Beyond Zika: 7 Things Rheumatologists Should Know About Chikungunya

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With the spread of Zika virus rating as a "public health emergency" by the World Health Organization, another emerging mosquito-borne illness is worrying rheumatologists: chikungunya.

With the spread of Zika virus rating as a "public health emergency" by the World Health Organization, another emerging mosquito-borne illness is worrying rheumatologists: chikungunya.

This disease, spread mainly through the bite of the Aedes aegypti mosquito, gets its name from a word in Africa's Makonde language that means "that which bends up." As that translation suggests, infection is marked by crippling joint pain, along with a high fever and, often, a rash. A painful arthritic condition may last for months or years after the acute infection.

Much like Zika, chikungunya has recently made an appearance in the western hemisphere - it was first detected on the Caribbean island of St. Martin in 2013. Over the course of the next year, the Pan American Health Organization reported 1.1 million suspected cases in the Americas. Since June 2014, public health researchers have confirmed 11 cases in Florida that had been transmitted within the United States, rather than imported by travelers to countries where the disease is known to be endemic.

Rheumatologists are on the front lines facing this rare but emerging illness. Here's what physicians need to know.  

1. What are the signs and symptoms of chickungunya? How long is the incubation period? [[{"type":"media","view_mode":"media_crop","fid":"45700","attributes":{"alt":"Leonard Calabrese, D.O. , Cleveland Clinic","class":"media-image media-image-right","id":"media_crop_3527540354989","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"5250","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"Leonard Calabrese, D.O., Cleveland Clinic","typeof":"foaf:Image"}}]]

Symptoms of chikunyunga develop within a week or two of experiencing a bite by a carrier mosquito, said Leonard Calabrese, D.O., the vice chair of rheumatic and immunologic diseases at the Cleveland Clinic. On average, the incubation type is short: A 2001 study in the journal Southeast Asian Journal of Tropical Medicine put the typical incubation time at two to four days during a 1998 outbreak in Malaysia.

The majority of infected patients will experience symptoms, according to the Centers for Disease Control and Prevention. Most commonly, these symptoms include a fever, a rash and joint pain. Data from the 1998 Malaysia epidemic and an outbreak on Réunion Island from 2005 to 2006 found that 78 percent to 100 percent of symptomatic patients experienced acute joint pain.  In both epidemics, more than half of patients also reported muscle pain.

Joint pain and stiffness can persist for days, weeks or months after the acute infection period. A small percentage of patients continue to have arthralgia, arthritis or both for years.

2. What is the difference between chikungunya and other mosquito-borne infections such as dengue and Zika?

These diseases share a carrier - mosquitos of the Aedes genus - but present differently. Zika infections are more likely to be asymptomatic than chikungunya, with 20 percent of those infected showing symptoms compared with more than 75 percent infected with the latter disease. Zika symptoms are usually milder than chikungunya symptoms.

Chikungunya "has an acute onset that is quite dramatic in most cases, with a fever and malaise and profound musculoskeletal aches and pains that make it difficult to move," Calabrese said.

Dengue fever also presents with symptoms of fever, severe pain and rash. A severe form of the disease, dengue hemorrhagic fever, can be fatal.

Serological testing exists for all three diseases (though the CDC and a few state health departments are the only labs that currently test for Zika). In chikungunya, IgM ELISA immunoflourescent assay can detect Immunoglobin M beginning within days of symptom onset up to three months later. Immoglobin G can be detected for years.

There have not yet been reports of long-term rheumatic complaints after previous Zika outbreaks, Calabrese told Rheumatology Network. One study of about 100 dengue fever patients in Cuba found that 30 percent reported ongoing muscle pain and 29 percent reported joint pain two years after their acute illness.

3. How did chikungunya reach the United States?

Two words: Mosquitos and travel.

Chikungunya was first recorded more than 50 years ago, when an outbreak hit Tanzania in 1952. The disease remained in southeast Asia, west and southern Africa and the Indian subcontinent until recently. In 2007, Europe reported the first cases of transmission within the continent  in northeastern Italy. A handful of within-country transmissions in France and Spain have since followed.

