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

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.

Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus

“…Combined with the intermingling of human and M. natalensis samples on the phylogenetic tree (Figure 2A), this is consistent with a genetically diverse pool of LASV being maintained in its rodent reservoir, with most human infections caused by genetically distinct viruses. A recent study suggested that human-to-human transmission of LASV may account for up to 20% of all cases (Lo Iacono et al, 2015), but we found little support for this in our dataset. This does not rule out human-to-human transmission entirely, but it suggests that human transmission chains are the exception rather than the rule.…”

“…Similarly, it has been suggested that up to 20% of LF cases also arise from human-to-human transmissions (Lo Iacono et al, 2015). Sustained human-to-human transmission should result in a ‘ladder-like’ structure of the phylogenetic tree along with a strong correlation between a sample's collection date and its genetic distance from the root of the tree over a short time period.…”

“…Case-fatality rates (CFRs) among hospitalized LF patients can exceed 50%, although numerous sub-clinical infections are believed to occur (Troup et al, 1970; McCormick and Fisher-Hoch, 2002). Most patients are infected by exposure to excreta from the rodent Mastomys natalensis , which functions as a reservoir and maintains persistent infections (Lecompte et al, 2006); human-to-human transmissions have also been reported, however, primarily in hospital settings (McCormick and Fisher-Hoch, 2002; Lo Iacono et al, 2015). …”

Lassa Fever Epidemic in Nigeria - Outbreak Investigation, Risk Factors and Empirical Analysis from 2012 To 2016

“…This puts the health workers, their families and the wider community at risk of secondary infections, inundation, other study also revealed significant knowledge gaps concerning LF among primary care providers in a LF endemic suburban community Andrew et al [22].…”

Pathogenicity Comparison Between the Kikwit and Makona Ebola Virus Variants in Rhesus Macaques

“…In addition, similar to minority clusters transmitting strain of higher virulence, increased viral loads in a minority subset of infected individuals would not necessarily result in an observable change in overall case-fatality rates. The concept of disease super spreaders had been hypothesized during past outbreaks with EBOV and with other pathogens [27][28][29][30] and is consistent with observations during the current outbreak, in which a traditional healer was shown to have directly infected 13 others after dying of EVD [20] and was eventually linked to >300 EBOV cases [31]. A recent study also reported several chains of EBOV transmissions in Guinea, showing how a small number of infected individuals can transmit the virus to a larger number of people and drive the overall spread of EBOV in the community, as opposed to the majority of patients, who infect few others [32].…”