Correction: Safety of Seasonal Malaria Chemoprevention (SMC) with Sulfadoxine-Pyrimethamine plus Amodiaquine when Delivered to Children under 10 Years of Age by District Health Services in Senegal: Results from a Stepped-Wedge Cluster Randomized Trial.

[This corrects the article DOI: 10.1371/journal.pone.0162563.].

Safety of Seasonal Malaria Chemoprevention (SMC) with Sulfadoxine-Pyrimethamine plus Amodiaquine when Delivered to Children under 10 Years of Age by District Health Services in Senegal: Results from a Stepped-Wedge Cluster Randomized Trial.

BACKGROUND: It is recommended that children aged 3 months to five years of age living in areas of seasonal transmission in the sub-Sahel should receive Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) during the malaria transmission season. The purpose of this study was to evaluate the safety of SMC with SPAQ in children when delivered by community health workers in three districts in Senegal where SMC was introduced over three years, in children from 3 months of age to five years of age in the first year, then in children up to 10 years of age. METHODS: A surveillance system was established to record all deaths and all malaria cases diagnosed at health facilities and a pharmacovigilance system was established to detect adverse drug reactions. Health posts were randomized to introduce SMC in a stepped wedge design. SMC with SPAQ was administered once per month from September to November, by nine health-posts in 2008, by 27 in 2009 and by 45 in 2010. RESULTS: After three years, 780,000 documented courses of SMC had been administered. High coverage was achieved. No serious adverse events attributable to the intervention were detected, despite a high level of surveillance. CONCLUSIONS: SMC is being implemented in countries of the sub-Sahel for children under 5 years of age, but in some areas the age distribution of cases of malaria may justify extending this age limit, as has been done in Senegal. Our results show that SMC is well tolerated in children under five and in older children. However, pharmacovigilance should be maintained where SMC is implemented and provision for strengthening national pharmacovigilance systems should be included in plans for SMC implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00712374.

Canine visceral leishmaniasis caused by Leishmania infantum in Senegal: risk of emergence in humans?

In the context of global warming and the risk of spreading arthropod-borne diseases, the emergence and reemergence of leishmaniasis should not be neglected. In Senegal, over the past few years, cases of canine leishmaniasis have been observed. We aim to improve the understanding of the transmission cycle of this zoonosis, to determine the responsible species and to evaluate the risk for human health. An epidemiological and serological study on canine and human populations in the community of Mont Rolland (Thiès area) was conducted. The data showed a high seroprevalence of canine leishmaniasis (>40%) and more than 30% seropositive people. The dogs' seroprevalence was confirmed by PCR data (concordance > 0.85, Kappa > 0.7). The statistical analysis showed strong statistical associations between the health status of dogs and seropositivity, the number of positive PCRs, clinical signs and the number of Leishmania isolates. For the first time, the discriminative PCRs performed on canine Leishmania strains clearly evidenced that the pathogenic agent is Leishmania infantum. The results obtained show that transmission of this species is well established in this area. That the high incidence of seropositivity in humans may be a consequence of infection with this species is discussed.

[Malaria morbidity in Barkedji, village of Ferlo, in Senegal Sahelian area]. / Morbidité palustre 'a Barkedji, village du Ferlo, en zone sahélienne du Sénégal.

A study of malaria morbidity was carried out from November 1994 to October 1995, in a Ferlo village (Barkedji) characterized by a long persistence of the temporary ponds. The objective was to evaluate the repercussions of the strong and long anopheles transmission in humans. A clinical follow-up of a group of residents was conducted at home every 10 days by an investigator trained for taking axillary temperature and making thick smears, when suspecting malaria. Were included in the group, 123 voluntary subjects among whom 50% were children under 10 years old. Any feverish subject (T degree >37 degrees 5) or subject presenting other malaria symptoms (headaches, hot body shivers, sweats, aches...) was regarded as having a malaria attack as well as a parasitemia >2500 P/mm3 in children aged of 0 to 14 years old and 1000 P/mm3 in the oldest. During the study subjects with at least one feverish access, plasmodium infection and malaria attack were 58%, 33% and 22%, respectively. On 172 hyperthermias observed, 49% were accompanied by a circulating parasitemia and 30% corresponded to malaria attack. The feverish subjects (74% vs. 42%), the subjects with parasitemia (51% vs. 16%) and the cases of malaria (34% vs. 10%) were more frequently encountered in children under10 than in the oldest. The cases of malaria attacks were more frequent from November to January (70%). The strong intensity of malaria transmission in Barkedji and the persistence of its temporary ponds until January were sufficient to influence the level of malaria morbidity and consequently the development of an anti-malaria immunity by the indigenous population.

