THE AUTOIMMUNE CONNECTION BLOG
August 27, 2016
As mosquito-borne Zika virus continues to spread in southern Florida and threaten other Gulf Coast states, its connections with autoimmunity are cause for concern.
In addition to causing birth defects and severe brain damage (microcephaly) in hundreds of babies born to Zika-infected women,1 the virus is also being blamed for an increase in cases of a rare autoimmune neurological disorder called Guillain-Barré syndrome (GBS).2
Viral infections have long been suspected as a potential cause of autoimmune diseases, notably Epstein Barr virus (EBV). Infections are also a frequent trigger for Guillain-Barré, which affects peripheral and sensory nerves, causing difficulty walking and temporary paralysis. The mechanism is thought to be “molecular mimicry,” in which the structure or proteins of a virus are similar to normal cells in the body, so the immune system not only attacks the virus, but also the healthy tissue.3
So far, 18 countries report an increased incidence of GBS associated with Zika, according to the World Health Organization.4 At least seven cases of Zika-associated GBS have been reported in the U.S.5 and 30 in Puerto Rico, one of them fatal. A public health emergency has been declared in Puerto Rico, with almost 11,000 cases of locally-acquired Zika, including more than 1,000 pregnant women.6
Researchers say a second rare, autoimmune neurological disorder -- acute disseminated encephalomyelitis (ADEM) -- may also be linked to Zika. ADEM, like multiple sclerosis, results from an autoimmune attack on the protective myelin coating on nerve cells in the brain and spinal cord.7
Zika has also been associated with cases of immune thrombocytopenia purpura (ITP), an autoimmune disease which causes destruction of platelets.8 Platelets help blood to clot and if too many are destroyed there’s a risk of serious hemorrhage. One death was reported in Puerto Rico from severe thrombocytopenia in an elderly man with a confirmed Zika infection.8
Systemic treatments for chronic autoimmune disease, especially biologic drugs, suppress an over-active immune system and carry a potential risk of serious infections, including tuberculosis. Just having an autoimmune disease puts you at risk of developing another.
So far, however, autoimmune patients don’t appear to be at particular risk from Zika, stresses Tyler M. Sharp, PhD, an epidemiologist with the Centers for Disease Control and Prevention (CDC) and co-author of a recent report on ITP and Zika.
“To date, there has not been a link established between having a history of autoimmune disease and developing either Guillain-Barré syndrome or immune thrombocytopenia purpura following Zika virus infection,” emphasizes Dr. Sharp. Still, he adds, “patients with pre-existing autoimmune disease should consult their physician before traveling to an area with ongoing Zika virus transmission.”
People Can Spread Zika, Too
Zika is an arbovirus similar to Dengue and yellow fever, carried by two types of mosquitoes -- Aedes aegypti found in southern and tropical climates and the more common Aedes albopictus mosquito, found in much of the U.S. But in the current Zika outbreak, human beings become unwitting disease carriers.
It's a dangerous cycle: A Zika-carrying mosquito bites and infects a human -- another mosquito bites that person and acquires Zika virus through a blood meal -- then that mosquito buzzes off to infect someone else.9 Since the virus doesn’t always cause symptoms, people may not even know they’ve been infected and the A. aegypti mosquito often bites multiple people in a single blood meal. That’s one reason Zika can spread quickly.9
Zika can also be transmitted sexually through semen and other body fluids, even before someone has symptoms of an infection -- and long after symptoms end.10 According to the CDC, Zika can remain in semen longer than in other body fluids (including vaginal fluids, urine, and blood). So safe sex, the use of condoms and other barrier methods, is highly advised in Zika-affected areas.11
Given the risks of sexual transmission, the Food and Drug Administration (FDA) is now calling for all donated blood in the U.S. to be tested for Zika.12
The Virus-Autoimmunity Connection
Zika isn’t the first mosquito-borne virus with an autoimmune connection.
Chikungunya virus and Dengue fever, arboviruses spread by the same mosquitoes as Zika, can cause joint pain and mimic other symptoms of rheumatoid arthritis (RA). Some people infected with Chikungunya have developed an inflammatory arthritis that can persist for months to years.13 A recent epidemic of Chikungunya in the Caribbean was associated with post-infection rheumatic and musculoskeletal disorders, including RA.14
While it’s possible that people with autoimmune diseases who become infected with Zika could develop GBS, the actual risks are unknown.
Also unknown: if Zika could pose a risk in people with suspected autoimmunity who haven’t been formally diagnosed. One recent study suggests that people with primary chronic ITP may be at an increased risk for infections up to 5 years before they are actually diagnosed.15
If people with an autoimmune condition -- or otherwise healthy individuals, for that matter -- have been in an area with ongoing Zika transmission and are pregnant or develop an illness consistent with Zika virus (fever, rash, joint pain, or conjunctivitis/red eyes) within a couple weeks after traveling, they should be evaluated by a clinician to determine if they should be tested for Zika, advises the CDC’s Dr. Sharp.
