Bayesian analysis of an epidemiologic model of Plasmodium falciparum malaria infection in Ndiop, Senegal.

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.

Increased susceptibility to malaria during the early postpartum period.

Background: Pregnancy is associated with increased susceptibility to malaria. It is generally agreed that this increased risk ends with delivery, but the possible persistence of increased susceptibility during the puerperium had not been investigated.

Methods: From June 1, 1990, to December 31, 1998, we monitored exposure to malaria, parasitemia, and morbidity among the residents of a village in Senegal in which the rate of transmission of malaria was high.

Host factors affecting the delay of reappearance of Plasmodium falciparum after radical treatment among a semi-immune population exposed to intense perennial transmission.

To investigate host factors affecting the delay of reappearance of malaria parasites after radical treatment, a study was undertaken in Dielmo, Senegal, an area of intense perennial malaria transmission. A 7-day course of quinine was administered to 173 asymptomatic persons from 1 to 85 years of age and reappearance of malaria parasites in the peripheral blood was monitored weekly for 14 weeks. Additional thick blood films were made in case of fever as part of a daily clinical surveillance.

Cytophilic immunoglobulin responses to Plasmodium falciparum glutamate-rich protein are correlated with protection against clinical malaria in Dielmo, Senegal.

The goal of this study was to analyze antibody responses to Plasmodium falciparum glutamate-rich protein (GLURP) using clinical data and plasma samples obtained from villagers of Dielmo, Senegal. This molecule was chosen because it is targeted by human antibodies which induce parasite growth inhibition in antibody-dependent cellular inhibition (ADCI) assays. The results showed a strong correlation between protection against malaria attacks and levels of immunoglobulin G2 (IgG2) and IgG3 against GLURP(94-489) (R0) and IgG3 against GLURP(705-1178) (R2) when corrected for the confounding effect of age-related exposure to malaria.

Antibiotics for prophylaxis of Plasmodium falciparum infections: in vitro activity of doxycycline against Senegalese isolates.

The in vitro activities of doxycycline, chloroquine, quinine, amodiaquine, artemether, pyrimethamine, and cycloguanil were evaluated against Plasmodium falciparum isolates from Senegal (Dielmo and Ndiop), using an isotopic, micro, drug susceptibility test. The 71-50% inhibitory concentration (IC50) values for doxycycline ranged from 0.7 to 108.

Plasmodium falciparum clinical malaria: lessons from longitudinal studies in Senegal.

Development of new antimalaria strategies and particularly vaccines, needs an in-depth understanding of the relationships between transmission, infection, immunity, morbidity and mortality. The intensive and longitudinal collection of entomological, parasitological and clinical data from the Senegalese populations of Dielmo (250-300 inhabitants), exposed to a perennial and intense transmission (about 200 infective bites/person/year) and of Ndiop (300-350 inhabitants) exposed to a seasonal transmission (about 20 infective bites/person/year), allows to respond to many questions about this subject. The acquisition of an antimalaria immunity as one gets older appears to reduce parasite density, complexity of infection, risk of new patent infection after a suppressive treatment but does not reduce the prevalence (as assessed by PCR) of infection which is commonly chronic and asymptomatic.

A cohort study of Plasmodium falciparum diversity during the dry season in Ndiop, a Senegalese village with seasonal, mesoendemic malaria.

Prolonged carriage of Plasmodium falciparum in humans during the dry season is critical for parasite survival, as the infected subjects constitute a major reservoir in the absence of transmission. Yet, very little is known about the host/parasite interactions contributing to parasite persistence. In order to study the characteristics of P.

Hyperexpression of ICAM-1 and CD36 in placentas infected with Plasmodium falciparum: a possible role of these molecules in sequestration of infected red blood cells in placentas.

