Minzi Omary, Maige Sylivester, Sasi Philip, Ngasala Billy
Unit of Pharmacology and Therapeutics, School of Pharmacy, Muhimbili University of Health and Allied Sciences, PO Box 65013, Dar Es Salaam, Tanzania.
Malar J. 2014 Jul 10;13:267. doi: 10.1186/1475-2875-13-267.
Adherence to multidosing is challenging worldwide. This study assessed the extent of adherence to multidosing artemether-lumefantrine (ALu) in a rural community in Tanzania, six years after switching from single dose policy of sulphadoxine-pyrimethamine.
This study was a prospective observational, open label, non-randomized study involving 151 patients with uncomplicated malaria recruited at Fukayosi dispensary in Bagamoyo district in Tanzania. Patients treated with ALu were visited at home on day 3 for interview on drug intake, capillary blood sample collection for microscopy and ALu tablets count. Venous blood samples (2 ml) for determination of blood lumefantrine concentrations and blood slides for microscopy were collected on day-7. Kappa's coefficient was used to assess agreement between pill count and self-report. Adherence was categorized depending on the tablets remaining and what the patient reported. Only those with empty blister pack available but no tablet remaining and reported taking all six doses of ALu at a correct dose and correct time were regarded as definite adherent. The rest were either probable adherent or probable non-adherent.
Only 14.9% of the patients were definite adherent the rest took the drug at incorrect time or did not finish the tablets. Out of 90 patients with analysed plasma samples for lumefantrine blood concentrations, 13/90 (14.4.0%) had lumefantrine concentrations <175 ng/ml. There was no difference in mean lumefantrine concentration in the patients who stated to have taken all doses as required (561.61 ng/ml 95% CI = 419.81-703.41) compared to those who stated to have not adhered well to drug intake (490.95 ng/ml, 95% CI = 404.18-577.7074 (p = 0.643). None of the patients had detectable parasites by microscopy on day-3 and day-7 regardless of adherence status and the level of day-7 blood lumefantrine. There was strong agreement between the self-reported responses on drug intake and pill-counts (kappa coefficient = 0.955). Age, sex, education and place where first dose was taken were associated with adherence.
The overall adherence six years after the change of malaria treatment policy was low. It is, therefore, important to continuously monitor the level of adherence to treatment in order to get the current situation and institute corrective measures on time.
在全球范围内，坚持多剂量服药具有挑战性。本研究评估了坦桑尼亚一个农村社区在从磺胺多辛 - 乙胺嘧啶单剂量政策转变六年后，对多剂量蒿甲醚 - 本芴醇（ALu）的依从程度。
本研究是一项前瞻性观察性、开放标签、非随机研究，涉及在坦桑尼亚巴加莫约区福卡约西药房招募的151例无并发症疟疾患者。接受ALu治疗的患者在第3天接受家访，进行药物服用情况访谈、采集毛细血管血样进行显微镜检查和清点ALu片剂数量。在第7天采集静脉血样（2毫升）用于测定血液中本芴醇浓度，并采集血涂片进行显微镜检查。使用卡帕系数评估片剂清点与自我报告之间的一致性。根据剩余片剂和患者报告情况对依从性进行分类。只有那些泡罩包装为空且无剩余片剂，并报告在正确时间以正确剂量服用了全部六剂ALu的患者才被视为确定依从者。其余患者则为可能依从或可能不依从。
只有14.9%的患者为确定依从者，其余患者在错误时间服药或未服完片剂。在90例分析了血浆样本中本芴醇血药浓度的患者中，13/90（14.4%）的本芴醇浓度<175 ng/ml。报告按要求服用了所有剂量的患者的平均本芴醇浓度（561.61 ng/ml，95% CI = 419.81 - 703.41）与报告服药依从性不佳的患者（490.95 ng/ml，95% CI = 404.18 - 577.7074）相比，无差异（p = 0.643）。无论依从性状态和第7天血液中本芴醇水平如何，在第3天和第7天通过显微镜检查均未发现患者有可检测到的寄生虫。药物服用自我报告与片剂清点之间存在高度一致性（卡帕系数 = 0.955）。年龄、性别、教育程度和首次服药地点与依从性有关。
疟疾治疗政策改变六年后的总体依从性较低。因此，持续监测治疗依从水平以了解当前情况并及时采取纠正措施非常重要。
