000; 143 from Dielmo and 79 from Ndiop in 2010) were used to assess the prevalence of antibodies against crude schizont extracts of Pf Sch07/03. Three ages groups were defined: [5-9] yrs, [10-14] yrs and [15-19] yrs. Statistical comparisons were performed. Seroprevalence and the magnitude of antibody responses were compared between age groups, villages and periods. Results Overall seroprevalence to P.fSch07/03 decreased between 2000 and 2010 in both villages: from 94.4% to 44.4% in Dielmo and from 74.4% to 34.6% in Ndiop. The difference between Dielmo and Ndiop was highly significant in 2000 (p < 0.001) but not in 2010 (p >0.20). The decrease in seroprevalence was larger in younger (more than 40%) than older (less than 19%) inhabitants. Longitudinal monitoring of the younger group showed that seroprevalence decreased between 2000 and 2010 in Dielmo from 98.7 to 79.3, but not in Ndiop from 67.6 to 66.7. The magnitude of antibody responses in seropositive individuals was significantly higher in 2000 than 2010 for both villages. Conclusions Crude extracts of P. falciparum are appropriate tools for evaluating malaria prevalence at different periods, and in both low and high endemic area. Using crude extracts from local strains to assess transmission may allow efficient evaluation of the consequences of control programs on malaria transmission. [ABSTRACT FROM AUTHOR]

The Health and Demographic Surveillance System (HDSS) in Niakhar, a rural area of Senegal, is located 135 km east of Dakar. The HDSS was established in 1962 by the Institut de Recherche pour le Développement (IRD) of Senegal to face the shortcomings of the civil registration system and provide demographic indicators.Some 65 villages in the Niakhar area were followed annually by the HDSS from 1962–1969. The study zone was reduced to 8 villages from 1969–1983, and from then on the HDSS was extended to include 22 other villages, covering a total of 30 villages for a population estimated at 43 000 in January 2012. Thus, 8 villages in the Niakhar area have been under demographic surveillance for almost 50 years and 30 villages for 30 years.Vital events, migrations, marital changes, pregnancies, and immunizations are routinely recorded every 4 months. The HDSS data base also includes epidemiological, economic, and environmental information obtained from specific surveys. Data were collected through annual rounds from 1962 to 1987. The rounds became weekly from 1987–1997, followed by routine visits conducted every 3 months between 1997 and 2007 and every 4 months since then. The data collected in the HDSS are not open to access, but can be fairly shared under conditions of collaboration and endowment. [ABSTRACT FROM AUTHOR]

Background: In tropical Africa, where the spectrum of the bacterial pathogens that cause fevers is poorly understood and molecular-based diagnostic laboratories are rare, the time lag between test results and patient care is a critical point for treatment of disease. Methodology/Principal Findings: We implemented POC laboratory in rural Senegal to resolve the time lag between test results and patient care. During the first year of the study (February 2011 to January 2012), 440 blood specimens from febrile patients were collected in Dielmo and Ndiop villages. All samples were screened for malaria, dengue fever, Borrelia spp., Coxiella burnetii, Tropheryma whipplei, Rickettsia conorii, R. africae, R. felis, and Bartonella spp. Conclusions/Significance: We identified DNA from at least one pathogenic bacterium in 80/440 (18.2%) of the samples from febrile patients. B. crocidurae was identified in 35 cases (9.5%), and R. felis DNA was found in 30 cases (6.8%). The DNA of Bartonella spp. was identified in 23/440 cases (4.3%), and DNA of C. burnetii was identified in 2 cases (0.5%). T. whipplei (0.2%) was diagnosed in one patient. No DNA of R. africae or R. conorii was identified. Among the 7 patients co-infected by two different bacteria, we found R. felis and B. crocidurae in 4 cases, B. crocidurae and Bartonella spp. in 2 cases, and B. crocidurae and C. burnetii in 1 case. Malaria was diagnosed in 54 cases. In total, at least one pathogen (bacterium or protozoa) was identified in 127/440 (28.9%) of studied samples. Here, the authors report the proof of concept of POC in rural tropical Africa. Discovering that 18.2% of acute infections can be successfully treated with doxycycline should change the treatment strategy for acute fevers in West Africa. Author Summary: In tropical Africa, clinical laboratories capable of performing complicated diagnostic studies like PCR are rare and are almost always found in large cities. Moreover, a number of infectious diseases, many of them are emerging and neglected, may be quickly and reliably diagnosed only by molecular biology. This is one of the reasons why the repertoire of bacterial infectious diseases in tropical Africa is poorly known. The laboratory based on the Point-of-Care (POC) principle has been designed in order to resolve the time lag between test results and patient care, which is the critical point for the treatment. We report here the first successful experience of the installation of POC laboratory in rural Senegal. During the first year of the study (February 2011 to January 2012) we identified DNA from at least one pathogenic bacterium in 80/440 (18.2%) of the samples from febrile patients. In most of the cases it was relapsing fever and rickettsiosis agents. Malaria was diagnosed in 54 cases. In total, at least one pathogen (bacterium or protozoa) was identified in 127/440 (28.9%) of studied samples. Discovering that at least 18.2% of acute infections can be successfully treated with doxycycline should change the treatment strategy for acute fevers in West Africa. [ABSTRACT FROM AUTHOR]

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

Background. The Demographic Surveillance System established in 1962 in Niakhar, Senegal, is the oldest in Africa. Here, we analyze trends in overall child mortality, malaria, and other causes of death in Niakhar from the beginning of data collection to 2010. Methods. After an initial census, demographic data were updated yearly from 1963 through 2010. From 1984, causes of death were determined by the verbal autopsy technique. Results. During 1963-2010, infant and under-5 mortality rates decreased from 223%0 to 18%0 and from 485%%0 to 41%0, respectively. The decrease was progressive during the entire observation period, except during 1990-2000, when a plateau and then an increase was observed. Malaria-attributable mortality in under-5 children decreased from 13.5%0 deaths per 1000 children per year during 1992-1999 to 2.2%0 deaths per 1000 children per year in 2010. During this period, all-cause mortality among children aged, 5 years decreased by 80%. Conclusions. Inadequate treatment for chloroquine-resistant malaria and an epidemic of meningitis during the 1990s were the 2 factors that interrupted a continuous decrease in child mortality. Direct and indirect effects of new malaria-control policies, introduced in 2003 and completed during 2006-2008, are likely to have been the key cause of the recent dramatic decrease in child mortality. [ABSTRACT FROM AUTHOR]

