Efficacy of amodiaquine alone and combined with sulfadoxine-pyrimethamine and of sulfadoxine pyrimethamine combined with artesunate.
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The safety and the efficacy of amodiaquine (AQ) alone, AQ plus sulfadoxine-pyrimethamine (SP) (AQ plus SP), and artesunate (ART) plus SP (ART plus SP), three possible alternatives to chloroquine (CQ), were investigated in 379 Rwandan children 6-59 months old with uncomplicated Plasmodium falciparum malaria who visited one urban/peri-urban health center and two rural health centers. The three treatment regimens were well tolerated and no serious adverse effects were observed. Children treated with AQ plus SP had less clinical failures than those treated with ART plus SP (odds ratio [OR] = 0.25, 95% confidence interval [CI] = 0.06-0.81, P = 0.01) or AQ alone (OR = 0.33, 95% CI = 0.07-1.10, P = 0.08). Even after new infections were excluded, AQ plus SP was still significantly more efficacious than ART plus SP (P = 0.05). At day 14, the mean packed cell volume was significantly higher in the AQ plus SP group compared with the ART plus SP group (P = 0.02) and with the AQ alone group (P = 0.01). In Rwanda, AQ plus SP has been chosen to replace CQ as a first-line treatment. However, this is considered an interim measure and new combinations, possibly co-formulated, should be identified and tested. (+info)
Malaria prophylaxis: taking aim at constantly moving targets.
(26/318)
The prevention of malaria infections is one of the most important functions that any clinician can perform for those traveling to tropical geographic regions where malaria risks are present. The prophylaxis question has become complicated by continued emergence of chloroquine-resistant strains of Plasmodium falciparum, the recent appearance of Plasmodium vivax resistance, and the availability of a wide choice of antimalarial pharmaceuticals. Chemoprophylaxis may produce different toxicities among various patient populations. With increasing numbers of women who travel during their professional lives, there are potential implications for using chemoprophylaxis during pregnancy. Children are unable to tolerate certain antimalarials because of toxicities unique for them. In some instances, the safest and most palatable formulations for children are not even available in the United States and must be purchased in Canada or elsewhere. Reliance upon chemoprophylaxis alone has proven to be increasingly futile. With the introduction of new repellent formulations and nontoxic insecticides for use on clothing or bed netting, there are non-pharmacologic adjunctive measures which can now be considered first-line for the prevention of malaria infections. (+info)
Plasmodium falciparum gametocytaemia in Nigerian children: before, during and after treatment with antimalarial drugs.
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We evaluated gametocyte carriage and intensities of gametocytaemia in 710 children presenting with acute, symptomatic, uncomplicated Plasmodium falciparum malaria who were treated with various antimalarial drug regimens: chloroquine (CQ); chloroquine plus chlorpheniramine, a histamine H1 receptor antagonist that reverses CQ resistance in P. falciparum in vitro and in vivo (CQCP); chloroquine plus ketotifen, a histamine H1 receptor antagonist that reverses CQ resistance in P. falciparum in vitro but not in vivo in the present study (CQK); chloroquine plus pyrimethamine-sulphadoxine (CQPS); amodiaquine (AQ); amodiaquine plus pyrimethamine-sulphadoxine (AQPS); and pyrimethamine-sulphadoxine (PS). On presentation, gametocyte carriage was significantly higher in CQ-resistant (CQ-R) than in CQ-sensitive (CQ-S) infections. Following CQ treatment, gametocyte carriage was significantly higher at all times after treatment and gametocyte density significantly higher on day 7 of follow-up in children with CQ-R than CQ-S infections. CQ treatment of CQ-R infections resulted in significantly higher density of gametocytaemia on day 7 compared with pre-treatment (day 0), but similar treatment of CQ-S infections resulted in significantly lower density of gametocytaemia on day 14 compared with day 0. Among children with CQ-R infections, those with mild (RI) resistance carried gametocytes significantly more often than those with moderate (RII) resistance on days 5 and 7 of follow-up (P = 0.04 and 0.01, respectively). Disposition kinetics of gametocytaemia using a non-compartmental method showed that the half life of gametocytaemia was longer and the clearance slower in children with CQ-R than in those with CQ-S infections. PS treatment was associated with significantly higher gametocyte carriage at all times between days 1 and 14, and significantly higher gametocytaemias on days 7 and 14 than in the other treatment regimens. Combination of AQ with PS significantly decreased gametocyte carriage at all times between days 1 and 14 of follow-up. Continuing use of CQ in CQ-R infections may encourage transmission of CQ-R infections; SP monotherapy is associated with significant gametocyte carriage and gametocytaemia and may encourage transmission of SP resistant infections as resistance to the drug increases. (+info)
Short report: association between chloroquine and amodiaquine resistance and allelic variation in the Plasmodium falciparum multiple drug resistance 1 gene and the chloroquine resistance transporter gene in isolates from the upper Nile in southern Sudan.
