Systematic review of amodiaquine treatment in uncomplicated malaria

Olliaro, Piero; Nevill, C.G.; Lebras, J.; Ringwald, Pascal; Mussano, Paola; Garner, Paul; Brasseur, Philippe

doi:10.1016/s0140-6736(96)06217-4

Cited by 237 publications

(156 citation statements)

References 9 publications

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“…In choosing between AQ and S/P, which are equally effective in parasite clearance, other aspects are important. AQ is significantly faster in fever clearance than S/P, as demonstrated in this study and by others (Ollario et al 1996), and the efficacy of AQ could be improved by a higher dosage regimen of 35 mg/kg, as used in West Africa (Dillen et al 1999). S/P, on the other hand, is superior to AQ both in reducing the symptoms on day 14 according to the Kigoma study (Muller et al 1996;Ollario et al 1996), and because of its single-dose administration.…”

Section: Discussionsupporting

confidence: 66%

In vivoefficacy study of amodiaquine and sulfadoxine/ pyrimethamine in Kibwezi, Kenya and Kigoma, Tanzania

Gorissen

Ashruf

Lamboo

et al. 2000

Tropical Med Int Health

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SummaryWe conducted two randomized clinical trials to determine the in vivo efficacy of amodiaquine and sulfadoxine/pyrimethamine in treating Plasmodium falciparum malaria. Seventy-five patients under the age of 10 years in Kibwezi, Kenya, and 171 patients in Kigoma, Tanzania, were enrolled for treatment. Due to loss of eight patients in Kibwezi and 37 in Kigoma to follow-up, we used best and worst case scenarios for the parasitological response. The in vivo sensitivity of Plasmodium falciparum to amodiaquine was 75% (no loss to follow-up) in Kibwezi and ranged from 85% in the best to 65% in the worst case scenario in Kigoma. The sensitivity to sulfadoxine/pyrimethamine was 70% to 88% in Kibwezi and 65% to 89% in Kigoma. R1 resistance to amodiaquine was 22% in Kibwezi and varied from 6% in the best to 26% for the worst case scenario in Kigoma. The R1 resistance to sulfadoxine/pyrimethamine was 5% to 23% in Kibwezi and 2% to 26% in Kigoma. R2 resistance was 3% for amodiaquine and 7% for sulfadoxine/pyrimethamine in Kibwezi and 9% in Kigoma for each treatment group. There was no statistically significant difference between treatment groups at either study site, except for a slight difference in R1 resistance in the best case scenario, Kibwezi, in favour of S/P. Although both amodiaquine and sulfadoxine/pyrimethamine resistance seems to be increasing, these antimalarials are still effective in parasite clearance.

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Section: Discussionsupporting

confidence: 66%

In vivoefficacy study of amodiaquine and sulfadoxine/ pyrimethamine in Kibwezi, Kenya and Kigoma, Tanzania

Gorissen

Ashruf

Lamboo

et al. 2000

Tropical Med Int Health

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“…A modest degree of cross-resistance was observed between chloroquine and monodesethylamodiaquine, the primary metabolite of amodiaquine (table S2) (26)(27)(28). These findings are consistent with the published data on amodiaquine efficacy in areas with a high prevalence of CQR malaria (29,30) and signal the need for close monitoring for resistance, including screening for possible additional changes in pfcrt sequence, with increased clinical use of amodiaquine. Further, these data suggest that CQR mediated by pfcrt point mutations now prevalent in endemic areas has a high degree of specificity for the chloroquine structure ( fig.…”

supporting

confidence: 82%

Chloroquine Resistance in Plasmodium falciparum Malaria Parasites Conferred by pfcrt Mutations

