This is the written version of our Hot Topic video presentation available at: MayoMedicalLaboratories.com/hot-topics Welcome to Mayo Medical Laboratories Hot Topics. These presentations provide short discussion of current topics and may be helpful to you in your practice. Today our topic is Chikungunya virus, an emerging arbovirus.

1

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

Our speaker for this program is Dr. Elli Theel, Director of the Infectious Disease Serology Laboratory at Mayo Clinic, Rochester, Minnesota. Dr. Theel, thank you for presenting today. Thank you for the introduction and also to the viewers for joining us today. For this Hot Topic, I will discuss both the clinical and diagnostic aspects of chikungunya virus, which as many of you are probably aware, is an emerging mosquito-borne arbovirus with the potential to spread into the United States.

2

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

Before we begin, I have no financial or other conflicts to disclose.

3

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

During this presentation, Ill briefly provide some background on chikungunya virus and discuss how the virus is transmitted, its current epidemiology, and the clinical manifestations following infection. Ill also discuss the available laboratory methods for diagnosis, treatment options, and finally, prevention strategies to avoid infection altogether.

4

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

5

Chikungunya virus is a single-stranded RNA alphavirus and a member of the Togaviridae family of viruses. Other notable vector-borne alphaviruses in the United States primarily includes Eastern equine encephalitis virus and also to a much lesser extent, Western equine encephalitis virus. Chikungunya virus was first isolated in Tanzania in 1952 but it wasnt until more recently, in 2004, that chikungunya virus spread throughout the larger portion of Africa and into India and Southeast Asia often causing large and sporadic epidemics in those regions. The name Chikungunya is derived from the language of the Makonde ethnic groups in southeast Africa and means that which bends or stooped walk. This is in reference to the hunched over appearance of individuals who are infected due to the characteristically painful and often times incapacitating arthralgia caused by the virus.

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

6

Regarding transmission, its important to remember that humans are the primary reservoir for chikungunya virus and that Aedes species mosquitos are the primary vectors, with the viral life-cycle circling between these 2 hosts. Aedes albopictus and Aedes aegypti are the 2 main mosquito species competent for transmission of chikungunya virus and are also responsible for transmission of dengue virus, another emerging vector-borne illness. Aedes mosquitos are notorious daytime biters and between the 2 Aedes species, Aedes albopictus can survive at more temperate latitudes and is therefore more widespread throughout the southeast United States, as indicated by the regions shaded in orange in this map. Other less commonly reported routes of infection, which have primarily been documented in regions endemic for chikungunya virus, include bloodborne transmission through needle sticks and in utero transmission, most often occurring during the antepartum period of pregnancy.

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

Until recently, chikungunya virus was primarily sequestered to Africa, Asia, and the Pacific islands as indicated by the dark green on this map. The first locally transmitted case in the Western Hemisphere, meaning that the index patient had not traveled to a chikungunya virus endemic region, occurred in December of 2013 on the island of St. Martin, indicated by the red arrow. As of June 2014, over 165,000 suspected cases of chikungunya virus infection have been reported, of which over 4,500 have been confirmed by laboratory testing and these numbers are continuing to increase. Importantly, indigenous or local transmission of chikungunya virus has not been reported in the United States or its territories, aside from Puerto Rico. And as of June 2014, the 57 reported US cases have thus far been associated with travel to endemic areas. However, due to the widespread distribution of a competent mosquito vector in the United States and a nave host population that has not yet been exposed to and lacks protective immunity to chikungunya virus, the possibility of chikungunya virus outbreaks in the United States is a very real public health threat.

7

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

Following transmission of the virus by the bite of an infected mosquito, the incubation period, prior to development of symptoms, ranges on average from 3 to 7 days. Unlike other mosquito-borne viruses like West Nile virus and dengue virus, the majority of individuals who are exposed to chikungunya virus become symptomatic, with the most severe manifestations observed at the extremes of age and in those with suppressed immunity. Importantly, however, it is believed that once exposed to chikungunya virus, individuals will develop lasting immunity and protection from reinfection. Also, fatalities due to chikungunya virus infection are uncommon, though they have been reported among elderly patients with significant underlying comorbidities or those with suppressed immune function.

