Newly transmitted Plasmodium falciparum malaria in the central highland plateaux of Madagascar: assessment of clinical impact in a rural community.

Plasmodium falciparum has recently reappeared in the central highland plateaux of Madagascar. To define its role in the overall malaria pathology occurring during the rainy season, we conducted a clinical and parasitological study among the 2776 consultants of a malaria field health centre which we established in the middle of the transmission area. From January to June 1988 the overall parasite rate was 63.2% and did not vary with age; the overall splenic rate was 46.9%, decreasing in individuals over 15 years of age. After the beginning of the main transmission season, an increase in parasite rates and parasite densities was observed, while febrile illnesses associated with malaria parasitaemia decreased. During the second part of the rainy season the parasite densities started to decrease, while parasite rates and malaria-associated fevers remained at the same level. The frequency of fevers was not related to the malaria parasite density owing to individual and seasonal variations.

Newly transmitted plasmodium falciparum malaria in the central highland plateaux of Madagascar : assessment of clinical impact in a rural community

Plasmodium falciparum has recently reappeared in the central highland plateaux of Madagascar. To define its role in the overall malaria pathology occurring during the rainy season, we conducted a clinical and parasitological study among the 2776 consultants of a malaria field health centre which we established in the middle of the transmission area. From January to June 1988 the overall parasite rate was 63.2% and did not vary with age; the overall splenic rate was 46.9%, decreasing in individuals over 15 years of age. After the beginning of the main transmission season, an increase in parasite rates and parasite densities was observed, while febrile illnesses associated with malaria parasitaemia decreased. During the second part of the rainy season the parasite densities started to decrease, while parasite rates and malaria-associated fevers remained at the same level. The frequency

[Malaria in Ile de Sainte Marie in 1988. Epidemiological approach. Chloroquine sensitivity of Plasmodium falciparum]. / Le paludisme dans l'Ile de Sainte Marie en 1988. Approche épidémiologique. Sensibilité de Plasmodium falciparum à la chloroquine.

The Malaria Research Unit of the Madagascar Pasteur Institute and the local health authorities carried out a study in the Sainte Marie Island in August 1988. Epidemiological results were in agreement with those previously reported in areas of endemic malaria. Parasite and splenomegaly rates were 34.6 and 35.9% respectively, by both active and passive cases detection. Analysis of parasite densities and clinical symptoms in the various age groups demonstrates that protective immunity is absent in infants and young children, and appears by the age of 2 to 9 years. An in vivo study of the sensitivity of Plasmodium falciparum to chloroquine was conducted in 41 patients. 39% of the infections were normally sensible (S) to WHO standard therapy (25 mg chloroquine/kg in 3 days), while 32% of the patients presented with a thick blood smear negative by D7, but positive by D14 (S/R1). Parasite resistance was observed in 29% of the infections: in 10% at the R1 level, and in 19% at the R2 level. Frequency and level of resistance to chloroquine are higher than those we observed in the East Coast in 1983 and 1985. However, chloroquine consistently achieves a high reduction in parasite densities and is still clinically active.

[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.

[In vitro sensitivity of Plasmodium falciparum to chloroquine in the highland region of Madagascar in 1987]. / Etude de la sensibilité in vitro de Plasmodium falciparum à la chloroquine en une région des hauts plateaux malgaches en 1987.

With the Le Bras's isotopic semi-microtest method, the authors have studied 139 strains of Plasmodium falciparum isolated in a village near Tananarive in the Highlands of Madagascar. Conditional malariometric rates show the increase of the recrudescence of Malaria in the area which was recently considered as "surveillance area". 5.8% of the 139 studied strains show an in vitro resistance higher than 120 nmoles/l, but whose the level is ever lower than in Africa. 4.3% exhibit a level between 90 and 120 nmoles/l. These values give better prospect for the Isle because the resistance strain rates have remain nearly stable since 1982. The resistance level is always low.

[Sensitivity of Plasmodium falciparum to quinolines and therapeutic strategies: comparison of the situation in Africa and Madagascar between 1983 and 1986]. / Sensibilité de Plasmodium falciparum aux quinoléines et stratégies thérapeutiques: comparaison de la situation en Afrique et à Madagascar entre 1983 et 1986.

