Sambe Babacar Souleymane, Zobrist Stephanie, Sheahan William, Soni Divya, Diagne Aissatou, Sarr Ibrahima, Diatta Arona Sabene, Diaw Serigne Ousmane Mbacke, Golden Allison, Slater Hannah, Jang Ihn Kyung, Roa Nerie, Pal Sampa, Sarr Fatoumata Diene, Faye Joseph, Vigan-Womas Inès, Dieye Yakou, Cisse Moustapha, Domingo Gonzalo J, Niang Makhtar
Institut Pasteur de Dakar, Dakar, Senegal.
PATH, Seattle, USA.
Parasit Vectors. 2025 Jul 12;18(1):280. doi: 10.1186/s13071-025-06914-9.
The emergence of Plasmodium falciparum (Pf) parasites with deleted histidine-rich protein 2 and 3 (hrp2/hrp3) genes threatens the performance of HRP2-based malaria rapid diagnostic tests (RDTs). RDTs targeting Pf lactate dehydrogenase (LDH) may address current product limitations and improve case management. The objective of this study was to evaluate the performance and usability of three LDH-based RDTs in febrile patients.
A cross-sectional diagnostic accuracy study was conducted in Kédougou, Senegal. Capillary blood was tested using the SD BIOLINE Ag Pf RDT (Abbott Diagnostics Korea Inc., Republic of Korea) and three LDH-based RDTs (BIOCREDIT Malaria Ag Pf [pLDH], BIOCREDIT Pf [pLDH/HRPII] and BIOCREDIT Pf/Pv [pLDH/pLDH]; Rapigen Inc., Republic of Korea). Venous blood was collected and used to repeat the BIOCREDIT RDTs and conduct microscopy. Frozen venous specimens were tested using a reference PCR assay. A quantitative multiplex malaria antigen assay measured antigen concentration. RDT performance was determined and analyzed as a function of antigen concentration distribution. Usability of the Pf-only BIOCREDIT tests was evaluated using a questionnaire.
Of the 220 participants, 154 (70%) were Pf-positive by PCR. The Pf (pLDH/HRPII) test demonstrated the highest sensitivity at 78% (95% confidence interval [CI] 70.9-84.5%); specificity was 89% (95% CI 79.4-95.6%). All RDTs performed better than microscopy (53% sensitivity). Although the HRP2 line on the Pf (pLDH/HRPII) test was more sensitive than the SD BIOLINE HRP2-based test (71%, 95% CI 63.6-78.4%), the sensitivities of the PfLDH lines alone on all three BIOCREDIT tests (61-64%) were lower than that of the SD BIOLINE HRP2 test. RDTs performed better when compared to antigen concentration over PCR results. Improved sensitivity of the Pf (pLDH/HRPII) test was driven by the HRP2 line. Line intensity correlated with antigen concentration. Predicted sensitivity using the analytical limit of detection (LOD) was comparable to the observed sensitivity. RDTs demonstrated acceptable usability.
Both HRP2 and LDH contributed to the sensitivity of the best-performing Pf-RDT. In populations such as this with low rates of hrp2/hrp3 deletions, the PfLDH line alone cannot compensate for the performance of the HRP2 line, even with the improved PfLDH LOD of the BIOCREDIT tests. RDT analytical LODs can be used to predict performance in populations with known antigen concentrations.
缺乏富含组氨酸蛋白2和3（hrp2/hrp3）基因的恶性疟原虫（Pf）寄生虫的出现，威胁到基于HRP2的疟疾快速诊断检测（RDT）的性能。针对Pf乳酸脱氢酶（LDH）的RDT可能解决当前产品的局限性并改善病例管理。本研究的目的是评估三种基于LDH的RDT在发热患者中的性能和可用性。
在塞内加尔的凯杜古进行了一项横断面诊断准确性研究。使用SD BIOLINE Ag Pf RDT（韩国雅培诊断公司）和三种基于LDH的RDT（BIOCREDIT疟疾Ag Pf [pLDH]、BIOCREDIT Pf [pLDH/HRPII]和BIOCREDIT Pf/Pv [pLDH/pLDH]；韩国Rapigen公司）检测毛细血管血。采集静脉血用于重复BIOCREDIT RDT检测并进行显微镜检查。使用参考PCR检测法检测冷冻静脉标本。定量多重疟疾抗原检测法测量抗原浓度。根据抗原浓度分布确定并分析RDT的性能。使用问卷评估仅针对Pf的BIOCREDIT检测的可用性。
220名参与者中，154人（70%）经PCR检测为Pf阳性。Pf（pLDH/HRPII）检测的灵敏度最高，为78%（95%置信区间[CI] 70.9 - 84.5%）；特异性为89%（95% CI 79.4 - 95.6%）。所有RDT的表现均优于显微镜检查（灵敏度为53%）。尽管Pf（pLDH/HRPII）检测上的HRP2条带比基于SD BIOLINE HRP2的检测更灵敏（71%，95% CI 63.6 - 78.4%），但所有三种BIOCREDIT检测中仅PfLDH条带的灵敏度（61 - 64%）低于SD BIOLINE HRP2检测。与基于PCR结果的抗原浓度相比，RDT表现更好。Pf（pLDH/HRPII）检测灵敏度的提高是由HRP2条带推动的。条带强度与抗原浓度相关。使用分析检测限（LOD）预测的灵敏度与观察到的灵敏度相当。RDT表现出可接受的可用性。
HRP2和LDH均有助于性能最佳的Pf - RDT的灵敏度。在像这样hrp2/hrp3缺失率较低的人群中，即使BIOCREDIT检测的PfLDH LOD有所提高，仅PfLDH条带也无法弥补HRP2条带的性能。RDT分析LOD可用于预测已知抗原浓度人群中的性能。
