Atroosh Wahib M, Al-Mekhlafi Hesham M, Snounou Georges, Al-Jasari Adel, Sady Hany, Nasr Nabil A, Lau Yee-Ling, Surin Johari
Department of Parasitology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Department of Microbiology and Parasitology, Faculty of Medicine and Health Sciences, University of Aden, Aden, Yemen.
Malar J. 2016 May 27;15(1):295. doi: 10.1186/s12936-016-1344-0.
In Yemen, artesunate plus sulfadoxine-pyrimethamine (AS + SP) has been used as first-line treatment for uncomplicated falciparum malaria, which accounts for about 99 % of malaria cases. There is evidence that resistance to SP is increasing, with potential negative impact on efficacy, and in particular on curbing transmission. This study aims: (a) to evaluate the therapeutic efficacy of AS + SP treatment for uncomplicated falciparum malaria in Yemen; (b) to investigate the frequency of mutations in Plasmodium falciparum genes associated with resistance to AS (Kelch 13 propeller domain, pfK13) and SP (dihydrofolate reductase, pfdhfr, and dihydropteroate synthase, pfdhps); and (c) to assess the adequacy of this ACT to clear gametocytes.
A 28-day in vivo evaluation of the clinical and parasitological response to three-day course of AS + SP was carried out in two areas of high endemicity (Hodeidah and Al-Mahwit provinces, Tehama region) in Yemen according to standard WHO protocol 2009. Clinical and parasitological indices were monitored over a 28-day follow-up, and the outcome was PCR-corrected. The frequencies of mutations in the pfdhfr, pfdhps, and pfK13 genes were obtained by sequencing following amplification.
Eighty-six patients completed the study, with a cure rate of 96.5 % (94.2 % PCR-uncorrected). Whereas four (4.7 %) patients still showed parasitaemia on day 2 post-treatment, all were found negative for asexual malaria stages on days 3 and 7. The efficacy of gametocyte clearance was poor (14.5, 42.5 and 86.0 % on days 7, 14 and 28, respectively), with gametocytes persisting throughout the study in some patients. All the isolates sequenced had the pfk13 propeller domain wild-type allele, and mutations associated with SP failure were observed only for pfdhfr with the double mutation (S108N + N51I) found in 65.4 % of the isolates sequenced.
In Yemen, AS + SP therapy remains effective for the treatment of uncomplicated falciparum malaria. Mutations were not detected in pfk13 or pfdhps, though double mutations were observed for pfdhfr. The observed persistent gametocytaemia re-enforces calls to add a single dose primaquine to this ACT in order to minimizes the potential for transmission and enhance regional efforts to eliminate malaria.
在也门，青蒿琥酯加磺胺多辛-乙胺嘧啶（AS + SP）一直被用作非复杂性恶性疟原虫疟疾的一线治疗药物，该国约99%的疟疾病例为此类型。有证据表明，对SP的耐药性正在增加，这可能对疗效产生负面影响，特别是对控制传播。本研究旨在：（a）评估AS + SP治疗也门非复杂性恶性疟原虫疟疾的疗效；（b）调查恶性疟原虫中与对AS（凯尔希13螺旋桨结构域，pfK13）和SP（二氢叶酸还原酶，pfdhfr，和二氢蝶酸合酶，pfdhps）耐药相关基因的突变频率；（c）评估这种青蒿素联合疗法清除配子体的充分性。
根据世界卫生组织2009年的标准方案，在也门两个高流行地区（荷台达和马赫维特省，提哈迈地区）对AS + SP三日疗程的临床和寄生虫学反应进行了为期28天的体内评估。在28天的随访期间监测临床和寄生虫学指标，并对结果进行PCR校正。通过扩增后的测序获得pfdhfr、pfdhps和pfK13基因的突变频率。
86名患者完成了研究，治愈率为96.5%（未经PCR校正的为94.2%）。虽然有4名（4.7%）患者在治疗后第2天仍有寄生虫血症，但在第3天和第7天所有患者的无性疟原虫阶段均为阴性。配子体清除效果较差（第7天、第14天和第28天分别为14.5%、42.5%和86.0%），在一些患者中，配子体在整个研究期间持续存在。所有测序的分离株均具有pfk13螺旋桨结构域野生型等位基因，仅在pfdhfr中观察到与SP治疗失败相关的突变，在65.4%的测序分离株中发现了双突变（S108N + N51I）。
在也门，AS + SP疗法对治疗非复杂性恶性疟原虫疟疾仍然有效。在pfk13或pfdhps中未检测到突变，尽管在pfdhfr中观察到了双突变。观察到的持续配子体血症进一步促使人们呼吁在这种青蒿素联合疗法中添加单剂量伯氨喹，以尽量减少传播的可能性，并加强该地区消除疟疾的努力。