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Amodiaquine, a 4-aminoquinoline compound, is being considered as an alternative to chloroquine and pyrimethamine/sulfadoxine where resistance in Plasmodium falciparum to both drugs has been selected. Although amodiaquine is more potent than chloroquine, its effectiveness is reduced in areas where chloroquine resistance is high. We report an association of the P. falciparum chloroquine resistance transporter (pfcrt) gene and the P. falciparum multiple drug resistance 1 (pfmdr1) gene, two chloroquine resistance markers, with chloroquine and amodiaquine efficacy in vivo in southern Sudan. The data show that the allele of the pfcrt gene with a lysine to threonine change at codon 76 is strongly associated with both chloroquine and amodiaquine resistance. No such association was observed with the pfmdr1 gene. (+info)
Mass administration of an antimalarial drug combining 4-aminoquinoline and 8-aminoquinoline in Tanganyika.
(29/318)
For the eradication of malaria from hyperendemic regions of tropical Africa it is apparent that use may have to be made of antimalarial drugs, administered individually on a census basis, in addition to measures directed against the mosquito. The suppressive activity of existing compounds among individuals having different degrees of immunity is well established, and trials among large groups of people have been conducted with single drugs and with combination of drugs. In the large-scale trials carried out in Tanganyika and described in this paper, such a combination, containing amodiaquine for schizontocidal effect and primaquine as a gametocytocide, was administered to three distinct population groups of more than 5000 at differing intervals of time, in order to determine the ability of this combination to interfere with transmission in the absence of other malaria control measures. It was found that treatment of 93% of the population at intervals of one or two weeks resulted in a reduction of the malaria indices to a very low level but such success was not obtained when the combination of drugs was administered every four weeks, although in the area concerned population coverage was less satisfactory owing to migration. (+info)
STUDIES ON A STRAIN OF CHLOROQUINE-RESISTANT PLASMODIUM FALCIPARUM FROM THAILAND.
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Infections with a strain of Plasmodium falciparum from Thailand, termed the Thailand (JHK) strain, were established in 25 non-immune volunteers in a non-endemic area under conditions precluding reinfection. Eleven volunteers received chloroquine in usually curative doses on a three-day schedule during acute clinical malaria attacks. Volunteers also received (again during acute clinical attacks) hydroxychloroquine, amodiaquine, mepacrine, pyrimethamine, proguanil or 377-C-54, alone or in combination. These regimens failed, both before and after passage of the strain through mosquitos, to effect radical cure of the infection. Radical cure was achieved by administration of 1350 mg or 1620 mg of quinine base daily for seven days.The authors point out that resistance to chloroquine by P. falciparum is being recognized with increasing frequency in South America and South-East Asia, and that the effect of this on global chemotherapy of malaria may be serious. (+info)
Molecular epidemiology of malaria in Cameroon. XV. Experimental studies on serum substitutes and supplements and alternative culture media for in vitro drug sensitivity assays using fresh isolates of Plasmodium falciparum.
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In vitro drug sensitivity assay is an important tool for various on-going studies aiming to establish the correlation between candidate molecular markers for drug resistance and drug response in laboratory-adapted strains and field isolates of Plasmodium falciparum. A widespread use of this technique in the field would require a suitable substitute that can replace human serum. In this study, several alternative sources of serum substitutes and supplements were evaluated for their capacity to sustain parasite growth for a single life cycle and their compatibility with in vitro assays for clinical isolates that have not been adapted to in vitro culture. Albumax, a commercial preparation of lipid-enriched bovine albumin, did not support parasite growth as much as human serum and fetal calf serum in several isolates. Other serum supplements (AmnioMax and Ultroser) supported parasite growth relatively well. The 50% inhibitory concentrations (IC50s) of chloroquine and antifolates determined with 0.05% Albumax were generally two or three times higher than with human serum. With 10% fetal calf serum, IC50s for chloroquine and antifolates were approximately two times higher and three times lower than with human serum, respectively. The use of AmnioMax and OptiMAb resulted in a greater than two-fold increase in IC50s and several uninterpretable assays. Despite possible batch-to-batch differences, fetal calf serum may be a suitable substitute for in vitro drug assays while awaiting the results of further studies on other serum substitutes and supplements. (+info)
The efficacy of antimalarial monotherapies, sulphadoxine-pyrimethamine and amodiaquine in East Africa: implications for sub-regional policy.
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Between 1998 and 2001, Kenya, Uganda, Tanzania, Zanzibar, Rwanda and Burundi changed antimalarial drug policy, in the face of widespread chloroquine resistance. The new first-line treatment is either sulphadoxine-pyrimethamine (SP) monotherapy, or a combination of SP with either chloroquine or amodiaquine. Two national malaria control programmes, Burundi and Zanzibar, have decided upon amodiaquine-artesunate as their first-line treatment, although SP will continue to fill this role until the new policy can be implemented. Given the broad uniformity of parasite chemoresistance in the six countries, The East African Network for Monitoring Antimalarial Treatment (EANMAT) has focused attention on, and worked towards, a sub-regional antimalarial drug policy, where the evidence base would be the entire portfolio of network in vivo test results. Currently, there are several different antimalarial drug policies within the EANMAT area: the intention is to eventually replace this plethora of policies with a single, sub-regional policy based upon combination therapy. Currently, successful malaria treatment depends primarily upon the efficacy of SP, and of amodiaquine, which is either a component of first-line treatment, or the second line drug. This report addresses the results of WHO in vivo tests on these two monotherapies within the network. Results are analysed to assess the evidence for change in parasite susceptibility over time; the range of susceptibility to each drug within countries, and the implications of test results on policy. (+info)