Sowunmi A
Department of Pharmacology and Therapeutics and Postgraduate Institute for Medical Research and Training, University of Ibadan, Nigeria.
Ann Trop Med Parasitol. 2002 Apr;96(3):227-38. doi: 10.1179/000349802125000763.
The increasing resistance of Plasmodium falciparum to antimalarial monotherapy (MT) has created an urgent need for the evaluation of alternative effective, safe, cheap, readily available and affordable, combination treatments (CT) with antimalarial drugs. In the present study, the efficacies of chloroquine (CQ) or amodiaquine (AQ) in the oral treatment of acute, symptomatic, uncomplicated, Plasmodium falciparum malaria were compared with those of oral treatments with the combination of CQ or AQ with pyrimethamine-sulfadoxine (PS). The CQ and AQ were each given at a dose of 10 mg/kg.day for 3 days (days 0, 1 and 2), with or without PS given as a single dose (25 mg sulfadoxine/kg) at presentation (day 0). Overall, 303 children aged 0.5-10 years (74 given CQ, 82 AQ, 72 CQPS and 75 AQPS) were evaluated. The fever-clearance time (FCT) was significantly shorter in those treated with AQPS than in those treated with CQ or CQPS. The proportions of patients with complete clearance of their parasitaemias on days 1 and 2 were significantly larger and the parasite-clearance times (PCT) were all significantly shorter with the drug combinations than with their corresponding MT. For example, the mean (S.D.) PCT were 2.6 (0.8) days for CQ v. 2.1 (0.8) days for CQPS (P=0.0002), and 2.6 (0.7) days for AQ v. 2.1 (0.7) days for AQPS (P=0.00001). The cure 'rates' on days 14, 21 and 28 were also significantly higher with AQ, CQPS and AQPS than with CQ; those on day 28, for example, were 47.2%, 98.7%, 100% and 100% for CQ, AQ, CQPS and AQPS, respectively (P=0.000001). Gametocyte carriages on day 3 or on days 3, 7 and/or 14 combined were significantly lower in those treated with CQPS than in those given CQ; there was no gametocyte carriage in the CT groups on day 28. In the CQ group, eight of 13 children with gametocytaemia on day 3 had a response indicative of resistance. However, the five CQ-resistant infections that were re-treated with AQPS responded promptly, with a PCT significantly shorter than that during the initial treatment with CQ and with a cure 'rate' of 100% on day 28. Adverse reactions to treatment were similar on the first and subsequent days of treatment and were tolerable except for pruritus, which was significantly more common in children treated with CQ alone than in the other treatment groups. Haematological and biochemical parameters were not adversely affected by any treatment. The CQPS and AQPS combinations appear to be well tolerated and may be useful as alternatives to monotherapy with CQ or AQ as resistance to the single drugs develops.
恶性疟原虫对抗疟单一疗法（MT）的耐药性不断增加，因此迫切需要评估抗疟药物的替代有效、安全、廉价、易于获得且可负担的联合疗法（CT）。在本研究中，将氯喹（CQ）或阿莫地喹（AQ）口服治疗急性、有症状、非复杂性恶性疟原虫疟疾的疗效，与CQ或AQ与乙胺嘧啶 - 磺胺多辛（PS）联合口服治疗的疗效进行了比较。CQ和AQ均以10 mg/kg·天的剂量给药，持续3天（第0、1和2天），就诊时（第0天）是否加用PS单剂量（25 mg磺胺多辛/kg）。总体而言，对303名年龄在0.5至10岁的儿童进行了评估（74名接受CQ治疗，82名接受AQ治疗，72名接受CQPS治疗，75名接受AQPS治疗）。接受AQPS治疗的患者发热清除时间（FCT）明显短于接受CQ或CQPS治疗的患者。与相应的单一疗法相比，联合用药组在第1天和第2天疟原虫血症完全清除的患者比例明显更高，寄生虫清除时间（PCT）均明显更短。例如，CQ组的平均（标准差）PCT为2.6（0.8）天，而CQPS组为2.1（0.8）天（P = 0.0002）；AQ组为2.6（0.7）天，而AQPS组为2.1（0.7）天（P = 0.00001）。第14、21和28天的“治愈率”，AQ、CQPS和AQPS组也明显高于CQ组；例如，第28天的治愈率分别为：CQ组47.2%，AQ组98.7%，CQPS组100%，AQPS组100%（P = 0.000001）。接受CQPS治疗的患者在第3天或第3、7和/或14天联合检测时配子体携带率明显低于接受CQ治疗的患者；联合治疗组在第28天无配子体携带。在CQ组中，第3天有疟原虫血症的13名儿童中有8名出现了耐药反应。然而，5例对CQ耐药的感染患者接受AQPS重新治疗后迅速起效，PCT明显短于最初接受CQ治疗时，第28天的“治愈率”为100%。治疗的不良反应在治疗的第一天和随后几天相似，除瘙痒外均可耐受，单独接受CQ治疗的儿童瘙痒明显比其他治疗组更常见。血液学和生化参数未受到任何治疗的不利影响。随着对单一药物耐药性的出现，CQPS和AQPS联合疗法似乎耐受性良好，可作为CQ或AQ单一疗法的替代方案。