[First autochthonous cases, caused by the Dengue-3 serotype in Federal District, Brazil]. / Apparition des premiers cas autochtones causes par le sérotype Dengue-3 dans le District fédéral, Brésil.

During the first four months of 2003, the survey laboratory of the Federal District (LACEN Laboratory of Virology), Brasília, Brazil, isolated ten strains of dengue virus serotype 3, five of them autochthonous, and the remaining ones from cases imported from Tocantins, Goias and Bahia States. The virus isolations were performed in C6/36 cell culture inoculated with total blood collected between the 1st and the 5th days after the onset of the symptoms. The age of the patients varied from 26 to 59 years old. The strains were typed as DEN-3 by indirect immunofluorescence assay using serotype-specific monoclonal antibodies. Viral RNAs were extracted from total blood using the trizol method. The nested RT-PCR method detected DNA products of 290 bp, confirming the serotype identifications. The introduction of DEN-3 in Brazil and especially in the Federal District represents a serious threat, since most people are susceptible to this serotype and many have already been infected by serotypes DEN-1 or DEN-2, thus increasing the risk of epidemic of more severe forms of the disease. The use of a fast and reliable method for continuous monitoring of the circulation of this serotype is of primary importance for the prevention and control of future epidemics.

[Role of Anopheles melas Theobald (1903) on malaria transmission in a mangrove swamp in Saloum (Senegal)]. / Rôle d'Anopheles melas Theobald (1903) dans la transmission du paludisme dans la mangrove du Saloum (Sénégal).

From June 1995 to January 1998, entomological studies carried out in five villages located in the Delta's Saloum have allowed to better understand the contribution of An. melas Theobald (1903) to malaria transmission in mangrove swamp. Among the five villages studied, three of them (Simal, Djilor and Marlothie) located along the Saloum river, are colonised by An. arabiensis; the two others (Djifere and Diakhanor) located between the sea and the river, are colonised by An. melas. During the rainy season and at the beginning of the dry season, An. melas and An. arabiensis are sympatric. The ratio of An. melas/An. arabiensis increases when we go closer the coast where An. melas becomes quite exclusive. When An. melas is predominant, endophagy, endophily and anthropophily are very marked. The parturity rates are lower in An. melas than in An. arabiensis. In the predominance area of each species, transmission is on the same level. During the period of sympatry, An. arabiensis is responsible for the transmission and when it is absent, An. melas carries on. Transmission occurs from July to March with a maximum at the beginning of the dry season. In the villages of the mangrove swamp, its prolongation until the middle of the dry season is due to An. melas.

[Zoophagia and alternative host selection of the marlaia vectors in Senegal]. / Zoophagie et hôtes alternatifs des vecteurs du paludisme au Sénégal.

Blood-engorged females of An. gambiae s.l., An. funestus, An. pharoensis and An. rufipes caught resting indoors were tested (precipitin or enzyme-linked immunosorbent assay) to determine the source of bloodmeal. The species of the An. gambiae complex fed mainly on human hosts in all prospected areas, except in those of the mid Senegal river valley where an important zoophily was observed within and near the irrigation zone. Among 4,597 blood-engorged females of An. gambiae s.l., 29% fed on cattle with 7.5% of mixed boodmeals, mainly human-bovine or human-equine. The presence of cattle, culicid population densities and individual mosquito safety devices were the most determinant factors of animal deviation. Blood of most domestic animals was found in the stomach of collected females, but according to areas, bovines and equines were the main hosts for zoophilic females of An. gambiae s.l. Females of An. funestus collected in the middle-west were more anthropophilic than those collected in south-eastern areas. An. pharoensis was most prevalent in the Senegal river delta where it was found to be very anthropophilic. An. rufipes was strongly endophilic but exclusively zoophilic in all prospected areas.

[Myths concerning malarial transmission among Amazonian Indians and their relation with 2 types of transmission encountered in the Amazonian forest]. / Les mythes représentant la transmission palustre chez les Indiens d'Amazonie et leurs rapports avec deux modes de transmission rencontrés en forêt.

