[Drug resistance of Plasmodium falciparum along the borders of the highlands in Madagascar: outlook for a national control program]. / Chimioresistance de Plasmodium falciparum sur les marges des hautes terres malgaches: perspectives pour le programme national de lutte.

Resistance of Plasmodium falciparum to chloroquine was first suspected in Madagascar in 1975 and later confirmed in vivo and in vitro. During the period from 1985 and 1990, the network of public health monitoring stations reported that 1% of the population living on the central Highlands of Madagascar died of malaria. Thereafter the National Malaria Control Program achieved good success by spraying homes with insecticide and reorganizing distribution of chloroquine in all villages. However data recorded between 1996 and 1998 indicates that, after four years of widespread chloroquine use, resistance to amino-4-quinolones is progressing in Madagascar. The tests described in this report were performed on patients with documented malaria included in cohorts and followed year round by a physician. The three villages studied were located along the borders of the highlands between the plateaus and coastal areas. In vivo tests showed that the incidence of chloroquine resistance was 0% in Mahakary, 32% in Ankazobe and 30% in Saharivo. Clinically, however, treatment was unsuccessful in only 16% and 8% of cases respectively. In vitro tests demonstrated chloroquine sensitivity in 79% of the 153 strains tested. No resistance to quinine or halofantrine was observed. In vitro tests indicated an onset of resistance to mefloquine. Although the success rate of chloroquine treatment is nearly 80%, spread of strongly chloroquine-resistant strains is a risk especially in subjects with mild immunity to malaria.

[The impact of curtains impregnated with deltamethrin on the vectors and morbidity of malaria: results in Ankazobe, on the plateaus of Madagascar]. / Impact des rideaux imprégnés de deltaméthrine sur les vecteurs et la morbidité palustre: résultats à Ankazobe, sur les plateaux de Madagascar.

To evaluate the efficacy of deltamethrin impregnated curtains on malaria morbidity in a low transmission area, we studied volunteer families in the village of Ankazobe in the Madagascar Highlands from February 1993 to June 1994. After randomization, we provided 46 houses having 244 inhabitants with impregnated curtains (I) and 45 others having 257 inhabitants with nonimpregnated curtains (NI) as controls. We first estimated the number of mosquito bites in the protected versus nonprotected households. Every month, we captured mosquitos on humans in 6 houses per night for 4 nights. For the I group compared to the NI group, the number of bites by the Anopheles funestus vector per human per night was reduced by 64% in 1993 and 39% in 1994. We also analyzed the malaria morbidity. Malaria morbidity was defined as patients having both temperatures greater than 37.5 degrees C and Plasmodium falciparum parasitemia greater than 1500/microliter with clinical symptoms. From February to July 1993, we observed no significant difference in morbidity: there were 103 cases of malaria among 244 inhabitants of the I group and 117 cases among 257 inhabitants of the NI group. However, during the period of highest transmission from March to May in 1993, there were significantly fewer cases in the I group (68) than in the NI group (94). From January to June 1994, the difference was clear: only 35 malaria cases were observed among the 208 inhabitants of the I group as compared to 65 cases among the 223 inhabitants of the NI group (Chi square = 9.17, p = 0.0024). Inhabitants of the I group could have been contaminated before the curtains were set up. After treatment of the cases and use of curtains during the second year, we observed a reduction in the number of mosquito bites and malaria cases. The small size of the trial made the interpretation of the data difficult. Nonetheless, the results tentatively support the use of impregnated curtains as an antimalaria tool in an integrated control program.

[Drug resistance and therapeutic strategy]. / Chimiorésistance et stratégie thérapeutique.

In Madagascar, Plasmodium falciparum resistance to chloroquine was clinically suspected in 1975 by Goasguen and demonstrated in 1981 by Arronson et al. Since then, many studies were conducted throughout the island, in the North, South, East and West, on the high Plateau and on the coasts. Two methods were used, including an in vivo method similar to the therapeutic standard protocol of the WHO, and an in vitro method employing the semi-microtest of Le Bras and Deloron. From 1982 to 1986, the 291 in vivo tests performed showed that 20% of the strains were of the types R1 or R2 (SR1 included). From 1987 to 1994, of the 621 in vivo tests performed, 369 (59.4%) of the cases responded to treatment. The deterioration of the situation observed in 1988 (Lepers et al.) seemed to be stabilized (Ringwald et al.). No strain of the type R3 was found. In conclusion, we report the absence of strain type R3 and also the clinical efficacy of chloroquine. The action of chloroquine was spectacular on the fevers and there was remarkable reduction of the parasitaemia. Thus, for treating outbreaks of simple malaria in Madagascar, chloroquine remains the best choice if it is administered at an efficacious dose.

[Epidemiological malaria surveillance in 3 villages of the Madagascar highlands]. / Surveillance épidémiologique du paludisme dans trois villages des Hautes Terres Malagaches.

Results of the epidemiological surveillance of falciparum malaria carried out since 1987 in three villages of the malagasy Highlands are reported. They clearly show the unsteady endemo-epidemic characteristic of the disease with highly variable transmission levels according to foci. At Manarintsoa, a south-western village 20km away from the Capital, the disease has now fully disappeared after the ravage of 1986. But it might reappear with new imported cases and by lack of antivectorial measures. Although Anopheles arabiensis had been rare and its aggressivity rate weak (0.91-2 infecting bites per year per man), surveillance is indispensable for the future. An Ankazobe and Mahavelona, two north-western localities respectively 100km and 65km away from Antananarivo, malaria is endemic with periodic outbreaks during rainy season. At Ankazobe, Anopheles funestus is the main vector maintaining endemic in this area while the role of Anopheles gambiae l.s. is only secondary. At Mahavelona, because of the weak presence of vectors, the treatment protocol by Quinimax has been applied in order to study transmission. This study obviously shows that contrary to set ideas in the Highlands, backward transmission is possible up to the first months of the austral winter (June-July). In these two last villages, adults have acquired some premunition.

[Aspects of Plasmodium falciparum sensitivity to chloroquine in Madagascar from 1982 to 1993]. / Aspects de la sensibilité de Plasmodium falciparum à la chloroquine à Madagascar de 1982 à 1993.

According to pharmaco-sensitivity studies, about 20% of local Plasmodium falciparum strains showed a certain degree of resistance to chloroquine. No resistance of R3 type has never been observed. During this whole period, the decrease of sensitivity phenomenon remains stable. Because of its remarkable action on parasitemia and fever, chloroquine remains the best antimalaria in simple malarial attacks in madagascar.