Swiss Tropical and Public Health Institute, Allschwil, Switzerland.
University of Basel, Basel, Switzerland.
PLoS Med. 2023 Feb 21;20(2):e1004189. doi: 10.1371/journal.pmed.1004189. eCollection 2023 Feb.
For a full treatment course of severe malaria, community-administered pre-referral rectal artesunate (RAS) should be completed by post-referral treatment consisting of an injectable antimalarial and oral artemisinin-based combination therapy (ACT). This study aimed to assess compliance with this treatment recommendation in children under 5 years.
This observational study accompanied the implementation of RAS in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020. Antimalarial treatment was assessed during admission in included referral health facilities (RHFs) in children under 5 with a diagnosis of severe malaria. Children were either referred from a community-based provider or directly attending the RHF. RHF data of 7,983 children was analysed for appropriateness of antimalarials; a subsample of 3,449 children was assessed additionally for dosage and method of ACT provision (treatment compliance). A parenteral antimalarial and an ACT were administered to 2.7% (28/1,051) of admitted children in Nigeria, 44.5% (1,211/2,724) in Uganda, and 50.3% (2,117/4,208) in DRC. Children receiving RAS from a community-based provider were more likely to be administered post-referral medication according to the guidelines in DRC (adjusted odds ratio (aOR) = 2.13, 95% CI 1.55 to 2.92, P < 0.001), but less likely in Uganda (aOR = 0.37, 95% CI 0.14 to 0.96, P = 0.04) adjusting for patient, provider, caregiver, and other contextual factors. While in DRC, inpatient ACT administration was common, ACTs were often prescribed at discharge in Nigeria (54.4%, 229/421) and Uganda (53.0%, 715/1,349). Study limitations include the unfeasibility to independently confirm the diagnosis of severe malaria due to the observational nature of the study.
Directly observed treatment was often incomplete, bearing a high risk for partial parasite clearance and disease recrudescence. Parenteral artesunate not followed up with oral ACT constitutes an artemisinin monotherapy and may favour the selection of resistant parasites. In connection with the finding that pre-referral RAS had no beneficial effect on child survival in the 3 study countries, concerns about an effective continuum of care for children with severe malaria seem justified. Stricter compliance with the WHO severe malaria treatment guidelines is critical to effectively manage this disease and further reduce child mortality.
ClinicalTrials.gov (NCT03568344).
对于重症疟疾的完整疗程，应在转诊后完成由注射用抗疟药物和口服青蒿素类复方疗法（ACT）组成的治疗，在此之前先进行社区卫生机构管理的直肠青蒿琥酯（RAS）治疗。本研究旨在评估 5 岁以下儿童对这一治疗建议的依从性。
本观察性研究在 2018 年至 2020 年期间在刚果民主共和国（DRC）、尼日利亚和乌干达实施 RAS 时进行。在包括转诊卫生机构（RHF）中，对患有重症疟疾的 5 岁以下儿童进行入院时的抗疟治疗评估。儿童要么是从社区卫生提供者转诊来的，要么是直接到 RHF 就诊的。对 7983 名儿童的 RHF 数据进行了抗疟药物的适宜性分析；对 3449 名儿童进行了额外的剂量和 ACT 给药方法（治疗依从性）评估。在尼日利亚，2.7%（28/1051）接受入院治疗的儿童使用了注射用抗疟药物，44.5%（1211/2724）在乌干达，50.3%（2117/4208）在 DRC。在 DRC，从社区卫生提供者处接受 RAS 的儿童更有可能根据指南接受转诊后的药物治疗（调整后的优势比（aOR）=2.13，95%CI 1.55 至 2.92，P<0.001），而在乌干达则不太可能（aOR=0.37，95%CI 0.14 至 0.96，P=0.04），这是在调整了患者、提供者、护理人员和其他背景因素后得出的。虽然在 DRC，住院患者的 ACT 管理很常见，但在尼日利亚（54.4%，229/421）和乌干达（53.0%，715/1349），ACT 经常在出院时开具。
由于研究的观察性质，无法独立确认重症疟疾的诊断，这存在一定的局限性。
直接观察的治疗往往是不完整的，存在部分寄生虫清除和疾病复发的高风险。未用口服 ACT 跟进的青蒿琥酯注射剂构成了青蒿素单药治疗，可能有利于耐药寄生虫的选择。结合在 3 个研究国家中，预转诊 RAS 对儿童生存没有有益影响的发现，人们对重症疟疾儿童有效护理连续性的担忧似乎是合理的。严格遵守世卫组织重症疟疾治疗指南对于有效管理这种疾病和进一步降低儿童死亡率至关重要。
ClinicalTrials.gov（NCT03568344）。