If you have an autoimmune disease and live in a Zika-zone (such as Miami-Dade County in Florida) or plan travel to such areas, “employ approaches to avoid mosquito bites, such as regular use of mosquito repellent, staying in areas that are air conditioned and/or have intact window screens, and wearing long sleeves and pants,” Dr. Sharp recommended in an email.
Right now, aerial spraying, removal of standing water and use of larvicides in affected areas are the best public health defense against mosquitos. While preliminary results from an early-phase clinical trial of a potential Zika vaccine are expected by the end of 2016, it could take several years for a vaccine to be approved by the FDA and enter the marketplace.16
Note: Read more about molecular mimicry and other suspected viral triggers of autoimmunity in "The Autoimmune Connection."
1 Centers for Disease Control and Prevention (CDC), Outcomes of Pregnancies with Laboratory Evidence of Possible Zika Virus Infection in the United States, 2016. http://www.cdc.gov/zika/geo/pregnancy-outcomes.html. Retrieved August 24, 2016.
2 Cao-Lormeau VM, Blake A, Mons S, et al., Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. Lancet 2016;387:1531–39. http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)00562-6.pdf. Retrieved August 24, 2016.
3 Anaya JM, Ramirez-Santana C, Salgado-Castaneda I, et al., Zika virus and neurologic autoimmunity: the putative role of gangliosides, BMC Medicine2016;14:49. DOI: 10.1186/s12916-016-0601-y. https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0601-y. Accessed August 25, 2016.
4 WHO Situation Report, Zika Virus Microcephaly and Guillain-Barré Syndrome, August 25, 2016. http://www.who.int/emergencies/zika-virus/situation-report/25-august-2016/en/ Retrieved August 24, 2016.
5 CDC, Zika Virus Case Counts in the US. http://www.cdc.gov/zika/geo/united-states.html . Zika Virus and Guillain-Barré Syndrome. http://www.cdc.gov/zika/healtheffects/gbs-qa.html. Retrieved August 24, 2016.
6 HHS declares a public health emergency in Puerto Rico in response to Zika outbreak. Health & Human Services (HHS) Press release, August 12, 2016. https://www.hhs.gov/about/news/2016/08/12/hhs-declares-public-health-emergency-in-puerto-rico-in-response-to-zika-outbreak.html. Retrieved August 24, 2016.
7 Zika Virus May Now Be Tied to Another Brain Disease, American Academy of Neurology Press Release, April 10, 2016. Abstract Title: Neurologic Manifestations of Arboviruses in the Epidemic in Pernambuco, Brazil. Author: Brito Ferreira ML. https://www.aan.com/PressRoom/home/GetDigitalAsset/12051. Accessed August 27, 2016.
8 Sharp TM, Muñoz-Jordán J, Perez-Padilla J, et al., Zika Virus Infection Associated with Severe Thrombocytopenia. Clin Infect Dis. (2016) doi: 10.1093/cid/ciw476. First published online: July 14, 2016.
9 Peterson LR, Jamieson DJ, Powers AM, Honein MA. Review Article: Zika Virus. N Engl J Med 2016;374:1552-63. DOI: 10.1056/NEJMra1602113.
10 CDC. Zika and Sexual Transmission. http://www.cdc.gov/zika/transmission/sexual-transmission.html. Retrieved August 25, 2016.
11 Brooks JT, MD1; Friedman A, Kachur RE, et al., Update: Interim Guidance for Prevention of Sexual Transmission of Zika Virus — United States, July 2016. MMWR, July 29, 2016;65(29):745-747.
12 FDA advises testing for Zika virus in all donated blood and blood components in the US. FDA News Release, August 26, 2016. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm518218.htm Retrieved August 26, 2016.
13 Miner JJ, Aw-Yeang HX, Fox JM et al., Brief Report: Chikungunya viral arthritis in the United States: A mimic of seronegative rheumatoid arthritis. Arthritis Rheumatol. 2015; 67(5): 1214–1220. doi:10.1002/art.39027.
14 Foissac M, Javelle E, Ray S, Guérin B, Simon F. Post-chikungunya rheumatoid arthritis, Saint Martin [letter]. Emerg Infect Dis. 2015 Mar. http://dx.doi.org/10.3201/eid2103.141397.
15 Ekstrand C, Linder M, Cherif H, et al. Patients with chronic ITP may have increased infection risk before diagnosis. J Thromb Haemost. 2016;14(4):807-814. doi:10.1111/jth.13267.
16 Safety and Immunogenicity of a Zika Virus DNA Vaccine, VRC-ZKADNA085-00-VP, in Healthy Adults. https://clinicaltrials.gov/ct2/show/NCT02840487 Retrieved August 24, 2016.