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

Date Published: January 8, 2015

Publisher: Public Library of Science

Author(s): Giovanni Lo Iacono, Andrew A. Cunningham, Elisabeth Fichet-Calvet, Robert F. Garry, Donald S. Grant, Sheik Humarr Khan, Melissa Leach, Lina M. Moses, John S. Schieffelin, Jeffrey G. Shaffer, Colleen T. Webb, James L. N. Wood, Anita K. McElroy.

Abstract: BackgroundZoonotic 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.Methodology/Principal FindingsHere, 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 .Conclusions/SignificanceThis 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.

Partial Text: Diseases at the animal-human interface are in general subjected to different modes of cross-species transmission: animal-to-animal, animal-to-human, human-to-human and even human-to-animal. Estimating the relative contribution of each is of fundamental importance for the planning and implementation of appropriate infection control and preventive measures. This can be an extremely difficult task if humans and animals share the same physical space, and/or if experimentation (e.g. to quantify the probability of animal-to-animal transmission) is subjected to serious limitations. This is the case of Lassa fever (LF), a rodent-borne disease endemic in West Africa. Despite its clear zoonotic origin, there are strong arguments, listed below, to hypothesize that a significant proportion of the burden of LF in humans arises from human-to-human transmission. The aim of this work is to test whether or not patterns in the epidemic curve describing the cases of LF observed in Sierra Leone [1], are compatible with patterns observed in chains of pure human-to-human transmission recorded in nosocomial and extra-nosocomial outbreaks [2], [3].

Disentangling the contribution of different hosts in spreading a zoonotic, emerging disease is a key challenge for determining effective, proportionate public health and safety measures. Such a conundrum has steered a scientific debate on LF, which appears to fluctuate around whether or not human-to-human transmission plays a major role compared to rodent-to-human transmission. The current work reconciles these two opposing paradigms. Here, we adopted a relatively simple mathematical approach to analyze data of hospitalized patients in KGH, Sierra Leone. The daily mean effective reproduction numbers, , observed in the nosocomial outbreaks (only human-to-human transmission) are much larger, and thus incompatible, with the ones estimated from the data from KGH, even if we assume human-to-human transmission. If we regard the extra-nosocomial cases observed in the Jos outbreak as representative of disease transmission in an endemic area, then a significant proportion of LF cases () arise from human-to-human transmission. A significant proportion of these secondary cases, however, are attributable to a few events with disproportionately large effective reproduction numbers: super-spreading events. In general, the distributions of the individual reproductive number, , and the average number of cases during an epidemic, , exhibits a tail heavier than the exponential or Poisson distributions, here used as benchmarks for thin-tailed distributions. This reveal over-dispersion indicating the presence of super-spreading events.



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