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Chikungunya fever
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Chikungunya fever
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2017. | This topic last updated: Aug 24, 2017.

INTRODUCTION — Chikungunya is an arthropod-borne alphavirus transmitted by mosquitoes that causes acute febrile polyarthralgia and arthritis [1]. The name chikungunya is derived from an African language meaning "that which bends up" or "stooped walk" because of the incapacitating arthralgia caused by the disease.

EPIDEMIOLOGY

Geographic distribution — The United States Centers for Disease Control and Prevention (CDC) maintains a website summarizing geographic distribution of chikungunya virus.

Chikungunya virus is endemic in certain parts of West Africa; human serosurveys have identified antibodies to chikungunya virus in 35 to 50 percent of the population in some areas [2,3].

Outbreaks of chikungunya disease have occurred in Africa, Asia, Europe, and islands in the Indian and Pacific Oceans and more recently in the Americas. Most outbreaks occur during the tropical rainy season and abate during the dry season. However, outbreaks in Africa have occurred after periods of drought, where open water containers serve as vector-breeding sites.

Chikungunya can cause large outbreaks with high attack rates, affecting one-third to three-quarters of the population in areas where the virus is circulating. An outbreak on Réunion Island in 2005 to 2006 involved approximately 266,000 individuals (34 percent of the island's population) [4].

Chikungunya is transmitted by the mosquito vectors Aedes aegypti and Aedes albopictus. Infected travelers can import chikungunya into new areas [1,5,6]; in areas with Ae. aegypti and/or Ae. albopictus mosquitoes, local transmission can follow. This has been described in many Asian and European countries as well as in the Americas and Australia [7-14].

Chikungunya was perceived as a tropical disease until an outbreak in Italy occurred in 2007 [15]. The first locally acquired cases of chikungunya in the Americas were reported in 2013 on islands in the Caribbean [6]. Since then, chikungunya virus infections have spread widely in the Caribbean and Americas [1,16]. The first cases of local transmission in the continental United States were reported in Florida in July 2014 [17]; local transmission has been reported widely in Puerto Rico, where serosurveys found nearly 25 percent of blood donors had been infected [18,19].

Dengue and Zika viruses are transmitted by the same mosquito vectors as chikungunya. The viruses can co-circulate in a geographic region, and coinfections have been documented [20,21].

Transmission — Chikungunya virus may be transmitted via the following:

Mosquito bites

Rarely via maternal-fetal transmission

Rarely via blood products and organ transplantation

Chikungunya virus is transmitted to people primarily via mosquito bites. Mosquitoes become infected when they feed on a person already infected with the virus. Infected mosquitoes can then spread the virus to other people via biting, after the virus reaches the mosquito salivary glands.

Mosquito transmission — In endemic areas of Africa, chikungunya virus transmission occurs in cycles involving humans, Aedes and other mosquitoes, and animals (nonhuman primates and perhaps other animals). Outside Africa, major outbreaks are sustained by mosquito transmission among susceptible humans. (See 'Epidemiology' above.)

The major chikungunya virus mosquito vectors are Ae. aegypti and Ae. albopictus (figure 1 and figure 2); they bite primarily during the day but also at night. These mosquito vectors are also capable of transmitting Zika virus and dengue virus [22]. (See "Zika virus infection: An overview", section on 'Transmission' and "Dengue virus infection: Epidemiology", section on 'Transmission cycle'.)

Ae. aegypti is well adapted to urban settings and is widely distributed in the tropics and subtropics worldwide. It prefers the human host and breeds readily in flowerpots and in trash. A single Ae. aegypti mosquito can infect more than one human since this species may feed on another host if its blood meal is interrupted.

