[Evidence of an urban, local transmission of malaria in Antananarivo, Madagascar]. / Mise en évidence d'une transmission urbaine autochtone du paludisme à Antananarivo, Madagascar.

Madagascar presents a large heterogeneity in terms of climate and altitude, which explains the uneven spread of malaria throughout the island. The capital, Antananarivo, counts more than one million inhabitants, altitude between 1250 and 1470 m, in an area where the transmission is low but malaria may cause deadly epidemic outbreaks. Numerous malaria cases are reported, without biological confirmation, and reliable data about urban malaria transmission are lacking. The " Institut Pasteur de Madagascar" together with the Malagasy Ministry of Health performed in 2003 a study about malaria transmission in Antananarivo. A prevalence survey of malaria among fever syndromes, with data collected from 43 urban dispensaries, showed that confirmed malaria cases represented only 2% of the total fever cases (15 cases out of 779 fever syndromes). The vast majority was imported from costal areas (13 cases out of 15), where malaria is hyperendemic. However, a local urban transmission was found for two patients and five other subjects identified during a proximity survey. Vectors A. arabiensis and A. funestus were found inside the patient houses, located in close proximity of flooded rice fields. Genetic analysis of P. falciparum strains allowed to distinguish three genotypes, aggregated by house. The analysis of parasite genome polymorphism proves here its validity for epidemic surveys in areas where malaria is unstable, with no premunition in the local urban population.

[Assessment of sulfadoxine-pyriméthamine (Fansidar, Paludar) efficacy in patients with uncomplicated malaria in Madagascar: preliminary study to propose a simplified study protocol]. / Surveillance de l'efficacité de sulfadoxine-pyriméthamine (Fansidar, Paludar) pour le traitement de l'accès palustre à Madagascar: proposition d'un protocole simplifié.

To alleviate the insufficient number of experienced medical teams invited to and accepting to monitor the effectiveness of drugs prescribed to patients with a diagnosis of uncomplicated malaria and to insure the surveillance of the susceptibility of P. falciparum to current antimalarials used in Madagascar, there is a need to draw a feasible study protocol carefully discussed with them. We carried out a preliminary study in two rural areas and assessed the efficacy of sulfadoxine-pyrimethamine (SP) for curing uncomplicated P. falciparum malaria, with a simplified protocol based on the principle of observational study. A single dose of SP was given on day 0 with paracetamol. The persons to whom the drugs were administered accepted two other interventions of one member of the medical teams on day 14 and day 28. Nineteen patients, 3-63 years old, fulfilled the follow-up. The efficacy of this combination was noted for the 19 persons. Our results show that P. falciparum strains are susceptible to SP. Since SP will be used in intermittent preventive treatment in pregnant women in Madagascar, one way to delay the occurrence of SP resistant parasites will be (a) to avoid massive use of SP for the non pregnant persons and (b) to monitor susceptibility of P. falciparum to SP as part of pilot studies using standard WHO protocol (which is not really easy for most of the peripheral health facilities--with the follow-up procedures with clinical examination and parasitological control at Days 0, 1, 2, 3, 7, 14, 21 and 28), and routinely with simplified protocol such as the analytical observational study illustrated in this present study. Limit and advantage of observational study are discussed.

Impact of the malaria control campaign (1993-1998) in the highlands of Madagascar: parasitological and entomological data.

Malaria transmission in the central highlands of Madagascar was interrupted in the 1960s by a national control program that used DDT indoor spraying and mass treatment with chloroquine. At the end of the 1980s in this region, epidemic malaria reappeared. Italian health authorities provided technical assistance to the National Malaria Control Program since the beginning of the resurgence of malaria in the central highlands. Yearly residual house spraying performed for 5 years (1993-1998) and the availability of antimalarial drugs reduced malaria transmission to very low levels, with improvement in parasitologic and entomologic indexes. A significant reduction of malaria prevalence was observed in the villages located at altitudes of 1,000-1,500 m, corresponding to the stratum of unstable malaria that was the main target of the antivector interventions. A significant reduction of malaria prevalence was also observed in the villages located at altitudes of 900-1,000 m, where malaria transmission is stable. The main vector Anopheles funestus was dramatically reduced in abundance and distribution in the sprayed areas.

Malaria prevention during pregnancy in unstable transmission areas: the highlands of Madagascar.

