Sowunmi A, Fateye B A, Happi T C, Gbotosho G O, Oduola A M J
Department of Pharmacology and Therapeutics and Postgraduate Institute for Medical Research and Training, University of Ibadan, Ibadan, Nigeria.
Ann Trop Med Parasitol. 2003 Jul;97(5):453-68. doi: 10.1179/000349803235002443.
A group of 161 children who presented with acute, symptomatic, uncomplicated, Plasmodium falciparum malaria in an endemic area of Nigeria was investigated. The aims of the study were to determine the clinical characteristics and responses to oral chloroquine (CQ) therapy of children who were gametocytaemic on presentation and those who were not [including those who were found to have developed peripheral immature gametocytaemias (PIG) when checked 72 h after commencing treatment], and to follow the development of PIG 72-336 h after the start of treatment. The 40 consecutive children who did have peripheral gametocytaemia on presentation and the 40 who did not were similar in their clinical characteristics and responses to oral CQ therapy. Nine of the 40 children who did not initially have gametocytaemias but who subsequently developed PIG (stages I-III) 72-336 h after commencing CQ treatment failed the treatment. In order to evaluate the presence of PIG as an indicator of response to CQ, the smears of blood from 81 children--66 classified as resistant to CQ (60, five and one considered RI, RII, RIII, respectively) and 15 who, though considered to have sensitive responses to CQ, cleared their peripheral parasitaemias > or =72 h after commencing CQ therapy--were examined for PIG. Most (42) of the 66 children with CQ-resistant (CQ-R) infections but none of the 15 with sensitive responses had PIG. Among the 66 children with CQ-R infections, the clinical features of those with PIG were generally similar to those without PIG, although those with PIG were more likely to have hepato-splenomegaly and less likely to have hepatomegaly alone. In the children with CQ-R infections, plasma concentrations of CQ on days 7 and 14 were generally above the level necessary to clear sensitive infections in the study area. The results of molecular analyses of isolates from children with both CQ-R infections and PIG revealed that all 14 checked for mutations in pfcrt had the T76 mutation associated with CQ resistance, and that four of the five also checked for mutations in pfmdr1 had the Y86 mutation associated with CQ resistance. The detection of PIG 72 h after the commencement of CQ treatment may be used as a microscopical indicator of a poor response to CQ in children from this endemic area.
对尼日利亚一个疟疾流行地区的161名患有急性、有症状、无并发症的恶性疟原虫疟疾的儿童进行了调查。该研究的目的是确定就诊时携带配子体的儿童和未携带配子体的儿童（包括开始治疗72小时后检查发现外周血出现未成熟配子体的儿童）的临床特征以及对口服氯喹（CQ）治疗的反应，并跟踪治疗开始后72 - 336小时未成熟配子体的发展情况。就诊时外周血有配子体的40名连续儿童和外周血无配子体的40名儿童在临床特征和对口服CQ治疗的反应方面相似。40名最初无配子体但在开始CQ治疗后72 - 336小时出现未成熟配子体（I - III期）的儿童中有9名治疗失败。为了评估未成熟配子体的存在作为对CQ反应的指标，对81名儿童的血涂片进行了检查，其中66名被分类为对CQ耐药（分别有60名、5名和1名被认为是RI、RII、RIII），15名虽然被认为对CQ有敏感反应，但在开始CQ治疗后≥72小时外周血疟原虫才清除。66名患有CQ耐药（CQ - R）感染的儿童中大多数（42名）有未成熟配子体，而15名有敏感反应的儿童均无未成熟配子体。在66名患有CQ - R感染的儿童中，有未成熟配子体的儿童的临床特征与无未成熟配子体的儿童总体相似，不过有未成熟配子体的儿童更易出现肝脾肿大，单独出现肝肿大的可能性较小。在患有CQ - R感染的儿童中，第7天和第14天的血浆CQ浓度总体上高于该研究地区清除敏感感染所需的水平。对患有CQ - R感染且有未成熟配子体的儿童的分离株进行分子分析的结果显示，检查的14名pfcrt突变儿童均有与CQ耐药相关的T76突变，检查的5名pfmdr1突变儿童中有4名有与CQ耐药相关的Y86突变。在CQ治疗开始72小时后检测到未成熟配子体可作为该流行地区儿童对CQ反应不佳的一个显微镜指标。
