Chikungunya fever: Epidemiology, clinical manifestations, and diagnosis

INTRODUCTION — Chikungunya virus is an arthropod-borne alphavirus transmitted by mosquitoes that causes acute febrile polyarthralgia and inflammatory arthritis as well as acute cutaneous eruptions and other systemic manifestations [1,2]. The name chikungunya is derived from an African language and means "that which bends up" or "stooped walk" because of the incapacitating arthralgia caused by the disease.

Issues related to epidemiology, clinical manifestations, and diagnosis of chikungunya fever are discussed here. Issues related to treatment and prevention of chikungunya fever are discussed separately. (See "Chikungunya fever: Treatment and prevention".)

Issues related to other viral causes of arthritis are presented separately. (See "Viral arthritis: Causes and approach to evaluation and management".)

EPIDEMIOLOGY

Geography — Chikungunya is a global public health concern. The United States Centers for Disease Control and Prevention maintains a website summarizing geographic distribution of chikungunya virus.

Chikungunya virus is endemic in parts of West Africa; human serosurveys have identified antibodies to chikungunya virus in 35 to 50 percent of the population in some areas [3,4].

Outbreaks of chikungunya disease have occurred in Africa, Asia, Europe, islands in the Indian and Pacific Oceans, and subsequently 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) [5].

Chikungunya is transmitted by the mosquito vectors Aedes aegypti and Aedes albopictus. Infected travelers can import chikungunya into new areas [1,6,7]; 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 [8-15].

Chikungunya was perceived as a tropical disease until an outbreak in Italy occurred in 2007 [16]. The first locally acquired cases of chikungunya in the Americas were reported in 2013 on islands in the Caribbean [7]. Since then, chikungunya virus infections have spread widely in the Caribbean and Americas [1,17-21]. The first cases of local transmission in the continental United States were reported in Florida in July 2014 [22]; local transmission has been reported widely in Puerto Rico where serosurveys found nearly 25 percent of blood donors had been infected [23,24].

Between 2014 and 2016, almost 4000 cases of chikungunya virus disease were reported in the United States among travelers; 92 percent were associated with travel in the Americas (most commonly the Dominican Republic, Puerto Rico, and Haiti). The remainder had traveled to Asia, Africa, or the Western Pacific [25].

Dengue and Zika viruses are transmitted by the same mosquito vectors as chikungunya virus. The viruses can cocirculate in a geographic region, and coinfections have been documented [26,27].

Transmission

Overview — Chikungunya virus may be transmitted via the following:

●Mosquito bites

●Rarely via maternal-fetal transmission

●Rarely via blood products

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.

In humans, chikungunya viremia may exceed 10⁹ RNA copies/mL plasma; in addition, viremia may be present prior to onset of symptoms [10,24,28]. In the setting of symptomatic infection, viremia usually disappears after six to seven days of illness; however, a virus has been isolated after eight days, and chikungunya genomic products can be detected as late as day 17 of illness [29].

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 [30]. (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. It often enters homes and will feed indoors and outdoors. 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 [31]. 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 [31]. 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 [32]. In addition, dissemination of mosquitoes can occur via transport of mosquito larvae and eggs by ships and air transport to new areas with suitable environmental and climatic conditions [33,34].

In general, the warmer the temperature and the shorter the extrinsic incubation period (the period between a mosquito blood meal from a viremic host and dissemination of the virus in the mosquito), 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 [1,35-37].

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 [8,10].

Thus far, transmission of chikungunya via solid organ transplantation has not been documented. Transmission via organ transplantation is theoretically possible; chikungunya viremia can occur prior to onset of symptoms and infection can be asymptomatic [10,24,28].

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 [38].

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 [39,40].

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 [39]. 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. Women may be encouraged to breastfeed even in areas where chikungunya virus is circulating [41].

PATHOGENESIS — Patients with chikungunya fever typically develop viremia within a few days of infection, and the virus directly invades and replicates within the joints. Animal models of chikungunya virus pathogenesis suggest the virus directly infects the synovium, tenosynovium, and muscle, leading to production of proinflammatory cytokines and chemokines and recruitment of leukocytes [42-45]. Studies in animal models suggest that drugs targeting monocytes, macrophages, and T cells may limit the severity of disease.

Typically, infectious virus is cleared from the circulation within days and from joints within a couple of weeks. However, viral nucleic acid has been reported to persist within tissues for weeks or months in humans, nonhuman primates, and mice [46]. However, in other studies, viral persistence in synovial fluid and biopsy has not been observed [47,48].

