Antibodies to the 4-mer repeat of the ring-infected erythrocyte surface antigen (Pf155/RESA) protect against Plasmodium falciparum malaria.

To investigate the protective role of antibodies to the ring-infected erythrocyte surface antigen (Pf155/RESA) epitopes against Plasmodium falciparum clinical malaria, a cohort study was conducted in a Malagasy village over 7 months. In the 304 individuals included, 127 experienced P. falciparum attacks of under 1500 parasites/microliters with no clinical symptoms (protected individuals) and 177 experienced at least one clinical or preclinical P. falciparum attack requiring therapy (unprotected individuals). Antibodies to whole Pf155/RESA, to single epitopes of the 3' terminus, (EENV)4 and EENVEHDA(EENV)2 had higher responses in protected than in unprotected individuals (P = 0.006, P = 0.005, P = 0.05 respectively). Within the whole pattern of antibodies to the Pf155/RESA epitopes, only anti-R4 was related to protection independently of age and anti-wR. The Pf155/RESA 4-mer repeated epitope might be of interest for inclusion in a vaccine against the asexual blood stages of P. falciparum.

Assessment of the protective value of antibodies to the Plasmodium falciparum ring-infected erythrocyte surface antigen (RESA): an epidemiologic study in Madagascar.

The ring-infected erythrocyte surface antigen (RESA), a Plasmodium falciparum merozoite antigen, is a major vaccine candidate against falciparum malaria. To investigate the protective role of antibodies to RESA and its 4-mer, 8-mer, and 11-mer repeated amino acid sequences under conditions of natural exposure, a case-control and a cohort study were carried out in 1988 in a rural community in Madagascar where malaria reappeared recently. Fifty cases with greater than 1,000 P. falciparum per microliter of blood, and 45 controls with a negative blood smear were enrolled and sera were collected. Forty-one controls were followed for 20 weeks to identify malarial attacks. Protection against clinical malaria was assessed by the absence of malarial attacks requiring therapy. At enrollment, positivity rates and reactivity levels to RESA or repeats were similar in cases and controls. The 11-mer repeat antibody level was higher in the 26 controls who experienced at least one malarial attack during follow-up than in the 15 other controls (p less than 0.01). Thus, antibodies to the 11-mer repeat were predictors of the subsequent appearance of the disease. After adjustment for antibodies to the 11-mer repeat, antibodies to whole RESA had a negative predictive value on the occurrence of malarial attacks (p = 0.04). Different epitopes within the RESA molecule may elicit production of antibodies with different activities.

[Ecological factors in the renewed outbreak of malaria in Madagascar]. / Facteurs écologiques de la recrudescence du paludisme à Madagascar.

The new epidemic of malaria which spread on the Madagascar high plateau in 1986-1987 is due to the combination of several factors (some of which are analysed by the authors, especially those related to anopheles, parasite and man). The authors compare the situations on the high Plateau and on St Mary Island, on the East Madagascar Coast, where the malaria is stable. Concerning the vector, the most interesting fact is the come-back of Anopheles funestus on the high Plateau from which it had disappeared at the beginning of the fifties. In this area, An.arabiensis seems to be the only representative of the gambiae complex whereas it is An. gambiae s.s. in St Mary Island. The parasite is getting more and more resistant to chloroquine. Nevertheless, man seems to develop protection, but it is difficult to analyse the markers which would prove the protection. However, that protection was assessed, on the humoral and cellular level, against the peptides of the RESA (Ring Infected Erythrocytes Surface Antigen), the circumsporozoite protein and the antigen E.

Efficacy of a 3-day oral regimen of a quinine-quinidine-cinchonine association (Quinimax) for treatment of falciparum malaria in Madagascar.

