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

Background 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. Methodology/Principal Findings 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 . Conclusions/Significance 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.

[1]  T. Monath,et al.  Lassa Virus Isolation from Mastomys natalensis Rodents during an Epidemic in Sierra Leone , 1974, Science.

[2]  A. Nicoll,et al.  The public health response to a case of Lassa fever in London in 2000. , 2004, The Journal of infection.

[3]  C P Farrington,et al.  Branching process models for surveillance of infectious diseases controlled by mass vaccination. , 2003, Biostatistics.

[4]  A. Schuchat,et al.  Superspreading SARS Events, Beijing, 2003 , 2004, Emerging infectious diseases.

[5]  W. Gransden,et al.  A case of Lassa fever: experience at St Thomas's Hospital. , 1982, British medical journal.

[6]  O. Heinonen,et al.  Explosive school-based measles outbreak: intense exposure may have resulted in high risk, even among revaccinees. , 1998, American journal of epidemiology.

[7]  Pardis C Sabeti,et al.  Lassa Fever in Post-Conflict Sierra Leone , 2014, PLoS neglected tropical diseases.

[8]  I. Lukashevich,et al.  Lassa virus activity in Guinea: Distribution of human antiviral antibody defined using enzyme‐linked immunosorbent assay with recombinant antigen , 1993, Journal of medical virology.

[9]  J. L. Montagne,et al.  Emerging infectious diseases. , 1994, The Journal of infectious diseases.

[10]  Pierre-Yves Boëlle,et al.  The R0 package: a toolbox to estimate reproduction numbers for epidemic outbreaks , 2012, BMC Medical Informatics and Decision Making.

[11]  P. Jahrling,et al.  Experimental studies of arenaviral hemorrhagic fevers. , 1987, Current topics in microbiology and immunology.

[12]  J. McCormick,et al.  Viral hemorrhagic fever antibodies in Nigerian populations. , 1988, The American journal of tropical medicine and hygiene.

[13]  T. Monath,et al.  A hospital epidemic of Lassa fever in Zorzor, Liberia, March-April 1972. , 1973, The American journal of tropical medicine and hygiene.

[14]  James O. Lloyd-Smith,et al.  Inference of R 0 and Transmission Heterogeneity from the Size Distribution of Stuttering Chains , 2013, PLoS Comput. Biol..

[15]  L. Brammer,et al.  Lassa fever in the United States. Investigation of a case and new guidelines for management. , 1990, The New England journal of medicine.

[16]  L. Hutwagner,et al.  Review of cases of nosocomial Lassa fever in Nigeria: the high price of poor medical practice , 1995, BMJ.

[17]  J. Frame,et al.  Endemic Lassa fever in Liberia. VI. Village serological surveys for evidence of Lassa virus activity in Lofa County, Liberia. , 1984, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[18]  A. Zucker CURABILITY OF BREAST CANCER , 1975, The Lancet.

[19]  G. Lloyd,et al.  MANAGING LASSA FEVER , 1984, The Lancet.

[20]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[21]  C. Helmick,et al.  NO EVIDENCE FOR INCREASED RISK OF LASSA FEVER INFECTION IN HOSPITAL STAFF , 1986, The Lancet.

[22]  E. Fichet-Calvet Lassa Fever: A rodent-human interaction , 2014 .

[23]  J. Chang-Claude,et al.  Hunting of peridomestic rodents and consumption of their meat as possible risk factors for rodent-to-human transmission of Lassa virus in the Republic of Guinea. , 1996, The American journal of tropical medicine and hygiene.

[24]  J. Desenclos,et al.  RAISIN - a national programme for early warning, investigation and surveillance of healthcare-associated infection in France. , 2009, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[25]  S. Günther,et al.  Imported Lassa fever in Germany: surveillance and management of contact persons. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[26]  J. Rose An outbreak of encephalomyelitis in Sierra Leone. , 1957, Lancet.

[27]  S. Günther,et al.  Seroepidemiological study reveals regional co‐occurrence of Lassa‐ and Hantavirus antibodies in Upper Guinea, West Africa , 2012, Tropical medicine & international health : TM & IH.

[28]  A. Anusz [Lassa fever]. , 1981, Pielegniarka i polozna.

[29]  B. Henderson,et al.  Lassa fever. Epidemiological aspects of the 1970 epidemic, Jos, Nigeria. , 1972, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[30]  W. Ian Lipkin,et al.  Genetic Detection and Characterization of Lujo Virus, a New Hemorrhagic Fever–Associated Arenavirus from Southern Africa , 2009, PLoS pathogens.