Chronic arthritis due to chikungunya virus develops in up to approximately 60 percent of infected individuals. Why some patients develop chronic joint pain while others do not is not well understood. Three hypotheses have been proposed to explain chronic arthritis: persistent viral replication, persistent viral RNA driving an inflammatory response, and autoimmunity. Persistent T cell activation has been reported in chronic arthritis due to chikungunya virus, but rheumatoid factor and anti-cyclic citrullinated peptide testing are typically negative [49].

CLINICAL MANIFESTATIONS

Adults and children with postnatal infection

Acute infection

Overview of acute presentation — Following an incubation period of 3 to 7 days (range 1 to 14 days), signs and symptoms begin abruptly with fever and malaise [50]. Joint pain may precede fever; in one outbreak among more than 1300 patients in 2017 in Dhaka, Bangladesh, joint pain preceded fever in 90 percent of cases [51]. Fever may be high grade (>39ºC); the usual duration of fever is 3 to 5 days (range 1 to 10 days). One analysis of 267 older patients (80 years plus or minus 8 years) found only 83.9 percent had fever when evaluated [52]. Other manifestations include joint symptoms and dermatologic involvement. The duration of acute illness is usually 7 to 10 days. The musculoskeletal manifestations of chikungunya infection can persist for weeks, months, or years. (See 'Chronic arthritis and arthralgia' below.)

Clinical manifestations of acute chikungunya virus infection include:

●Arthralgia and arthritis – Arthralgia is a prominent feature of acute symptomatic chikungunya virus infection and is the first symptom in about 70 percent of patients. Polyarthralgia is present in 70 to 100 percent of patients; joint swelling has been reported in 44 to 63 percent of patients [53-55].

Sometimes symptoms begin in one or two joints, but almost always eventually involve many joints (often 10 or more joint groups) within 24 to 48 hours of onset of inflammatory arthritis [8,49,56-58]. Arthralgia is usually bilateral and symmetric, involves distal joints more than proximal joints, and is associated with morning stiffness and imaging findings consistent with inflammatory arthritis (picture 1) [49,54,59]. In one large outbreak, joint pain was reported as the presenting symptom by >70 percent of patients [54]. Most frequently affected joints include hands (50 to 76 percent), wrists (29 to 81 percent), and ankles (41 to 68 percent) [49,60]. Involvement of the axial skeleton was noted in 34 to 52 percent of cases [61]. Pain may be intense and disabling, leading to immobilization.

On physical examination, synovitis or periarticular swelling has been observed in 32 to 95 percent of cases. In one series, large joint effusions were noted in 15 percent of cases. Other manifestations include edematous polyarthritis of fingers and toes and severe tenosynovitis (especially of wrists, hands, and ankles) [62-64]. Grip strength may be diminished.

●Dermatologic involvement – Skin manifestations have been reported in 40 to 75 percent of patients [56,58]. 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) (picture 2). 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.

Atypical dermatologic manifestations include bullous skin lesions (described most often in children) and hyperpigmentation [65]. External ear redness may reflect chondritis [66]. Hemorrhagic manifestations are uncommon.

●Additional manifestations – Additional manifestations during the acute illness may include headache, myalgia, facial puffiness, red eyes, and gastrointestinal symptoms; these are usually self-limited and resolve within one to three weeks. Peripheral lymphadenopathy (most often cervical) may be present (9 to 41 percent of cases) [9,67]. Conjunctivitis may be observed [68]. Oral lesions, often painful ulcers, were found in approximately 20 percent of patients in one series [69,70].

The most common laboratory abnormalities are lymphopenia and thrombocytopenia; these occur in approximately 40 to 50 percent of patients and are transient [53]. Hepatic transaminases and creatinine may be elevated.

The majority of infected individuals are symptomatic; asymptomatic seroconversion occurs in less than 15 percent of patients [1,28].

Severe complications — Severe complications and death have been reported during chikungunya outbreaks. These occur more often among patients >65 years and patients with underlying chronic medical problems (eg, most commonly diabetes and cardiovascular disease) [1,71,72]. In one series including nearly 4000 patients in the United States with travel-acquired chikungunya virus infection, 18 percent were hospitalized and four patients died [25]. The reasons for hospitalization were not provided; hospitalization rates were highest among patients <10 years old (31 percent) and patients ≥70 years old (33 percent) and higher among males than females (23 versus 17 percent) [25].

Severe complications include respiratory failure, cardiovascular decompensation, myocarditis, acute hepatitis, renal failure, hemorrhage, and neurologic involvement [73]. Meningoencephalitis is the most common neurologic complication; other neurologic manifestations include acute flaccid paralysis, Guillain-Barré syndrome, myelitis, seizures (primarily in children), and cranial nerve palsies [72,74-78]. These severe complications occur during the acute phase of infection and their likelihood is influenced by age and underlying medical conditions, including diabetes [79]. Although most are uncommon or rare, during massive outbreaks they are common in patients hospitalized with chikungunya infections.