Aims: During pregnancy, Plasmodium falciparum malaria is frequent and associated with maternofetal complications. This could be the consequence of sequestration by several adhesion molecules of parasite-infected red blood cells in syncytiotrophoblast. To investigate the expression of ICAM-1 and CD36, two of the adhesion molecules for Plasmodium falciparum, an immunohistochemical study was carried out in malaria-infected placentas.

Development of substituted Benzo[c]quinolizinium compounds as novel activators of the cystic fibrosis chloride channel.

Chloride channels play an important role in the physiology and pathophysiology of epithelia, but their pharmacology is still poorly developed. We have chemically synthesized a series of substituted benzo[c]quinolizinium (MPB) compounds. Among them, 6-hydroxy-7-chlorobenzo[c]quinolizinium (MPB-27) and 6-hydroxy-10-chlorobenzo[c]quinolizinium (MPB-07), which we show to be potent and selective activators of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel.

Plasmodium falciparum clinical malaria in Dielmo, a holoendemic area in Senegal: no influence of acquired immunity on initial symptomatology and severity of malaria attacks.

Six hundred eighty-nine Plasmodium falciparum malaria attacks were observed during a three-year period among 226 inhabitants of the village of Dielmo, Senegal, an area of high malaria transmission. Malaria attacks were defined as clinical episodes with fever (body temperature > or = 38.0 degrees C) or reporting of fever or headache or vomiting, associated with a parasite:leukocyte ratio above an age-dependent pyrogenic threshold identified in this population.

Variation of Plasmodium falciparum msp1 block 2 and msp2 allele prevalence and of infection complexity in two neighbouring Senegalese villages with different transmission conditions.

To investigate the impact of transmission on the development of immunity to malaria and on parasite diversity, longitudinal surveys have been conducted for several years in Dielmo and Ndiop, 2 neighbouring Senegalese villages with holo- and mesoendemic transmission conditions, respectively. We analysed Plasmodium falciparum msp1 block 2 and msp2 genotypes of isolates collected from 58% of the Dielmo villagers during the same week as those studied recently from Ndiop. Allele frequencies differed in both villages, indicating considerable microgeographical heterogeneity of parasite populations.

Acute effects of adenosine triphosphates, cyclic 3',5'-adenosine monophosphates, and follicle-stimulating hormone on cytosolic calcium level in cultured immature rat Ssertoli cells.

The ability of ATP and FSH to induce intracellular calcium [Ca(2+)](i) changes in Sertoli cells is imperfectly understood and reports are conflicting. We have applied the single-cell microfluorometry technique with the calcium probe indo-1 to investigate [Ca(2+)](i) in individual cultured Sertoli cells. When cells were exposed to ATP, cAMP, and FSH, a fast and biphasic increase in [Ca(2+)](i) was obtained in 100%, 70%, and 56% of cells, respectively.

[In vitro sensitivity of Plasmodium falciparum isolates from Gabon to chloroquine and cycloguanil].

The in vitro susceptibility of 91 Plasmodium falciparum isolates obtained from malaria-infected children living near Libreville (Gabon) was evaluated against chloroquine and cycloguanil (biologically active metabolite of proguanil), using an isotopic micro-drug susceptibility test. In vitro resistance to chloroquine and cycloguanil was observed in 83% (35/42) and in 38% (30/78) of the patients, respectively. Our data showed that 41% (16/39) of Gabonese field isolates were resistant both to chloroquine and cycloguanil.

Quantitative computer image analysis of chondroitin sulfate A expression in placentas infected with Plasmodium falciparum.

Most pathological conditions resulting from infection with the human malaria parasite Plasmodium falciparum occur as a consequence of the sequestration by several adhesion molecules of parasite-infected red blood cells (IRBCs). Recent reports have provided evidence that placental vascular endothelial ligands for IRBCs were mostly restricted to chondroitin sulfate A (CSA). The expression of CSA in malaria-infected placentas was investigated in a prospective case-control study in a hypoendemic area (Dakar, Senegal).

In vitro activities of benflumetol against 158 Senegalese isolates of Plasmodium falciparum in comparison with those of standard antimalarial drugs.