Ae. albopictus (known as the Asian tiger mosquito) can survive more temperate environments than Ae. aegypti so has a wider potential distribution. It has been considered a relatively inefficient vector since it bites a range of animal species, and blood meals from nonsusceptible hosts do not contribute to virus transmission [23]. However, some populations of Ae. albopictus may be more anthropophilic (ie, preferring human blood) than others; in some settings, humans may be the most abundant host [23]. Ae. albopictus is competent to transmit a number of arboviruses (including yellow fever, West Nile, Japanese encephalitis, and Eastern equine encephalitis viruses).

Chikungunya virus can spread geographically via travel of infected individuals between regions with appropriate season/climate where competent mosquitoes exist for perpetuation of local transmission [24]. In addition, dissemination of mosquitoes can occur via transport of mosquito larvae and eggs by ships and air traffic to new areas with suitable environmental and climatic conditions [25,26].

In general, the warmer the temperature, the shorter the extrinsic incubation period (the period between a mosquito blood meal from a viremic host and the transmission of virus to a new host), and the sooner the mosquito can transmit virus to a new host. In cool temperatures in temperate areas, a mosquito may die before the extrinsic incubation period is complete. In addition, mutations in some strains of the chikungunya virus may shorten the extrinsic incubation period, allowing more mosquitoes to survive long enough to transmit virus [1,27-29].

Blood products and organ transplantation — Transmission of chikungunya via blood products has been described in France, where a nurse was infected by exposure to blood while caring for a patient infected in Réunion [7,9].

Transmission via organ transplantation could also occur since chikungunya viremia (may exceed 109 RNA copies/mL plasma) is likely prior to onset of symptoms [9,19,30].

Chikungunya virus infects the human cornea and might be transmitted via corneal grafts. Infected corneas have been documented in individuals in the absence of systemic manifestations of chikungunya infection [31].

Maternal-fetal transmission — Pregnant women infected with chikungunya virus are not at increased risk for atypical or severe disease. Maternal-fetal transmission of chikungunya virus has been described, and maternal chikungunya virus infection has been associated with miscarriage [32,33].

The risk of maternal-fetal transmission is highest when pregnant women are symptomatic during the intrapartum period (two days before delivery to two days after delivery). During this period, vertical transmission occurs in approximately half of cases; among 39 women in the Réunion outbreak with viremia at the time of delivery, the rate of vertical transmission was 49 percent [32]. Cesarean delivery was not protective against vertical transmission. (See 'Neonatal infection' below.)

Chikungunya virus has not been detected in breast milk, and transmission of chikungunya virus via breastfeeding has not been reported.

CLINICAL MANIFESTATIONS

Adults and children with postnatal infection

Acute infection — Following an incubation period of 3 to 7 days (range 1 to 14 days), clinical manifestations begin abruptly with fever and malaise [34]. The majority of infected individuals have symptoms; asymptomatic seroconversion occurs in less than 15 percent of patients [1,30].

Fever may be high grade (>39ºC); the usual duration of fever is 3 to 5 days (range 1 to 10 days). Polyarthralgia begins two to five days after onset of fever and commonly involves multiple joints (often 10 or more joint groups) [7,35-37]. Arthralgia is usually bilateral and symmetric and involves distal joints more than proximal joints. Affected joints include hands (50 to 76 percent), wrists (29 to 81 percent), and ankles (41 to 68 percent). Involvement of the axial skeleton was noted in 34 to 52 percent of cases. Pain may be intense and disabling, leading to immobilization.

Skin manifestations have been reported in 40 to 75 percent of patients [35,37]. The most common skin manifestation is macular or maculopapular rash (usually appearing three days or later after onset of illness and lasting three to seven days). The rash often starts on the limbs and trunk, can involve the face, and may be patchy or diffuse. Pruritus has been reported in 25 to 50 percent of patients in some series.

Additional manifestations may include headache, myalgia, facial puffiness, and gastrointestinal symptoms. Atypical dermatologic manifestations include bullous skin lesions (described most often in children) and hyperpigmentation [38]. External ear redness may reflect chondritis [39]. Hemorrhagic manifestations are uncommon.