Sidhu

Verdier-Pinard

Fidock

2002

Science

640

663

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Plasmodium falciparum chloroquine resistance is a major cause of worldwide increases in malaria mortality and morbidity. Recent laboratory and clinical studies have associated chloroquine resistance with point mutations in the gene pfcrt. However, direct proof of a causal relationship has remained elusive and most models have posited a multigenic basis of resistance. Here, we provide conclusive evidence that mutant haplotypes of the pfcrt gene product of Asian, African, or South American origin confer chloroquine resistance with characteristic verapamil reversibility and reduced chloroquine accumulation. pfcrt mutations increased susceptibility to artemisinin and quinine and minimally affected amodiaquine activity; hence, these antimalarials warrant further investigation as agents to control chloroquine-resistant falciparum malaria.Chloroquine has for decades been the primary chemotherapeutic means of malaria treatment and control (1). This safe and inexpensive 4-aminoquinoline compound accumulates inside the digestive vacuole of the infected red blood cell, where it is believed to form complexes with toxic heme moieties and interfere with detoxification mechanisms that include heme sequestration into an inert pigment called hemozoin (2-4). Chloroquine resistance (CQR) was first reported in Southeast Asia and South America and has now spread to the vast majority of malaria-endemic countries (1). pfcrt was recently identified as a candidate gene for CQR after the analysis of a genetic cross between a chloroquine-resistant clone (Dd2, Indochina) and a chloroquine-sensitive clone (HB3, Honduras) (5-7). The PfCRT protein localizes to the digestive vacuole membrane and contains 10 putative transmembrane domains (7,8). Point mutations in PfCRT, including the Lys 76 → Thr (K76T) mutation in the first predicted transmembrane domain, show an association with CQR in field isolates and clinical studies (7,9,10). Episomal complementation assays demonstrated a low-level, atypical CQR phenotype in chloroquine-selected, transformed, pseudo-diploid parasite lines that coexpressed the Dd2 form of pfcrt (containing eight point mutations; Table 1), under the control of a heterologous promoter, with the wild-type endogenous allele (7).To address whether mutations in pfcrt are sufficient to confer CQR, we implemented an allelic exchange approach to replace the endogenous pfcrt allele of a chloroquine-sensitive line (GC03) with pfcrt alleles from chloroquine-resistant lines of Asian, African, or South American origin (Table 1) (fig. S1) (11). This approach maintained the endogenous promoter and terminator regulatory elements for correct stage-specific expression and did not use chloroquine during the selection procedure. As a result of this gene's highly interrupted nature * To whom correspondence should be addressed. dfidock@aecom.yu.edu. Wootton et al. (39) recently presented compelling evidence for rapid evolutionary sweeps of mutant pfcrt sequences throughout malaria-endemic areas, starting from a limited number of initi...

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“…In view of the growing need to replace CQ as first-line malaria treatment in endemic countries, combinations with AQ for the treatment of uncomplicated malaria may provide an interim effective and affordable alternative to CQ monotherapy (Bloland 2003). Urgent steps are therefore needed to protect the useful lifespan of AQ to prevent any cross resistance with CQ (Olliaro et al 1996) as any further increase in its treatment failure may render it useless in future combination treatment.…”

Section: Discussionmentioning

confidence: 99%

A randomized comparative study of chloroquine, amodiaquine and sulphadoxine-pyrimethamine for the treatment of uncomplicated malaria in Ghana

Oduro

Anyorigiya

Hodgson

et al. 2005

Trop Med Int Health

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SummaryThe study examined the efficacy of chloroquine (CQ), amodiaquine (AQ) and sulphadoxinepyrimethamine (SP) for the treatment of uncomplicated Plasmodium falciparum malaria in Ghana.A total of 351 children were randomized to receive either of the three study drugs. Patients were evaluated using the WHO 14-day in vivo antimalarial testing guidelines. The 14-day adequate clinical and parasitological response analysis revealed that CQ, 46.7% (95% CI 37.5, 56.0) has the least efficacy compared with AQ, 86.1% (95% CI 78.3, 91.8) and SP, 77.6% (95% CI 68.9, 84.8). Late parasite failures were also lower and similar in the AQ and SP (9.6% and 10.3%) than in the CQ (32.5%) group. However, CQ and AQ groups showed better fever clearance compared with SP throughout except for day 7 and after when possibly due to its significant late clinical failures, clearance by CQ was lower. Our findings suggest that CQ is no longer useful in Ghana and should be replaced as a first-line treatment of malaria. Replacement of CQ preferably with AQ combination treatment will be an effective and an affordable alternative for the treatment of uncomplicated malaria.

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Systematic review of amodiaquine treatment in uncomplicated malaria

Cited by 237 publications

References 9 publications

In vivoefficacy study of amodiaquine and sulfadoxine/ pyrimethamine in Kibwezi, Kenya and Kigoma, Tanzania

In vivoefficacy study of amodiaquine and sulfadoxine/ pyrimethamine in Kibwezi, Kenya and Kigoma, Tanzania

Chloroquine Resistance in Plasmodium falciparum Malaria Parasites Conferred by pfcrt Mutations

A randomized comparative study of chloroquine, amodiaquine and sulphadoxine-pyrimethamine for the treatment of uncomplicated malaria in Ghana

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