Berhane Araia, Russom Mulugeta, Bahta Iyassu, Hagos Filmon, Ghirmai Michael, Uqubay Selam
Communicable Diseases Control Division, Ministry of Health, Asmara, Eritrea.
Eritrean Pharmacovigilance Center, Ministry of Health, Asmara, Eritrea.
Malar J. 2017 Mar 6;16(1):105. doi: 10.1186/s12936-017-1752-9.
Relatively large number of false-negative malaria rapid diagnostic test (RDT) results for microscopically confirmed Plasmodium falciparum cases were reported from five of the six administrative regions of Eritrea in 2015. This activated the Ministry of Health to conduct an initial exploratory investigation. The main objective of the investigation was to confirm the sensitivity of the RDTs in the field in microscopically confirmed malaria cases, identify the possible causes of the failure and recommend further actions to be taken.
A team composed of the National Malaria Control Programme, National Medicines and Food Administration and Laboratory Unit of the Ministry of Health was established to confirm the sensitivity of the SD Bioline RDTs. A 'Malaria RDT quality monitoring form' was prepared and distributed to 13 health facilities selected on availability of microscopy services, experienced laboratory personnel and malaria endemicity, to carry out preliminary investigation on the suspected RDT quality defect. In parallel, field visits to central and regional medical warehouses as well as selected health facilities were conducted to assess the storage conditions, handling and operator procedures. Furthermore, joint field assessment was conducted with the manufacturer, SD Bioline RDTs. During the time frame of 15 July 2015 to 19 January 2016, 65 microscopically confirmed patients were tested with Malaria RDTs SD Bioline Pf/Pv/Mixed Combo cassettes.
A total of 65 blood specimens (50 P. falciparum, 13 Plasmodium vivax and 2 mixed) confirmed microscopically were tested against the available lots of malaria RDTs. Out of the 50 P. falciparum infected blood specimens, only 10 were confirmed positive with all the lots of PfHRP-2 detecting RDTs making the false negativity rate at 80% [41/51]. The false negative result for RDT targeting PfHRP2 antigen ranged from 65% [11/17] in Gash Barka region to 100% [12/12] in Northern Red Sea Region. In addition, supervisory visits undertaken by the study team have ruled out storage, handling and operator errors as causes of false negative results as the above parameter were found to be up to standards.
The investigation confirmed high false-negativity rate in PfHRP-2 detecting RDTs and has ruled out quality of RDTs, storage, handling and operator error as causes of the reported problem. Therefore, molecular characterization of the P. falciparum is highly recommended to explore if parasite characteristics can be considered as causes of false negative results.
2015年，厄立特里亚六个行政区中的五个行政区报告了相对大量经显微镜确诊为恶性疟原虫病例的疟疾快速诊断检测（RDT）假阴性结果。这促使卫生部开展了初步探索性调查。调查的主要目的是确认RDT在经显微镜确诊的疟疾病例现场的敏感性，确定检测失败的可能原因，并建议采取进一步行动。
成立了一个由国家疟疾控制规划、国家药品和食品管理局以及卫生部实验室部门组成的小组，以确认SD Bioline RDT的敏感性。编制了一份“疟疾RDT质量监测表”，并分发给13家具备显微镜检查服务、有经验的实验室人员且疟疾流行的卫生设施，对疑似RDT质量缺陷进行初步调查。同时，对中央和地区医疗仓库以及选定的卫生设施进行实地考察，以评估储存条件、处理和操作人员程序。此外，还与SD Bioline RDT制造商进行了联合实地评估。在2015年7月15日至2016年1月19日期间，对65例经显微镜确诊的患者使用疟疾RDT SD Bioline Pf/Pv/混合组合检测卡进行检测。
总共对65份经显微镜确诊的血液标本（50份恶性疟原虫、13份间日疟原虫和2份混合感染）进行了现有批次疟疾RDT检测。在50份感染恶性疟原虫的血液标本中，所有检测PfHRP-2的RDT批次仅10份被确诊为阳性，假阴性率达80%[41/51]。针对PfHRP2抗原的RDT假阴性结果在加什-巴尔卡地区为65%[11/17]，在红海北部地区为100%[12/12]。此外，研究小组进行的监督检查排除了储存、处理和操作人员错误作为假阴性结果的原因，因为上述参数均符合标准。
调查证实检测PfHRP-2的RDT假阴性率很高，并排除了RDT质量、储存、处理和操作人员错误作为所报告问题的原因。因此，强烈建议对恶性疟原虫进行分子特征分析，以探究寄生虫特征是否可被视为假阴性结果产生的原因。