On physical examination, periarticular edema or swelling has been observed in 32 to 95 percent of cases. In one series, large joint effusions were noted in 15 percent of cases. Peripheral lymphadenopathy (most often cervical) may be present (9 to 41 percent of cases) [8,40]. Conjunctivitis may be observed [41].

The most common laboratory abnormalities are lymphopenia and thrombocytopenia. Hepatic transaminases and creatinine may be elevated. High viral load during the acute illness was associated with poor prognosis in the post-acute phase in a large series in India [42].

The duration of acute illness is usually 7 to 10 days.

Severe complications — Severe complications and death have been reported during chikungunya outbreaks. Severe complications and death occur more often among patients older than 65 years and patients with underlying chronic medical problems (eg, most commonly diabetes and cardiovascular disease) [1,43].

Severe complications include respiratory failure, cardiovascular decompensation, myocarditis, acute hepatitis, renal failure, hemorrhage, and neurologic involvement [44]. Meningoencephalitis is the most common neurologic complication; other neurologic manifestations include acute flaccid paralysis, Guillain-Barré syndrome, myelitis, and cranial nerve palsies [45-48].

Ocular manifestations (iridocyclitis, retinitis, episcleritis, macular choroiditis, uveitis) and sensorineural hearing loss have also been described [41,49,50]. One report described extensive skin necrosis of the nose in three severely ill adults [51]. In Réunion, the estimated incidence of severe disease (eg, hospitalized patients with complications, such as respiratory failure, meningoencephalitis, acute hepatitis, or kidney failure) was 17 per 100,000 population [4,48,52,53].

Deaths associated with chikungunya virus infection were reported during outbreaks in Mauritius, Réunion, and India [52,54-56]. In Réunion, there were 228 deaths; the mean age was 78 years [52]. During the chikungunya epidemic in Ahmedabad, India, in 2006, about 60,000 cases were described; the number of deaths during the four months of peak epidemic activity exceeded the average death rate during those months in the previous four years by almost 3000 [56].

Persistent or relapsed disease — Some patients have persistence or relapse of signs and symptoms in the months following acute illness; manifestations include arthritis/arthralgia, edematous polyarthritis of fingers and toes, morning pain and stiffness, and severe tenosynovitis (especially of wrists, hands, and ankles) [57,58]. Carpal tunnel syndromes may result from hypertrophic tenosynovitis. In addition, patients may report joint or bone pain at sites of previous injury. Occasionally, sternoclavicular or temporomandibular joints are involved. New-onset Raynaud phenomena in the second or third month following infection have been described in up to 20 percent of cases [36]. Cryoglobulinemia has also been found in patients with persistent symptoms attributed to chikungunya infection (>90 percent in one series) [59].

Chronic manifestations usually involve joints affected during the acute illness and can be relapsing or unremitting and incapacitating. Patients may develop a new chronic inflammatory polyarthritis [60] or may have flares of preexisting joint conditions (whether noninflammatory, mechanical, or inflammatory) during and following infection [61]. In one systematic review including approximately 5700 patients with chikungunya virus infection, about 25 to 35 percent of patients developed chronic joint symptoms [62]. Of these, approximately half of patients developed chronic inflammatory arthritis (rheumatoid arthritis, nonspecific post-viral polyarthritis, or seronegative spondylitis); other manifestations included arthralgia and other musculoskeletal pain conditions (eg, fibromyalgia, frozen shoulder, and plantar fasciitis).

The duration of symptoms is variable. As an example, among 47 patients with acute chikungunya fever followed in Marseilles, France, 82 percent had persistent joint symptoms. At one, three, and six months following acute illness, symptoms persisted in 88, 86, and 48 percent of patients, respectively; at 15 months, 4 percent remained symptomatic [36]. In contrast, among 88 patients in Réunion evaluated a mean of 18 months after confirmation of acute chikungunya infection, 63 percent reported persistent polyarthralgia [40]. Morning stiffness was reported by 75 percent of individuals, and almost half reported that the pain had a negative impact on daily activities. Another study of 180 patients from Réunion with viremic chikungunya virus infection found that, at 36 months, 60 percent still had arthralgias [60]. One study in South Africa reported arthralgia three years after the acute illness in 12 percent of patients [63].