The strain of chikungyunga that arrived in the Caribbean in 2013 is an Asian genotype related to strains found in the Philippines, Indonesia and China, according to the European Center for Disease Prevention and Control. Travelers to and from the Caribbean subsequently brought the disease to the United States. The A. aegypti  mosquito can be found in Florida, south Texas, Arizona and other southern reaches of the United States, Calabrese said. Once the virus is present in the human population of these regions, mosquito-borne transmission can begin.

Humans have also spread potential vectors for chikungyunga infection. Chikungunya can also be carried by the Asian tiger mosquito (A. albopictus), which has been introduced to Europe and the Americans in tires and potted plants, according to 1995 research in the journal Parassitologia.

4. When should doctors consider chikungunya as a diagnosis?

For now, American physicians should focus on travel history in patients showing symptoms of chikungunya - usually a vacation to Mexico or the Caribbean, Calabrese said.

"Should it become endemic in the United States - and there have been a few cases in Florida that have been endemically spread - it will become a much more complex issue," he said.

Recent research suggests that chikungunya-related rheumatic disease can mimic seronegative rheumatoid arthritis. Both groups of patients have elevated activated and effector CD4+ and CD8+ T cells, researchers reported in May 2015 in the journal Arthritis & Rheumatology. It's important to consider chikungunya in patients with a relevant travel history, study researcher Wayne Yokoyama, M.D., of the Washington University School of Medicine said in a statement.

5. How common are long-term joint complications in chikungunya? How long do symptoms persist?

Arthralgia and arthritis affect between 73 percent and 80 percent of patients during the acute infection stage, according to a 2007 review in The Lancet Infectious Diseases. After 4 months, 33 percent patients report continuing joint involvement, a number that drops to 15 percent 20 months after the acute infection. About 10 percent of patients report joint complications lasting three to five years. 

6. What is the best way to treat chronic chikungunya-related joint disease?

There is no treatment for acute chikungunya infection other than rest, hydration and pain and fever-reducers.

"There is no antiviral therapy, there is no vaccine," Calabrese said. "Once the diagnosis is secure, a rheumatologist would be a likely person to manage these musculoskeletal symptoms."

For now, there are no significant reports on the safety and effectiveness of biologics in treating post-chikungunya rheumatic disorders, and only anecdotal use of hydroxychloroquine, he said.

"There is great controversy other than simple supportive measures such as steroidal anti-inflammatory drugs and analgesic," Calabrese said. Steroid options can have serious adverse effects, however, he noted, pointing to the well-known systemic side effects of these drugs.

7. How can people avoid chikungunya?

Avoiding chikungunya is as simple (and as difficult) as avoiding mosquito bites.

"When you have patients that ask you about this, and they're going on a Caribbean vacation, what do you tell them?" Calabrese said. "You tell them to take extraordinary precautions."

Aedes mosquitos bite during the day and frequent urban areas. The CDC recommends that travelers to Africa, Asia, the Caribbean and other chikungunya-endemic areas wear long sleeves, pants and hats and apply insect repellents containing DEET, Picaridin, oil of lemon eucalyptus or IR3535. Permethrin treatments on clothing and gear can also repel the biting insects. Sleep should be in a closed room or under a bed net.

 

References:

Lam SK, Chua KB, Hooi PS, et al. "Chikungunya infection-an emerging disease in Malaysia." Southeast Asian J Trop Med Public Health 2001; 32: 447–51.

Knudsen AB. "Global distribution and continuing spread of Aedes albopictus." Parassitologia 1995; 37: 91–97.

Garcia, Gonzalex, Perex, et al. "Long-term persistence of clinical symptoms in dengue-infected persons and its association with immunological disorders." Int Journ Infect Disease 2011; 15: e38-e43. doi:10.1016/j.ijid.2010.09.008

PIaloux G, Gauzere BA, Jaureguiberry S, Strobel M. "Chikungunya, an epidemic arbovirosis." Lancet Infect Dis. 2007 May; 7(5):319-27. DOI: http://dx.doi.org/10.1016/S1473-3099(07)70107-X

Miner, J. J., Aw Yeang, H. X., Fox, J. M., Taffner, S., Malkova, O. N., Oh, S. T., Kim, A. H. J., Diamond, M. S., Lenschow, D. J. and Yokoyama, W. M. (2015), "Brief Report: Chikungunya Viral Arthritis in the United States: A Mimic of Seronegative Rheumatoid Arthritis." Arthritis & Rheumatology, 67: 1214–1220. doi: 10.1002/art.39027

 

 

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