Ocular manifestations (iridocyclitis, retinitis, episcleritis, macular choroiditis, uveitis) and sensorineural hearing loss have also been described [68,80,81]. One report described extensive skin necrosis of the nose in three severely ill adults [82]. 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 [5,77,83,84].

Deaths associated with chikungunya virus infection were reported during outbreaks in Mauritius, Réunion, India, and the Caribbean [72,83,85-87]. In Réunion, there were 228 deaths; the mean age was 78 years [83]. 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 [87].

Chronic arthritis and arthralgia — In studies of patients with chronic disease due to chikungunya infection, there is a wide range of disease frequency and severity; chronic musculoskeletal disease occurs in 25 to 75 percent of patients [20,61,88]. The range may be due to variability in geography, virus strain, and individual comorbidities. There also is variation among study definitions or distinguished between arthralgias and arthritis.

Chronic manifestations usually involve joints affected during acute illness (see 'Acute infection' above). The joint disease can be relapsing or unremitting and incapacitating. Patients may develop a new chronic inflammatory polyarthritis [61] or may have flares of pre-existing arthritis during and following infection [89] (picture 1 and picture 3). Risk factors for development of chronic rheumatologic manifestations may include age ≥45 years, severity of acute arthritis, and pre-existing osteoarthritis [88].

Most descriptions of chikungunya disease and their sequelae rely upon data from large outbreaks. Persistent and sometimes severe polyarthralgia is the most prominent feature, often without objective signs of inflammation on examination. These patients typically have prolonged morning stiffness and may respond clinically to conventional disease-modifying anti-inflammatory drugs, suggesting that inflammatory arthritis is likely to be the underlying cause of symptoms. This view is further supported by imaging findings in a small number of studies [90-92]. (See "Chikungunya fever: Treatment and prevention", section on 'Chronic arthritis'.)

In addition to arthritis, reported musculoskeletal manifestations include tenosynovitis, frozen shoulder, and plantar fasciitis. New-onset Raynaud phenomena in the second or third month following infection has been observed in up to 20 percent of cases [57]. Patients with chronic arthritis may report joint or bone pain at sites of previous injury. Carpal tunnel syndrome may result from hypertrophic tenosynovitis. Occasionally, sternoclavicular or temporomandibular joints are involved [47]. These findings were observed in a study using ultrasound imaging of 50 patients with chronic chikungunya arthritis, which demonstrated small joint synovitis in 84 percent, wrist synovitis in 74 percent, and finger tenosynovitis in 70 percent [90]. Doppler exam did not show increased vascular flow, and radiography did not demonstrate erosions.

In a 2016 meta-analysis including approximately 5700 patients in 18 studies, chronic inflammatory rheumatism (defined as new-onset arthritis, musculoskeletal pain, or arthralgia) occurred in approximately 40 percent of individuals with chikungunya virus infection; symptoms persisted beyond 18 months in 56 percent of these patients [60]. In a 2018 meta-analysis of studies in the Americas, approximately half of patients with chikungunya virus infection developed chronic disease [93]. In a cohort including more than 480 patients from Colombia followed for 20 months, persistent patient-reported joint pain was observed in 25 percent of cases [94].

The reported duration of symptoms is variable as well. As an example, among 47 patients with acute chikungunya fever followed in one study 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 [57]. In contrast, among 88 patients in Réunion evaluated a mean of 18 months after confirmation of acute chikungunya infection, 63 percent reported persistent polyarthralgia [67]. 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 including 180 patients from Réunion with viremic chikungunya virus infection found that, at 36 months, 60 percent still had arthralgias [61]. A long-term observational study of chikungunya virus induced arthritis in Reunion Island found that 17 out of 30 patients that had previously been diagnosed with chikungunya virus-related chronic inflammatory rheumatic disease had persistent symptoms 13 years later [95]. One study in South Africa reported arthralgia three years after the acute illness in 12 percent of patients [96].

Synovial fluid analysis has been reported in very few patients; some patients exhibit inflammatory joint fluids. In a study describing 19 patients who had undergone arthrocentesis and had a mean duration of symptoms of three months, the mean synovial fluid cell counts were 1900 leukocytes per mL (range 40 to 6500); differential white counts were not reported [47]. Reverse-transcription polymerase chain reaction testing was negative for chikungunya virus genomes in 10 of 10 samples tested by this method, even in two viremic patients [47]. In another study, synovial biopsy of a patient with chronic arthralgia demonstrated inflammatory cell infiltrates with histologic changes similar to rheumatoid arthritis [97].