Background: Tropheryma whipplei is known as the cause of Whipple's disease, but it is also an emerging pathogen, detected in stool, that causes various chronic localized infections without histological digestive involvement and is associated with acute infections, including gastroenteritis and bacteremia. Methods/Principal Findings: We conducted a study in 2008 and 2009 using 497 non-diarrheic and diarrheic stool samples, 370 saliva samples, 454 sera samples and 105 samples obtained from water samples in two rural Sine-Saloum villages (Dielmo and Ndiop) in Senegal. The presence of T. whipplei was investigated by using specific quantitative PCR. Genotyping was performed on positive samples. A serological analysis by western blotting was performed to determine the seroprevalence and to detect seroconversion. Overall, T. whipplei was identified in 31.2% of the stool samples (139/446) and 3.5% of the saliva samples (13/370) obtained from healthy subjects. The carriage in the stool specimens was significantly (p<10−3) higher in children who were between 0 and 4 years old (60/80, 75%) compared to samples obtained from individuals who were between 5 to 10 years old (36/119, 30.2%) or between 11 and 99 years old (43/247, 17.4%). The carriage in the stool was also significantly more common (p = 0.015) in subjects with diarrhea (25/51, 49%). We identified 22 genotypes, 16 of which were new. Only one genotype (#53) was common to both villages. Among the specific genotypes, one (#52) was epidemic in Dielmo (15/28, 53.4%, p<10−3) and another (#49) in Ndiop (27.6%, p = 0.002). The overall seroprevalence was estimated at 72.8% (291/400). Seroconversion was detected in 66.7% (18/27) of children for whom PCR became positive in stools between 2008 and 2009. Conclusions/Significance: T. whipplei is a common bacterium in the Sine-Saloum area of rural Senegal that is contracted early in childhood. Epidemic genotypes suggest a human transmission of the bacterium. Author Summary: Tropheryma whipplei is known as the cause of Whipple's disease. It is also an emerging pathogen, detected in stool that causes various chronic localized infections without histological digestive involvement and is associated with acute infections, including gastroenteritis and bacteremia. We have studied the presence of T. whipplei on non-diarrheic and diarrheic stool samples, saliva samples, and sera samples in two rural Sine-Saloum villages (Dielmo and Ndiop) in Senegal. T. whipplei was identified in 31.2% of the stool samples and 3.5% of the saliva samples from healthy subjects. The carriage in the stool specimens was higher in children who were between 0 and 4 years old (75%) compared to samples obtained from individuals between 5 to 10 (30.2%) or between 11 and 99 (17.4%). The carriage in the stool was also more common in subjects with diarrhea (49%). We identified 22 different genotypes of T. whipplei. Only one genotype was common to both villages. Among the specific genotypes, one was epidemic in Dielmo and another in Ndiop. The seroprevalence was estimated at 72.8%. T. whipplei is a common bacterium in the Sine-Saloum area of rural Senegal that is contracted early in childhood. Epidemic genotypes suggest a human transmission of the bacterium. [ABSTRACT FROM AUTHOR]

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

Background: Rickettsioses are one of the most important causes of systemic febrile illness among travelers from developed countries, but little is known about their incidence in indigenous populations, especially in West Africa. Methodology/Principal Findings: Overall seroprevalence evaluated by immunofluorescence using six rickettsial antigens (spotted fever and typhus group) in rural populations of two villages of the Sine-Saloum region of Senegal was found to be 21.4% and 51% for spotted fever group rickettsiae for Dielmo and Ndiop villages, respectively. We investigated the role of tick-borne rickettsiae as the cause of acute non-malarial febrile diseases in the same villages. The incidence of rickettsial DNA in 204 blood samples from 134 (62M and 72F) febrile patients negative for malaria was studied. DNA extracted from whole blood was tested by two qPCR systems. Rickettsial DNA was found in nine patients, eight with Rickettsia felis (separately reported). For the first time in West Africa, Rickettsia conorii was diagnosed in one patient. We also tested 2,767 Ixodid ticks collected in two regions of Senegal (Niakhar and Sine-Saloum) from domestic animals (cows, sheep, goats, donkeys and horses) by qPCR and identified five different pathogenic rickettsiae. We found the following: Rickettsia aeschlimannii in Hyalomma marginatum rufipes (51.3% and 44.8% in Niakhar and Sine-Saloum region, respectively), in Hyalomma truncatum (6% and 6.8%) and in Rhipicephalus evertsi evertsi (0.5%, only in Niakhar); R. c. conorii in Rh. e. evertsi (0.4%, only in Sine-Saloum); Rickettsia massiliae in Rhipicephalus guilhoni (22.4%, only in Niakhar); Rickettsia sibirica mongolitimonae in Hyalomma truncatum (13.5%, only in Sine-Saloum); and Rickettsia africae in Rhipicephalus evertsi evertsi (0.7% and 0.4% in Niakhar and Sine-Saloum region, respectively) as well as in Rhipicephalus annulatus (20%, only in Sine-Saloum). We isolated two rickettsial strains from H. truncatum: R. s. mongolitimonae and R. aeschlimannii. Conclusions/Significance: We believe that together with our previous data on the high prevalence of R. africae in Amblyomma ticks and R. felis infection in patients, the presented results on the distribution of pathogenic rickettsiae in ticks and the first R. conorii case in West Africa show that the rural population of Senegal is at risk for other tick-borne rickettsioses, which are significant causes of febrile disease in this area. Author Summary: Spotted fever rickettsioses are endemic diseases known since the beginning of the 21st century. They may be severe, like Rocky Mountain Spotted fever in the Americas, and are always transmitted by the tick bite. In Africa, little is known about the prevalence of these diseases; most available data is from the travelers who felt ill after coming back to Europe and USA. We have studied the distribution of bacteria causing different spotted fevers (rickettsiae) in rural Senegal, as well as the role of these bacteria in human pathology among indigenous population. We have found that up to half of tested villagers have serological evidence of contact with rickettsiae and in some cases these bacteria may be found in the blood of feverish patients. From the other side, almost all species of ticks that may be collected in the villages on domestic animals also harbor the pathogenic bacteria. In total, six different species of rickettsiae were identified in ticks. We believe that our data cast light on the problem of unexplained fevers in West Africa. [ABSTRACT FROM AUTHOR]

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

Background: Q fever is a worldwide zoonotic disease caused by Coxiella burnetii. Epidemiologically, animals are considered reservoirs and humans incidental hosts. Methodology/Principal Findings: We investigated Q fever in rural Senegal. Human samples (e.g., sera, saliva, breast milk, feces) were screened in the generally healthy population of two villages of the Sine-Saloum region. Ticks were collected in four regions. Seroprevalence was studied by immunofluorescence, and all other samples were tested by two qPCR systems for detection of C. burnetii. Positive samples were genotyped (multispacer typing) by amplification and sequencing of three spacers. Strains were isolated by cell culture. We found that the seroprevalence may be as high as 24.5% (59 of 238 studied) in Dielmo village. We identified spontaneous excretion of C. burnetii by humans through faeces and milk. Hard and soft ticks (8 species) were infected in 0–37.6%. We identified three genotypes of C. burnetii. The previously identified genotype 6 was the most common in ticks in all studied regions and the only one found in human samples. Three strains of genotype 6 of C. burnetii were also recovered from soft tick Ornithodoros sonrai. Two other genotypes found in ticks, 35 and 36, were identified for the first time. Conclusions/Significance: Q fever should be considered a significant public health threat in Senegal. Humans, similar to other mammals, may continuously excrete C. burnetii. Author Summary: Q fever is a zoonotic disease known since 1937. The disease may be severe, causing pneumonia, hepatitis and endocarditis. Q fever agent has been described as a possible biological weapon. Animals—especially domestic cows, goats and sheep—are considered reservoirs for this infection. They are capable of sustaining the infection for long periods and excreting viable bacteria, infecting other animals and, occasionally, humans. Here we studied the distribution of Q fever in a poorly studied region, Senegal. We studied the agent of Q fever both in ticks parasitizing domestic animals and in humans (antibodies in serum, bacteria in feces, saliva and milk). We found from the studied regions the bacterium is highly prevalent in rural Senegal. Up to 37.6% of five different and most prevalent tick species may carry the bacterium. Humans living in such areas, as other mammals, may occasionally excrete Q fever agent through feces and milk. [ABSTRACT FROM AUTHOR]

