Using Modelling to Disentangle the Relative Contributions of Zoonotic and Anthroponotic Transmission: The Case of Lassa Fever

Abstract

Zoonotic infections, which transmit from animals to humans, form the majority of new human pathogens. Following zoonotic transmission, the pathogen may already have, or may acquire, the ability to transmit from human to human. With infections such as Lassa fever (LF), an often fatal, rodent-borne, hemorrhagic fever common in areas of West Africa, rodent-to-rodent, rodent-to-human, human-to-human and even human-to-rodent transmission patterns are possible. Indeed, large hospital-related outbreaks have been reported. Estimating the proportion of transmission due to human-to-human routes and related patterns (e.g. existence of super-spreaders), in these scenarios is challenging, but essential for planned interventions. Here, we make use of an innovative modeling approach to analyze data from published outbreaks and the number of LF hospitalized patients to Kenema Government Hospital in Sierra Leone to estimate the likely contribution of human-to-human transmission. The analyses show that almost of the cases at KGH are secondary cases arising from human-to-human transmission. However, we found much of this transmission is associated with a disproportionally large impact of a few individuals (‘super-spreaders’), as we found only of human cases result in an effective reproduction number (i.e. the average number of secondary cases per infectious case) , with a maximum value up to . This work explains the discrepancy between the sizes of reported LF outbreaks and a clinical perception that human-to-human transmission is low. Future assessment of risks of LF and infection control guidelines should take into account the potentially large impact of super-spreaders in human-to-human transmission. Our work highlights several neglected topics in LF research, the occurrence and nature of super-spreading events and aspects of social behavior in transmission and detection. Many pathogens have the ability to infect different species. Lassa fever virus is an important example; this virus infects a species of rodent in West Africa, and can cause a severe disease in people. Lassa fever virus is transmitted from rodent-to-rodent, rodent-to-human, human-to-human and perhaps human-to-rodent. So far, the relative importance of these routes has not been assessed. Here we focus on the risk for humans; undoubtedly, most human infections are acquired by contact with rodents or their urine, but the relative risk of rodent-to-human and human-to-human transmission is unknown. We use mathematical modeling to address this. First, we identified Lassa fever outbreaks known to be due to human-to-human chains of transmission. Then, we looked at people hospitalized with the disease in Kenema Government Hospital, Sierra Leone (KGH), who could have been infected either by rodents or humans. We asked, what should the proportion of patients be who get infected by humans, assuming the statistical patterns observed in the human-to-human chains are the same in both instances? We found that around of patients with Lassa fever in KGH probably acquired the disease from another person. In addition, the patterns of disease in people suggest that these of cases are probably initiated by only a small number of infected people (who could be thought of as super-spreaders).