Among the Indians Desana's (Tukano amerindians) in the Upper Rio Negro, the interseasonal variation of the malarial fevers were associated with two myths (localised in two distinguishable places). One myth associates the malarial with the rivers which contain "malaria pots". Conception based on an observation of localised water collection in the banks and the rocky rapids ("banks and rocky's fever"). The transmission and the anophelian density present variation between the seasons in relation to the river's level. Another myth associates malarial fevers in the forest, with the song of a frog ("fever's frog") and the flowering and fructification of a tree (Poaqueira sericea Thul.). There is in South America a particular type of forest malaria, known as "Bromelia malaria" and denounced in human and/or simian transmission. This forest malaria is transmitted by the a sub-genus anopheles (Kerteszia) which larval breeding are areal in the canopy. The breeding places are found in the forest in the epiphyte bromeliads. To understand this type of transmission, we must take reference to the previous endomological data at the Upper Oyapock Wayâpi (Tupi amerindians). This Bromelia malaria could fluctuated according larval density variation, related to washing of epiphytes (end of the rainy season) or to their flowering (end of the dry season). The "fever's frog" myth collected at the Desana's in the Upper Rio Negro can be related to the existence of Bromelia malaria in this amazonian habitat. These myths showed the perfect adaptation of the amerindians to their environment and their complete knowledge of the neotropical forest.

Plasmodium falciparum: population genetic analysis by multilocus enzyme electrophoresis and other molecular markers.

Abderrazak, S. B., Oury, B, Lal, A. A., Bosseno, M.-F., Force-Barge, P., Dujardin, J.-P., Fandeur, T., Molez, J.-F., Kjellberg, F., Ayala, F. J., and Tibayrenc, M. 1999. Plasmodium falciparum: Population genetic analysis by multilocus enzyme electrophoresis and other molecular markers. Experimental Parasitology 92, 232-238. The population structure of Plasmodium falciparum, the agent of malignant malaria, is uncertain. We have analyzed multilocus enzyme electrophoresis (MLEE) polymorphisms at 7-12 gene loci in each of four populations (two populations in Burkina Faso, one in Sudan, one in Congo), plus one "cosmopolitan" sample consisting of parasite cultures from 15 distant localities in four different continents. We have also performed random amplified polymorphic DNA analysis (RAPD) and restriction fragment length polymorphism (RFLP) and characterized gene varia tion at four antigen genes in the Congo population. All genetic assays show abundant genetic variability in all populations analyzed. With the isoenzyme assays, strong linkage disequilibrium is apparent in at least two local populations, the Congo population and one population from Burkina Faso, as well as in the cosmopolitan sample, and less definitely in the other Burkina Faso population. However, no linkage disequilibrium is detected in the Congo population with the molecular assays. We failed to detect any nonrandom association between the different kinds of genetic markers; that is, MLEE with RAPD or RFLP, RAPD with RFLP, and so on. Although isoenzyme data show statistical departures from panmictic expectations, these results suggest that in the areas under survey, P. falciparum populations do not undergo predominant clonal evolution and show no clear-cut subdivisions, un like Trypanosoma cruzi, Leishmania sp., and other major parasitic species. We discuss the epidemiological and taxonomical significance of these results.

Different Plasmodium falciparum recombinant MSP1(19) antigens differ in their capacities to stimulate in vitro peripheral blood T lymphocytes in individuals from various endemic areas.

This study reports on T-cell proliferative responses to the 19-kDa C-terminal domain of the Plasmodium falciparum merozoite surface protein (MSP1(19)). Three different recombinant proteins were used: an Escherichia coli product expressing the first EGF-like domain and Saccharomyces cerevisiae and baculovirus/insect-cell-produced proteins containing both EGF-like domains, the latter protein being produced with or without N-glycosylation. Cell donors were P. falciparum-immune adults with no recent history of clinical malaria and recruited from three Senegalese settings with different epidemiological parasite transmission. Each mononuclear-blood-cell preparation was stimulated with a range of concentrations of the three proteins. Most subjects' mononuclear cells were reactive to at least one protein, but significant differences in lymphoproliferation were seen between the settings and within individual cultures depending on the protein source and concentration. Importantly, lymphoproliferation indices correlated inversely with the intensity of P. falciparum malaria transmission. When purified T lymphocytes were cultured in the presence of MSP1(19) plus autologous monocytes, B lymphocytes or a proposed CD1+ dendritic-cell population as costimulatory cells, significant differences were observed depending on the individual's previous exposure to parasites. This study shows that the stimulation of lymphocyte proliferation in vitro with MSP1(19) depends on several factors, including epidemiological conditions and protein preparations.