[31]  J. Sagripanti,et al.  Persistence in darkness of virulent alphaviruses, Ebola virus, and Lassa virus deposited on solid surfaces , 2010, Archives of Virology.

[32]  M. Leach Rainforest relations: Gender and resource use among the Mende of Gola, Sierra Leone , 1994 .

[33]  M. Wolfe,et al.  Historical Lassa Fever Reports and 30-year Clinical Update , 2006, Emerging infectious diseases.

[34]  T. Brooks,et al.  A fatal case of Lassa fever in London, January 2009. , 2009, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[35]  P. Chiodini,et al.  Early risk assessment for viral haemorrhagic fever: experience at the Hospital for Tropical Diseases, London, UK. , 2007, The Journal of infection.

[36]  E. Stephenson,et al.  Effect of environmental factors on aerosol‐induced lassa virus infection , 1984, Journal of medical virology.

[37]  J. Hand,et al.  The first case of Lassa fever imported from Mali to the United Kingdom, February 2009. , 2009, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[38]  C. Fraser,et al.  Transmission Dynamics of the Etiological Agent of SARS in Hong Kong: Impact of Public Health Interventions , 2003, Science.

[39]  E. Tkachenko,et al.  [Clinico-epidemiologic and laboratory research on hemorrhagic fevers in Guinea]. , 1987, Bulletin de la Societe de pathologie exotique et de ses filiales.

[40]  P. E. Kopp,et al.  Superspreading and the effect of individual variation on disease emergence , 2005, Nature.

[41]  R. Cline-Cole Rainforest Relations, Gender and Resource Use among the Mende of Gola, Sierra Leone , 1996 .

[42]  N. Gay,et al.  Interpretation of serological surveillance data for measles using mathematical models: implications for vaccine strategy , 1995, Epidemiology and Infection.

[43]  S. Fisher-Hoch Lessons from nosocomial viral haemorrhagic fever outbreaks. , 2005, British medical bulletin.

[44]  J. Wallinga,et al.  Different Epidemic Curves for Severe Acute Respiratory Syndrome Reveal Similar Impacts of Control Measures , 2004, American journal of epidemiology.

[45]  R. Stein Super-spreaders in infectious diseases , 2011, International Journal of Infectious Diseases.

[46]  J. Frame,et al.  Lassa fever, a new virus disease of man from West Africa. I. Clinical description and pathological findings. , 1970, The American journal of tropical medicine and hygiene.

[47]  M. Oldstone The epidemiology, molecular and cell biology of arenaviruses , 2002 .

[48]  E. S. Smith,et al.  A prospective study of the epidemiology and ecology of Lassa fever. , 1987, The Journal of infectious diseases.

[49]  T. Monath,et al.  Lassa fever: review of epidemiology and epizootiology. , 1975, Bulletin of the World Health Organization.

[50]  P. Ebhodaghe,et al.  Assessment of knowledge and attitude towards Lassa fever among Primary care providers in an endemic suburban community of Edo state: implications for control , 2013 .

[51]  Stuart T. Nichol,et al.  Genetic Diversity among Lassa Virus Strains , 2000, Journal of Virology.

[52]  Rosamund F. Lewis,et al.  Prevalence and Risk Factors of Lassa Seropositivity in Inhabitants of the Forest Region of Guinea: A Cross-Sectional Study , 2009, PLoS neglected tropical diseases.

[53]  S. Kline,et al.  Outbreak of tuberculosis among regular patrons of a neighborhood bar. , 1995, The New England journal of medicine.

[54]  J. Robins,et al.  Transmission Dynamics and Control of Severe Acute Respiratory Syndrome , 2003, Science.

[55]  T. Monath Lassa fever: review of epidemiology and epizootiology. , 1975, Bulletin of the World Health Organization.

[56]  J. McCormick,et al.  SAFE INTENSIVE-CARE MANAGEMENT OF A SEVERE CASE OF LASSA FEVER WITH SIMPLE BARRIER NURSING TECHNIQUES , 1985, The Lancet.

[57]  M. Leach,et al.  The social and political lives of zoonotic disease models: narratives, science and policy. , 2013, Social science & medicine.

[58]  N. Beeching,et al.  Travellers and viral haemorrhagic fevers: what are the risks? , 2010, International journal of antimicrobial agents.