Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
BMC Med. 2020 Feb 20;18(1):28. doi: 10.1186/s12916-020-1497-0.
An acute episode of malaria can be followed by multiple recurrent episodes either due to re-infection, recrudescence of a partially treated parasite or, in the case of Plasmodium vivax or P. ovale, relapse from the dormant liver stage of the parasite. The aim of this study was to quantify the impact of recurrent malaria episodes on morbidity and mortality in Papua, Indonesia.
We undertook a retrospective analysis of routinely collected data from malaria patients attending the primary referral hospital in Papua, Indonesia, between April 2004 and December 2013. Multi-state modelling was used to estimate the effect of recurring malaria episodes on re-presentation and admission to hospital and death. The risks of early (≤ 14 days) and late (15 to 365 days) hospital admission and death were estimated separately in our study to distinguish between the direct and indirect effects of malaria recurrence on adverse outcomes.
A total of 68,361 patients were included in the analysis, of whom 37,168 (54.4%) presented initially with P. falciparum, 22,209 (32.5%) with P. vivax, and 8984 (13.1%) with other species. During 12 months of follow-up after each of the first four malaria episodes, 10,868 (15.9%) patients were admitted to hospital and 897 (1.3%) died. The risk of re-presenting to the hospital with malaria increased from 34.7% (95% CI 34.4%, 35.1%) at first episode to 58.6% (57.5%, 59.6%) following the third episode of malaria. After adjusting for co-factors, infection with P. vivax was a significant risk factor for re-presentation (hazard ratio (HR) = 1.48 (95% CI 1.44, 1.51)) and late admission to hospital (HR = 1.17 (1.11, 1.22)). Patients infected with P. falciparum had a greater overall rate of mortality within 14 days (HR = 1.54 (1.25, 1.92)), but after multiple episodes of malaria, there was a trend towards a higher rate of early death in patients infected with P. vivax compared to P. falciparum (HR = 1.91 (0.73, 4.97)).
Compared to patients initially infected with P. falciparum, those infected with P. vivax had significantly more re-presentations to hospital with malaria, and this contributed to a high risk of inpatient admission and death. These findings highlight the importance of radical cure of P. vivax to eliminate the dormant liver stages that trigger relapses.
疟疾的急性发作之后可能会反复发作，这可能是由于再次感染、部分治疗的寄生虫复发，或者在间日疟原虫或卵形疟原虫的情况下，寄生虫从休眠的肝脏阶段复发。本研究旨在量化复发性疟疾发作对印度尼西亚巴布亚地区发病率和死亡率的影响。
我们对 2004 年 4 月至 2013 年 12 月期间在印度尼西亚巴布亚的主要转诊医院就诊的疟疾患者的常规收集数据进行了回顾性分析。多状态模型用于估计反复发作疟疾对再次就诊和住院及死亡的影响。在本研究中，我们分别估计了早期（≤14 天）和晚期（15 至 365 天）住院和死亡的风险，以区分疟疾复发对不良结局的直接和间接影响。
共纳入 68361 例患者，其中 37168 例（54.4%）最初感染恶性疟原虫，22209 例（32.5%）感染间日疟原虫，8984 例（13.1%）感染其他疟原虫。在首次发作后的 12 个月随访期间，10868 例（15.9%）患者住院，897 例（1.3%）死亡。疟疾再次就诊的风险从首次发作时的 34.7%（95%CI 34.4%，35.1%）增加到第三次发作时的 58.6%（57.5%，59.6%）。在调整了协变量后，感染间日疟原虫是再次就诊的显著危险因素（风险比（HR）=1.48（95%CI 1.44，1.51））和晚期住院的危险因素（HR=1.17（1.11，1.22））。感染恶性疟原虫的患者在 14 天内总死亡率更高（HR=1.54（1.25，1.92）），但在多次疟疾发作后，与感染恶性疟原虫相比，感染间日疟原虫的患者早期死亡的风险呈上升趋势（HR=1.91（0.73，4.97））。
与最初感染恶性疟原虫的患者相比，感染间日疟原虫的患者因疟疾再次就诊的次数明显更多，这导致住院和死亡的风险更高。这些发现强调了根治间日疟原虫的重要性，以消除引发复发的休眠肝脏阶段。
