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Biomedical subjects

J F Molez

Publications and source records attributed to J F Molez.

At least 19 recordsLinked to original sources

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.

Adult

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.

Antimalarials

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.

Acquired Immunodeficiency Syndrome

[Bioecology in Haiti of 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.

Animals

[Establishing a strain of Anopheles arabiensis (Diptera:Culicidae) in an insectarium].

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.

Animals

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.

Animals

[In vivo chemosensitivity tests of Plasmodium falciparum to chloroquine in Senegal: the development of resistance and the assessment of therapeutic efficacy].

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.

Administration, Oral

[Specific antibodies against Plasmodium falciparum antigens in immune subjects: II. Screening of responses against the merozoite major surface antigen (MSP!)].

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.

Adolescent

Short report: gametocytes, chloroquine pressure, and the relative parasite survival advantage of resistant strains of falciparum malaria in west Africa.

Patients with Plasmodium falciparum infections were selected with an in vivo chloroquine sensitivity assay. Fourteen days after treatment, the gametocytes were studied in relation to asexual parasite responses classified as drug-sensitive or showing RI or RII resistance. Gametocyte prevalence and density appeared significantly higher in RII than RI strains and higher in RI than in sensitive strains. This finding on gametocyte variation in vivo may explain why the RII type of chloroquine resistance has became more prevalent than RI everywhere in tropical Africa in the short time since its emergence. The biological and epidemiologic advantage of chloroquine-resistant malaria mediated through gametocytes is discussed in the context of the present drug pressure in Africa.

Adolescent

[The utilization of molecular biological tools in the study of malaria transmission: example of programs conducted in Senegal].

Some informations about malaria transmission, which has until nox difficult to get, can be obtained thanks to the use of molecular biology tools, PCR mainly. In Senegal, we use that technique to solve two kinds of problems: -Identification of species of the Anopheles gambiae complex: PCR technique is useful compared to other diagnostic methods (chromosome pattern, DNA probes, etc.) because it enables quickly and simply identification of captured anopheles from the DNA contained in their legs. The rest of the mosquito is tested by circumsporozoite protein antigen ELISA and blood meal ELISA. The data obtained are used to determine distribution, cycles, trophic preferences and comparative vectorial capacities of Anopheles gambiae, Anopheles arabiensis and Anopheles melas. -Identification in a mosquito blood meal of the individual bitten: we propose to evaluate factors (weight, age, sex, location of bedroom, etc.) which could explain why individuals are more, or less, bitten by a Plasmodium vector. Genetic typing is used on inhabitants'leukocytes DNA and on the leukocyte DNA extracted from the blood meal of resting anopheles. Through the high degree of polymorphism of three (AAAG)n microsatellites markers, we hope, using PCR, to attribute each blood meal to one individual. Statistical analysis will be used to identify attractivity factors and to determine more precisely the inoculation rates for each group rather than the classical rate calculated with male adults volunteers.

Adult

[Malaria and rice growing in the Senegal River delta (Senegal)].

An epidemiological survey of malaria was carried out from September 1992 to November 1994 in three villages located in the Senegal river delta, two villages growing rice in irrigated fields and one practicing traditional rain water agriculture. Entomological observations showed that Anopheles pharoensis is the main anopheline species caught in the area with a high population density in the rice growing villages. The population density of species of the An. gambiae complex, represented by An. gambiae s.s., An. arabiensis and An. melas is low. Agressivity rates and anthropophlic indexes of An. pharoensis females are high but their parity rates are low. The malaria transmission is weak and was not perceptible in the area as shown by the negative results obtained with the ELISA tests and the examination of salivary glands. Parasitological indexes, malaria morbidity and incidence rates are low and are in agreement with the entomological data. In the Senegal river delta, irrigation has, on the whole, increased the An. pharoensis density but both malaria transmission and incidence rates did not rise.

Agriculture

[Anopheles of Senegal. An annotated and illustrated list].

Twenty species of Anopheles are presently known from Senegal. An. gambiae, An. arabiensis, An. pharoensis, An. rufipes and An. ziemanni have an extensive distribution. Probably because of climatic change, An. funestus is no more found in some areas and An. paludis tend to disappear. An. melas is located in coastal areas. The other species, namely An. coustani, An. brohieri, An. brunnipes, An. domicola, An. flavicosta, An. freetownensis, An. hancocki, An. maculipalpis, An. nili, An. pretoriensis, An. squamosus and An. wellcomei, are mainly found in southern Senegal. Only An. gambiae, An. arabiensis and An. funestus are of epidemiological significance as vectors of malaria and bancroftian filariasis. Twelve arboviruses have been isolated from eight Anopheles species. Each Anopheles species is illustrated and an identification key is given.

Animals

[Placental infections with Plasmodium in an endemic zone. Risk factors].

A survey has been carried out during eight months in the hospital of Bobo-Dioulasso (Burkina Faso) in view to observe the infection of the placentas by Plasmodium and their risk factors. One thousand forty pregnant women were included. Infection rates were 6.5% during the low transmission season and 24.5% during the high transmission season. P. falciparum was present in all the infections. Thirty eight per cent of the women under 18 years old and 26% of the primigravidae were infected. The mean difference in birth weights between the newborn babies of primigravidae with infected or non-infected placentas was 275 g. The regular visits to antenatal clinics, a high level of education and sufficient income were linked with a low level of placental infection. The use of bed nets was linked with a low level of placental infections even after suppression of the other socio-economic data. These observations are discussed in view of an action against malaria in endemic areas.

Adolescent

High human malarial infectivity to laboratory-bred Anopheles gambiae in a village in Burkina Faso.

The malarial infectivity of an African village population was tested by selecting a demographically representative sample of individuals for study, regardless of parasitemia or gametocytemia. The infectivity of this population people to laboratory-bred mosquitoes was investigated using membrane feeding techniques. Tests on 322 subjects (greater than four years of age) indicated that approximately 48.4% were capable of infecting mosquitoes. There were similar proportions of infectious individuals among gametocyte carriers (52.5%) and nongametocyte carriers (46.6%). All age groups appeared to contribute equally to this infective reservoir. Most of the infections resulted in low oocyst loads (1.8 oocysts) on the midgut of the positive mosquitoes and only a few mosquitoes per batch were infected (11.5%). A previous entomologic survey estimated 90 infected bites/person/year and a low parity index in Anopheles gambiae (< 60%) as well as in An. funestus (< 40%), the two main malaria vectors in this region. This low parity index could indicate a low life expectancy for infected mosquitoes and could therefore explain an inoculation rare lower than expected considering the high degree of infectivity of the human population studied.

Adolescent

[Iterative placental infection by P. falciparum during 2 successive pregnancies in Bobo-Dioulasso (Burkina-Faso)].

A young woman living in a malaria endemic area in West Africa, was contaminated twice with placental infection by Plasmodium falciparum, in two successive pregnancies. No parasites were observed on blood smears both in mother peripheral blood and in cord blood. A parasitemia was described in the intervillous space in the placental. The first placental infection was attributed to a febrile illness ten days before the end of gestation. No reliable symptoms of malaria were found for the second infection. Treatment for fever during pregnancy were given, at 6 and 9 months for the first gestation, and at 4 months for the second gestation. Investigations are correlated with the age of the two placental infections, the second infection is a very young and synchronous parasitemia. No foetal diseases, no low birth weight o congenital malaria were observed on newborns during the both gestations.

Adult