Lyimo Eric, Makenga Geofrey, Turner Louise, Lavstsen Thomas, Lusingu John P A, Van Geertruyden Jean-Pierre, Minja Daniel T R, Wang Christian W, Baraka Vito
Tanga Research Centre, National Institute for Medical Research, Tanga, Tanzania.
Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania.
PLoS One. 2025 Jan 30;20(1):e0316482. doi: 10.1371/journal.pone.0316482. eCollection 2025.
Several interventional strategies have been implemented in malaria endemic areas where the burden is high, that include among others, intermittent preventive treatment (IPT), a tactic that blocks transmission and can reduce disease morbidity. However, the implementation IPT strategies raises a genuine concern, intervening the development of naturally acquired immunity to malaria which requires continuous contact with parasite antigens. This study investigated whether dihydroartemisinin-piperaquine (DP) or artesunate-amodiaquine (ASAQ) IPT in schoolchildren (IPTsc) impairs IgG reactivity to six malaria antigens. An IPTsc trial in north-eastern Tanzania administered three doses of DP or ASAQ at four-monthly intervals and the schoolchildren were followed up. This study compared IgG reactivity against GLURP-R2, MSP1, MSP3, and CIDR domains (CIDRa1.1, CIDRa1.4, and CIDRa1.5) of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1) in intervention and control groups using enzyme linked immunosorbent assay (ELISA) technique. During the study, 369 schoolchildren were available for analysis, 119, 134 and 116 participants in the control, DP and ASAQ groups, respectively. Breadth of malaria antigen recognition increased significantly during and after the intervention phases and did not differ between the study groups (Trend test: DP, z-score = 5.92, p < 0.001, ASAQ, z-score = 6.64, p < 0.001 and control, z-score = 5.85, p < 0.001). There were no differences between the control and ASAQ group in the recognition of any of the tested antigens at all visits. In the DP group, however, during the intervention period IPTsc did not impair antibody against MSP1, MSP3, CIDRa1.1, CIDRa1.4 and CIDRa1.5, but it did impair against GLURP-R2. The current study has shown that effective IPTsc with DP or ASAQ does not interfere with the development of antibodies against malaria antigens of the blood stages, suggesting that the advancement of naturally acquired immunity to malaria is not impeded by IPTsc interventions.
在疟疾负担较重的流行地区已实施了多种干预策略，其中包括间歇性预防治疗（IPT），这是一种阻断传播并可降低疾病发病率的策略。然而，IPT策略的实施引发了一个切实的担忧，即干预自然获得的疟疾免疫力的发展，而这需要持续接触寄生虫抗原。本研究调查了在校儿童中使用双氢青蒿素 - 哌喹（DP）或青蒿琥酯 - 阿莫地喹（ASAQ）进行间歇性预防治疗（IPTsc）是否会损害对六种疟疾抗原的IgG反应性。在坦桑尼亚东北部进行的一项IPTsc试验，每四个月给予三剂DP或ASAQ，并对在校儿童进行随访。本研究使用酶联免疫吸附测定（ELISA）技术比较了干预组和对照组中针对恶性疟原虫红细胞膜蛋白1（PfEMP - 1）的GLURP - R2、MSP1、MSP3和CIDR结构域（CIDRa1.1、CIDRa1.4和CIDRa1.5）的IgG反应性。在研究期间，有369名在校儿童可供分析，对照组、DP组和ASAQ组分别有119、134和116名参与者。在干预阶段期间及之后，疟疾抗原识别广度显著增加，且研究组之间无差异（趋势检验：DP，z分数 = 5.92，p < 0.001；ASAQ，z分数 = 6.64，p < 0.001；对照组，z分数 = 5.85，p < 0.001）。在所有访视中，对照组和ASAQ组在任何测试抗原的识别方面均无差异。然而，在DP组中，在干预期间IPTsc并未损害针对MSP1、MSP3以及CIDRa1.1、CIDRa1.4和CIDRa1.5的抗体，但确实损害了针对GLURP - R2的抗体。当前研究表明，使用DP或ASAQ进行有效的IPTsc不会干扰针对血液阶段疟疾抗原的抗体的发展, 这表明IPTsc干预不会阻碍自然获得的疟疾免疫力的进展。