Neonatal infection — Clinical manifestations among neonates in the Réunion outbreak were observed within three to seven days after delivery and included fever, poor feeding, rash, and peripheral edema; 89 percent had thrombocytopenia [32]. Some infants developed neurologic disease (eg, meningoencephalitis, cerebral edema, and intracranial hemorrhage) or myocardial disease. Neurocognitive outcome was poor in children with perinatal transmission from infected mothers [64].

Laboratory abnormalities included elevated liver function tests, reduced platelet and lymphocyte counts, and increased prothrombin time.

DIAGNOSIS — The diagnosis of chikungunya virus infection should be suspected in patients with acute onset of fever and polyarthralgia and relevant epidemiologic exposure (residence in or travel to an area where mosquito-borne transmission of chikungunya virus infection has been reported).

The diagnosis of chikungunya is established by detection of chikungunya viral RNA via real-time reverse-transcription polymerase chain reaction (RT-PCR) or chikungunya virus serology [65]:

For individuals presenting 1 to 7 days following onset of symptoms, RT-PCR for detection of chikungunya virus RNA should be performed; a positive result establishes a diagnosis of chikungunya virus infection. A negative result should prompt chikungunya virus serologic testing via enzyme-linked immunosorbent assay (ELISA) or indirect fluorescent antibody (IFA).

For individuals presenting ≥8 days following onset of symptoms, chikungunya virus serologic testing via ELISA or IFA should be performed. A positive result establishes a diagnosis of chikungunya virus infection.

Testing for dengue virus infection and Zika virus infection should also be pursued. A single polymerase chain reaction test to evaluate for the presence of all three infections is available through the United States Centers for Disease Control and Prevention (CDC) and other qualified laboratories [66].

Chikungunya virus RNA can be detected by RT-PCR during the first five days following onset of symptoms with excellent sensitivity and specificity [9]. Immunoglobulin (Ig)M anti-chikungunya virus antibodies (detected by direct ELISA) are present starting about 5 days (range 1 to 12 days) following onset of symptoms and persist for several weeks to three months [1]. IgG antibodies begin to appear about two weeks following onset of symptoms and persist for years.

Viral culture is generally a research tool [9,35,67]. The sensitivity of culture for chikungunya virus is high in early infection but drops five days after onset of illness. Virus isolation allows identification of the viral strain and can be important for epidemiologic and research purposes.

In endemic areas, chikungunya virus infection may be suspected based on characteristic clinical findings; in areas where no laboratory facilities are available, infection may remain undiagnosed.

Patients who present with persistent or chronic joint symptoms and relevant epidemiologic exposure should have confirmation of chikungunya virus infection with serologic testing if not already performed. In addition, testing to evaluate the level of inflammation and to screen for the presence of other musculoskeletal conditions distinct from the chikungunya-induced arthropathy should be performed based on the history and clinical findings. (See 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — Prominent arthralgia, high fever, diffuse rash, and absence of respiratory symptoms can help to distinguish chikungunya from other illnesses. The differential diagnosis includes mimics of acute chikungunya virus infection as well as mimics of chronic conditions associated with arthritis, as summarized below.

Mimics of acute infection — Mimics of acute chikungunya virus infection include:

Other viral causes of arthritis:

Dengue fever – Dengue and chikungunya virus infections share many clinical manifestations and areas of geographic distribution (table 1). Chikungunya virus infection is more likely to cause high fever, severe arthralgia, arthritis, rash, and lymphopenia, whereas dengue virus infection is more likely to cause neutropenia, thrombocytopenia, hemorrhage, shock, and death. The diagnosis of dengue fever is established via polymerase chain reaction (PCR) or serology. (See "Dengue virus infection: Clinical manifestations and diagnosis".)

