Evaluation de l'efficacité des amino-4 quinoléines en zone de chimiorésistance : proposition de nouveaux schémas thérapeutiques

Les auteurs comparent l'efficacité thérapeutique de la chloroquine et de l'amodiaquine dans le traitement de l'accès palustre à #Plasmodium falciparum$ au niveau de dispensaires urbains. La chloroquine a un taux d'efficacité constant quelle que soit la posologie et la durée du traitement et devrait être réservée au traitement présomptif à domicile de l'accès palustre. L'amodiaquine à raison de 35 mg/kg en 3 jours apporte un bénéfice appréciable (96,5 % de succès clinique), ce qui la place en thérapeutique de première intention dans le traitement de l'accès palustre biologiquement confirmé en dispensaire. (Résumé d'auteur

Evaluation par test simplifié in vivo de la chimiosensibilité du Plasmodium falciparum à la chloroquine et à l'amodiaquine dans le Sud du Cameroun

La sensibilité in vivo du #Plasmodium falciparum$à la chloroquine et à l'amodiaquine à la dose de 25 mg/kg per os en trois jours a été évaluée par six enquêtes effectuées en 1989 dans le Sud-Ouest du Cameroun. La prévalence plasmodiale chez les écoliers est de 75$ est présent dans 96 % des infections. Parmi 357 enfants traités à la chloroquine, 24 % sont porteurs de trophozoïtes au 3ème jour du traitement et 17 % au 7ème jour. Une résistance complète de type R III est observée dans 4 % des cas. Parmi les 55 enfants traités à l'amodiaquine, 13 % et 10 % sont trouvés porteurs de rares trophozoïtes à J3 ET J7. La signification de ces résultats est discutée. (Résumé d'auteur

Declining Artesunate-Mefloquine Efficacy against Falciparum Malaria on the Cambodia–Thailand Border

Emerging resistance in Southeast Asia raises concern over possible spread or similar evolution of resistance to other artemisinin-based combination therapies in Africa

Invasion of Africa by a single pfcrt allele of South East Asian type

BACKGROUND: Because of its dramatic public health impact, Plasmodium falciparum resistance to chloroquine (CQ) has been documented early on. Chloroquine-resistance (CQR) emerged in the late 1950's independently in South East Asia and South America and progressively spread over all malaria areas. CQR was reported in East Africa in the 1970's, and has since invaded the African continent. Many questions remain about the actual selection and spreading process of CQR parasites, and about the evolution of the ancestral mutant gene(s) during spreading. METHODS: Eleven clinical isolates of P. falciparum from Cambodia and 238 from Africa (Senegal, Ivory Coast, Bukina Faso, Mali, Guinea, Togo, Benin, Niger, Congo, Madagascar, Comoros Islands, Tanzania, Kenya, Mozambique, Cameroun, Gabon) were collected during active case detection surveys carried out between 1996 and 2001. Parasite DNA was extracted from frozen blood aliquots and amplification of the gene pfcrt exon 2 (codon 72–76), exon 4 and intron 4 (codon 220 and microsatellite marker) were performed. All fragments were sequenced. RESULTS: 124 isolates with a sensitive (c76/c220:CVMNK/A) haplotype and 125 isolates with a resistant c76/c220:CVIET/S haplotype were found. The microsatellite showed 17 different types in the isolates carrying the c76/c220:CVMNK/A haplotype while all 125 isolates with a CVIET/S haplotype but two had a single microsatellite type, namely (TAAA)3(TA)15, whatever the location or time of collection. CONCLUSION: Those results are consistent with the migration of a single ancestral pfcrt CQR allele from Asia to Africa. This is related to the importance of PFCRT in the fitness of P. falciparum point out this protein as a potential target for developments of new antimalarial drugs

Molecular monitoring of Plasmodium falciparum resistance to artemisinin in Tanzania

Artemisinin-based combination therapies (ACTs) are recommended for use against uncomplicated malaria in areas of multi-drug resistant malaria, such as sub-Saharan Africa. However, their long-term usefulness in these high transmission areas remains unclear. It has been suggested that documentation of the S769N PfATPase6 mutations may indicate an emergence of artemisinin resistance of Plasmodium falciparum in the field. The present study assessed PfATPase6 mutations (S769N and A623E) in 615 asymptomatic P. falciparum infections in Tanzania but no mutant genotype was detected. This observation suggests that resistance to artemisinin has not yet been selected in Tanzania, supporting the Ministry of Health's decision to adopt artemether+lumefantrine as first-line malaria treatment. The findings recommend further studies to assess PfATPase6 mutations in sentinel sites and verify their usefulness in monitoring emergency of ACT resistance

Reduced in vitro susceptibility to artemisinin derivatives associated with multi-resistance in a traveller returning from South-East Asia

Decreased in vitro susceptibility to dihydroartemisinin (21.2 nM) and artesunate (16.3 nM) associated with decreased susceptibility or resistance to quinine (1131 nM), mefloquine (166 nM), lumefantrine (114 nM), pyronaridine (70.5 nM) and piperaquine (91.1 nM) is reported in a patient returning from South-East Asia after trekking along the Mekong from the south of Laos to the north of Thailand. Decreased in vitro susceptibility to artemisinin derivatives did not appear to be mediated by the number of copies of pfmdr1 or pfATPase6, pfcrt, pfmdr1 or pfmrp polymorphism. The high IC50 to mefloquine of this Asian isolate was not associated with pfmdr1 copy number. Pfnhe-1 microsatellite ms4760 showed a profile 7 (ms4760-7) with three repeats of DNNND and one repeat of DDDNHNDNHNN, which is associated with high quinine reduced susceptibility. The patient recovered in three days without relapse after treatment with the association of quinine and doxycycline. Decreased in vitro susceptibility to quinine and the delayed effect of doxycycline may both have contributed to the delayed parasite clearance time, D4 (0.5%) and D7 (0.004%). The in vitro data, with IC50 for dihydroartemisinin and artesunate were up to ten times those of the reference clone W2, which suggests that this isolate may be resistant to artemisinin derivatives, associated with a decreased susceptibility to quinine

Trials

After publication of the original article [1], the authors have notified us of an additional acknowledgement they wish to bring for their paper