Possible New Virus Discovered In Kawasaki Research

“Kawasaki? I thought that was a motorcycle.” This was my mother’s response when I told her my topic for this week’s article. She is not alone in her unfamiliarity with a term that is more commonly found in racing magazines than scientific journals. Kawasaki Disease (KD) has mystified scientists since 1976, when it was first described as an unknown illness affecting young children, with no identifiable cause.  Even now, more than 30 years later, only a handful of researchers have dedicated their time to determining the etiology of KD.  

One of these researchers is Dr. Anne Rowley at the Northwestern Feinberg School of Medicine. In 2011, Dr. Rowley published an article in the Journal of Infectious Diseases, in which she unveils that her research may have identified a new virus as the agent behind KD.

In the past, clinical and epidemiological studies suggested that a microbial agent might be the cause of KD. Yet, data was always inconclusive on exactly what this agent is. In an interview with Scientific American, Dr. Rowley disclosed that a new, previously unknown virus might be responsible. “So we suspect that it would represent a new virus family and we think that that’s why it’s been so difficult to identify the causative agent,” Rowley said.

 

A combination of genetic and infectious factors

Rowley’s research studied the coronary arteries of children who died after being diagnosed with Kawasaki Disease. After isolating antibodies from immune cells and incubating them with tissues from the deceased children, her team discovered that the antibodies were bound to inclusion bodies in the respiratory tract. Inclusion bodies are abnormal structures in a cell nucleus or cytoplasm that often represent sites of viral reproduction. Similar inclusion bodies are made by respiratory pathogens, suggesting the possibility that KD is caused by a respiratory virus.

Further research under an electron microscope revealed that no bacteria were present. Instead, Rowley and her team of researchers found both rod and spherical shaped particles, which resemble viruses. However, since the particles’ characteristics are not fully compatible with any known viruses, it is possible that the team uncovered an entirely new family of viruses.

In an effort to learn more about KD, the viral genomics discovery group at Washington University in St. Louis is looking at the genetic factors associated with the disease. The group is trying to assemble the longest possible gene sequence from deceased KD patients. The group then hopes to test living children with KD to determine whether the sequence is prevalent within these patients as well. If so, a genetic link could be established.

 

Gone with the wind

To add to KD’s mysteriousness, researchers were never able to identify how the disease develops or spreads between patients. If an infectious agent is indeed the culprit, evidence suggests that it could be transmitted by wind.

Dr. Jane Burns, the director of the Kawasaki Research Center at the University of California, San Diego (UCSD), and a team of medical and climate scientists believe that the wind can carry the disease across oceans, from Japan to the United States. A study published in 2011 in Nature suggests that there is a causal relationship between an increase in KD cases and large-scale wind currents that begin in central Asia and cross the Pacific ocean. 

By investigating three major epidemics in Japan, and the year-to-year variability in Japan and San Diego, the researchers reveal a distinct pattern between fluctuations in the number of cases and fluctuations in wind circulation.

A similar study conducted by Burns analyzed Kawasaki disease incidence in Japan between 1987 and 2000. The detailed records allowed Burns and her colleagues to establish a seasonal trend within the country: cases peaked in the winter, early spring, and early summer. This implies that an environmental factor is involved.

Additional data is needed to fully support the hypothesis. However if it is correct, the Kawasaki disease agent will be the first human-disease pathogen to cross oceans by natural means. This information will likely spur scientists to look at other diseases that could be spread in this manner, such as influenza.

 

What is Kawasaki Disease?

Kawasaki Disease is a rare form of blood vessel inflammation, or vasculitis, that usually affects children under the age of five. People of all ethnic origins can develop KD, however it is most prevalent in children of Japanese and Korean descent. Capillaries, veins, and more significantly arteries, may all become inflamed. In patients who are left untreated, 20 to 25 percent develop inflammation of the coronary arteries. This may lead to thrombosis (formation of a blood clot within the blood vessel), segmental stenosis (dangerous narrowing of a blood vessel), and on rare occasions, rupture. The most common cause of death among KD patients is myocardial infarction, or heart attack.

Children with KD usually suffer from a very high fever for one to two weeks. Their eyes, tongue, and lips will be very red, as will the skin of their palms and soles. Children with KD often have very dry and cracked lips and a swollen tongue. A rash usually appears on the main trunk of the body and on the genitals. Children may also develop swollen lymph nodes in the neck and possibly in other parts of the body. Later symptoms will include peeling of the skin, often in large sheets, diarrhea, vomiting, and abdominal and joint pain.

The country with the highest incidence of Kawasaki Disease is Japan, where the average annual incidence is approximately 12,000 cases. The Kawasaki Disease Foundation estimates that approximately 4,200 patients per year are diagnosed with KD in the U.S. However, it is likely that this number is an underestimate, as the disease often goes undiagnosed in countries outside of Japan, that are not as well acquainted with the symptoms of the disease.

 

Treatment

Early treatment of KD is very effective in preventing blood vessel and heart damage. Often, children are treated with one or two doses of intravenous immunoglobulin (IVIG) to reduce inflammation of the blood vessels. Long-term aspirin therapy over a course of 2 to 3 months lowers the risk of developing blood clots. In more serious cases, anticoagulants may be prescribed. Although early treatment will improve fever and inflammation, it may take several weeks before the child has fully recovered.

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