ABSTRACT
INTRODUCTION: Cholera remains a significant public health threat for many countries, and the severity largely varies by the population and local conditions that drive disease spread, especially in endemic areas prone to natural disasters and flooding. Epidemiological models can provide useful information to military planners for understanding disease spread within populations and the effectiveness of response options for preventing the transmission among deployed and stationed personnel. This study demonstrates the use of epidemiological modeling to understand the dynamics of cholera transmission to inform emergency planning and military preparedness in areas with highly communicable diseases. MATERIALS AND METHODS: Areas with higher probability for a potential cholera outbreak in Haiti followed by a natural disaster were identified. The hotspots were then used to seed an extended compartmental model, EpiGrid, to simulate notional spread scenarios of cholera originating in three distinct areas in Haiti. Disease parameters were derived from the 2010 cholera outbreak in Haiti, and disease spread was simulated over a 12-week period under uncontrolled and controlled spread. RESULTS: For each model location, scenarios of mitigated (intervention with 30% transmission reduction via international aid) and unmitigated (without intervention) are simulated. The results depict the geographical spread and estimate the cumulative cholera infection for each notional scenario over the course of 3 months. Disease transmission differs considerably across origin site with an outbreak originating in the department of Nippes spanning the largest geographic area and resulting in the largest number of cumulative cases after 12 weeks under unmitigated (79,518 cases) and mitigated (35,667 cases) spread scenarios. CONCLUSIONS: We modeled the notional re-emergence and spread of cholera following the August 2021 earthquake in Haiti while in the midst of the global COVID-19 pandemic. This information can help guide military and emergency response decision-making during an infectious disease outbreak and considerations for protecting military personnel in the midst of a humanitarian response. Military planners should consider the use of epidemiological models to assess the health risk posed to deployed and stationed personnel in high-risk areas.
ABSTRACT
BACKGROUND: Junín virus (JUNV), the etiologic agent of Argentine hemorrhagic fever (AHF), is classified by the NIAID and CDC as a Category A priority pathogen. Presently, antiviral therapy for AHF is limited to immune plasma, which is readily available only in the endemic regions of Argentina. T-705 (favipiravir) is a broadly active small molecule RNA-dependent RNA polymerase inhibitor presently in clinical evaluation for the treatment of influenza. We have previously reported on the in vitro activity of favipiravir against several strains of JUNV and other pathogenic New World arenaviruses. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the efficacy of favipiravir in vivo, guinea pigs were challenged with the pathogenic Romero strain of JUNV, and then treated twice daily for two weeks with oral or intraperitoneal (i.p.) favipiravir (300 mg/kg/day) starting 1-2 days post-infection. Although only 20% of animals treated orally with favipiravir survived the lethal challenge dose, those that succumbed survived considerably longer than guinea pigs treated with placebo. Consistent with pharmacokinetic analysis that showed greater plasma levels of favipiravir in animals dosed by i.p. injection, i.p. treatment resulted in a substantially higher level of protection (78% survival). Survival in guinea pigs treated with ribavirin was in the range of 33-40%. Favipiravir treatment resulted in undetectable levels of serum and tissue viral titers and prevented the prominent thrombocytopenia and leucopenia observed in placebo-treated animals during the acute phase of infection. CONCLUSIONS/SIGNIFICANCE: The remarkable protection afforded by i.p. favipiravir intervention beginning 2 days after challenge is the highest ever reported for a small molecule antiviral in the difficult to treat guinea pig JUNV challenge model. These findings support the continued development of favipiravir as a promising antiviral against JUNV and other related arenaviruses.