Zika virus – Zika and chikungunya viruses share many clinical manifestations and areas of geographic distribution (table 1). Symptoms and signs of Zika virus infection include fever, rash, headache, arthralgia, myalgia, and conjunctivitis. Chikungunya typically presents with higher fever and more intense joint pain than Zika virus infection, though there is considerable overlap in clinical manifestations. The diagnosis of Zika virus infection is established by PCR or serology. (See "Zika virus infection: An overview".)

Parvovirus – Parvovirus infection can present with acute and symmetric arthritis or arthralgia, most frequently involving the small joints of the hands, wrists, knees, and feet. Rash may or may not be present. The diagnosis is established via serology. (See "Clinical manifestations and diagnosis of parvovirus B19 infection".)

Rubella – Clinical manifestations of rubella include low-grade fever, coryza, conjunctivitis, and lymphadenopathy. Macular rash begins on the face and spreads to the trunk, and arthritis may be present. The diagnosis is established via serology. (See "Rubella".)

Ross river virus – Clinical manifestations of Ross River virus infection include fever, arthritis, and rash. Epidemiologic history can help to exclude Ross River virus infection as it is transmitted only in Australia. The diagnosis of Ross River virus is typically established by serology. (See "Ross River virus infection".)

A number of other viruses including enterovirus, adenovirus, other alphaviruses, and hepatitis C may also cause arthritis; these are discussed further separately. (See "Specific viruses that cause arthritis".)

Measles – Clinical manifestations of measles include fever, cough, sore throat, coryza, conjunctivitis, and lymphadenitis. Koplik spots may precede generalized rash. The diagnosis is established via serology. (See "Measles: Clinical manifestations, diagnosis, treatment, and prevention".)

Leptospirosis – Leptospirosis is characterized by fever, rigors, myalgia, and headache. Less common manifestations include cough, nausea, vomiting, diarrhea, abdominal pain, and arthralgia. Presence of conjunctival suffusion and jaundice are suggestive of leptospirosis, and the diagnosis is established via serology. (See "Epidemiology, microbiology, clinical manifestations, and diagnosis of leptospirosis".)

Malaria – Malaria is characterized by fever, malaise, nausea, vomiting, abdominal pain, diarrhea, myalgia, and anemia. Fever in the setting of malaria is often intermittent, whereas fever in the setting of chikungunya infection is typically persistent. The diagnosis of malaria is established by visualization of parasites on peripheral smear. (See "Clinical manifestations of malaria in nonpregnant adults and children".)

African tick bite fever – African tick bite fever is observed among travelers to Africa and the Caribbean and is characterized by headache, fever, myalgia, solitary or multiple eschars with regional lymphadenopathy, and generalized rash; the diagnosis is established via serology. (See "Other spotted fever group rickettsial infections".)

Relapsing fever is characterized by fever, headache, neck stiffness, arthralgia, myalgia, and nausea; diagnostic tools include direct smear and PCR. (See "Clinical features, diagnosis, and management of relapsing fever".)

Enteric fever – Clinical manifestations of enteric fever include fever, bradycardia, abdominal pain, and, infrequently, a rash (rose spots). The presentation of enteric fever is typically subacute, whereas the presentation of chikungunya infection is typically abrupt in onset. The diagnosis is established by stool and/or blood culture. (See "Epidemiology, microbiology, clinical manifestations, and diagnosis of enteric (typhoid and paratyphoid) fever".)

Infectious mononucleosis – Clinical manifestations of mononucleosis include fever, malaise, and pharyngitis. Lymphadenopathy and splenomegaly may be present along with atypical lymphocytosis. The diagnosis is established via serology. (See "Infectious mononucleosis in adults and adolescents".)