Background: Intermittent preventive treatment in children (IPTc) is a promising strategy to control malaria morbidity. A significant concern is whether IPTc increases children's susceptibility to subsequent malaria infection by altering their anti-Plasmodium acquired immunity. Methods: To investigate this concern, IgG antibody (Ab) responses to Plasmodium falciparum schizont extract were measured in Senegalese children (6 months-5 years old) who had received three rounds of IPTc with artesunate + sulphadoxine-pyrimethamine (or placebo) at monthly intervals eight months earlier. Potential confounding factors, such as asexual malaria parasitaemia and nutritional status were also evaluated. Results: Firstly, a bivariate analysis showed that children who had received IPTc had lower anti-Plasmodium IgG Ab levels than the non-treated controls. When epidemiological parameters were incorporated into a multivariate regression, gender, nutritional status and haemoglobin concentration did not have any significant influence. In contrast, parasitaemia, past malaria morbidity and increasing age were strongly associated with a higher specific IgG response. Conclusions: The intensity of the contacts with P. falciparum seems to represent the main factor influencing antischizont IgG responses. Previous IPTc does not seem to interfere with this parasite-dependent acquired humoral response eight months after the last drug administration. [ABSTRACT FROM AUTHOR]

Background: The United Nations forecasts that by 2050, more than 60% of the African population will live in cities. Thus, urban malaria is considered an important emerging health problem in that continent. Remote sensing (RS) and geographic information systems (GIS) are useful tools for addressing the challenge of assessing, understanding and spatially focusing malaria control activities. The objectives of the present study were to use high spatial resolution SPOT (Satellite Pour l'Observation de la Terre) satellite images to identify some urban environmental factors in Dakar associated with Anopheles arabiensis densities, to assess the persistence of these associations and to describe spatial changes in at-risk environments using a decadal time scale. Methods: Two SPOT images from the 1996 and 2007 rainy seasons in Dakar were processed to extract environmental factors, using supervised classification of land use and land cover, and a calculation of NDVI (Normalized Difference Vegetation Index) and distance to vegetation. Linear regressions were fitted to identify the ecological factors associated with An. arabiensis aggressiveness measured in 1994-97 in the South and centre districts of Dakar. Risk maps for populated areas were computed and compared for 1996 and 2007 using the results of the statistical models. Results: Almost 60% of the variability in anopheline aggressiveness measured in 1994-97 was explained with only one variable: the built-up area in a 300-m radius buffer around the catching points. This association remained stable between 1996 and 2007. Risk maps were drawn by inverting the statistical association. The total increase of the built-up areas in Dakar was about 30% between 1996 and 2007. In proportion to the total population of the city, the population at high risk for malaria fell from 32% to 20%, whereas the low-risk population rose from 29 to 41%. Conclusions: Environmental data retrieved from high spatial resolution SPOT satellite images were associated with An. arabiensis densities in Dakar urban setting, which allowed to generate malaria transmission risk maps. The evolution of the risk was quantified, and the results indicated there are benefits of urbanization in Dakar, since the proportion of the low risk population increased while urbanization progressed. [ABSTRACT FROM AUTHOR]

Background: In 2006, the Senegalese National Malaria Control Programme (NMCP) has recommended artemisininbased combination therapy (ACT) as the first-line treatment for uncomplicated malaria and, in 2007, mandated testing for all suspected cases of malaria with a Plasmodium falciparum HRP-2-based rapid diagnostic test for malaria (RDT(Paracheck®). Given the higher cost of ACT compared to earlier anti-malarials, the objectives of the present study were i) to study the accuracy of Paracheck® compared to the thick blood smear (TBS) in two areas with different levels of malaria endemicity and ii) analyse the cost-effectiveness of the strategy of the parasitological confirmation of clinically suspected malaria cases management recommended by the NMCP. Methods: A cross-sectional study was undertaken in the villages of Dielmo and Ndiop (Senegal) nested in a cohort study of about 800 inhabitants. For all the individuals consulting between October 2008 and January 2009 with a clinical diagnosis of malaria, a questionnaire was filled and finger-prick blood samples were taken both for microscopic examination and RDT. The estimated costs and cost-effectiveness analysis were made considering five scenarios, the recommendations of the NMCP being the reference scenario. In addition, a sensitivity analysis was performed assuming that all the RDT-positive patients and 50% of RDT-negative patients were treated with ACT. Results: A total of 189 consultations for clinically suspected malaria occurred during the study period. The sensitivity, specificity, positive and negative predictive values were respectively 100%, 98.3%, 80.0% and 100%. The estimated cost of the reference scenario was close to 700€ per 1000 episodes of illness, approximately twice as expensive as most of the other scenarios. Nevertheless, it appeared to us cost-effective while ensuring the diagnosis and the treatment of 100% of malaria attacks and an adequate management of 98.4% of episodes of illness. The present study also demonstrated that full compliance of health care providers with RDT results was required in order to avoid severe incremental costs. Conclusions: A rational use of ACT requires laboratory testing of all patients presenting with presumed malaria. Use of RDTs inevitably has incremental costs, but the strategy associating RDT use for all clinically suspected malaria and prescribing ACT only to patients tested positive is cost-effective in areas where microscopy is unavailable. [ABSTRACT FROM AUTHOR]

Background: According to entomological studies conducted over the past 30 years, there was low malaria transmission in suburb of Dakar but little evidence of it in the downtown area. However; there was some evidence of local transmission based on reports of malaria among permanent residents. An entomological evaluation of malaria transmission was conducted from May 2005 to October 2006 in two areas of Dakar. Methods: Mosquitoes were sampled by human landing collection during 34 nights in seven places in Bel-air area (238 person-nights) and during 24 nights in five places in Ouakam area (120 person-nights). Mosquitoes were identified morphologically and by molecular methods. The Plasmodium falciparum circumsporozoïte indexes were measured by ELISA, and the entomological inoculation rates (EIR) were calculated for both areas. Molecular assessments of pyrethroid knock down resistance (Kdr) and of insensitive acetylcholinesterase resistance were conducted. Results: From May 2005 to October 2006, 4,117 and 797 Anopheles gambiae s.l. respectively were caught in Belair and Ouakam. Three members of the complex were present: Anopheles arabiensis (> 98%), Anopheles melas (< 1%) and An. gambiae s.s. molecular form M (< 1%). Infected mosquitoes were caught only during the wintering period between September and November in both places. In 2005 and 2006, annual EIRs were 9,5 and 4, respectively, in Bel-air and 3 and 3, respectively, in Ouakam. The proportion of host-seeking An. gambiae s.l. captured indoors were 17% and 51% in Bel air and Ouakam, respectively. Ace 1 mutations were not identified in both members of the An. gambiae complex. Kdr mutation frequency in An. arabiensis was 12% in Bel-air and 9% in Ouakam. Conclusion: Malaria is transmitted in Dakar downtown area. Infected mosquitoes were caught in two subsequent years during the wintering period in two distant quarters of Dakar. These data agree with clinical data from a Senegalese military Hospital of Dakar (Hospital Principal) where most malaria cases occurred between October and December. It was the first detection of An. melas in Dakar. [ABSTRACT FROM AUTHOR]

