National Institute for Medical Research, Tanga Research Centre, Tanga, Tanzania.
Kilimanjaro Christian Medical University College, Moshi, Tanzania.
Malar J. 2019 Mar 25;18(1):99. doi: 10.1186/s12936-019-2740-z.
The Tanzanian National Malaria Control Programme (NMCP) and its partners have been implementing regular therapeutic efficacy studies (TES) to monitor the performance of different drugs used or with potential use in Tanzania. However, most of the recent TES focused on artemether-lumefantrine, which is the first-line anti-malarial for the treatment of uncomplicated falciparum malaria. Data on the performance of other artemisinin-based combinations is urgently needed to support timely review and changes of treatment guidelines in case of drug resistance to the current regimen. This study was conducted at two NMCP sentinel sites (Kibaha, Pwani and Ujiji, Kigoma) to assess the efficacy and safety of artesunate-amodiaquine (ASAQ) and dihydroartemisinin-piperaquine (DP), which are the current alternative artemisinin-based combinations in Tanzania.
This was a single-arm prospective evaluation of the clinical and parasitological responses of ASAQ and DP for directly observed treatment of uncomplicated falciparum malaria. Children aged 6 months to 10 years and meeting the inclusion criteria were enrolled and treated with either ASAQ or DP. In each site, patients were enrolled sequentially; thus, enrolment of patients for the assessment of one artemisinin-based combination was completed before patients were recruited for assessment of the second drugs. Follow-up was done for 28 or 42 days for ASAQ and DP, respectively. The primary outcome was PCR corrected cure rates while the secondary outcome was occurrence of adverse events (AEs) or serious adverse events (SAEs).
Of the 724 patients screened at both sites, 333 (46.0%) were enrolled and 326 (97.9%) either completed the 28/42 days of follow-up, or attained any of the treatment outcomes. PCR uncorrected adequate clinical and parasitological response (ACPR) for DP on day 42 was 98.8% and 75.9% at Kibaha and Ujiji, respectively. After PCR correction, DP's ACPR was 100% at both sites. For ASAQ, no parasite recurrence occurred giving 100% ACPR on day 28. Only one patient in the DP arm (1.1%) from Ujiji had parasites on day 3. Of the patients recruited (n = 333), 175 (52.6%) had AEs with 223 episodes (at both sites) in the two treatment groups. There was no SAE and the commonly reported AE episodes (with > 5%) included, cough, running nose, abdominal pain, diarrhoea and fever.
Both artemisinin-based combinations had high cure rates with PCR corrected ACPR of 100%. The two drugs had adequate safety with no SAE and all AEs were mild, and not associated with the anti-malarials. Continued TES is critical to monitor the performance of nationally recommended artemisinin-based combination therapy and supporting evidence-based review of malaria treatment policies. Trial registration This study is registered at ClinicalTrials.gov, No. NCT03431714.
坦桑尼亚国家疟疾控制规划（NMCP）及其合作伙伴一直在进行定期的治疗效果研究（TES），以监测在坦桑尼亚使用或有潜力使用的不同药物的疗效。然而，最近的大多数 TES 都集中在青蒿素-本芴醇上，它是治疗无并发症恶性疟原虫疟疾的一线抗疟药。急需有关其他青蒿素为基础的联合疗法的数据，以支持及时审查和改变目前治疗方案，以防对当前方案产生抗药性。本研究在 NMCP 的两个哨点（基巴哈、潘尼和乌吉吉、基戈马）进行，以评估青蒿琥酯-阿莫地喹（ASAQ）和双氢青蒿素-哌喹（DP）的疗效和安全性，这两种药物是坦桑尼亚目前替代青蒿素为基础的联合疗法。
这是一项对 ASAQ 和 DP 直接观察治疗无并发症恶性疟原虫疟疾的临床和寄生虫学反应的单臂前瞻性评估。年龄在 6 个月至 10 岁之间且符合纳入标准的儿童被纳入并接受 ASAQ 或 DP 治疗。在每个地点，患者都是按顺序入组的；因此，在招募评估一种青蒿素为基础的联合疗法的患者之前，已经完成了评估第二种药物的患者的招募。分别对 ASAQ 和 DP 进行 28 天或 42 天的随访。主要结局是 PCR 校正后的治愈率，次要结局是不良事件（AE）或严重不良事件（SAE）的发生。
在两个地点共筛查了 724 名患者，其中 333 名（46.0%）入组，326 名（97.9%）要么完成了 28/42 天的随访，要么达到了任何治疗结局。DP 在第 42 天的 PCR 未校正的充分临床和寄生虫学反应（ACPR）在基巴哈和乌吉吉分别为 98.8%和 75.9%。经过 PCR 校正后，DP 在两个地点的 ACPR 均为 100%。对于 ASAQ，在第 28 天没有寄生虫复发，ACPR 为 100%。在 DP 组中，只有 1 名来自乌吉吉的患者（1.1%）在第 3 天有寄生虫。在招募的患者（n=333）中，175 名（52.6%）有 AE，两组共发生 223 例（两个地点）。没有 SAE，常见的 AE 发作（发生率>5%）包括咳嗽、流鼻涕、腹痛、腹泻和发热。
两种青蒿素为基础的联合疗法均具有较高的治愈率，PCR 校正后的 ACPR 为 100%。两种药物均具有良好的安全性，无 SAE，所有 AE 均为轻度，与抗疟药无关。继续进行 TES 对于监测国家推荐的青蒿素为基础的联合疗法的疗效以及支持基于证据的疟疾治疗政策审查至关重要。试验注册本研究在 ClinicalTrials.gov 注册，编号为 NCT03431714。