Acute human immunodeficiency virus (HIV) infection – Clinical manifestations of acute HIV infection may include fever, lymphadenopathy, sore throat, rash, myalgia/arthralgia, and headache. The diagnosis is established via immunoassay and/or an HIV virologic (viral load) test. (See "Acute and early HIV infection: Clinical manifestations and diagnosis".)

Group A Streptococcus – Clinical manifestations of group A Streptococcus infection include fever, myalgia, cutaneous manifestations (cellulitis, fasciitis), pharyngitis, and shock. The diagnosis established by positive cultures from the blood or other tissues. (See "Group A streptococcal (Streptococcus pyogenes) bacteremia in adults".)

Meningococcal infection – Meningococcal infection may be associated with meningitis and hemorrhagic rash. The diagnosis is established based on cerebrospinal fluid examination. (See "Clinical manifestations of meningococcal infection".)

The possibility of dual infection should be considered if the clinical course is atypical or fever persists longer than five to seven days [68]. Chikungunya virus outbreaks have occurred simultaneously with outbreaks of dengue, Zika virus [69], and yellow fever [70], and coinfection with chikungunya virus and other pathogens has been described (eg, chikungunya and dengue [71], chikungunya and yellow fever [68], chikungunya and ameba [72], chikungunya and Zika virus [21]).

Mimics of persistent or relapsed disease — Mimics of persistent or relapsed disease include:

Seronegative rheumatoid arthritis – Chikungunya viral arthritis can closely resemble seronegative rheumatoid arthritis [73]. Clinical manifestations of seronegative rheumatoid arthritis include inflammatory arthritis involving three or more joints for >6 weeks, with negative rheumatoid factor and anti–cyclic citrullinated peptide (CCP) antibody tests. It is a diagnosis of exclusion. (See "Diagnosis and differential diagnosis of rheumatoid arthritis", section on 'Patients not meeting above criteria'.)

Reactive arthritis – Reactive arthritis refers to arthritis associated with a coexisting or recent antecedent extraarticular infection. Clinical manifestations include at least one of the following: asymmetric oligoarthritis (often affecting the lower extremities), enthesitis (inflammation at the insertion site of ligaments and tendons to bone), dactylitis (inflammation of an entire digit), and inflammatory back pain. The diagnosis is established clinically based on the presence of characteristic features with a preceding or ongoing enteric or genitourinary infection, with exclusion of other causes of arthritis. (See "Reactive arthritis".)

Systemic lupus erythematosus (SLE) – Patients with SLE may have disease characterized by fever, rash, and inflammatory polyarthritis or arthralgias, similar to patients with persistent chikungunya virus infection. SLE can be distinguished by absence of serologic evidence for the viral disease and the presence of antinuclear antibodies and often other systemic manifestations or organ system involvement characteristic of SLE. (See "Diagnosis and differential diagnosis of systemic lupus erythematosus in adults".)

Hepatitis C virus infection – Chronic infection with hepatitis C virus can be associated with arthralgia or arthritis and a variety of dermatologic manifestations. Appropriate serologic testing for chikungunya virus and for hepatitis C, together with a history of potential exposure to one or the other virus, should help distinguish these conditions. (See "Specific viruses that cause arthritis", section on 'Hepatitis C virus' and "Extrahepatic manifestations of hepatitis C virus infection", section on 'Porphyria cutanea tarda'.)

TREATMENT

Acute disease — There is no specific antiviral therapy for acute chikungunya virus infection. Treatment during the acute phase of disease consists of supportive care and can include rest, fluids, and use of acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) to relieve acute pain and fever [36,74,75].

In the patient who may have dengue, aspirin and other NSAIDs should not be used until the patient is afebrile ≥48 hours and there are no warning signs for severe dengue (severe abdominal pain, persistent vomiting, mucosal bleeding, pleural effusion or ascites, lethargy, enlarged liver, and increased hematocrit with decrease in platelet count); this is important given the risk of bleeding complications associated with dengue infection and because of the potential risk of Reye syndrome in children. (See "Dengue virus infection: Prevention and treatment".)

