R. Durand

Evidence basis for antimalarial policy change in Sierra Leone: five in vivo efficacy studies of chloroquine, sulphadoxine–pyrimethamine and amodiaquine

Objectivesu2002 To provide nationally relevant information on the antimalarial efficacy of chloroquine (CQ), sulphadoxine–pyrimethamine (SP) and amodiaquine (AQ) in Sierra Leone, with a view to updating antimalarial policy in the country.

High Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine in Harper, Liberia: results in vivo and analysis of point mutations

In Liberia, little information is available on the efficacy of antimalarials against Plasmodium falciparum malaria. We measured parasitological resistance to chloroquine and sulfadoxine-pyrimethamine (SP) in Harper, south-west Liberia in a 28-d study in vivo. A total of 50 patients completed follow-up in the chloroquine group, and 66 in the SP group. The chloroquine failure rate was 74.0% (95% confidence interval [95% CI] 59.7-85.4%) after 14 d of follow-up and 84.0% (95% CI 70.9-92.8%) after 28 d (no polymerase chain reaction [PCR] analysis was performed to detect reinfections in this group). In the SP group, the failure rate was 48.5% (95% CI 36.2-61.0%) after 14 d and 69.7% (95% CI 57.1-80.4%) after 28 d, readjusted to 51.5% (95% CI 38.9-64.0%) after taking into account reinfections detected by PCR. Genomic analysis of parasite isolates was also performed to look for point mutations associated with resistance. Genotyping of parasite isolates revealed that all carried chloroquine-resistant K-76T mutations at gene pfcrt, whereas the triple mutation (S108N, N511, C59R) at dhfr and the A437G mutation at dhps, both associated with resistance to SP, were present in 84% and 79% of pretreatment isolates respectively. These results seriously question the continued use of chloroquine and SP in Harper and highlight the urgency of making alternative antimalarial therapies available. Our study confirms that resistance to chloroquine may be high in Liberia and yields hitherto missing information on SP.

Low efficacy of the combination artesunate plus amodiaquine for uncomplicated falciparum malaria among children under 5 years in Kailahun, Sierra Leone

Objectiveu2002 In 2004, Sierra Leone adopted artesunate plus amodiaquine as first‐line antimalarial treatment. We evaluated the efficacy of this combination in Kailahun, where a previous study had shown 70.2% efficacy of amodiaquine in monotherapy.

Molecular survey of Plasmodium falciparum resistance in south–eastern Iran

Abstract In south-eastern Iran, the sulfadoxine-pyrimethamine (SP) combination has been used to treat malaria caused by chloroquine-resistant Plasmodium falciparum. To explore the molecular basis of antimalarial resistance in this region, the dhfr, dhps and pfcrt genes of 50 clinical isolates of P. falciparum, collected from cases of uncomplicated malaria in 2000-2001, were checked for the point mutations that appear associated with SP or chloroquine (CQ) resistance. The results of the study, which was based on a PCR followed by DNA sequencing, indicated that all 50 isolates presented the DHFR S108N mutation associated with pyrimethamine resistance. Seven isolates (14%) had a triple DHFR mutation (S108N, N51I, C59R) and 32 (64%) had a double mutation in this domain. Thirty-nine isolates (78%) had the wild-type DHFR 51 codon but only 15 (30%) had the wild-type DHFR 59 codon. Eleven isolates (22%) only had the DHFR S108N mutation. All isolates had the wild-type DHPS 436 and 540 codons and all but two of the isolates had the wild-type DHPS 437 codon. All isolates but one had the PFCRT K76T mutation associated with CQ treatment failure. The results of this preliminary investigation indicate that SP may remain the treatment of choice for cases of uncomplicated malaria in south-eastern Iran.

Increased incidence of cycloguanil resistance in malaria cases entering France from Africa, determined as point mutations in the parasites' dihydrofolate-reductase genes

The incidence of cycloguanil resistance in 501 Plasmodium falciparum isolates from individuals entering France from Africa was estimated by a method based on PCR-restriction-fragment-length polymorphisms. None of the subjects had taken antifol prophylaxis. Annual incidence of the resistance, detected as a point mutation at codon 108 in the parasites dihydrofolate-reductase gene, increased from 19.8% in 1995 to 43.6% in 1997 (P < 0.001). The proportion of isolates found to be susceptible (i.e. wild-type) among travellers returning from the African countries known as Group 2 in France (i.e. Burkina Faso, Côte dIvoire, Gambia, Ghana, Guinea, Liberia, Madagascar, Mali, Mauritania, Niger, Senegal, Sierra Leone, Tchad and Togo) was reasonably high (62.9%) and much higher than in the other subjects returning from other identifiable countries in Africa (35.3%). The antimalarial prophylaxis recommended in France to those travelling to Group-2 countries, chloroquine-proguanil, therefore still seems reasonable, although cycloguanil resistance may seriously undermine the efficacy of this drug combination in the future.

Chimiosensibilité du paludisme d'importation à Plasmodium falciparum en France en 1997

En 1997, cinq centres hospitaliers sentinelles ont envoye lintegralite de leurs isolats de Plasmodium afin dobtenir un echantillon representatif du paludisme dimportation : le CHU CI. Bernard X. Bichat a Paris, le CHG Delafontaine a St-Denis, lHIA Begin a St Mande, le CHU Purpan de Toulouse et lHIA Laveran de Marseille. Le CNRCP et lIMTSSA continuent detudier la chimiosensibilite des isolats envoyes par dautres hopitaux ou par des laboratoires de ville.

Perfil y evolución de la quimiosensibilidad al paludismo por P. falciparum importado en Francia en 2000

En 2000, la quimiosensibilidad al paludismo importado en Francia fue estable. Si se tienen en cuenta todos los paises de infeccion, la doble resistencia a la cloroquina y el cicloguanil no ha cambiado desde 1996 hasta 2000. La monoterapia a base de quinina o mefloquina sigue siendo el primer tratamiento contra el paludismo por P. falciparum. La resistencia a estos dos antipaludicos en Africa no es frecuente ni ha evolucionado durante los ultimos 15 anos.

Profil et évolution de la chimiosensibilité du paludisme d'importation à Plasmodium falciparum en France en 2000

En 2000, la chimiosensibilite du paludisme d’importation est restee stable en France. Tous pays d’infection confondus, la bi-resistance a la chloroquine et au cycloguanil n’a pas evolue de 1996 a 2000. La monotherapie par quinine ou mefloquine reste le traitement de premiere intention au paludisme a P. falciparum. Pour ces antipaludiques, la resistance est rare en Afrique et sans evolution au cours des 15 dernieres annees.