[Bioecology in Haiti of Anopheles albimanus Wiedemann, 1820 (Diptera:Culicidae)]. / Bio-écologie en Haïti d'Anopheles albimanus Wiedemann, 1820 (Diptera: Culicidae).

Hispaniola has the highest malaria rate in the West Indies. A study of the bio-ecology of the major vector Anopheles albimanus was carried out in Haïti. Our observations concerned the length of pre-imaginal stages, biting rates and the gonotrophic cycle. A table of its complete life cycle, stage by stage, was produced as well as a graph illustrating its whole larval development in its natural habitat. Results in the field and insectarium were compared. In the laboratory, the development was shorter, except for pupae. The temperature was the main factor governing the length of pre-imaginal development. Preimaginal development decreased from 15 days in the field to 9 days in the insectarium whereas the temperature was a high of 4 degrees C. The nycthemeral activity and seasonal variations of An. albimanus were studied, by monthly all-night captures on human volunteers, during a full year in exo- and endophilic situations. Two sampling sites were chosen for comparison, An. albimanus were caught at every hour of the nycthemeral cycle, with a peak around midnight. Monthly variations were affected by the rains. The vector was more exophagous, when its density was high. The parity rate of the biting population varied between 85.8% and 20.0%; it was low at the beginning of the rains and increased when the rains stopped and breeding places dried out. To study the gonotrophic cycle of wild An. albimanus, several techniques were used jointly; follicles dissection; follicular relics; length of maturation of follicles. The length of the full cycle and of each of its components was estimated (quest of host for blood meal; maturation phase; breeding site seeking). In Haïti 41 h (nulliparous), or 21 h (parous) were necessary for females to have a complete maturation of the follicles. The lengthening of the gonotrophic cycle of parous An. albimanus, in the natural field site, was estimated to last about 4 days. For nulliparous it was 5 days, and 7 days if a pregravid stage was necessary. Considering the sporogonic cycle of Plasmodium falciparum (12 days), the wild population of An. albimanus females could become infective at the third blood feeding in Haïti.

[Establishing a strain of Anopheles arabiensis (Diptera:Culicidae) in an insectarium]. / Mise en place en insectarium d'une souche d'Anopheles arabiensis (Diptera: Culicidae).

For the first time in Dakar (Senegal), we managed to establish a local colony of Anopheles arabiensis (Diptera: Culicidae) in insectarium. The observations on the productivity of the colony showed a gradual adaptation of the preimaginal stages to insectarium conditions. The estimated duration of the development of the various preimaginal stages showed an interval of 24 hours for egg hatching, 48 h for stage I, 24 h for stage II, 24 h for stage III and 36 h for the pupal stage. Stage IV which makes the difference in the duration of the adult-egg cycle, varied from 1 to 13 days. Pupal moulting occurred mainly between 11 h and 19 h, with a peak between 14 h and 15 h. The duration of the preimaginal cycle in insectarium was from 8 to 11 days. This fits with the duration shown in natural breeding places during the rainy season (the best period for the development) which was from 9.5 to 13.3 days. Emergence, faster in males, occurred in the evening around 6.30-7 p.m. The emergence rate was higher in insectarium (92.9%) compared with that shown in the field (6 to 20%) (the natural breeding places are subject to biological and biochemical variations and to predators's action). The sex-ratio is equal to 1. The studies in insectarium showed that the gonotrophic cycle is 3 days in neonate blood fed after day 2 and also in parous ones. This cycle is 5 days in nulliparous with pregravid stage. The average longevity is 16 days with a maximum of 26 days in females and 43 days in males.

[Prediction and prevention of malaria epidemics in the valley of the Senegal River]. / Prévision et prévention des épidémies de paludisme dans la vallée du fleuve Sénégal.