Background: The adaptation of Anopheles gambiae to humans and its environment involves an ongoing speciation process that can be best demonstrated by the existence of various chromosomal forms adapted to different environments and of two molecular forms known as incipient taxonomic units. Methods: The aim of this study was to compare the epidemiologic role of Anopheles arabiens is and the molecular forms M and S of Anopheles gambiae in the transmission of Plasmodium in a rural areas of southern Senegal, Dielmo. The sampling of mosquitoes was carried out monthly between July and December 2004, during the rainy season, by human volunteers and pyrethrum spray catches. Results: Anopheles arabiensis, An. gambiae M and S forms coexisted during the rainy season with a predominance of the M form in September and the peak of density being observed in August for the S form. Similar parity rates were observed in An. arabiensis [70.9%] (n = 86), An. gambiae M form [68.7%] (n = 64) and An. gambiae S form [81.1%] (n = 156). The circumsporozoite protein (CSP) rates were 2.82% (n = 177), 3.17% (n = 315) and 3.45% (n = 405), with the mean anthropophilic rates being 71.4% (n = 14), 86.3% (n = 22) and 91.6% (n = 24) respectively for An. arabiensis and An. gambiae M and S forms. No significant difference was observed either in host preference or in Plasmodium falciparum infection rates between sympatric M and S populations. Conclusion: No difference was observed either in host preference or in Plasmodium falciparum infection rates between sympatric M and S populations, but they present different dynamics of population. These variations are probably attributable to different breeding conditions. [ABSTRACT FROM AUTHOR]

Summary. In the Sahel, most malaria deaths occur among children 1-4 years old during a short transmission season. A trial of seasonal intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) and a single dose of artesunate (AS) showed an 86% reduction in the incidence of malaria in Senegal but this may not be the optimum regimen. We compared this regimen with three alternatives. Methods. 2102 children aged 6-59 months received either one dose of SP plus one dose of AS (SP+1AS) (the previous regimen), one dose of SP plus 3 daily doses of AS (SP+3AS), one dose of SP plus three daily doses of amodiaquine (AQ) (SP+3AQ) or 3 daily doses of AQ and AS (3AQ+3AS). Treatments were given once a month on three occasions during the malaria transmission season. The primary end point was incidence of clinical malaria. Secondary end-points were incidence of adverse events, mean haemoglobin concentration and prevalence of parasites carrying markers of resistance to SP. Findings. The incidence of malaria, and the prevalence of parasitaemia at the end of the transmission season, were lowest in the group that received SP+3AQ: 10% of children in the group that received SP+1AS had malaria, compared to 9% in the SP+3AS group (hazard ratio HR 0.90, 95%CI 0.60, 1.36); 11% in the 3AQ+3AS group, HR 1.1 (0.76-1.7); and 5% in the SP+3AQ group, HR 0.50 (0.30-0.81). Mutations associated with resistance to SP were present in almost all parasites detected at the end of the transmission season, but the prevalence of Plasmodium falciparum was very low in the SP+3AQ group. Conclusions. Monthly treatment with SP+3AQ is a highly effective regimen for seasonal IPT. Choice of this regimen would minimise the spread of drug resistance and allow artemisinins to be reserved for the treatment of acute clinical malaria. [ABSTRACT FROM AUTHOR]

Using data from malaria cases in Senegal, Pierre Druilhe and colleagues found that antibodies of the IgG3 isotype directed to merozoite surface protein 3 (MSP3) were strongly predictive of clinical outcome. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum has a complex transmission cycle. Public health planning and research would benefit from the ability of a calibrated model to predict the epidemiologic characteristics of populations living in areas of malaria endemicity. This paper describes the application of Bayesian calibration to a malaria transmission model using longitudinal data gathered from 176 subjects in Ndiop, Senegal, from July 1, 1993, to July 31, 1994. The model was able to adequately predict P. falciparum parasitemia prevalence in the study population. Further insight into the dynamics of malaria in Ndiop was provided. During the dry season, the estimated fraction of nonimmune subjects goes down to 20% and then increases up to 80%. The model-predicted time-weighted average incidences contributed by nonimmune and immune individuals are 0.52 cases per day and 0.47 cases per day, respectively. The median times needed to acquire infection (conversion delay) for nonimmune and immune individuals are estimated at 39 days and 285 days, respectively. Am J Epidemiol 2000;152:760–70. [ABSTRACT FROM PUBLISHER]

During November 2008-July 2009, we investigated the origin of unknown fever in Senegalese patients with a negative malaria test result, focusing on potential rickettsial infection. Using molecular tools, we found evidence for Rickettsia felis-associated illness in the initial days of infection in febrile Senegalese patients without malaria [ABSTRACT FROM AUTHOR]

We tested fecal samples from 150 healthy children 2-10 years of age who lived in rural Senegal and found the prevalence of Tropheryma whipplei was 44%. Unique genotypes were associated with this bacterium. Our findings suggest that T. whipplei is emerging as a highly prevalent pathogen in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

The ability to accurately measure the intensity of malaria transmission in areas with low transmission is extremely important to guide elimination efforts. Plasmodium falciparum Cell-traversal protein for ookinetes and sporozoites (PfCelTOS) is an important conserved sporozoite antigen reported as one of the promising malaria vaccine candidates, and could be used to estimate malaria transmission intensity. This study aimed at determining whether the diversity of PfCelTOS gene reflects the changes in malaria transmission that occurred between 2007 and 2014 in Dielmo, a Senegalese village, before and after the implementation of insecticide treated bed nets (ITNs). Of the 109 samples positive for PfCelTOS PCR, 96 (88%) were successfully sequenced and analysed for polymorphisms and population diversity. The number of segregating sites was higher during the pre-intervention period (13) and the malaria resurgences (11) than during the intervention period (5). Similarly, the number and diversity of haplotypes were higher during the pre-intervention period (16 and 0.914, respectively) and the malaria resurgences (6 and 0.821, respectively) than during the intervention period (4 and 0.758, respectively). Moreover, the average number of nucleotide differences was higher during the pre-intervention (3.792) and during malaria resurgences (3.467) than during the intervention period (2.189). The 3D7 KSSFNEP haplotype was only observed during the intervention period. Only two haplotypes were shared in both the pre-intervention and intervention periods while four haplotypes were shared between the pre-intervention and the malaria resurgences. The Fst values indicate moderate differentiation between pre-intervention and intervention periods (0.17433), and between intervention and malaria resurgences period (0.19198) as well as between pre-intervention and malaria resurgences periods (0.06607). PfCelTOS genetic diversity reflected changes of malaria transmission, with higher polymorphisms recorded before the large-scale implementation of ITNs and during the malaria resurgences. PfCelTOS is also a candidate vaccine; mapping its diversity across multiple endemic environments will facilitate the design and optimisation of a broad and efficacious vaccine. • PfCelTOS is an important conserved sporozoite antigen which could be used to estimate malaria transmission intensity. • We aimed to determine whether the genetic diversity of PfCelTOS can reflect the changes in malaria transmission that occurred in Dielmo, a Senegalese village. • We found higher number of segregating sites during the pre-intervention period (13) and the malaria resurgences (11) than during the intervention period (5). • Similarly, the haplotype diversity was higher during the pre-intervention period (0.914) and the malaria resurgences (0.821) than during the intervention period (0.758). • We report a moderate genetic differentiation denoted by Fst value between the three periods. • PfCelTOS genetic diversity varied with intensity of transmission, with higher polymorphisms recorded during the pre-intervention period and malaria resurgences. [ABSTRACT FROM AUTHOR]

