Thursday, June 23, 2016

The Origin(s) of Outbreaks

Fig.1. Color print of Aedes aegypti mosquito
Credit: Emil August Goeldi, 1905

On Monday, the Democratic Republic of the Congo (DRC) declared a yellow fever epidemic in three provinces, including the heavily populated capital of Kinshasa. The current outbreak has killed more than 300 people in Angola and depleted the world’s vaccine stockpile to protect people in Angola, DRC, and Uganda. Although the outbreak is largely confined to central Africa, scientists worry about its potential spread to Asia, where 2 billion people live in areas infested with the disease’s vector, the Aedes aegypti mosquito.

Public health officials do not yet know which factors led to this event becoming the deadliest yellow fever outbreak since 1971. Whether the virus became more virulent or it came in contact with new populations, the question of why now sits at the heart of every outbreak. To answer this question, scientists are teasing apart the genetic and environmental factors that make a disease tick. 

Fig.2. 3D representation of Zika virus (Credit: Malmriv, 2016)

A Modern Disease

A recent article in Scientific American highlighted ongoing research at the University of Texas Medical Branch in Galveston. The university holds the world’s largest collection of Zika virus, and scientists there are part of an international effort to combat the disease. Scott Weaver, the director of the university’s Institute for Human Infections and Immunity, worked with a team of researchers to isolate the cause of the Zika outbreak. 

The Galveston group examined three Zika strains - also spread by A. aegypti - and measured how fast the virus traveled from mosquitos’ guts to their saliva. This speed was used to determine how transmissible and virulent particular types of the virus were. Of the three strains - Senegal (1984), Cambodia (2010), and Mexico (2015) - the newest one did not appear to pass through the vector as quickly or be more easily transmissible than prior strains.

These results are only a small part of the work being done to understand the virus, but they point to a worrisome reason behind the outbreak. If genetic changes did not make the virus more virulent, perhaps the disease’s spread is due to new environmental conditions such as temperature or precipitation; even a new host population can affect an outbreak. Increased precipitation may cause a boom in animal populations, increasing spillover of disease to humans. If those human populations have never encountered this disease or are unvaccinated, the risk or spread of an outbreak magnifies.

Fig.3. Great Plague of London in 1665 (Public Domain)

A Medieval Disease

When scientists study an ongoing outbreak, returning to the past can help show how a simple illness could explode into an epidemic. One example was published last year in Nature Communications, in which researchers at the Northwestern University's Feinberg School of Medicine used ancestral strains of Yersinia pestis to determine what made it so dangerous. Y. pestis bacteria is the famous pathogen responsible for the Black Death and other plague epidemics.

By examining the bacteria in mice, the researchers found that ancestral strains of Y. pestis could colonize the lungs but failed to cause the deadly pneumonic plague. Only a slight change in the genome - the addition of a surface protein Pla, to be precise - allowed the ancestral strain to bring about a fatal lung infection. 

In comparing the modern strains, the researchers found that a single modification to this gene allowed the bacteria to go beyond the lungs and infect the lymph nodes. From colonization to a respiratory disease to the bubonic plague, small genetic changes created one of the deadliest diseases in human history. 

Fig.4. CDC researchers examining rats during a Lassa fever outbreak in 1993
Credit: Mike Blyth, 1993

Predicting and Preparing for the Future

In a recent study published in the journal Methods in Ecology and Evolution, the number of cases of Lassa fever in Africa may double by 2070. This dangerous disease is a viral hemorrhagic illness, similar to Ebola, and is spread by rats. Currently the virus affects between 100,000 and 1 million people per year in western sub-Saharan Africa. With climate change, however, the researchers predict an increase in rat populations and spillover events. Whether vector populations increase in range or size, or human activities bring individuals closer to disease-carrying animals, environmental factors change the physical landscape of a disease.

These studies reveal important details about infectious diseases and remind us that outbreaks rarely fit into a simple “nature versus nurture” paradigm. Pathogens may constantly mutate, and environmental factors are always at play. Climate change, habitat loss, and even a shifting behavior of animal hosts affect how a disease spreads.

The HIV/AIDS pandemic has been called a “perfect storm” of factors, which combined a mutated and virulent pathogen with urban growth, unsanitary conditions, and a heavily used railway. Oftentimes, epidemics occur due to a similar mix of factors, and even then, defining which are genetic versus which are environmental can be difficult. Nevertheless, understanding the molecular and ecological mechanisms behind each one is vital to help predict - and ultimately prepare for - future outbreaks.

Maron, D. F. (2016, May 24). How Zika Spiraled Out of Control. Scientific American. Retrieved from:

McKenna, M. (2016, May 26). Africa’s Yellow Fever Outbreak is a Glimpse of Our Connected Future. National Geographic. Retrieved from:

Redding, D. W., Moses, L. M., Cunningham, A. A., Wood, J., & Jones, K. E. Environmental-mechanistic modelling of the impact of global change on human zoonotic disease emergence: a case study of Lassa fever. Methods in Ecology and Evolution, vol. 7 (5): 646-655. Doi: 10.1111/2041-210X.12549

Wasserman, S., Tambyah, P. A., & Lim, P. L. (2016, July). Yellow fever cases in Asia: primed for an epidemic. International Journal of Infectious Diseases, vol. 48: 98-103. Doi: 10.1016/j.ijid.2016.04.025

Zimbler, D. L., Schroeder, J. A., Eddy, J., L., & Lathem, W. W. (2015, June 30). Early emergence of Yersinia pestis as a severe respiratory pathogen. Nature Communications, vol. 6 (7487). Doi:10.1038/ncomms8487


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