8

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

Chikungunya virus infection can progress through 3 distinct stages, the acute, subacute, and chronic forms, each of which I will briefly cover. During the acute stage of infection, most individuals will experience a sudden onset, high fever along with severe and often incapacitating joint pain or polyarthralgia. The polyarthralgia is typically bilateral and symmetric, involving multiple joints, most commonly in the hands and feet. A fair percentage of patients will also present with a maculopapular rash involving the trunk and extremities that develops 2 to 5 days following fever onset. Other less common symptoms include severe headache, myalgias, and back pain, and laboratory findings are fairly nonspecific, including thrombocytopenia, leukopenia, and elevated liver function tests. This stage of infection can last anywhere from 3 to 10 days, after which most patients will feel significant symptom relief and improvement. Unfortunately, symptom relapse can occur in some individuals, most often reappearing 2 to 3 months following the initial infection. This is defined as the subacute stage and patients primarily experience rheumatic symptoms including exacerbation of pain in previously affected joints. While most individuals will recover from the acute or subacute stages, for some patients, symptoms can persist for months to years following initial infection, leading to chronic rheumatism and fatigue. In studies from Africa and India, the percentage

9

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

of individuals with chronic symptoms at 10 months postinfection varies from 12 to 50% with the elderly at greatest risk.

Chikungunya Virus 7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved. 9

Chikungunya virus infection should be suspected in any individual with sudden onset fever and polyarthralgia who has recently traveled to an endemic region. As chikungunya and dengue viruses often cocirculate in these regions and can present similarly, it is important to distinguish between these 2 agents as dengue virus infections are associated with higher mortality rates and proper clinical management has been shown to significantly improve patient outcomes. Three primary laboratory methods are available for detection of chikungunya virus, including PCR, serology, and culture, which is primarily available at the CDC. For routine clinical testing, the choice between PCR and serology is largely based on the timing of specimen collection relative to symptom onset. To better depict this, Ive outlined the general viremic and serologic profiles of a patient infected with chikungunya virus in the graph below. Following the bite of an infected mosquito, patients will become viremic during the 3 to 7-day incubation period and viral RNA will typically be detectable by PCR during the majority of the acute phase of disease. Approximately 3 to 4 days following onset of symptoms, IgM-class antibodies to chikungunya virus will develop and become detectable, followed 3 to 4 days later by the development of IgG-class antibodies. IgM antibodies will typically remain detectable for 2 to 3 months before titers begin to decline, though some individuals may remain IgM positive for longer periods of time. IgG antibodies on the other hand, can remain detectable for years following

10

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

initial infection.

Chikungunya Virus 7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved. 10

Based on these profiles, use of PCR to detect chikungunya virus RNA is most useful during the acute stage of infection and up to 8 days following symptom onset. PCR is typically performed on blood, however, PCR on cerebrospinal fluid and tissue can be performed by the CDC. With regards to serologic testing, diagnosis of a recent exposure or acute infection with chikungunya virus is supported by either detection of IgM-class antibodies to chikungunya virus, a negative-to-positive seroconversion of IgG-class antibodies between acute and convalescent serum samples, and/or a 4-fold rise in anti-chikungunya virus IgG levels. Notably, collection of a serum sample too early following symptom onset may result in negative serologic results and should not be used alone to rule-out infection.

11

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

As with the majority of mosquito-borne viral infections, there is no specific antiviral treatment for chikungunya virus. However, as mentioned earlier, it is important to exclude other, more serious infections for which there is targeted treatment or alternative clinical interventions available, including malaria and dengue virus, respectively. Treatment of patients with chikungunya virus infection is entirely supportive, including rest, fluids, and pain and fever management. Individuals who have persistent joint pain may require additional supportive care including corticosteroids and/or physiotherapy.

12

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

Due to the lack of targeted antiviral therapy and the often severe nature of the disease, infection prevention is essential. Unfortunately, there is currently no vaccine available against chikungunya virus. In an effort to minimize the spread of chikungunya virus to nave mosquitos in areas where it is not currently endemic, including the United States, it is recommended that individuals who are acutely infected and viremic avoid situations where they may be bitten by mosquitos. Additionally, all individuals are advised to prevent infection by using EPA-approved insect repellent, including DEET-containing lotions or sprays and permethrin-treated clothing or long-sleeved shirts and long pants. Finally, everyone is encouraged to minimize mosquito breeding sites around their homes, including dumping containers with standing water.

13

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

In summary, chikungunya virus is an emerging, vector-borne threat to the Americas, including the United States where we have both a large nave host population and widespread distribution of transmission competent Aedes species mosquitos. Infection with chikungunya virus is typically severe presenting with high fever, polyarthralgia, and often a maculopapular rash. Diagnosis is based on clinical suspicion supported by serologic findings and/or PCR and, unfortunately, care is largely supportive only. And finally, minimizing mosquito bites is key for both prevention of infection and spread of chikungunya virus to nonendemic areas.

14

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

15

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus

16

7/1/2014

2014 Mayo Foundation for Medical Education and Research. All rights reserved.

Chikungunya Virus