U.S. chikungunya epidemic would likely put rheumatologists on front line
SNOWMASS, COLO. – The continental United States is vulnerable to an epidemic of chikungunya virus disease, an event which would have profound consequences for rheumatologists, Robert T. Schoen, MD, said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
“We certainly have all the factors in place where we could have a major epidemic of chikungunya, particularly in Florida, Texas, and neighboring states. As rheumatologists, I think we can own this infection if we want to because it causes an arthritis that is a true arthritis in a significant percentage of patients,” said Dr. Schoen, a rheumatologist at Yale University in New Haven, Conn.
“That’s a major impact when you think that these epidemics affect tens of thousands of individuals. If 25% of them develop long-term arthritis disability, that’s a whole new world for us,” the rheumatologist observed.
,Chikungunya is a single-stranded RNA virus in the togaviridae family, which also contains rubella. The infection is transmitted by Aedes aegypti and A. albopictus, also known as the yellow fever and Asian tiger mosquitoes, respectively. Both mosquitoes are established inhabitants of much of the United States.
“This infection is a one-bite deal. These are very aggressive mosquitoes,” Dr. Schoen observed. “If you haven’t seen a case of chikungunya yet, you will soon,” he added.
In 2014, at the height of a massive Caribbean epidemic which included half a million cases in Puerto Rico, roughly 2,800 cases of chikungunya were imported into 46 U.S. states. In 2015, however, as the Caribbean epidemic waned and herd immunity developed, that figure fell to 653 imported cases. But the epidemic in India, which began in 2008, remains ongoing with no end in sight. Several of Dr. Schoen’s patients with chikungunya had recently returned from India when they first became ill.
“India provides an unlimited reservoir of immunologically naive patients to perpetuate the infection,” he observed.
Course of illness
The rate of asymptomatic infection has been variously estimated at 3%-25%. Symptomatic chikungunya is a biphasic illness. After a 2- to 6-day incubation period, patients develop rapid-onset fever with severe joint pain and muscle aches. Indeed, chikungunya means “bent over” in Makonde, an African Bantu language.
Roughly 60% of patients develop a rash during the acute febrile phase of the illness, which lasts about a week. The dermatitis is most often a maculopapular rash on the trunk which is “absolutely indistinguishable” from the rash caused by Zika virus infection, transmitted by the same vectors, Dr. Schoen noted.
During this acute phase, almost all patients develop a severe polyarthritis which can last for weeks or, less commonly, for months or years. This polyarthritis mimics seronegative rheumatoid arthritis. It is usually symmetric and often affects the hands, wrists, and feet.
The acute febrile phase is characterized by high levels of viremia, with up to 1 billion viral particles per milliliter of blood. During this period, definitive diagnosis of chikungunya can be made through reverse transcriptase–polymerase chain reaction testing or viral culture.
Typically, though, patients make their way to a rheumatologist only well after the viremic period is over. In that situation, the diagnostic mainstay is serologic testing. Antichikungunya virus Immunoglobulin M is detectable starting on about day 5 after symptom onset, and it persists for the next 1-3 months. Immunoglobulin G (IgG) antibodies become detectable in the same time frame and remain elevated for years.
Dr. Schoen highlighted a small but intriguing study from Singapore that suggests that the early appearance of chikungunya-specific neutralizing IgG3–antibodies may constitute a marker for favorable long-term prognosis. The observational study involved 30 patients hospitalized for severe acute chikungunya infection. The investigators classified them into two groups: 14 patients had low levels of acute viremia, a less severe acute illness, and late development of IgG3 antibodies; the other 16 had a high initial viral load, a more severe acute phase, and a rapid IgG3 and interleukin-6 response to infection.
The patients with a robust early IgG3 response cleared the virus faster and none of them developed chronic arthritis. In contrast, those without early, chikungunya-specific IgG3 had a high rate of persistent arthralgia (J Infect Dis. 2012 Apr 1;205[7]:1147-54).