In the search for an effective, safe and field-adapted alternative to chloroquine for therapy of chloroquine-resistant Plasmodium falciparum infections in Africa, a 3-d oral regimen of Quinimax (an association of quinine, quinidine and cinchonine) was evaluated in 35 individuals with P. falciparum in Madagascar, an area with chloroquine resistance. 63% of the parasite strains isolated were resistant in vitro to chloroquine, and 59% of the infections were present despite previous chloroquine intake. Three daily oral doses of 10 mg/kg Quinimax for 3 d cleared parasitaemia and improved clinical status in all subjects. Mean parasite and fever clearance times were 51.7 and 37.4 h, respectively. All patients were aparasitaemic at the end of the 7-d follow-up. When formulating therapy guidelines, the 3-d Quinimax regimen should be considered as a valuable alternative to chloroquine for treating falciparum malaria in African areas with clinical resistance to chloroquine.

[Antimalarial serology in 1987-1988 in the Highland Plateaux, the East coast and the South of Madagascar]. / Sérologies antipalustres en 1987-1988 sur les Hauts Plateaux, la côte Est et le Sud de Madagascar.

We studied 521 serum samples collected in 1987-88 in the Highland Plateaux and the East coast of Madagascar, two areas presenting different levels of malaria endemicity. Total anti-Plasmodium falciparum antibodies were investigated by an indirect immunofluorescence assay (IFA). Antibodies directed to the ring-infected erythrocyte surface antigen (RESA) were investigated by a modified IFA (MIFA). Results were analysed in regards to malariological parameters (parasite and splenomegaly rates) collected simultaneously. IFA appears as a good epidemiological tool as it closely parallels the classical malariological parameters. In selected studies, the presence of P. falciparum parasites in blood was less frequent in individuals presenting with anti-RESA antibody, as detected by MIFA, than in the other individuals were consistently lower in subjects with anti-RESA antibody than in others.

[Malaria in 1988 in a village of the Malagasy Highland Plateaux. Epidemiological findings]. / Le paludisme en 1988 dans un village des hauts plateaux malgaches. Données épidémiologiques.

In 1988, the Malaria Research Unit of the Madagascar Pasteur Institute settled an out-patients clinic in Manarintsoa, a village of the Highland Plateaux where epidemic malaria appeared recently. 2776 consultants presented between January and June. In addition, the 200 schoolchildren were examined thrice. For each individual, clinical examination and thick and thin blood smears were performed. In the out-patients, parasite rates were above 50% each month and in each age group; the mean parasite rate being 74%. Splenomegaly rates were above 60% in individuals less than 15 years of age, and around 20% in adults. In schoolchildren, parasite and splenomegaly rates are consistently above 50%. Gametocyte indexes were 7.5% and 7% in May and October, respectively. Plasmodium falciparum is the most encountered species (in 85% of the cases), but P. vivax and P. ovale are also present. P. malariae is very rare. Early diagnosis and adequate therapy were very effective against mortality. During the high transmission time, monthly mortality rates varied from 12% before our arrival to 0.66% after. The number of malaria attacks was estimated at 2 per man and per year. In this area of unstable malaria, presence of fever appears to be of poor predictive value of the malaria infection. Systematic chloroquine therapy of fevers would be adapted to only 43% of the cases.

[Sensitivity of Plasmodium falciparum to different antimalarials. A study in 1988 in a village in the Hauts-Plateaux of Madagascar]. / Sensibilité de Plasmodium falciparum à divers antimalariques. Etude en 1988 dans un village des Hauts-Plateaux malgaches.

Since a few years, malaria has reappeared in the Central Highland Plateaux of Madagascar. From 1983 to 1987, Plasmodium falciparum resistance to chloroquine remained stable, with a low frequency of R2 therapeutic failures. In 1988, a study was conducted in the village of Manarintsoa, 15 km from Tananarive. Ninety-one WHO in vivo standard tests were performed. In vitro efficacy of amodiaquine and quinine was also studied. In vitro, the efficacy of chloroquine, quinine, and mefloquine was measured against 104, 64, and 23 P. falciparum isolates, respectively, by an isotopic semi-microtest.