Malaria morbidity and mortality following introduction of a universal policy of artemisinin-based treatment for malaria in Papua, Indonesia: A longitudinal surveillance study

BackgroundMalaria control activities can have a disproportionately greater impact on Plasmodium falciparum than on P. vivax in areas where both species are coendemic. We investigated temporal trends in malaria-related morbidity and mortality in Papua, Indonesia, before and after introduction of a universal, artemisinin-based antimalarial treatment strategy for all Plasmodium species.Methods and findingsA prospective, district-wide malariometric surveillance system was established in April 2004 to record all cases of malaria at community clinics and the regional hospital and maintained until December 2013. In March 2006, antimalarial treatment policy was changed to artemisinin combination therapy for uncomplicated malaria and intravenous artesunate for severe malaria due to any Plasmodium species. Over the study period, a total of 418,238 patients presented to the surveillance facilities with malaria. The proportion of patients with malaria requiring admission to hospital fell from 26.9% (7,745/28,789) in the pre–policy change period (April 2004 to March 2006) to 14.0% (4,786/34,117) in the late transition period (April 2008 to December 2009), a difference of −12.9% (95% confidence interval [CI] −13.5% to −12.2%). There was a significant fall in the mortality of patients presenting to the hospital with P. falciparum malaria (0.53% [100/18,965] versus 0.32% [57/17,691]; difference = −0.21% [95% CI −0.34 to −0.07]) but not in patients with P. vivax malaria (0.28% [21/7,545] versus 0.23% [28/12,397]; difference = −0.05% [95% CI −0.20 to 0.09]). Between the same periods, the overall proportion of malaria due to P. vivax rose from 44.1% (30,444/69,098) to 53.3% (29,934/56,125) in the community clinics and from 32.4% (9,325/28,789) to 44.1% (15,035/34,117) at the hospital. After controlling for population growth and changes in treatment-seeking behaviour, the incidence of P. falciparum malaria fell from 511 to 249 per 1,000 person-years (py) (incidence rate ratio [IRR] = 0.49 [95% CI 0.48–0.49]), whereas the incidence of P. vivax malaria fell from 331 to 239 per 1,000 py (IRR = 0.72 [95% CI 0.71–0.73]). The main limitations of our study were possible confounding from changes in healthcare provision, a growing population, and significant shifts in treatment-seeking behaviour following implementation of a new antimalarial policy.ConclusionsIn this area with high levels of antimalarial drug resistance, adoption of a universal policy of efficacious artemisinin-based therapy for malaria infections due to any Plasmodium species was associated with a significant reduction in total malaria-attributable morbidity and mortality. The burden of P. falciparum malaria was reduced to a greater extent than that of P. vivax malaria. In coendemic regions, the timely elimination of malaria will require that safe and effective radical cure of both the blood and liver stages of the parasite is widely available for all patients at risk of malaria.

背景 在恶性疟原虫(Plasmodium falciparum)与间日疟原虫(P. vivax)共同流行的地区，疟疾防控措施对恶性疟原虫的防控效果往往显著优于间日疟原虫。本研究针对印度尼西亚巴布亚地区，在针对所有疟原虫物种推行通用青蒿素类抗疟治疗策略(artemisinin-based antimalarial treatment strategy)前后，对与疟疾相关的发病与死亡的时间变化趋势展开了调查。

方法与结果 本研究于2004年4月建立全区疟疾监测系统，对社区诊所及区域医院的所有疟疾病例进行记录，监测持续至2013年12月。2006年3月，当地抗疟治疗政策调整为：无并发症疟疾患者采用青蒿素联合疗法(artemisinin combination therapy)，任意疟原虫感染导致的重症疟疾患者采用青蒿琥酯静脉给药治疗。本研究周期内，共有418238名疟疾患者在监测医疗机构就诊。政策调整前（2004年4月至2006年3月），疟疾患者的住院比例为26.9%（7745/28789）；至过渡后期（2008年4月至2009年12月），该比例降至14.0%（4786/34117），降幅达12.9%（95%置信区间(confidence interval, CI)：-13.5%~-12.2%）。
医院收治的恶性疟原虫感染患者死亡率出现显著下降：从0.53%（100/18965）降至0.32%（57/17691），差值为-0.21%（95%CI：-0.34~-0.07）；但间日疟原虫感染患者的死亡率无明显变化（0.28%[21/7545] vs 0.23%[28/12397]；差值=-0.05%，95%CI：-0.20~0.09）。
同期，社区诊所中由间日疟原虫导致的疟疾占比从44.1%（30444/69098）升至53.3%（29934/56125）；医院内该占比则从32.4%（9325/28789）升至44.1%（15035/34117）。
在控制人口增长与就诊行为变化的混杂因素后，恶性疟的发病率从每1000人年(person-years, py)511例降至249例（发病率比(incidence rate ratio, IRR)=0.49，95%CI：0.48~0.49）；间日疟的发病率则从每1000人年331例降至239例（IRR=0.72，95%CI：0.71~0.73）。
本研究的主要局限性包括：医疗服务体系变化带来的潜在混杂、人口增长，以及新抗疟政策实施后就诊行为发生显著改变。

结论 在本高抗疟药耐药性地区，针对任意疟原虫感染的疟疾患者推行通用的高效青蒿素类治疗政策，可显著降低归因于疟疾的总体发病与死亡负担。其中恶性疟的疾病负担降幅显著大于间日疟。在共同流行地区，若要及时消除疟疾，需为所有疟疾高危人群广泛提供针对疟原虫红内期与肝内期的安全有效根治方案。