Estimating the contribution of human-to-human transmission to Lassa fever'

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Dynamic Drivers of Disease in AfricaIntegrating our understandings of zoonoses, ecosystems and wellbeing

Estimating the contribution of human-to-human transmission to Lassa feverGianni Lo Iacono, University of Cambridge

Background

False-colour transmission electron micrograph of the Lassa fever virus. Photo from Science Photo Library

Viral hemorrhagic fever caused by Arenavirus Lassa

Background

Mastomys Nataliensis. Photo from Lina Moses

Vector and reservoir: Mastomys Natalensis

Background

Map of the Mano River Union countries (Sierra Leone, Guinea, and Liberia). The approximate known endemic area for Lassa fever is shown by the dotted oval. From Khan et al (2008)

Endemic in West Africa

Background

Unclear routes of transmission (contaminated excreta, aerosol..)

Background

Unclear role of human-to-human transmission

Background

Unclear role of human-to-human transmission

Existing Data

Nosocomial Outbreak in Jos, NigeriaFrom Carey et al (1972)

Existing Data

Existing Data: Kenema Governament Hospital (KGH).

The Kenema Government Hospital Laboratory. From Khan et al. (2008)

Kenema Governament Hospital (KGH)Shaffer et al (2014)

Methods: How to disentangle the two contributions?

• First, we identified Lassa fever outbreaks known to be due to human-to-human chains of transmission (Jos situation)

• Then, we looked at people hospitalized with the disease in 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?

Methods: How to disentangle the two contributions?

Effective Reproductive Number for nosocomial cases

From www.cmaj.ca

Average Number of secondary cases arising from the primary case

Effective Reproductive Number for nosocomial cases

The relative likelihood that case i has been infected by case j proportional on the time of exposure (based on Wallinga & Teunis (2004))

Human-to-human transmission From Carey et al (1972)

Effective Reproductive number for nosocomial cases

Generation Time

Effective Reproductive number for data from KGH (Based on Wallinga & Teunis (2004) )

Super-spreading

An illustration of Typhoid Mary (Mary Mallon) that appeared in the New York American article of June 20, 1909.

Effective Reproductive number for nosocomial cases

Conclusions

• 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

• Reconciliation of two opposing paradigms

Acknowledgments

Andrew A. Cunningham 2, Elisabeth Fichet-Calvet 3, Robert F. Garry 4, Donald S. Grant 7, Sheik Humarr Khan 7, Melissa Leach 8, Lina M. Moses 4, John S. Schieffelin 10, Jeffrey G. Shaffer 11, Colleen Webb 12, James L. N. Wood 1

1 Department of Veterinary Medicine, Disease Dynamics Unit, University of Cambridge, Cambridge, United Kingdom.2 Institute of Zoology, Zoological Society of London. United Kingdom3 Bernhard-Nocht Institute of Tropical Medicine. Hamburg, Germany4 Department of Microbiology and Immunology, Tulane University, New Orleans, Louisiana, USA 5 Broad Institute, Cambridge, Massachusetts, USA7 Lassa Fever Program, Kenema Government Hospital, Kenema, Sierra Leone8 Institute of Development Studies, University of Sussex. Brighton, United Kingdom.10 Sections of Infectious Disease, Departments of Pediatrics and Internal Medicine, School of Medicine, Tulane University, New Orleans, LA, USA11 Department of Biostatistics and Bioinformatics, Tulane School of Public Health and Tropical Medicine, New Orleans, LA, USA12 Department of Biology, Colorado State University, Fort Collins, USA

This work for the Dynamic Drivers of Disease in Africa Consortium was funded with support from the Ecosystem Services for Poverty Alleviation (ESPA) programme. The ESPA programme is funded by the Department for International Development (DFID), the Economic and Social Research Council (ESRC) and the Natural Environment Research Council (NERC). See more at www.espa.ac.uk

In memoriam of Dr. Sheik Humarr Khan, who has recently died

from Ebola virus. Dr Khan was a leading doctor on the front

lines fighting the Ebola outbreak in Sierra Leone. Dr Khan was

called a "national hero" for his "tremendous sacrifice" in

working to save the lives of more than 100 infected patients

The ‘20-80’ rule

Existing Data: Kenema Governament Hospital (KGH).

Estimating the contribution of human-to-human transmission to Lassa fever'

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