Although fluctuating asymmetry is a sensitive indicator of stress, its links with health remains controversial, especially in humans. Here, we explored for the first time the association between fluctuating asymmetry and malaria infections in humans, from 107 participants involved in a long term medical survey in Senegal. No clear relationship was detected. Depending on traits considered, associations were not significant, or (marginally) significant but not in the same directions. We discuss the possible reasons for the global weakness of the signals detected in this study. [ABSTRACT FROM AUTHOR]

Summary: Background: The ongoing drought in sub-Saharan countries has led to the colonisation of west African Savanna by Ornithodoros sonrai; this tick acts as a vector for Borrelia crocidurae, which causes tick-borne relapsing fever (TBRF). Our aim was to ascertain the incidence of TBRF in west Africa. Methods: From 1990 to 2003, we monitored the incidence of TBRF in Dielmo, Senegal, by daily clinical surveillance and by blood testing of individuals with a fever. From 2002 to 2005, we investigated the presence of O sonrai in 30 villages in Senegal, Mauritania, and Mali, and measured by PCR the prevalence of B crocidurae. Findings: The average incidence of TBRF over 14 years was 11 per 100 person-years (range from 4 in 1990 to 25 in 1997). All age-groups presented a high incidence of the disease. In addition to relapses, repeated infections in the same individuals were common, with some affected by up to six distinct infections during the study period. Epidemiological studies indicated that 26 of the 30 studied villages (87%) were colonised by the vector tick O sonrai and that the average B crocidurae infection rate of the vector was 31%. Interpretation: The incidence of TBRF at the community level is the highest described in Africa for any bacterial disease. The presence of the vector tick in most villages investigated and its high infection rate suggest that TBRF is a common cause of fever in most rural areas of Senegal, Mauritania, and Mali. [ABSTRACT FROM AUTHOR]

Pyruvate kinase (PKLR) is a critical erythrocyte enzyme that is required for glycolysis and production of ATP. We have shown that Pklr deficiency in mice reduces the severity (reduced parasitemia, increased survival) of blood stage malaria induced by infection with Plasmodium chabaudi AS. Likewise, studies in human erythrocytes infected ex vivo with P. falciparum show that presence of host PK-deficiency alleles reduces infection phenotypes. We have characterized the genetic diversity of the PKLR gene, including haplotype structure and presence of rare coding variants in two populations from malaria endemic areas of Thailand and Senegal. We investigated the effect of PKLR genotypes on rich longitudinal datasets including haematological and malaria-associated phenotypes. A coding and possibly damaging variant (R41Q) was identified in the Thai population with a minor allele frequency of ~4.7%. Arginine 41 (R41) is highly conserved in the pyruvate kinase family and its substitution to Glutamine (R41Q) affects protein stability. Heterozygosity for R41Q is shown to be associated with a significant reduction in the number of attacks with Plasmodium falciparum, while correlating with an increased number of Plasmodium vivax infections. These results strongly suggest that PKLR protein variants may affect the frequency, and the intensity of malaria episodes induced by different Plasmodium parasites in humans living in areas of endemic malaria.

Background: Identification of plasmodial antigens targeted by protective immune mechanisms is important for malaria vaccine development. Among functional assays, the neutrophil antibody-dependent respiratory burst (ADRB) induced by opsonized Plasmodium falciparum merozoites has been correlated with acquired immunity to clinical malaria in endemic areas, but the target merozoite antigens are unknown. Here, the contribution of antibodies to the conserved C-terminal domain of the P. falciparum merozoite surface protein-1 (PfMSP1p19) in mediating ADRB was investigated in sera from individuals living in two Senegalese villages with differing malaria endemicity., Methods: Anti-PfMSP1p19 antibody levels in sera from 233 villagers were investigated and the involvement of anti-PfMSP1p19 antibodies in ADRB was explored in a subset of samples using (1) isogenic P. falciparum parasite clones expressing P. falciparum or Plasmodium chabaudi MSP1p19; (2) PfMSP1p19-coated plaque ADRB; and, (3) ADRB triggering using sera depleted from PfMSP1p19 antibodies by absorption onto the baculovirus recombinant antigen., Results: ADRB activity correlated with anti-PfMSP1p19 IgG levels (P < 10(-3)). A substantial contribution of PfMSP1p19 antibody responses to ADRB was confirmed (P < 10(-4)) in an age-adjusted linear regression model. PfMSP1p19 antibodies accounted for 33.1 % (range 7-54 %) and 33.2 % (range 0-70 %) of ADRB activity evaluated using isogenic merozoites (P < 10(-3)) and depleted sera (P = 0.0017), respectively. Coating of PfMSP1p19 on plates induced strong ADRB in anti-PfMSP1p19-positive sera., Conclusion: These data show that naturally acquired P. falciparum MSP1p19 antibodies are potent inducers of neutrophil ADRB and support the development of PfMSP1p19-based malaria vaccine using ADRB assay as a functional surrogate for protection.

Malaria transmission intensity is highly heterogeneous even at a very small scale. Implementing targeted intervention in malaria transmission hotspots offers the potential to reduce the burden of disease both locally and in adjacent areas. Transmission of malaria parasites from man to mosquito requires the production of gametocyte stage parasites. Cluster analysis of a 19-year long cohort study for gametocyte carriage revealed spatially defined gametocyte hotspots that occurred during the time when chloroquine was the drug used for clinical case treatment. In addition to known risk factors for gametocyte carriage, notably young age (<15 years old) and associated with a clinical episode, blood groups B and O increased risk compared to groups A and AB. A hotspot of clinical P. falciparum clinical episodes that overlapped the gametocyte hotspots was also identified. Gametocyte positivity was found to be increased in individuals who had been treated with chloroquine, as opposed to other drug treatment regimens, for a clinical P. falciparum episode up to 30 days previously. It seems likely the hotspots were generated by a vicious circle of ineffective treatment of clinical cases and concomitant gametocyte production in a sub-population characterized by an increased prevalence of all the identified risk factors. While rapid access to treatment with an effective anti-malarial can reduce the duration of gametocyte carriage and onward parasite transmission, localised hotspots represent a challenge to malaria control and eventual eradication.