One thousand and twenty six P. falciparum strains isolated from cases imported in France and field surveys in four regions of Africa and Madagascar were studied in vitro against chloroquine, monodesethylamodiaquine, quinine and mefloquine, 917 in vivo tests were performed during field studies with chloroquine (10 and 25 mg/kg) and amodiaquine (10, 25, 35 mg/kg). In Madagascar, the chemoresistance remained low and stable during the study period, concerning mostly chloroquine (11% in vitro and in vivo) without obvious geographical variation. 25 mg/kg chloroquine or amodiaquine were satisfactory as respectively first and second line therapeutic regimen. In Central Africa, chemoresistance emerged with an epidemic profile and increased dramatically in disseminated urban focus. High level and prevalence of chloroquine resistance and multiresistance were observed few months after the index cases in these foci. In South West Cameroon, amodiaquine remained efficient as curative treatment but only at a dose of 35 mg/kg/5 days. Decrease of in vitro sensitivity and in vivo efficacy of quinine is a matter of concern. Given the heterogeneous and evolutive situation of drug resistance, the need for epidemiological surveillance and monitoring of P. falciparum drug sensitivity in Africa is obvious to adjust therapeutic regimen.

Plasmodium falciparum in Madagascar: in vivo and in vitro sensitivity to seven drugs.

The sensitivity level of Plasmodium falciparum isolates to chloroquine and the activity of six other antimalarials were studied in the different climatic zones of Madagascar in 1983. In vivo tests were done with 10 and 25 mg kg-1 of chloroquine and amodiaquine. Early recrudescence or RII resistance was observed after treatment with 10 mg kg-1 of these drugs in 34% of the cases for chloroquine and 6.5% for amodiaquine, and after the 25 mg kg-1 dose in 7% and 0% of the cases respectively. In vitro sensitivity of 84 P. falciparum isolates to seven drugs were studied with a semi-microtest. For chloroquine, 9% of the isolates had an IC50 above 250 nM, indicating resistance. In vitro activity of piperaquine was high for all isolates except two. In vitro activity of amodiaquine, dichlorquinazine, quinine, mefloquine and halofantrine was good against all isolates (maximum IC50 was 76, 92, 560, less than or equal to 20 and less than or equal to 12 nM, respectively). Correlation between the WHO standard field test and the in vitro semi-microtest was good. Resistance of P. falciparum to chloroquine was observed in the six survey areas, but the other tested drugs showed good activity. Since no cross-resistance to 4-aminoquinolines seems to exist in Madagascar, amodiaquine (the only one available at present) should be studied as an alternative to chloroquine in the prevention and treatment of falciparum malaria in this area.

[In vivo and in vitro sensitivity to 4-aminoquinolines of Plasmodium falciparum in Madagascar: results of 2 years' study]. / Sensibilité in vivo et in vitro aux amino-4-quinoléines de Plasmodium falciparum a Madagascar: résultats de deux années d'étude.

563 cases of Falciparum malaria were detected in 1984 and 1985 in 7 malarial zones covering 3 climatic regions in Madagascar. All subjects underwent a therapeutic test; 175 strains of Plasmodium falciparum were isolated for in vitro drug sensitivity studies. 28 strains which were moderately chloroquine resistant in vitro were identified in 1983 in these various zones. However, 16% strains studied in 1984 in Alatsinainy (plateaux area), were chloroquine-resistant in vitro. The in vitro sensitivity to the other amino-4-quinolines seemed to be retained. In vivo, 7% of resistance type RI or RII were noted with 25 mg/kg of chloroquine but none with 25 mg/kg of amodiaquine. The usual therapeutic schedule for partially immune subjects (10 mg/kg in one dose) was ineffective on day 7 in 34% of the cases with chloroquine and 5% of the cases with amodiaquine. In conclusion to this study, we recommend that chemoprophylaxis should be stopped in schools in Madagascar and that presumed malarial attacks should be treated with a minimum dose of 25 mg/kg of chloroquine in 3 days. We suggest that amodiaquine should be used in cases of therapeutic failure with chloroquine.