Systemic glucocorticoids and other immunosuppressive medications should generally be avoided in patients during acute infection [75].

Persistent or relapsed disease — Management of persistent or relapsed manifestations, particularly joint disease, depends upon the duration of the symptoms and findings. Symptomatic control with anti-inflammatory drugs and analgesics is appropriate in the several months immediately following the acute phase of disease; more longstanding disease, beyond three months after the onset of infection, may require the use of disease-modifying antirheumatic drug (DMARD) therapy, such as methotrexate (MTX). (See 'Post-acute disease' below and 'Chronic disease' below.)

Post-acute disease — In patients with joint symptoms persisting into the post-acute phase (between one month and up to the end of the third month after onset of infection) treatment includes continued analgesia (eg, acetaminophen) and NSAIDs. Additional analgesic benefit may be provided by use of medications for neuropathic pain (eg, pregabalin or gabapentin). Physical therapy may also be of benefit.

In patients resistant to NSAIDs who exhibit inflammatory arthritis, tendinitis, or bursitis, a short course of systemic glucocorticoids (prednisone 10 mg daily for five days, tapered off over the next 10 days) can be used; more severely affected patients may require higher doses (0.5 mg/kg daily) [75]. Some patients require up to one to two months of glucocorticoid therapy [76].

Chronic disease — Patients with clinical manifestations (particularly suspected inflammatory arthritis) persisting three months after the onset of infection should be referred to a rheumatologist for further assistance in diagnosis and management and to determine if treatment with a DMARD is appropriate.

Methotrexate has been the most commonly used DMARD, typically using the same approach as in rheumatoid arthritis (RA) (see "Initial treatment of rheumatoid arthritis in adults"). Sulfasalazine has also been used as in patients with peripheral spondyloarthritis (SpA) (see "Treatment of peripheral spondyloarthritis"). DMARD combinations have been used in some patients, and tumor necrosis factor (TNF) inhibitors have been effective in patients resistant to or unable to take MTX [61,77]. This treatment approach is based upon the available case series and expert opinion, and there are no randomized trials comparing DMARDs for this condition [61,74-76,78]. The approach is similar to that used for DMARD therapy of other chronic inflammatory arthritides, such as RA and SpA.

Patients with preexisting rheumatic disease on nonbiologic and biologic DMARDs, including TNF inhibitors, were reported in a small case series to be effectively managed with NSAIDs and rest and to experience a normal course of the infection without an exacerbation of the rheumatic disease being treated with these therapies [79].

In patients with a sustained complete response for at least several months, an expert panel has suggested that the DMARD may be discontinued as symptoms may resolve and not return in some patients [75]. However, this approach has not been systematically studied, and the optimal approach remains to be determined.

PREVENTION — There is no licensed vaccine for prevention of chikungunya virus infection [80-84]. Prevention consists of minimizing mosquito exposure [58]. Aedes mosquitoes bite primarily during the daytime but also at night; they breed in standing water (particularly containers) [85]. Measures to avoid mosquito bites include personal protection and environmental control measures. (See "Prevention of arthropod and insect bites: Repellents and other measures" and "Zika virus infection: An overview", section on 'Mosquito protection'.)

Individuals with chikungunya may reduce spread of infection to others by following precautions to avoid mosquito bites during the first week of illness (the likely period of viremia).

Transmission of chikungunya virus via breastfeeding has not been reported; women may be encouraged to breastfeed even in areas where chikungunya virus is circulating [86].

SUMMARY

Chikungunya virus is an arthropod-borne alphavirus transmitted by mosquitoes that causes acute febrile polyarthralgia and arthritis. Chikungunya virus is endemic in West Africa; outbreaks have occurred in Africa, Asia, Europe, islands in the Indian and Pacific Oceans, and more recently in the Americas. Infected travelers can import chikungunya virus into new areas, where local transmission can occur if competent mosquitoes are present. (See 'Geographic distribution' above.)