Background: Numerous Plasmodium falciparum antigens elicit humoral responses in humans living in endemic areas. Use of multiplex assays is a convenient approach to monitor the antibody response against multiple antigens, but to integrate multiplex assay-derived data with datasets, generated previously using ELISA, comparative studies are needed. This work compares antibody responses to two P. falciparum antigens monitored using both technologies., Methods: The IgG response against the merozoite surface protein-1 PfMSP1p19 and the PF13-DBL1α1 domain of the P. falciparum Erythrocyte Membrane Protein1, expressed by the rosette-forming parasite 3D7/PF13 (PF13), was investigated using ELISA and a MAGPIX®-Luminex duplex assay. Archived plasma samples collected before the rainy season from 217 villagers living in Ndiop, a Senegalese meso-endemic setting, were studied. ROC analysis was used to define the optimal antibody measure readout. Association of antibody levels with protection against clinical malaria was analysed using Poisson regression in a retrospective study from active case detection records performed during the 5.5-month transmission season that followed blood sampling., Results: There was a strong positive correlation (P<10(-3)) between ELISA and MAGPIX®-Luminex-MFI (median fluorescence intensity) values for antibody to PfMSP1p19 (rho=0.78) and PF13-DBL1α1 (rho=0.89), with a similar degree of concordance in all age groups. Antibody levels to both antigens were high but displayed a different age-associated pattern. Independent age-adjusted Poisson regression analysis showed a significant association with protection only for IgG responses to MSP1p19 (P<0.01 RR=0.71 [0.53-0.93]) measured by ELISA., Conclusion: The individual ELISA and duplex-MAGPIX assays provide a concordant evaluation of age-associated antibody responses to MSP1p19 and PF13-DBL1α1, irrespective of the formulation of antibody levels (values, ratios or ROC-adjusted figures) but do diverge with regard to the association of antibody levels with clinical protection in age-adjusted models. This may reflect incomplete overlap of the epitopes presented in the two formats. Further development for multiplex assessment of antibody responses to a larger panel of antigens with the robust and cost effective MAGPIX®-Luminex technology is warranted.

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

Rickettsiosis caused by Rickettsia felis is an emerging infection in Africa and may account for 3-4% of ambulatory febrile fevers. We report herein a case of R. felis infection, for which we propose the name "yaaf", meaning vesicle, in an 8-month-old girl who was diagnosed in the field by real-time PCR analysis of a skin lesion; these PCR analysis was performed at a local experimental point-of-care laboratory. The clinical presentation was polymorphous skin lesions, including papules, vesicles, erosions and ulcers. The patient did not produce antibodies against Rickettsia. We suggest that this disease may be a primary infection caused by R. felis., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Tropheryma whipplei, the bacterium linked to Whipple's disease, is involved in acute infections and asymptomatic carriage. In rural Senegal, the prevalence of T. whipplei is generally high but is not homogeneous throughout households in the same village. We studied environmental samples collected in two Senegalese villages and conducted the survey to investigate the difference between households. Overall, the comparison between five households with very high T. whipplei prevalence and three households without any registered cases showed that the only difference was the presence of toilets in the latter (1/5 versus 3/3; P = 0.01423). Among the 1,002 environmental specimens (including domestic and synanthropic animals and dust sampled in households) tested for T. whipplei DNA, only four specimens were slightly positive. Humans are currently the predominant identified reservoir and source of T. whipplei in these populations. Limited access to toilets and exposure to human feces facilitate the fecal-oral transmission of T. whipplei.

There exists great disparity in the number of clinical P. falciparum episodes among children of the same age and living in similar conditions. The epidemiological determinants of such disparity are unclear. We used a data-mining approach to explore a nineteen-year longitudinal malaria cohort study dataset from Senegal and identify variables associated with increased risk of malaria episodes. These were then verified using classical statistics and replicated in a second cohort. In addition to age, we identified a novel high-risk group of children in whom the history of P. falciparum clinical episodes greatly increased risk of further episodes. Age and a high number of previous falciparum clinical episodes not only play major roles in explaining the risk of P. falciparum episodes but also are risk factors for different groups of people. Combined, they explain the majority of falciparum clinical attacks. Contrary to what is widely believed, clinical immunity to P. falciparum does not de facto occur following many P. falciparum clinical episodes. There exist a sub-group of children who suffer repeated clinical episodes. In addition to posing an important challenge for population stratification during clinical trials, this sub-group disproportionally contributes to the disease burden and may necessitate specific prevention and control measures.

Head and body lice are strict, obligate human ectoparasites with three mitochondrial clades (A, B, and C). Body lice have been implicated as vectors of human diseases, and as the principal vectors of epidemic typhus, relapsing fever, and Bartonella quintata-associated diseases (trench fever, bacillary angiomatosis, endocarditis, chronic bacteremia, and chronic lymphadenopathy). Using molecular methods (real-time and traditional PCR), we assessed the presence of Bartonella quintana DNA in black head lice collected from three locations in Sénégal. DNA from B. quintana was identified in 19 lice (6.93%) collected from 7 patients (7%) in Dakar. B. quintana-positive lice collected from three subjects were identified as clades C and A.

The insects of the order Siphonaptera, commonly named fleas, are vectors of pathogens around the world. Our previous studies showed that 4.4% of acute febrile diseases in the Sine-Saloum region of Senegal were due to Rickettsia felis. The aim of this study was to explain the high prevalence of R. felis infections in two rural Senegalese populations by an entomological, systematic monitoring protocol. A total of 232 fleas from three species (Ctenocephalides felis, Echidnophaga gallinacea, and Synosternus pallidus) were collected by candle trapping and manually from pets in the villages of Dielmo and Ndiop during the year 2010. The fleas were then tested for the presence of Bartonella and Rickettsia species. No fleas were found to be positive for any Bartonella species or R. felis. Surprisingly, we found that 91.4% of S. pallidus were infected by a new Rickettsia species, which, based on sequence analysis of gltA, ompB, and two fragments of rpoB, was found to be closely related to R. felis. The results from this study did not explain the high incidence of R. felis infections in these Senegalese populations.

