From Suspect to Host: Dynamics of Emerging Infectious Diseases

Part II of the Signal to Noise Infectious Disease Primer

In Part I of this series we introduced viruses, bacteria, fungi and parasites as the major pathogens of infectious diseases. Part II explores how these diseases emerge and reviews the complex interplay of factors influencing disease spread.

 

This article is part of our Infectious Disease theme! Click here to read more about infectious disease.

 

Emerging infectious diseases (EIDs), defined as diseases that show an increased frequency of appearance in humans, present an important risk to global health [1, 2]. There are multiple ways for a disease to become emergent. A pathogen can travel and infect people in a new geographical area. Alternatively, if a pathogen evolves new traits, such as resistance to drug treatments or the ability to more efficiently infect a new host species, the frequency of infectious incidence may increase in the same geographical location [3]. Evolution of such traits often results in animal-to-human transmission. Zika virus is an example of a traveling pathogen, as it traveled from the Zika Forest of Uganda, Africa, to Brazil, South America [4], whereas bird flu (avian influenza A H5N1) evolved from a less harmful strain naturally circulating in domestic poultry [5].

 

More than 60% of EIDs are caused by infectious disease of animals that can readily be transmitted to humans [1]. These diseases, called zoonoses, usually derive from wildlife sources rather than domesticated animals [1]. A familiar example of a zoonotic disease is the Ebola virus, which derived from bats [6]. Often the animals infected with the pathogen do not get the disease, or it is asymptomatic and non-lethal. These animal carriers are long-term hosts, or natural reservoirs: they maintain the pool of pathogen.

 

Scientists often categorize zoonotic diseases based on their route of transmission, type of pathogen, or degree of person-to-person transmissibility [5]. Understanding how the virus enters the human host is often a first crucial piece of information when we attempt to stop disease spread. Direct contact between reservoirs and humans has been shown to cause disease, as seen in 2009 during the H1N1 swine-flu epidemic [1]. Pathogens can also find alternative routes from natural reservoirs to the human host. Foodborne pathogens such as Salmonella travel via food. Vector-borne pathogens such as Plasmodium (the parasite that causes malaria) are introduced by animal or parasitic carriers called vectors, such as mosquitos [5].

 

Vector-borne diseases often take center stage in the international spread of pathogens. Travel and commerce are two of the main drivers of pathogen introduction to new locations. Shipping during the 17th to 19th centuries transported larvae of several important mosquito species around the world including Aedes (Stegomyia) aegypti, which has extensively colonized and spread in tropical regions and is a vector for dengue virus, zika virus, yellow fever, and others [7-10]. In the 20th century this problem was further compounded with the addition of Aedes (Stegomyia) albopictus that spread from its home of the tropical forests of Southeast Asia to 26 countries in Africa, Europe and the Americas and is a carrier of chikungunya virus, and West Nile virus, as well as other pathogens [7-10].

 

Major studies have confirmed the long-standing hypothesis that changes in human activities and  difficult socioeconomic conditions are all significantly correlated with outbreak events, and that regions provide “hotspots” of where new EIDs are most likely to originate [1]. Activities such as expansions into new habitats for dwelling or resource exploitation, or reforestation of previously agricultural areas can escalate the frequency of human interaction with infected vectors, increasing the risk of human infection [3, 11]. For example, there is a higher incidence of dengue fever on the Mexican side of the Mexico-Texas border where open windows compensate for the absence of air-conditioning, exposing more people to mosquitos [12]. Another example is Lyme disease, which appears to be more prevalent in people with high income as a result of more outdoor recreational opportunities that expose them to disease-carrying ticks [13]. On the other hand, destitution and population displacement due to civil conflicts or natural disasters can lead to increases in human-vector contacts [14]. In 2009 vector-borne encephalitis spread by ticks experienced an upsurge in three former eastern European countries following their collapse, a scenario amplified by high rates of poverty and people harvesting food from forests for subsistence [15].

 

EIDs disproportionally impact impoverished nations (e.g. West Africa during the Ebola outbreak) and industrialized nations with large populations experiencing class disparities, such as Brazil during the Zika virus outbreak. Economic duress restricts the potential for ameliorative actions, limiting vaccine programs or vector suppression efforts. Furthermore, EIDs can have long-term economic impacts as they can perpetuate poverty by compromising maternal and child health as well as productivity and labor. Political instability affects large populations and can have a sudden upsurge of disease incidence, as is the case in Syria and Pakistan as poliomyelitis is remerging due to a loss of vaccine efforts [3, 16]. Coupled to this problem are large-scale human migrations due to civil strife, introducing immunologically naïve populations to new pathogens and thus disease spread and containment is a major concern to world health organizations [3].

 

Conversely, human activities not only impact the frequency of interaction with natural reservoirs or disease vectors, they can also directly impact the pathogen itself [1, 6]. Environmental changes due to growing human populations, alternative land use, and relocation of vectors exerts pressure on pathogens to adapt and take advantage of new environments [3]. Both the West Nile virus and chikungunya virus adapted after being introduced to a new location and became more easily transmissible by the native mosquito species [17, 18]. Furthermore, it appears that vector-borne pathogens transmit less efficiently if their vector feeds on multiple host species, not all of which can be infected by the pathogen. Therefore, there is a tremendous driving force on pathogens of zoonotic disease to evolve traits which allow them to be efficiently spread by vectors that exclusively target humans [19].