Malaria transmission in Madagascar is highly variable from one region to the next, and the consequences of the disease on pregnant women and their foetuses are not fully documented. In midwestern Madagascar, the high-transmission lowlands in the west of the country meet the central plateaux, where malaria is unstable because of the high altitude and annual indoor spraying of DDT since 1993. We studied five of the region's main maternity clinics. We began by interviewing sample groups of women of childbearing age living within the vicinity of each clinic. This enabled us to determine the extent to which they had accessed and made use of available maternal health services during pregnancy and delivery, and, hence, to estimate the feasibility of boosting the prophylaxis. We then spent a whole year (from June 1996 to May 1997) observing deliveries at the five clinics in order to gauge the prevalence of placental infection and its consequences on birthweight in various transmission situations. Although only between 2 and 15% of the women said that they had taken prophylaxis during their previous pregnancy, the vast majority had benefited from preventive care: 97% had attended an antenatal visit on at least one occasion and 84% had had the assistance of medical or paramedical staff during delivery, even when their homes were situated relatively far away from the clinic (76%). In total, we observed 1637 deliveries with a mean placental malaria prevalence rate of 8.1%. Individual prevalence rates, however, were found to differ significantly between the maternity clinics situated in the east (minimum 2.1%) and west (maximum 26.2%) of the region. There were also marked variations in line with the seasonal fluctuations in entomological transmission. On the whole, a greater percentage of low birthweights (LBWs) was recorded at the lowland clinics than at the highland ones (17.1% vs. 9.7%), possibly because of the higher malaria infection rate in low altitude areas. On the other hand, the relative risk of LBW linked to placental infection was far greater in the highlands [4.9 (3.3-7.3)] than in the lowlands [1.9 (1.2-3.0)]. Although the rate of placental malaria among women inhabiting the country's central plateaux may be low, it means that transmission--and, hence, the risk of LBW because of placental infection--still persists in spite of the indoor DDT spraying programme. For maximum efficacy, we recommend a combination of vector control (extended to lower altitude areas outside the current OPID zone) and preventive care--i.e. individual chemoprophylaxis--for all highland women during pregnancy.

[Epidemiologic surveillance system and control of malaria in the central highlands of Madagascar: results 1999-2000]. / Système de surveillance épidémiologique et d'alerte du paludisme sur les Hautes Terres Centrales de Madagascar: résultats 1999-2000.

The central highlands in Madagascar are characterized by an unstable occurrence of malaria with the risk of sporadic outbreaks. In major parts of the region DDT indoor spraying campaigns have been carried out from 1993 to 1998. This strategy was in 1999 replaced by another anti-vector intervention program targeting residual foci as detected by a surveillance and early warning system. This system is based on monitoring of presumptive malaria cases in the communities by which the number of presumptive cases exceeded a defined warning threshold value per month. The system was in the follow-up period shown to be very sensitive to variation of the coverage of anti-vector interventions: the number of presumptive cases decreased in the villages in which indoor spraying had been carried out and a minor increase was observed in those villages, where indoor spraying has been suspended. An increase of malaria cases was observed in 44 (20.8%) out of 212 study sites in the same period. The increase was in particular predominant in areas at lower attitude at the outer zones of the central highlands.

[The campaign against malaria in central western Madagascar: comparison of the efficacy of lambda-cyhalothrin and DDT house spraying. I--Entomological study]. / Lutte contre le paludisme dans le moyen-ouest de Madagascar: comparaison de l'efficacité de la lambda-cyhalothrine et du DDT en aspersions intra-domiciliaires. I--Etude entomologique.

For malaria vector control in Madagascar, the efficacy of lambda-cyhalothrin 10% wettable powder (ICON 10 WP) was compared with DDT 75% WP for house-spraying. This evaluation was conducted from November 1997 to September 1998 in highland villages of Vakinankaratra Region, at the fringe of the malaria epidemic zone, outside the zone covered by routine DDT house-spraying (Opération de pulvérisation intro-domiciliaire de DDT: OPID zone). Treatments were compared by house-spraying in four areas: 1) application of DDT 2g ai/m2 and 2) lambda-cyhalothrin 30 mg ai/m2 in previously unsprayed villages; 3) no intervention (control); 4) OPID 5th cycle of DDT 2g ai/m2. The prevalent vector Anopheles funestus almost disappeared from both the DDT and ICON sprayed areas, whereas in the unsprayed (control) area An. funeslus density went up to 60 females per room in April and there were two seasonal peaks of malaria transmission in January and March (see following paper). In the area sprayed with ICON, the parous rate of An. funestus decreased from 47% pre-spray to 39% six months post-spraying, while the parous rate increased in DDT-sprayed area (from 57% pre-spray to 64% six months post-spray). Bioassays of An. funestus on treated walls, six months post-spray, gave mortality rates of 100% on DDT and 90% on ICON. Conversely, ICON appeared to be more effective than DDT on thatched roofs (66% versus 100%, respectively, six months post-spray). In areas sprayed with DDT or ICON the density of An. arabiensis were little affected. This study demonstrated that, under equivalent conditions, both DDT and lambda-cyhalothrin were effective in reducing malaria transmission on the western fringes of the malaria epidemic zone of the malagasy highlands, with a residual effect lasting at least for six months. Lambda-cyhalothrin appeared to be more effective than DDT in reducing the longevity of malaria vectors. In addition to efficacy, the choice of insecticide for malaria vector control should take into account their acceptability by human populations and their toxicity and persistence in the environment.

