A growing number of patients in the United States are being tested—and testing positive—for the mosquito-borne chikungunya virus, according to a study presented at the recent Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Washington, DC.
The study, by scientists from Focus Diagnostics, a business of Quest Diagnostics, is believed to be the first to characterize clinical test-ordering patterns and the positivity rate for the chikungunya virus among patients in the United States since an outbreak in the Caribbean in late 2013 heightened concerns of the virus’s possible spread to North America.
The sudden and rapid spread of the virus in the United States led the New England Journal of Medicine to devote two articles to the subject in its September 4, 2014, issue. One of the articles is by David M. Morens, MD, and Anthony S. Fauci, MD, respectively senior advisor and director of the National Institute of Allergy and Infectious Diseases—the investigators who predicted the emergence of dengue fever in the United States well before an outbreak in Florida. Of the emergence of chikungunya virus, they write: “We now face a new threat posed by the unrelated chikungunya virus, which causes a disease clinically similar to dengue in a similar epidemiologic pattern, which is transmitted by the same mosquito vectors, and for which we also lack vaccines and specific treatments.”1,2
Focus Diagnostics specializes in diagnostics for emerging infectious diseases, and was the first, and continues to be the only, commercial clinical laboratory to provide antibody and molecular testing for the chikungunya virus in the United States.
“Chikungunya is not a major health threat in the United States, and the real risk of contracting the virus at this time is exceedingly small unless traveling to an area of an active outbreak without proper mosquito prevention,” says lead author Hollis Batterman, MD, medical director at Focus Diagnostics. “Our research is important because it provides insights into the strengths and limitations of clinical diagnostics to diagnose the infection. With these insights, public health authorities and the medical community will be better positioned to reliably identify infected patients, provide appropriate supportive care, and differentiate between other infections—such as dengue fever—that can have a similar clinical presentation.”
Chikungunya is an infectious disease that causes fever, rash and, for a subset of patients, chronic joint pain. Pregnant women who acquire chikungunya infection within one week of delivery can transmit the virus to their baby, which can lead to severe infection. Long endemic in parts of Asia and Africa, laboratory-confirmed cases of the disease in the United States have, until recently, been limited to individuals who had contracted the virus in Africa or Asia. In late 2013, chikungunya virus was found for the first time in the Western Hemisphere. Locally acquired cases were identified for the first time in Puerto Rico and the US Virgin Islands in April 2014 and in Florida in July 2014.
As of September 2, 2014, a total of 758 chikungunya virus disease cases have been reported from US states to ArboNET, the national surveillance system for arthropod-borne diseases. This compares to an average of 28 people annually to test positive for recent chikungunya virus infection between 2006 and 2013 in the United States, according to the US Centers for Disease Control and Prevention (CDC).
Early symptoms of chikungunya can mimic other infectious diseases, including dengue fever. While chikungunya is rarely fatal, dengue can be, and reliable diagnosis is necessary for appropriate treatment. There is currently no standard treatment for chikungunya, other than supportive care.
Recent Increase in Testing Volume and Positivity Rate
Clinical laboratory testing for chikungunya virus may involve molecular reverse transcription polymerase chain reaction (RT-PCR), which identifies the RNA of the virus, and immunoassays, which assess blood-serum levels of the antibodies immunoglobulin M and G (IgM and IgG). Focus Diagnostics introduced the first and currently the only commercial PCR test for chikungunya in February 2008, and introduced IgG and IgM tests for the virus in July 2008. The laboratory-developed tests were validated and are provided through the company’s clinical laboratory in Cypress, Calif.
For the study, a team of medical experts at Focus Diagnostics analyzed deidentified clinical results of RT-PCR and IgG/IgM tests for chikungunya ordered by clinicians between January 1 and August 2, 2014. Key findings:
- The volume of tests increased over the summer. The investigators determined that the Focus Diagnostics clinical laboratory tested 2,947 patient samples for antibodies to the virus between January 1 and August 2, 2014. Of this total, 2,402 (82%) were tested in June and July, suggesting a surge in test volume over the summer. Another 589 RT-PCR tests were also performed on patients. For 88 specimens, tests by both methods were ordered and performed.
- One in five patients tested for antibodies were positive for the virus. Of the total tested for antibodies, 642 specimens (about 22%) were IgG and/or IgM positive, suggesting a diagnosis of chikungunya.
- Most patients underwent antibody testing well after initial infection. Among those tested for antibodies, 16% of specimens exhibited an IgG positive/IgM positive antibody pattern, compared to 5% of specimens that were IgG negative/IgM positive. In addition, the rate of IgG/IgM positive specimens increased after June. These findings suggest that most patients were tested well after initial infection with the virus.
The investigators also determined that of 589 specimens tested by RT-PCR, 168—nearly one in three (28%)—were positive for the chikungunya virus. All positive PCR tests were performed during or after April 2014, possibly because of increased awareness of chikungunya infection and PCR’s role in diagnosing early infection. RT-PCR is helpful for detecting the virus within the first week of infection, but is less reliable afterward.
According to CDC, individuals suspected of having chikungunya should be protected from further mosquito exposure during the first week of illness to reduce the risk of further transmission.
The study’s researchers did not have access to medical records to corroborate test results with clinical diagnosis by a physician. While a small percentage of specimens tested were from Puerto Rico and the US Virgin Islands, where chikungunya is active, the vast majority of specimens originated in the continental United States. The investigators were not able to confirm whether the patients who tested positive were infected locally within the continental United States or as a result of travel to locations where chikungunya or mosquitos that carry the virus are active.
The patients who tested positive came from 40 states, with New York reporting 123 of the 608 confirmed positive cases for which the investigators had residence information. Florida was next (84), followed by Massachusetts (69), Pennsylvania (37), and New Jersey (36). The investigators did not examine reasons for this pattern in the study, but possible explanations include greater travel by individuals in these states to regions where chikungunya is endemic; higher rates of Quest testing by physicians in these states; or a hot, humid summer with precipitation in areas with high population density.
“Our findings suggest that PCR and antibody testing should be considered in anyone with a compatible clinical syndrome who has traveled to or lives in areas with the species of mosquitos that carry the virus,” says Batterman. “The majority of seropositive samples were IgG/IgM positive, suggesting that most patients were tested later in the onset of infection. In the absence of PCR testing, antibody IgG/IgM patterns may be useful to infer onset of illness, and potential risk of transmission if bitten by mosquitoes.”
1. Morens DM, Fauci AS. Chickungunya at the door—déjà vu all over again? N Engl J Med. 2014;371:885–887; doi: 10.1056/NEJMp1408509.
2. Staples JE, Fischer M. Chikungunya virus in the Americas—what a vectorborne pathogen can do. N Engl J Med. 2014;371:887-889; doi: 10.1056/NEJMp1407698.