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

Background: Previous studies in Dakar have highlighted the spatial and temporal heterogeneity of Anopheles gambiae s.l. biting rates. In order to improve the knowledge of the determinants of malaria transmission in this city, the present study reports the results of an extensive entomological survey that was conducted in 45 areas in Dakar from 2007 to 2010., Methods: Water collections were monitored for the presence of anopheline larvae. Adult mosquitoes were sampled by human landing collection. Plasmodium falciparum circumsporozoïte (CSP) protein indexes were measured by ELISA (enzyme-linked immunosorbent assay), and the entomological inoculation rates were calculated., Results: The presence of anopheline larvae were recorded in 1,015 out of 2,683 observations made from 325 water collections. A water pH of equal to or above 8.0, a water temperature that was equal to or above 30°C, the absence of larvivorous fishes, the wet season, the presence of surface vegetation, the persistence of water and location in a slightly urbanised area were significantly associated with the presence of anopheline larvae and/or with a higher density of anopheline larvae. Most of the larval habitats were observed in public areas, i.e., freely accessible. A total of 496,310 adult mosquitoes were caught during 3096 person-nights, and 44967 of these specimens were identified as An.gambiae s.l. The mean An. gambiae s.l. human-biting rate ranged from 0.1 to 248.9 bites per person per night during the rainy season. Anopheles arabiensis (93.14%), Anopheles melas (6.83%) and An. gambiae s.s. M form (0.03%) were the three members of the An. gambiae complex. Fifty-two An. arabiensis and two An. melas specimens were CSP-positive, and the annual CSP index was 0.64% in 2007, 0.09% in 2008-2009 and 0.12% in 2009-2010. In the studied areas, the average EIR ranged from 0 to 17.6 infected bites per person during the entire transmission season., Conclusion: The spatial and temporal heterogeneity of An. gambiae s.l. larval density, adult human-biting rate (HBR) and malaria transmission in Dakar has been confirmed, and the environmental factors associated with this heterogeneity have been identified. These results pave the way for the creation of malaria risk maps and for a focused anti-vectorial control strategy.

Background: The different taxa belonging to Anopheles gambiae complex display phenotypic differences that may impact their contribution to malaria transmission. More specifically, their susceptibility to infection, resulting from a co-evolution between parasite and vector, might be different. The aim of this study was to compare the susceptibility of M and S molecular forms of Anopheles gambiae and Anopheles arabiensis to infection by Plasmodium falciparum., Methods: F3 progenies of Anopheles gambiae s.l. collected in Senegal were infected, using direct membrane feeding, with P. falciparum gametocyte-containing blood sampled on volunteer patients. The presence of oocysts was determined by light microscopy after 7 days, and the presence of sporozoite by ELISA after 14 days. Mosquito species and molecular forms were identified by PCR., Results: The oocyst rate was significantly higher in the molecular S form (79.07%) than in the M form (57.81%, Fisher's exact test p<0.001) and in Anopheles arabiensis (55.38%, Fisher's exact test vs. S group p<0.001). Mean±s.e.m. number of oocyst was greater in the An. gambiae S form (1.72±0.26) than in the An. gambiae M form (0.64±0.04, p<0.0001) and in the An. arabiensis group (0.58±0.04, vs. S group, p<0.0001). Sporozoite rate was also higher in the molecular form S (83.52%) than in form M (50.98%, Fisher's exact test p<0.001) and Anopheles arabiensis 50.85%, Fisher's exact test vs. S group p<0.001)., Conclusion: Infected in the same experimental conditions, the molecular form S of An. gambiae is more susceptible to infection by P. falciparum than the molecular form M of An. gambiae and An. arabiensis.

Detecting spirochetes remains challenging in cases of African tick-borne relapsing fever. Using real-time PCR specific for the 16S rRNA Borrelia gene, we found 27 (13%) of 206 samples from febrile patients in rural Senegal to be positive, whereas thick blood smear examinations conducted at dispensaries identified only 4 (2%) as positive.

Background: Assessment exposure and immunity to malaria is an important step in the fight against the disease. Increased malaria infection in non-immune travellers under anti-malarial chemoprophylaxis, as well as the implementation of malaria elimination programmes in endemic countries, raises new issues that pertain to these processes. Notably, monitoring malaria immunity has become more difficult in individuals showing low antibody (Ab) responses or taking medications against the Plasmodium falciparum blood stages. Commonly available techniques in malaria seroepidemiology have limited sensitivity, both against pre-erythrocytic, as against blood stages of the parasite. Thus, the aim of this study was to develop a sensitive tool to assess the exposure to malaria or to bites from the vector Anopheles gambiae, despite anti-malarial prophylactic treatment., Methods: Ab responses to 13 pre-erythrocytic P. falciparum-specific peptides derived from the proteins Lsa1, Lsa3, Glurp, Salsa, Trap, Starp, CSP and Pf11.1, and to 2 peptides specific for the Anopheles gambiae saliva protein gSG6 were tested. In this study, 253 individuals from three Senegalese areas with different transmission intensities and 124 European travellers exposed to malaria during a short period of time were included., Results: The multiplex assay was optimized for most but not all of the antigens. It was rapid, reproducible and required a small volume of serum. Proportions of Ab-positive individuals, Ab levels and the mean number of antigens (Ags) recognized by each individual increased significantly with increases in the level of malaria exposure., Conclusion: The multiplex assay developed here provides a useful tool to evaluate immune responses to multiple Ags in large populations, even when only small amounts of serum are available, or Ab titres are low, as in case of travellers. Finally, the relationship of Ab responses with malaria endemicity levels provides a way to monitor exposure in differentially exposed autochthonous individuals from various endemicity areas, as well as in travellers who are not immune, thus indirectly assessing the parasite transmission and malaria risk in the new eradication era.

Background: The United Nations forecasts that by 2050, more than 60% of the African population will live in cities. Thus, urban malaria is considered an important emerging health problem in that continent. Remote sensing (RS) and geographic information systems (GIS) are useful tools for addressing the challenge of assessing, understanding and spatially focusing malaria control activities. The objectives of the present study were to use high spatial resolution SPOT (Satellite Pour l'Observation de la Terre) satellite images to identify some urban environmental factors in Dakar associated with Anopheles arabiensis densities, to assess the persistence of these associations and to describe spatial changes in at-risk environments using a decadal time scale., Methods: Two SPOT images from the 1996 and 2007 rainy seasons in Dakar were processed to extract environmental factors, using supervised classification of land use and land cover, and a calculation of NDVI (Normalized Difference Vegetation Index) and distance to vegetation. Linear regressions were fitted to identify the ecological factors associated with An. arabiensis aggressiveness measured in 1994-97 in the South and centre districts of Dakar. Risk maps for populated areas were computed and compared for 1996 and 2007 using the results of the statistical models., Results: Almost 60% of the variability in anopheline aggressiveness measured in 1994-97 was explained with only one variable: the built-up area in a 300-m radius buffer around the catching points. This association remained stable between 1996 and 2007. Risk maps were drawn by inverting the statistical association. The total increase of the built-up areas in Dakar was about 30% between 1996 and 2007. In proportion to the total population of the city, the population at high risk for malaria fell from 32% to 20%, whereas the low-risk population rose from 29 to 41%., Conclusions: Environmental data retrieved from high spatial resolution SPOT satellite images were associated with An. arabiensis densities in Dakar urban setting, which allowed to generate malaria transmission risk maps. The evolution of the risk was quantified, and the results indicated there are benefits of urbanization in Dakar, since the proportion of the low risk population increased while urbanization progressed.

