Disease Control and Elimination Theme, Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Banjul, The Gambia.
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Clin Infect Dis. 2020 Jun 10;70(12):2544-2552. doi: 10.1093/cid/ciz740.
We assessed the impact of exposure to Plasmodium falciparum on parasite kinetics, clinical symptoms, and functional immunity after controlled human malaria infection (CHMI) in 2 cohorts with different levels of previous malarial exposure.
Nine adult males with high (sero-high) and 10 with low (sero-low) previous exposure received 3200 P. falciparum sporozoites (PfSPZ) of PfSPZ Challenge by direct venous inoculation and were followed for 35 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction. Endpoints were time to parasitemia, adverse events, and immune responses.
Ten of 10 (100%) volunteers in the sero-low and 7 of 9 (77.8%) in the sero-high group developed parasitemia detected by TBS in the first 28 days (P = .125). The median time to parasitemia was significantly shorter in the sero-low group than the sero-high group (9 days [interquartile range {IQR} 7.5-11.0] vs 11.0 days [IQR 7.5-18.0], respectively; log-rank test, P = .005). Antibody recognition of sporozoites was significantly higher in the sero-high (median, 17.93 [IQR 12.95-24] arbitrary units [AU]) than the sero-low volunteers (median, 10.54 [IQR, 8.36-12.12] AU) (P = .006). Growth inhibitory activity was significantly higher in the sero-high (median, 21.8% [IQR, 8.15%-29.65%]) than in the sero-low group (median, 8.3% [IQR, 5.6%-10.23%]) (P = .025).
CHMI was safe and well tolerated in this population. Individuals with serological evidence of higher malaria exposure were able to better control infection and had higher parasite growth inhibitory activity.
NCT03496454.
我们评估了在两个既往疟疾病史暴露水平不同的队列中，经控制人体疟疾感染（CHMI）后，疟原虫 falciparum 暴露对寄生虫动力学、临床症状和功能性免疫的影响。
9 名既往高暴露（血清高）和 10 名既往低暴露（血清低）的成年男性通过静脉直接接种 3200 个疟原虫孢子（PfSPZ）的 PfSPZ 挑战，并通过厚血涂片（TBS）和定量聚合酶链反应（PCR）在 35 天内对寄生虫血症进行跟踪。终点为寄生虫血症时间、不良事件和免疫反应。
在血清低组中，10 名志愿者（100%）在第 28 天之前通过 TBS 检测到寄生虫血症，而在血清高组中，7 名志愿者（77.8%）在 TBS 中检测到寄生虫血症（P =.125）。血清低组的寄生虫血症中位时间明显短于血清高组（9 天[四分位距 {IQR}7.5-11.0]与 11.0 天[IQR7.5-18.0]，对数秩检验，P =.005）。血清高组（中位数 17.93[IQR12.95-24]个单位[AU]）的疟原虫孢子抗体识别明显高于血清低组（中位数 10.54[IQR8.36-12.12] AU）（P =.006）。血清高组（中位数 21.8%[IQR8.15%-29.65%]）的寄生虫生长抑制活性明显高于血清低组（中位数 8.3%[IQR5.6%-10.23%]）（P =.025）。
在该人群中，CHMI 是安全且耐受良好的。有血清学证据表明暴露水平较高的个体能够更好地控制感染，并具有更高的寄生虫生长抑制活性。
NCT03496454。
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