Moore Sean M, Rapheal Erica, Mendoza Guerrero Sandra, Dean Natalie E, Stoddard Steven T
Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America.
Independent Consultant, Minneapolis, Minnesota, United States of America.
PLoS Negl Trop Dis. 2025 Jul 29;19(7):e0012751. doi: 10.1371/journal.pntd.0012751. eCollection 2025 Jul.
Lassa fever (LF) is an acute viral hemorrhagic disease endemic to West Africa that has been declared a priority disease by the World Health Organization due to its severity and the lack of a vaccine or effective treatment options. Several candidate vaccines are currently in development and are expected to be ready for phase III field efficacy trials soon. However, most LF cases and deaths are believed to go unreported, and as a result we lack a clear understanding of several aspects of LF epidemiology and immunology that are critical to the design of vaccine efficacy trials.
To help guide vaccine trial design and trial site selection we estimated the force of infection (FOI) from rodent hosts to humans in all 1st and 2nd administrative units in West Africa from published seroprevalence studies. We next estimated LF reporting probabilities using these FOI estimates and LF case and death reports and then projected FOI in all admin1 and admin2 areas without seroprevalence data. We then extrapolated age-specific LF incidence rates from FOI estimates under different assumptions regarding the level of protection against reinfection among seropositive and seronegative individuals with a history of prior infection.
Projected FOI estimates and modeled annual LF incidence rates indicate that Sierra Leone, southern Guinea, and a few areas within Nigeria would likely experience the highest LF case incidence rates for a vaccine trial. Estimated LF incidence rates were highly sensitive to assumptions about Lassa immunology, particularly the frequency of seroreversion among previously infected individuals and the extent to which seroreverted individuals retain protection against reinfection and more severe disease outcomes.
Our spatial LF incidence rate estimates, along with the interannual and seasonal variability in these estimates and estimates of baseline seroprevalence, could be used for vaccine trial site selection, choosing the target population (e.g., age and serostatus), and maximizing a trial's statistical power.
拉沙热（LF）是一种西非特有的急性病毒性出血热疾病，由于其严重性以及缺乏疫苗或有效的治疗选择，已被世界卫生组织列为重点疾病。目前有几种候选疫苗正在研发中，预计很快将准备好进行III期现场疗效试验。然而，大多数拉沙热病例和死亡据信未被报告，因此我们对拉沙热流行病学和免疫学的几个关键方面缺乏清晰的了解，而这些方面对于疫苗疗效试验的设计至关重要。
为了帮助指导疫苗试验设计和试验地点选择，我们根据已发表的血清阳性率研究，估算了西非所有第一和第二行政单位中从啮齿动物宿主到人类的感染率（FOI）。接下来，我们利用这些FOI估算值以及拉沙热病例和死亡报告来估算拉沙热报告概率，然后在没有血清阳性率数据的所有行政1和行政2地区预测FOI。然后，我们根据不同假设，即既往感染的血清阳性和血清阴性个体中针对再感染的保护水平，从FOI估算值推断特定年龄的拉沙热发病率。
预测的FOI估算值和模拟的年度拉沙热发病率表明，塞拉利昂、几内亚南部以及尼日利亚的一些地区可能会出现疫苗试验中最高的拉沙热病例发病率。估算的拉沙热发病率对拉沙热免疫学假设高度敏感，特别是既往感染个体中血清逆转的频率以及血清逆转个体对再感染和更严重疾病结局保持保护的程度。
我们对拉沙热发病率的空间估算，以及这些估算值的年际和季节变化以及基线血清阳性率估算值，可用于疫苗试验地点选择、选择目标人群（如年龄和血清状态）以及最大化试验的统计效力。
