Mahidol Oxford Research Unit, Mahidol University, Bangkok, Thailand.
Adv Parasitol. 2012;80:113-50. doi: 10.1016/B978-0-12-397900-1.00002-5.
Plasmodium vivax is a major cause of febrile illness in endemic areas of Asia, Central and South America, and the horn of Africa. P. vivax infections are characterized by relapses of malaria arising from persistent liver stages of the parasite (hypnozoites), which can be prevented currently only by 8-aminoquinoline anti-malarials. Tropical P. vivax infections relapse at approximately 3-week intervals if rapidly eliminated anti-malarials are given for treatment, whereas in temperate regions and parts of the sub-tropics, P. vivax infections are characterized by either a long incubation or a long-latency period between illness and relapse - in both cases approximating 8-10 months. The epidemiology of the different relapse phenotypes has not been defined adequately despite obvious relevance to malaria therapeutic assessment, control, and elimination. The number of sporozoites inoculated by the anopheline mosquito is an important determinant of both the timing and the number of relapses. The intervals between P. vivax relapses display a remarkable periodicity which has not been explained. Evidence is presented that the proportion of patients who have successive relapses is relatively constant and that the factor which activates hypnozoites and leads to regular interval relapse in vivax malaria is the systemic febrile illness itself. It is proposed that in endemic areas, a large proportion of the population harbours latent hypnozoites which can be activated by a systemic illness such as vivax or falciparum malaria. This explains the high rates of vivax following falciparum malaria, the high proportion of heterologous genotypes in relapses, the higher rates of relapse in people living in endemic areas compared with artificial infection studies, and, by facilitating recombination between different genotypes, contributes to P. vivax genetic diversity particularly in low transmission settings. Long-latency P. vivax phenotypes may be more widespread and more prevalent than currently thought. These observations have important implications for the assessment of radical treatment efficacy and for malaria control and elimination.
间日疟原虫是亚洲、中美洲和非洲之角流行地区发热疾病的主要病因。间日疟原虫感染的特征是寄生虫（休眠子）的持续肝脏阶段引起的疟疾复发，目前只能用 8-氨基喹啉抗疟药预防。如果用快速消除的抗疟药治疗，热带间日疟感染每 3 周复发一次，而在温带地区和亚热带部分地区，间日疟感染的特征是潜伏期长或发病与复发之间的潜伏期长——在这两种情况下，大约为 8-10 个月。尽管对疟疾治疗评估、控制和消除具有明显的相关性，但不同复发表型的流行病学尚未得到充分定义。疟原虫按蚊接种的子孢子数量是决定复发时间和数量的重要决定因素。间日疟复发的间隔时间显示出一种显著的周期性，目前尚未得到解释。有证据表明，连续复发的患者比例相对稳定，导致间日疟中休眠子激活并导致定期间隔复发的因素是全身发热性疾病本身。有人提出，在流行地区，很大一部分人口携带潜伏的休眠子，全身发热性疾病（如间日疟或恶性疟）可激活这些休眠子。这解释了恶性疟后间日疟的高发病率、复发中异源基因型的高比例、与人工感染研究相比，生活在流行地区的人复发率较高的原因，并且通过促进不同基因型之间的重组，有助于特别是在低传播环境中增加间日疟原虫的遗传多样性。长潜伏期的间日疟表型可能比目前认为的更为广泛和普遍。这些观察结果对评估根治性治疗效果以及疟疾控制和消除具有重要意义。