[The campaign against malaria in central western Madagascar: comparison of lambda-cyhalothrin and DDT house spraying. II--Parasitological and clinical study]. / Lutte contre le paludisme dans le moyen-ouest de Madagascar: comparaison de l'efficacité de la lambda-cyhalothrine et du DDT en aspersions intra-domiciliaires. II--Etude parasitologique et clinique.

For malaria vector control in Madagascar, 10 WP (lambda-cyhalothrin 10% wettable powder) was compared with DDT 75% WP for house-spraying, from November 1997 to September 1998. This study was implemented at the fringe of the malaria epidemic zone, in villages on western slopes of the central highlands, outside the area covered for the past five years by routine DDT house-spraying (OPID). Four types of treatment were compared in different areas: 1) DDT 2 g ai/m2 and 2) lambda-cyhalothrin 30 mg ai/m2 in previously unsprayed villages, 3) no intervention (control); 4) yearly DDT spraying (OPID fifth cycle). To investigate the malariological impact of spraying, cross-sectional surveys of the village populations were performed in each study area at intervals of two months, before and after spraying. In the newly sprayed areas, from December to June, malaria indices decreased by 62% in the ICON area and 44% in the DDT area, whereas in the unsprayed village malaria increased by 32% during the same season. There was a similar decrease in the number of gametocyte carriers in the newly sprayed areas. Active malaria case detection among febrile individuals was performed fortnightly in each village outside the OPID area. Results showed decreased malaria incidence from February (two months post-spraying) in the sprayed villages, despite the rainy season, whereas in the unsprayed area the decline occurred only after the main transmission season. This study demonstrated that, parasitologically as well as entomologically, house-spraying with residual insecticide (DDT or ICON) was an effective method for controlling malaria on the western fringes of the Madagascar highlands epidemic zone. Both products were effective, but ICON had slightly better impact than DDT, i.e. more reduction of malaria indices and of vector longevity, less irritancy of mosquitoes. For best results in this area of transition between stable and unstable malaria, we recommend earlier annual spraying (as soon as November) and extension of the OPID barrier towards western and northern slopes of the Plateau.

Control of epidemic malaria on the highlands of Madagascar.

The Malagashy national malaria control programme ('Programme National de Lutte contre le Paludisme', PNLP) has been developing, since 1996, an epidemiological early warning system for malaria epidemics in the Central Highlands with the support of the Italian Development Cooperation. The system is based on the monitoring of malaria morbidity (clinical diagnosis) in 536 peripheral health centres (CSB) of the Highlands. The intervention area corresponds to 27 districts of the Antananarivo and Fianarantsoa provinces (4.7 million inhabitants) and spans around 100,000 square km. For each CSB a monthly warning threshold, defined as the 1993-1996 monthly mean number of malaria cases plus two standard deviations, was established. Three levels of epidemic alert have been defined according to the number of times the cases of presumptive malaria surpassed the threshold and according to the reported presence of severe malaria cases. The surveillance system relies also on the monitoring, in district hospitals of the Highlands, of the Plasmodium falciparum infection rate among clinically diagnosed malaria cases. A total of 185,589 presumptive malaria cases, corresponding to a 42/1000 malaria incidence, were recorded in 1997 by the surveillance system. During the same year 184 alerts of 2nd degree were reported. During 1998 173,632 presumptive malaria cases corresponding to a 38/1000 incidence were reported and 207 alerts of 2nd degree were detected; 75 of these alerts were investigated with ad hoc surveys and 3 initial malaria epidemics identified and controlled. Out of 6884 presumptive malaria cases diagnosed in the district hospitals during 1997-1998, only 835 (12.1%) have been confirmed by microscopy (P. falciparum 81.7%, P. vivax 15.0%, P. malariae 2.5%, P. ovale 0.2%, mixed infections 0.6%); 22.4% of these infections were imported cases from coastal endemic areas. The efficiency of the system in monitoring the trend of malaria morbidity and in the rapid detection and response to malaria epidemics is still being evaluated.