Amodiaquine fails to cure chloroquine resistant Plasmodium falciparum in the Punjab

Abstract

We evaluated amodiaquine as a replacement drug for treating falciparum malaria in an area of Pakistani Punjab where chloroquine-resistant Plasmodium falciparum has recently emerged. Amodiaquine appeared to be 4 to 8 times more effective than chloroquine when P. falciparum isolates were tested in vitro. However, the recrudescence rate was greater than 50% after oral treatment with 20 mg/kg amodiaquine given over two successive days. This lack of therapeutic response from amodiaquine may have been due to selection of resistant parasites in the villages where the study was performed through extensive use of chloroquine for presumptive malaria treatment during the preceding 18 months. We conclude that amodiaquine is not a suitable replacement for chloroquine for treating falciparum malaria in our study area despite in vitro sensitivity data suggesting that it would be efficacious. Baseline in vitro sensitivity to mefloquine is also reported.

The disposition of amodiaquine in Zambians and Nigerians with malaria.

“…There is cross resistance of parasites to AQ and chloroquine and the MIC value for the Indochina-1 strain (chloroquine resistant) (Mount et al, 1987) was not exceeded beyond 4 days by nearly half the patients in the present study . Childs et al (1989) (Khaliq et al, 1987;Watt et al, 1987). Chloroquineresistant malaria is increasingly common in east Africa (Brandling-Bennett et al, 1988), and has been documented in Zambia and Nigeria.…”

Efficacy of combination therapy with artesunate plus amodiaquine compared to monotherapy with chloroquine, amodiaquine or sulfadoxine–pyrimethamine for treatment of uncomplicated Plasmodium falciparum in Afghanistan

“…Because of AQ's affordability (its price is comparable with that of CQ) there is considerable interest in its use when CQ fails. Cross‐resistance between CQ and AQ in vivo has been reported in South Asia on a few occasions (Khaliq et al. 1987; Pandya et al.…”

Amodiaquine Resistance in Plasmodium falciparum Malaria in Afghanistan Is Associated with the pfcrt SVMNT Allele at Codons 72 to 76

“…In many countries, predominantly in Africa, the in vivo efficacy of AQ was found to be good even in the face of increasing CQ resistance (12). However, reports of AQ resistance have come from South America, Asia, and East Africa (7,8,10).Mutations in the P. falciparum chloroquine resistance transporter gene (pfcrt) and multidrug resistance gene 1 (pfmdr1) have been associated with clinical resistance to both CQ and AQ (13). The presence of the pfcrt codon 72 to 76 haplotype SVMNT (Ser-Val-Met-Asn-Thr) correlates with high-level resistance to the AQ metabolite desethylamodiaquine (DEAQ) in in vitro tests (14) and has been detected with a high prevalence in parasite populations from Brazil, Papua New Guinea, Laos, Iran, and India (9,18).…”

“…In many countries, predominantly in Africa, the in vivo efficacy of AQ was found to be good even in the face of increasing CQ resistance (12). However, reports of AQ resistance have come from South America, Asia, and East Africa (7,8,10).…”