In tropical and subtropical regions of the world, mosquito born illnesses pose a serious threat to public health. Over half the world’s population lives in areas where disease carrying mosquito species are present and the number of cases of dengue, malaria and yellow fever are increasing each year. Mild infections can often go undiagnosed and may appear to have little lasting impact; however, recent research reveals how sequential and co-infection with mosquito born viruses can alter the nature of these diseases, making them even more deadly and furthering their ability to spread and infect already vulnerable populations.

Zika virus, named after the Zika Forest in Uganda where it was first discovered in 1947, has quickly become one of the most feared emerging mosquito-borne pathogens of the 21st century. While cases and minor outbreaks across Africa and Asia occurred throughout the end of the 20th century, the disease finally made its way to the Americas in 2013, when an outbreak occurred in Brazil. By 2016 the World Health Organization (WHO) announced zika as a public health emergency, following the birth of a large number of infants with microcephaly by women infected with the virus in Brazil.

Microcephaly is a condition in characterized by smaller than average head size due to improper brain development. Zika related microcephaly along with a distinct pattern of other birth defects has been termed congenital Zika syndrome, and babies born under these devastating circumstances face serious health challenges and, in some cases, the irrevocable nerve damage can lead to death. The virus is able to gain access to the fetus by infecting placental cells, disrupting a barrier that normally prevents viral and bacterial infections from being transmitted vertically from a mother to a child. Studies have indicated that the inflammatory immune response of the fetus to infection may be responsible for brain and developmental defects, but it is still largely unclear exactly how the pathogen causes congenital Zika syndrome [i].

Zika is transmitted by mosquitoes of the Aedes genus. Adults who are infected may have mild symptoms or none at all which makes it an especially difficult disease to monitor. The lack of effective disease monitoring prior to larger, more recent outbreaks along with the common misdiagnosis of Zika as other tropical illnesses has left health and governmental organizations with minimal information regarding both short and long term effects of infection with Zika virus.

Chikungunya virus is closely related to Zika virus. It is spread by the same mosquitoes, has a similar set of symptoms and has a large overlap in global distribution. The first case of Chikungunya documented in the Americas occurred in the Caribbean in 2013, around the same time as the first reported case of Zika hit Brazil. Symptoms of infection include fever and joint pain, usually lasting no longer than a week, and infection rarely leads to death. Due to the relatively mild nature of the disease, chikungunya is not usually considered as large of a threat as Zika or Dengue viruses.

In 2017 it was discovered that mosquitoes can become infected with and transmit both Zika virus and Chikungunya virus simultaneously[ii] and researchers became interested in the dynamics of the interactions between these two “sister viruses” in the mosquito host.

Co-infection, or infection with two pathogens at one time, can generally have two outcomes. The immune system of the infected person may be enhanced or “shifted into high gear” by an initial infection and thus reduce the likelihood of secondary infection. Alternatively, immune system may become suppressed or “overwhelmed” by the subsequent infection, resulting in enhancement of one or both infections.

While it was clear that mosquitoes could be simultaneously infected with the two viruses, researchers from Colorado State University[iii] wondered how sequential infection, that is, infection with one virus followed, after a delay, by another, would change the diseases dynamics and effect how mosquitoes were able to transmit the disease.

They fed mosquitoes with either blood containing Chikungunya or Zika virus, followed by a seven-day delay after which they were fed blood containing the alternative virus. After allowing time for a secondary infection to become detectable, mosquitoes were analyzed to determine the presence of an infection with Chikungunya and/or Zika as well as the severity of their infection.

They determined that infection with Chikungunya or Zika virus in no way prevented secondary infection with the other virus. Their study also showed that mosquitoes that were infected with Chikungunya first actually had a higher rate of getting secondarily infected with Zika and had a higher viral load, an indicator of the severity of the infection. These results demonstrated that co-infection with Chikungunya both enhanced transmission of and infection with Zika virus.

As Zika and Chikungunya viruses have a large amount of overlap in regions of historical and projected transmission, these findings demonstrate the need for better outbreak monitoring and accurate diagnosis of tropical diseases to ascertain at risk populations and ensure that co-infection is prevented.

Additionally, recent climatic changes have altered the range of Aedes mosquitoes and are projected to facilitate the spread of all Aedes born viruses to regions that were previously more temperate. Areas of the United States and South America that were previously unaffected may see some of their first cases in the coming years. New understanding regarding the associations between secondary infection and levels of transmission and infection makes the potential spread of both of these diseases to new, susceptible populations all the more alarming.

As of now there is no vaccine for either Zika or Chikungunya Virus, although extensive work has been conducted following outbreaks in the early 2000s to develop a Zika vaccine that might protect susceptible individuals, especially pregnant women.  The ability of Chikungunya infection to potentially facilitate the spread of zika virus, known to produce devastating deformations in newborns, is yet another piece of information revealing the urgent need for information and answers about the complex nature of tropical diseases.

References

[i] Wen, Zhexing, Hongjun Song, and Guo-li Ming. “How Does Zika Virus Cause Microcephaly?” Genes & Development 31, no. 9 (May 1, 2017): 849–61. https://doi.org/10.1101/gad.298216.117.

[ii] Göertz, Giel P., Chantal B. F. Vogels, Corinne Geertsema, Constantianus J. M. Koenraadt, and Gorben P. Pijlman. “Mosquito Co-Infection with Zika and Chikungunya Virus Allows Simultaneous Transmission without Affecting Vector Competence of Aedes Aegypti.” PLOS Neglected Tropical Diseases 11, no. 6 (June 1, 2017): e0005654. https://doi.org/10.1371/journal.pntd.0005654.

[iii] Magalhaes, Tereza, Alexis Robison, Michael C. Young, William C. Black, Brian D. Foy, Gregory D. Ebel, and Claudia Rückert. “Sequential Infection of Aedes Aegypti Mosquitoes with Chikungunya Virus and Zika Virus Enhances Early Zika Virus Transmission.” Insects 9, no. 4 (December 2018): 177. https://doi.org/10.3390/insects9040177.

Madeline Standen (‘19) is senior completing a BS in Animal Behavior and a minor in Dance. 

At Bucknell, Madi works as a TA for the biology department and is a member of the Bucknell Dance Company and Alpha Delta Pi sorority. This semester she is assisting a faculty member in the animal behavior department with a study attempting to assess the effects that working with live animals have on students' learning and motivation. 

During the summer of 2017, Madi acted as a research assistant of behavioral ecology at the Rocky Mountain Biological Laboratory, studying yellow bellied marmots and their evolution of alarm calling and social variation, anti predator behavior, and response to alpine climate change. In the spring semester of her junior year, she studied ecology and evolution at the University of San Fransisco de Quito, spending one month in Quito, Ecuador followed by three months in the Galapagos Islands. 

Madi is passionate about conservation and after graduation she hopes to hopes to use her degree to pursue a career in environmental education or public health.