The United States Centers for Disease Control and Prevention (CDC) maintains a website summarizing the geographic distribution of chikungunya virus. The first locally acquired cases of chikungunya in the Americas were reported in 2013 on islands in the Caribbean. Since then, chikungunya virus has spread widely in the Americas. The first cases of local transmission in the continental United States were reported in Florida in July 2014; local transmission has been reported widely in Puerto Rico. (See 'Geographic distribution' above.)

Chikungunya virus is transmitted to people primarily via mosquito bites. The major chikungunya virus mosquito vectors are Aedes aegypti and Aedes albopictus (figure 1 and figure 2); they bite primarily during the day but also at night. These mosquito vectors are also capable of transmitting Zika virus and dengue virus (table 1). Transmission of chikungunya virus can also occur via maternal-fetal transmission as well as blood products and organ transplantation. (See 'Transmission' above.)

Following an incubation period of 3 to 7 days (range 1 to 14 days), clinical manifestations of chikungunya begin abruptly with high fever. Polyarthralgia begins two to five days after onset of fever and commonly involves multiple joints (often 10 or more joint groups). Arthralgia is usually bilateral and symmetric and involves distal joints more than proximal joints. The most common skin manifestation is macular or maculopapular rash (usually appearing three days or later after onset of illness and lasting three to seven days). Additional manifestations may include headache, myalgia, and gastrointestinal symptoms. Severe complications (including meningoencephalitis, cardiopulmonary decompensation, acute renal failure, and death) have been described with greater frequency among patients older than 65 years and those with underlying chronic medical problems. (See 'Acute infection' above and 'Severe complications' above.)

Some patients have persistence or relapse of signs and symptoms in the months following acute illness. These may include polyarthralgia, morning stiffness, tenosynovitis, and Raynaud phenomena. (See 'Persistent or relapsed disease' above.)

The risk of maternal-fetal virus transmission is highest when pregnant women are symptomatic during the intrapartum period (two days before delivery to two days after delivery); during this period, vertical transmission occurs in approximately half of patients. Clinical manifestations of neonatal infection occur three to seven days after delivery and include fever, rash, peripheral edema, neurologic disease (meningoencephalitis, cerebral edema, and intracranial hemorrhage), and myocardial disease. Laboratory abnormalities include elevated liver function tests, reduced platelet and lymphocyte counts, and increased prothrombin time. (See 'Maternal-fetal transmission' above and 'Neonatal infection' above.)

The diagnosis of chikungunya virus infection should be suspected in patients with acute onset of fever and polyarthralgia and relevant epidemiologic exposure (residence in or travel to an area where mosquito-borne transmission of chikungunya virus infection has been reported). The diagnosis of chikungunya is established by detection of chikungunya viral RNA via real-time reverse-transcription polymerase chain reaction (RT-PCR) or chikungunya virus serology. Testing for dengue virus infection and Zika virus infection should also be pursued. (See 'Diagnosis' above.)

There is no specific antiviral therapy for treatment of chikungunya virus infection. Treatment consists of supportive care and can include rest, fluids, and anti-inflammatory and analgesic agents. If the patient may have dengue, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) should not be used until the patient is afebrile ≥48 hours and there are no warning signs for severe dengue. Some patients with chronic arthritis may warrant treatment with systemic glucocorticoids or disease-modifying antirheumatic drugs, such as methotrexate or other agents. (See 'Treatment' above.)

There is no vaccine for prevention of chikungunya virus infection; prevention consists of minimizing mosquito exposure. Individuals with chikungunya may reduce spread of infection to others by following precautions to avoid mosquito bites during the first week of illness (the likely window of viremia). (See 'Prevention' above.)

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