Cryoglobulins have been reported in patients with persistent symptoms attributed to chikungunya infection (>90 percent in one series) [98], and positive antinuclear antibodies (ANA) have been observed occasionally following infection (although ANA status prior to disease was unknown) [49]. No increase in the frequency of positive rheumatoid factor or anti-citrullinated peptide antibodies has been observed [48,49,91,99].

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 [39]. 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 [100].

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). Fever may be absent in older patients [52].

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 [101]:

●For individuals presenting one to seven 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. Chikungunya virus RNA can be detected by RT-PCR during the first five days following onset of symptoms with excellent sensitivity and specificity (100 and 98 percent, respectively) [10,102].

A negative RT-PCR 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.

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.

A positive IgG antibody test result indicates prior chikungunya infection; it does not indicate whether arthritic symptoms are a consequence of prior infection. The time between possible exposure and clinical history should be evaluated carefully when making a diagnosis of chronic chikungunya viral arthritis in a patient with a positive IgG test.

Testing for dengue virus infection and Zika virus infection should also be pursued. A single PCR test to evaluate for the presence of all three infections is available through the United States Centers for Disease Control and Prevention and other qualified laboratories [103].

Viral culture is a research tool [10,56,104]. 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 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 upon 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".)

●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".)

The possibility of dual infection should be considered if the clinical course is atypical or fever persists longer than five to seven days [105]. Chikungunya virus outbreaks have occurred simultaneously with outbreaks of dengue, Zika virus [106], and yellow fever [107]. In addition, coinfection with chikungunya virus and other pathogens has been described (eg, chikungunya, dengue, and Zika [108], chikungunya and dengue [109], chikungunya and Zika virus [27], chikungunya and yellow fever [105], chikungunya and amebiasis [110]).

A number of other viruses including parvovirus, rubella, enterovirus, adenovirus, other alphaviruses, and hepatitis C may also cause arthritis; these are discussed further separately. (See "Viral arthritis: Causes and approach to evaluation and management".)

Mimics of chronic arthritis — Other causes of chronic arthritis include:

●Seronegative rheumatoid arthritis – Polyarthritis involving hands, wrists, and feet prominently may be a presentation of both rheumatoid arthritis and chikungunya. Chikungunya viral arthritis can closely resemble seronegative rheumatoid arthritis [49]. 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 antibody tests. It is a diagnosis of exclusion. (See "Diagnosis and differential diagnosis of rheumatoid arthritis", section on 'Seronegative rheumatoid arthritis'.)

●Reactive arthritis – Both chikungunya and reactive arthritis can present with acute oligoarthritis. Reactive arthritis refers to arthritis associated with a coexisting or recent antecedent extra-articular 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 – Patients with systemic lupus erythematosus (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 "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults".)

SUMMARY

●Chikungunya virus is an arthropod-borne alphavirus transmitted by mosquitoes that causes acute febrile polyarthralgia and inflammatory arthritis, as well as acute cutaneous eruptions and other systemic manifestations. Chikungunya virus has spread from its ancestral home in West Africa; outbreaks have occurred in Africa, Asia, Europe, islands in the Indian and Pacific Oceans, and in the Americas. Infected travelers can import chikungunya virus into new areas, where local transmission can occur if competent mosquitoes are present. (See 'Epidemiology' above.)

●The United States Centers for Disease Control and Prevention 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 2014; local transmission has been reported widely in Puerto Rico. (See 'Epidemiology' 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 via maternal-fetal transmission and blood products have been described; thus far, transmission of chikungunya via solid organ transplantation has not been documented. (See 'Transmission' above.)

●Following an incubation period of 3 to 7 days (range 1 to 14 days), signs and symptoms of acute infection begin abruptly with fever and malaise. Polyarthralgia often 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, involves distal joints more than proximal joints, and is associated with morning stiffness. The most common skin manifestation is macular or maculopapular rash (usually appearing 3 days or later after onset of illness and lasting 3 to 7 days). The duration of acute illness is usually 7 to 10 days. 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.)

●Patients commonly develop chronic musculoskeletal manifestations, including inflammatory polyarthritis, polyarthralgia, and tenosynovitis during and following acute infection. Inflammatory arthritis can persist for weeks, months, or years. The chronic manifestations usually involve joints affected during the acute illness and can be relapsing or unremitting and incapacitating. (See 'Chronic arthritis and arthralgia' 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 cases. 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 or chikungunya virus serology. Testing for dengue virus infection and Zika virus infection should also be pursued. (See 'Diagnosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Jonathan J Miner, MD, PhD, who contributed to an earlier version of this topic review.