The 50% inhibitory concentration (IC50s) of benflumetol (range, 12.5 to 240 nM; mean, 55.1 nM) for 158 Senegalese isolates were evaluated.

Plasmodium ovale in a highly malaria endemic area of Senegal.

During 4 months, from June to September 1990, the population of Dielmo village, Senegal, an area of intense and perennial malaria transmission, was enrolled in a follow-up study including daily clinical surveillance and bi-weekly malaria parasitaemia monitoring. Thick blood film examinations indicated that 48.5% of children (49/101) and 32.

No influence of age on infection complexity and allelic distribution in Plasmodium falciparum infections in Ndiop, a Senegalese village with seasonal, mesoendemic malaria.

We have shown previously that in Dielmo, a Senegalese village with intense perennial Plasmodium falciparum transmission, the infection complexity and the distribution of some allelic types harbored by asymptomatic carriers was age-dependent. We report here an investigation of these parameters in Ndiop, a village located 5 km from Dielmo, where malaria is mesoendemic and seasonal, and where immunity is acquired at a very low rate, as indicated by the lifelong distribution of P. falciparum clinical attacks.

[Comparative evaluation of the plasmodial infection of Anopheles using ELISA and dissection. Consequences for the estimation of the transmission of malaria in 1995 in Ndiop, Senegal].

An entomological study was carried out in Ndiop village, Senegal, an area of sudan-type savana, from January to December 1995, to compare the malaria inoculation rate measured by the dissection of salivary glands of anophelines and the enzyme-linked immunosorbent assay (ELISA). Mosquitoes were sampled by night-bite collections. Species from the Anopheles gambiae complex were identified using the polymerase chain reaction.

In vitro activity of artemether against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial drugs.

The in vitro activity of artemether against 56 African isolates of Plasmodium falciparum from Senegal was evaluated using an isotope-based drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0.8 to 15.

Four years' entomological study of the transmission of seasonal malaria in Senegal and the bionomics of Anopheles gambiae and A. arabiensis.

From 1993 to 1996, an entomological survey was conducted in the village of Ndiop, Senegal, as part of a research programme on malaria epidemiology and the mechanisms of protective immunity. Mosquitoes were captured on human bait and by indoor spraying. Species from the Anopheles gambiae complex were identified using the polymerase chain reaction, and Plasmodium falciparum infections were detected by enzyme-linked immunosorbent assay for circumsporozoite protein.

Imbalanced distribution of Plasmodium falciparum MSP-1 genotypes related to sickle-cell trait.

Background: The sickle-cell trait protects against severe Plasmodium falciparum malaria and reduces susceptibility to mild malaria but does not prevent infection. The exact mechanism of this protection remains unclear. We have hypothesized that AS individuals are protected by virtue of being less susceptible to a subset of parasite strains; thus we compared some genetic characteristics of parasites infecting AS and AA subjects.

Prognostic value of anti-Plasmodium falciparum-specific immunoglobulin G3, cytokines, and their soluble receptors in West African patients with severe malaria.

Forty-one African patients suffering from clinically defined severe malaria were studied in the intensive medical care unit of the main hospital in Dakar, Senegal, West Africa. All of these individuals lived in Greater Dakar, an area of low and seasonal Plasmodium falciparum endemicity. Twenty-seven patients (mean age +/- 1 standard deviation, 19.

Incidence of clinical malaria in pregnant women exposed to intense perennial transmission.

The interaction between pregnancy and malaria attacks was investigated from 1990 to 1994 among women in the village of Dielmo, a holoendemic area in Senegal where malaria transmission is intense and perennial. Clinical and parasitological data collected during the daily follow-up of 48 pregnancies among 31 women were compared with those collected from the same women using the same methods during the year which preceded or followed their pregnancy. The parasite prevalence, mean and maximum parasite density in Plasmodium falciparum infections were significantly higher during pregnancy.