The Sahel region has been suffering from severe drought for the last thirty years, with large deficits and a high degree of variability in the amount of annual rainfall. Agricultural production in the Sahelian zone of the Senegal River valley depends on the flooding of the river. The management of this flooding affects malaria transmission. The area is prone to malaria epidemics because the immunity level of the population is low. We studied epidemiological, meteorological and river level data to identify epidemic risk factors. We propose an epidemiological and managerial system for the early detection of risks and early intervention. This system is based mainly on the water level of the Senegal River and the early detection of unusual increases in the number of cases.

Impact of chloroquine resistance on malaria mortality.

Over 12 years, from 1984 to 1995, we conducted a prospective study of overall and malaria specific mortality among three rural populations in the Sahel, savanna and forest areas of Senegal. The emergence of chloroquine resistance has been associated with a dramatic increase in malaria mortality in each of the studied populations. After the emergence of chloroquine resistance, the risk of malaria death among children 0-9 years old in the three populations was multiplied by 2.1, 2.5 and 5.5, respectively. This is the first study to document malaria mortality at the community level in Africa before and after the emergence of chloroquine resistance. Findings suggest that the spread of chloroquine resistance has had a dramatic impact on the level of malaria mortality in most epidemiological contexts in tropical Africa.

The historical question of acquired immunodeficiency syndrome in the 1960s in the Congo River basin area in relation to cryptococcal meningitis.

In Europe before the advent of the acquired immunodeficiency syndrome (AIDS), fatal cases of infection with Cryptococcus neoformans resembling acute meningitis were rarely described and never in young adults. However, rapidly fatal cryptococcal meningitis in young Africans has been known to exist in central Africa for at least 30 years, mainly in the lower area of the Congo River basin. Cases have been reported in this area since 1953, particularly in young patients during the 1950s. It is also known that central African AIDS patients frequently suffer from cryptococcosis, and there is a possibility that earlier clinical reports of encephalitis were actually fatal cases of AIDS in young Africans. It appears possible that the central part of the African continent is the area where human immunodeficiency virus originated.

PIP: Rapidly fatal cryptococcal meningitis has existed in central Africa for more than 30 years, mainly in the lower area of the Congo River basin. Cases have been reported in that area since 1953, especially among young patients during the 1950s. People with AIDS in central Africa also often have cryptococcosis, and it is possible that earlier clinical reports of encephalitis were actually fatal cases of AIDS in young Africans. Before the advent of AIDS in Europe, fatal cases of infection with Cryptococcus neoformans resembling acute meningitis were rare and nonexistent in young adults. The available evidence suggests that HIV may have originated in central Africa, where it had long remained in a specific, but unknown and overlooked habitat. Cryptococcosis infection, cryptococcosis in the Congo River basin, the historical presence of HIV, and HIV in Haiti and among Haitians are discussed.

[Impact of the use of permethrin pre-impregnated mosquito nets on malaria transmission in a hyperendemic village of Senegal]. / Impact de l'utilisation des moustiquaires pré-imprégnées de perméthrine sur la transmission du paludisme dans un village hyperendémique du Sénégal.

The efficacy of permethrin-treated bednets was evaluated in Wassadou, a hyperendemic village located in the Sudanese grasslands of southeast Senegal. Pretreatment data were collected between 1992 and 1993. Bednets were distributed to the whole population in June 1995 and impact of their use on vector populations and malaria transmission was evaluated until November 1995. This period corresponds to the rainy season during which malaria transmission is highest. Data were compared with a control village in which bednets were not distributed. Findings showed that use of bednets led to a sharp decrease in the density of the vector population and malaria transmission. The number of bites by Anopheles gambiae s.1. decreased 69%. The density of blood-laden and pregnant females inside dwellings decreased 91% and 96% respectively. The sporozoite index of females captured on the skin decreased 76% and the daily rate of entomological inoculation decreased 88%. This impact was not great enough to eliminate the risk of infection. Prolonged study over a period of 4 to 5 years is needed to evaluate the impact of long-term use of insecticide-treated bednets on vector population and malaria transmission.

Comparison of behavior and vector efficiency of Anopheles gambiae and An. arabiensis (Diptera:Culicidae) in Barkedji, a Sahelian area of Senegal.