Background: Tropheryma whipplei not only causes Whipple disease but also is an emerging pathogen associated with gastroenteritis and pneumonia that is commonly detected in stool samples in rural West Africa. We investigated the role of T. whipplei in febrile patients from rural Senegal who had a negative test result for malaria., Methods: From November 2008 through July 2009, we conducted a prospective study in 2 Senegalese villages; 204 blood specimens from febrile patients were collected. DNA extraction of whole-blood samples collected by finger pricks with a lancet stick was performed in Senegal; elution and quantitative polymerase chain reaction assays for T. whipplei were performed in France. In April 2009, we conducted a screening to look for the presence of T. whipplei in the saliva and stools of the overall population. Blood from French patients with chronic T. whipplei in stool samples was also analyzed., Results: The presence of T. whipplei DNA was detected in blood from 13 (6.4%) of 204 tested patients, mostly in children and in December and January. None of the French carriers tested positive. The patients with T. whipplei bacteremia presented with fever (13 patients), cough (10), thirst (8), fatigue (7), rhinorrhea (6), and sleep disorders (5). Cough and sleep disorders were significantly more frequent in febrile carriers than in the 191 febrile episodes without T. whipplei bacteremia (P = .002 and .005, respectively). No correlation was observed between the presence of T. whipplei in the stools and saliva and bacteremia., Conclusions: Our findings suggest that T. whipplei is an agent of unexplained cold season fever with cough in rural West Africa.

Background: Genetic evidence for diversifying selection identified the Merozoite Surface Protein1 block2 (PfMSP1 block2) as a putative target of protective immunity against Plasmodium falciparum. The locus displays three family types and one recombinant type, each with multiple allelic forms differing by single nucleotide polymorphism as well as sequence, copy number and arrangement variation of three amino acid repeats. The family-specific antibody responses observed in endemic settings support immune selection operating at the family level. However, the factors contributing to the large intra-family allelic diversity remain unclear. To address this question, population allelic polymorphism and sequence variant-specific antibody responses were studied in a single Senegalese rural community where malaria transmission is intense and perennial., Results: Family distribution showed no significant temporal fluctuation over the 10 y period surveyed. Sequencing of 358 PCR fragments identified 126 distinct alleles, including numerous novel alleles in each family and multiple novel alleles of recombinant types. The parasite population consisted in a large number of low frequency alleles, alongside one high-frequency and three intermediate frequency alleles. Population diversity tests supported positive selection at the family level, but showed no significant departure from neutrality when considering intra-family allelic sequence diversity and all families combined. Seroprevalence, analysed using biotinylated peptides displaying numerous sequence variants, was moderate and increased with age. Reactivity profiles were individual-specific, mapped to the family-specific flanking regions and to repeat sequences shared by numerous allelic forms within a family type. Seroreactivity to K1-, Mad20- and R033 families correlated with the relative family genotype distribution within the village. Antibody specificity remained unchanged with cumulated exposure to an increasingly large number of alleles., Conclusion: The Pfmsp1 block2 locus presents a very large population sequence diversity. The lack of stable acquisition of novel antibody specificities despite exposure to novel allelic forms is reminiscent of clonal imprinting. The locus appears under antibody-mediated diversifying selection in a variable environment that maintains a balance between the various family types without selecting for sequence variant allelic forms. There is no evidence of positive selection for intra-family sequence diversity, consistent with the observed characteristics of the antibody response.

Background: The time necessary for malaria parasite to re-appear in the blood following treatment (re-infection time) is an indirect method for evaluating the immune defences operating against pre-erythrocytic and early erythrocytic malaria stages. Few longitudinal data are available in populations in whom malaria transmission level had also been measured., Methods: One hundred and ten individuals from the village of Ndiop (Senegal), aged between one and 72 years, were cured of malaria by quinine (25 mg/day oral Quinimax in three equal daily doses, for seven days). Thereafter, thick blood films were examined to detect the reappearance of Plasmodium falciparum every week, for 11 weeks after treatment. Malaria transmission was simultaneously measured weekly by night collection of biting mosquitoes., Results: Malaria transmission was on average 15.3 infective bites per person during the 77 days follow up. The median reappearance time for the whole study population was 46.8 days, whereas individuals would have received an average one infective bite every 5 days. At the end of the follow-up, after 77 days, 103 of the 110 individuals (93.6%; CI 95% [89.0-98.2]) had been re-infected with P. falciparum. The median reappearance time ('re-positivation') was longer in subjects with patent parasitaemia at enrolment than in parasitologically-negative individuals (58 days vs. 45.9; p = 0.03) and in adults > 30 years than in younger subjects (58.6 days vs. 42.7; p = 0.0002). In a multivariate Cox PH model controlling for the sickle cell trait, G6PD deficiency and the type of habitat, the presence of parasitaemia at enrolment and age >/= 30 years were independently predictive of a reduced risk of re-infection (PH = 0.5 [95% CI: 0.3-0.9] and 0.4; [95% CI: 0.2-0.6] respectively)., Conclusion: Results indicate the existence of a substantial resistance to sporozoites inoculations, but which was ultimately overcome in almost every individual after 2 1/2 months of natural challenges. Such a study design and the results obtained suggest that, despite a small sample size, this approach can contribute to assess the impact of intervention methods, such as the efficacy vector-control measures or of malaria pre-erythrocytic stages vaccines.

Background: Urbanization has a great impact on the composition of the vector system and malaria transmission dynamics. In Dakar, some malaria cases are autochthonous but parasite rates and incidences of clinical malaria attacks have been recorded at low levels. Ecological heterogeneity of malaria transmission was investigated in Dakar, in order to characterize the Anopheles breeding sites in the city and to study the dynamics of larval density and adult aggressiveness in ten characteristically different urban areas., Methods: Ten study areas were sampled in Dakar and Pikine. Mosquitoes were collected by human landing collection during four nights in each area (120 person-nights). The Plasmodium falciparum circumsporozoite (CSP) index was measured by ELISA and the entomological inoculation rates (EIR) were calculated. Open water collections in the study areas were monitored weekly for physico-chemical characterization and the presence of anopheline larvae. Adult mosquitoes and hatched larvae were identified morphologically and by molecular methods., Results: In September-October 2007, 19,451 adult mosquitoes were caught among which, 1,101 were Anopheles gambiae s.l. The Human Biting Rate ranged from 0.1 bites per person per night in Yoff Village to 43.7 in Almadies. Seven out of 1,101 An. gambiae s.l. were found to be positive for P. falciparum (CSP index = 0.64%). EIR ranged from 0 infected bites per person per year in Yoff Village to 16.8 in Almadies. The An. gambiae complex population was composed of Anopheles arabiensis (94.8%) and Anopheles melas (5.2%). None of the An. melas were infected with P. falciparum. Of the 54 water collection sites monitored, 33 (61.1%) served as anopheline breeding sites on at least one observation. No An. melas was identified among the larval samples. Some physico-chemical characteristics of water bodies were associated with the presence/absence of anopheline larvae and with larval density. A very close parallel between larval and adult densities was found in six of the ten study areas., Conclusion: The results provide evidence of malaria transmission in downtown Dakar and its surrounding suburbs. Spatial heterogeneity of human biting rates was very marked and malaria transmission was highly focal. In Dakar, mean figures for transmission would not provide a comprehensive picture of the entomological situation; risk evaluation should therefore be undertaken on a small scale.