Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial

Adjuik, Martin; Agnamey, Patrice; Babiker, Ahmed; Borrmann, Steffen; Brasseur, Philippe; Cisse, M.; Cobelens, Frank; Diallo, S.; Faucher, Jean‐François; Garner, Paul; Gikunda, S.; Kremsner, Peter G.; Krishna, Sanjeev; Lell, Bertrand; Loolpapit, Mores; Matsiégui, Pierre-Blaise; Missinou, Michel A.; Mwanza, Jean-Claude; Ntoumi, Francine; Olliaro, Piero; Osimbo, P.; Rezbach, Philipp; Some, Eliab; Taylor, Walter R. J.

doi:10.1016/s0140-6736(02)08348-4

Cited by 276 publications

(255 citation statements)

References 24 publications

Supporting

Mentioning

230

Contrasting

Unclassified

Order By: Relevance

“…However, it must be noted that SP monotherapy is not a favoured treatment for uncomplicated malaria in Africa at least in areas of high transmission due to the early emergence and spread of its resistance across the continent. Our results confer the same level of usefulness of AQ for the treatment of uncomplicated falciparum malaria across Africa as previously described (Adjuik et al 2002). 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).…”

Section: Discussionsupporting

confidence: 80%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 80%

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

View full text Add to dashboard Cite

show abstract

“…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: 81%

Chloroquine Resistance in Plasmodium falciparum Malaria Parasites Conferred by pfcrt Mutations

Sidhu

Verdier-Pinard

Fidock

2002

Science

640

663

View full text Add to dashboard Cite

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...

show abstract

“…These combinations include artesunate with mefloquine, amodiaquine, SP, and atovaquone-proguanil, artemether with lumefantrine, and dihydroartemisinin with piperaquine. 7,73,[97][98][99][100] The safety of these combinations needs to be further assessed.…”

Section: Prospects For New Drugsmentioning

confidence: 99%

Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development

Guérin¹,

Olliaro

Nosten

et al. 2002

The Lancet Infectious Diseases

320

207

View full text Add to dashboard Cite

Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial

Cited by 276 publications

References 24 publications

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

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

Chloroquine Resistance in Plasmodium falciparum Malaria Parasites Conferred by pfcrt Mutations

Malaria: current status of control, diagnosis, treatment, and a proposed agenda for research and development

Contact Info

Product

Resources

About