The ecology, population dynamics, and malaria vector efficiency of Anopheles gambiae and An. arabiensis were studied for 2 yr in a Sahelian village of Senegal. Anophelines were captured at human bait and resting indoors by pyrethrum spray. Mosquitoes belonging to the An. gambiae complex were identified by polymerase chain reaction. Of 26,973 females, An. arabiensis represented 79% of the mosquitoes captured and remained in the study area longer than An. gambiae after the rains terminated. There were no differences in nocturnal biting cycles or endophagous rates between An. gambiae and An. arabiensis. Based on an enzyme-linked immunosorbent assay test of bloodmeals, the anthropophilic rate of these 2 vectors were both approximately 60%, when comparisons were made during the same period. Overall, 18% of the resting females had patent mixed bloodmeals, mainly human-bovine. The parity rates of An. gambiae and An. arabiensis varied temporally. Despite similar behavior, the Plasmodium falciparum circumsporozoite protein (CSP) rates were different between An. gambiae (4.1%) and An. arabiensis (1.3%). P. malariae and P. ovale only represented 4% of the total Plasmodium identified in mosquitoes. Transmission was seasonal, occurring mainly during 4 mo. The CSP entomological inoculation rates were 128 bites per human per year for the 1st yr and 100 for the 2nd yr. Because of the combination of a high human biting rate and a low CSP rate, An. arabiensis accounted for 63% of transmission. Possible origin of differences in CSP rate between An. gambiae and An. arabiensis is discussed in relation to the parity rate, blood feeding frequency, and the hypothesis of genetic factors.

[In vivo chemosensitivity tests of Plasmodium falciparum to chloroquine in Senegal: the development of resistance and the assessment of therapeutic efficacy]. / Tests in vivo de chimiosensibilité de Plasmodium falciparum à la chloroquine au Sénégal: évolution de la résistance et estimation de l'efficacité thérapeutique.

The efficacity of oral chloroquine was assessed in 360 out-clinic patients with symptomatic Plasmodium falciparum malaria who were enrolled at five sites, in four administrative regions of Senegal, between 1991 and 1995. They were three rural areas: Mlomp (Casamance), Bandafassilbel (Eastern Senegal), Diohine (Sine-Saloum) and one urban area: Pikine (agglomeration of Dakar). Parasitological failure at Day-7 was observed in 108 patients (30%) and ranged from 14% to 50% according to the study areas. The proportion of RI, RII and RIII responses were 6%, 23% and 1%, respectively. Chloroquine resistance was lowest in Bandafassi, one of the most remote area of Senegal. It was highest in Mlomp where a malaria control programme with mass chemoprophylaxis had been carried out since 1975. The therapeutic failure rate defined by the persistence or reappearance of fever and P. falciparum trophozoites on days 4-7 was 6%. The percentages of therapeutic failure for RI, RII and RIII patients were respectively 14%, 19% and 100%. These results and those of previous studies in Senegal suggest that chloroquine resistance, which first emerged in vivo in 1988 in Dakar, spread between 1990 and 1993 in all regions of this country. The limitations of in vivo tests for the determination of the therapeutic efficacy of chloroquine in malaria endemic regions with increasing chemoresistance are discussed. The low proportion of potentially severe malaria infections in semi-immune persons, the biases in patients selection, and the possibility of delayed complications, considerably limit the potential of these tests for guiding the choice of the best adapted first line treatment.

[Specific antibodies against Plasmodium falciparum antigens in immune subjects: II. Screening of responses against the merozoite major surface antigen (MSP!)]. / Anticorps spécifiques d'antigènes de Plasmodium falciparum chez les sujets immuns: II. Criblage des réponses vis à vis d'un antigène majeur de la surface des mérozoïtes (MSP1).

Specific immune responses to asexual blood stages of P. falciparum antigens (a lysate of parasitized red blood cells and a characterized vaccine candidate i.e. MSP1 p19) were analyzed in plasma samples from immune adult individuals living in three different areas of Senegal, where malaria transmission is different. Most individuals in the three sites had specific IgG and IgM to total P. falciparum antigens, whereas approximately 50% had either IgG or IgM specific to MSP1 p19. Further, no anti-MSP1 p19 IgG2 and IgG4 antibody was noticed in any individual whereas the distribution of anti-MSP1 p19 IgG1 and IgG3 was different upon the epidemiological context. In addition, no relationship was found between antibody responses and in vitro T cell responses against P. falciparum antigens upon those experimental conditions. These data stress on the relatively elevated distribution of specific antibodies to MSP1 p19 in P. falciparum hyperendemic areas and suggest a differential regulation of isotypes depending on individual parasite exposure.