 

Surveillance and reporting of disease incidence at global hotspots is, most scientists agree, our first line of defense against novel infectious diseases. In the post-SARS era, there has been a rapid increase in nation co-operation and an explosion of understanding of EIDs in human hosts as well as natural reservoirs. Under the International Health Regulations law, studies also survey the human and wildlife interface, improving our knowledge of disease transmission [20]. Furthermore, work sponsored by the United States Agency for International Development (USAID) explores disease emergence at the animal interface as part of the PREDICT program that tries to identify risks before they reach the human population. It remains a challenging task, however, to completely counter disease emergence and spread. We will explore these challenges in Part III of this series [20, 21].

 

Nisar Farhat
Co-Founder and CFO, Signal to Noise Magazine
PhD Candidate, Molecular and Medical Pharmacology, UCLA

 

References

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[2] International Livestock Research Institute. Mapping of poverty and likely zoonoses hotspots. Zoonoses Project 4. Report to Department for International Development, UK. Nairobi, Kenya: International Livestock Research Institute, 2012.

[3] Randolph, S. E, Kilpatrick, A.M. “Drivers, dynamics, and control of emerging vector-borne zoonotic diseases. Lancet 380, 1946-1955, (2012).

[4] Sikka, V., Chattu, V.K., Popli, R.J., Galwankar, S.C., Kelkar, D., Sawicki, S.G., Stawicki, S.P., Papadimos, T.J. “The emergence of zika virus as a global health security threat: A review and a consensus statement of the INDUSEM Joint working (JWG)” Journal of Global Infectious Disease 8, 3-15, (2016).

[5] Karesh, W.B., Dobson, A., Lloyd-Smith, J.O., Lubroth, J., Dixon, M.A., Bennet, M., Aldrich, S., Harrington, T., Formenty, P., Loh, E.H., Machalaba, C.C., Thomas, M.J., Heymann, D.L. “Ecology of zoonoses: natural and unnatural histories” Lancet 380, 1936-1945, (2012).

[6] Smith, I., Wang, L.F. “Bats and their virome: an important source of emerging viruses capable of infecting humans.” Current Opinion in Virology 8, 84-91, (2013).

[7] Hotez, P.J., Neglected Tropical Diseases in the Anthropocene: The cases of Zika, Ebola, and Other Infections” PLOS Neglected Tropical Diseases 10, 1-6, (2016).

[8] Fonseca, D.M., Smith, J.L., Wilkerson, R.C., Fleischer, R.C. “Pathways of expansion and multiple introductions illustrated by large genetic differentiation among worldwide populations of the southern house mosquito.” Am J Trop Med Hyg 74, 284–89, (2006).

[9] Bryant, J.E., Holmes, E.C., Barrett, A.D.T. “Out of Africa: a molecular perspective on the introduction of yellow fever virus into the Americas.” PLoS Pathogens 3, 668–73, (2007).

[10] Farajollahi, A., Fonseca, D.M., Kramer, L.D., Kilpatrick, A.M. “Bird biting mosquitoes and human disease: a review of the role of Culex pipiens complex mosquitoes in epidemiology” Inf Gen Evol 11, 1577–85, (2011).

[11] Lambin, E.F., Tran, A., Vanwambeke, S.O., Linard, C., Soti, V. “Pathogenic landscapes: interactions between land, people, disease vectors,and their animal hosts.” Int J Health Geog 9, 54, (2010).

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[13] Linard C, Lamarque P, Heyman P, et al. Determinants of the geographic distribution of Puumala virus and Lyme borreliosis infections in Belgium. Int J Health Geog 6, 15, (2007).

[14] Randolph, S.E., on behalf of the EDEN-TBD team. “Human activities predominate in determining changing incidence of tick-borne zoonoses in Europe.” Euro Surveill 15, 24–31, (2010).

[15] Godfrey ER, Randolph SE. Economic downturn results in tick-borne disease upsurge. Paras Vec 4, e35, (2011).

[16] World Health Organization. “Poliomyelitis”. WHO. 2016.

[17] Davis CT, Ebel GD, Lanciotti RS, et al. Phylogenetic analysis of North American West Nile virus isolates, 2001–2004: evidence for the emergence of a dominant genotype. Virology 342, 252–65, (2005).

[18] de Lambellerie X, Leroy E, Charrel RN, Tsetsarkin KA, Higgs S, Gould EA. Chikungunya virus adapts to tiger mosquito via evolutionary convergence: a sign of things to come? Virol J 3, 33, (2008).

[19] Kilpatrick AM, Kramer LD, Jones MJ, Marra PP, Daszak P,Fonseca DM. Genetic influences on mosquito feeding behavior and the emergence of zoonotic pathogens. Am J Trop Med Hyg77, 667–71, (2007).

[20] Bogich TL, Chunara R, Scales D, et al. Preventing pandemics via international development: a systems approach. PLoS Med 9, (2012).

[21] United States Agency for International Development. “Emerging Pandemic Threats”. USAID. 2016. https://www.usaid.gov/news-information/fact-sheets/emerging-pandemic-threats-program