Exposure and infection to Plasmodium knowlesi in case study communities in Northern Sabah, Malaysia and Palawan, The Philippines

BackgroundPrimarily impacting poor, rural populations, the zoonotic malaria Plasmodium knowlesi is now the main cause of human malaria within Malaysian Borneo. While data is increasingly available on symptomatic cases, little is known about community-level patterns of exposure and infection. Understanding the true burden of disease and associated risk factors within endemic communities is critical for informing evidence-based control measures.Methodology/Principal findingsWe conducted comprehensive surveys in three areas where P. knowlesi transmission is reported: Limbuak, Pulau Banggi and Matunggung, Kudat, Sabah, Malaysia and Bacungan, Palawan, the Philippines. Infection prevalence was low with parasites detected by PCR in only 0.2% (4/2503) of the population. P. knowlesi PkSERA3 ag1 antibody responses were detected in 7.1% (95% CI: 6.2–8.2%) of the population, compared with 16.1% (14.6–17.7%) and 12.6% (11.2–14.1%) for P. falciparum and P. vivax. Sero-prevalence was low in individuals P. falciparum and P. vivax consistent with decreased transmission of non-zoonotic malaria species. Results indicated marked heterogeneity in transmission intensity between sites and P. knowlesi exposure was associated with agricultural work (OR 1.63; 95% CI 1.07–2.48) and higher levels of forest cover (OR 2.40; 95% CI 1.29–4.46) and clearing (OR 2.14; 95% CI 1.35–3.40) around houses. Spatial patterns of P. knowlesi exposure differed from exposure to non-zoonotic malaria and P. knowlesi exposed individuals were younger on average than individuals exposed to non-zoonotic malaria.Conclusions/SignificanceThis is the first study to describe serological exposure to P. knowlesi and associated risk factors within endemic communities. Results indicate community–level patterns of infection and exposure differ markedly from demographics of reported cases, with higher levels of exposure among women and children. Further work is needed to understand these variations in risk across a wider population and spatial scale.

本研究背景：诺氏疟原虫（Plasmodium knowlesi）所致的畜源性疟疾（zoonotic malaria）主要侵袭贫困农村人群，目前已成为马来西亚婆罗洲地区人类疟疾的首要致病原。尽管有症状病例的相关数据日益完备，但学界对人群层面的暴露与感染模式仍知之甚少。明确流行社区内疾病的真实负担及相关危险因素，对于制定循证防控策略至关重要。
研究方法与主要发现：我们在三处报告存在诺氏疟原虫传播的区域开展了全面流行病学调查，分别为马来西亚沙巴州古达县的林布阿克（Limbuak）、邦吉岛（Pulau Banggi）与马通贡（Matunggung），以及菲律宾巴拉望省的巴库南（Bacungan）。经聚合酶链式反应（PCR）检测，人群中疟原虫感染率极低，仅为0.2%（4/2503）。针对诺氏疟原虫PkSERA3抗原1型的抗体应答阳性率为7.1%（95%置信区间（CI）：6.2%~8.2%），而恶性疟原虫（P. falciparum）与间日疟原虫（P. vivax）的抗体阳性率分别为16.1%（14.6%~17.7%）与12.6%（11.2%~14.1%）。非畜源性疟疾物种的传播水平较低，对应人群的血清阳性率（sero-prevalence）亦偏低。结果显示，不同调查位点的传播强度存在显著异质性；诺氏疟原虫暴露与农业劳作（比值比（OR）=1.63；95%置信区间1.07~2.48）、住宅周边较高的森林覆盖率（OR=2.40；95%置信区间1.29~4.46）以及森林砍伐程度（OR=2.14；95%置信区间1.35~3.40）显著相关。诺氏疟原虫暴露的空间分布模式与非畜源性疟疾存在显著差异，且诺氏疟原虫暴露者的平均年龄低于非畜源性疟疾暴露者。
研究结论与意义：本研究首次描述了流行社区内诺氏疟原虫的血清学暴露特征及相关危险因素。结果表明，人群层面的感染与暴露模式与报告病例的人口学特征存在显著差异，女性与儿童的暴露水平更高。未来仍需开展更多研究，以在更大范围的人群与空间尺度上阐明此类风险差异。