Differentials
Dengue fever
SIGNS / SYMPTOMS
When dengue is symptomatic the manifestations are quite prominent; however, many patients may have a subclinical presentation. Chikungunya virus infection is almost always symptomatic.
Joint symptoms are an important difference. Their presence favors a diagnosis of chikungunya virus infection.
Incubation period for dengue can be longer, extending from 3 to 14 days.
In severe cases, dengue can cause a hemorrhagic syndrome, which is unusual with chikungunya virus infection. Circulatory collapse is also characteristic of severe dengue.
In children, fever lasting <2 days, presence of skin rash concomitantly with the fever, and a white blood cell count of >5000 cells/mm³ suggests chikungunya virus infection.
Cases of coinfection have been described in endemic areas.[69][70]
INVESTIGATIONS
The diagnosis of dengue is based on detection of antibodies or molecular diagnosis using polymerase chain reaction.
The World Health Organization has produced a tool to help physicians differentiate between chikungunya, dengue, and Zika virus infection.[62]
Zika virus infection
SIGNS / SYMPTOMS
Characterized by fever, rash, myalagia, arthralgia, headache, retro-orbital pain, conjunctivitis, and vomiting. Symptoms may be indistinguishable from chikungunya virus infection or dengue fever.
Transmitted by Aedes mosquitoes and has been reported in Mexico, South America, Africa, and South East Asia.
INVESTIGATIONS
The diagnosis is confirmed by reverse transcription polymerase chain reaction. Serology tests are available, but they strongly cross-react with other flaviviruses, such as dengue and West Nile viruses.
The World Health Organization has produced a tool to help physicians differentiate between chikungunya, dengue, and Zika virus infection.[62]
Oropouche virus disease
SIGNS / SYMPTOMS
Residence in/travel from Oropouche virus-endemic region (or area with an ongoing outbreak). Endemic to the Amazon region, but has spread to other countries in the Americas in recent years.
Clinical signs and symptoms are similar to other arboviral diseases so it is difficult to differentiate without laboratory testing.[71]
Most cases are mild; however, hemorrhagic manifestations or neuroinvasive disease can occur rarely.
Vertical transmission has been reported with adverse pregnancy outcomes, including fetal deaths and congenital abnormalities.[71]
INVESTIGATIONS
The diagnosis is based on viral RNA or antibody detection.[72]
Yellow fever
SIGNS / SYMPTOMS
The infection can be transmitted by Aedes aegypti, but it occurs only in Africa and South America.
Patients with yellow fever usually have a more toxic appearance and higher fever. The liver can be tender and enlarged on examination. Elevated aminotransferases are more prominent. Deterioration can occur with renal and liver failure and with hemorrhagic manifestations.
INVESTIGATIONS
The diagnosis is confirmed via detection of IgM by enzyme-linked immunosorbent assay, molecular diagnosis, or direct virus isolation.
Mayaro virus infection
SIGNS / SYMPTOMS
The clinical presentation may be indistinguishable from chikungunya virus infection; however, Mayaro infection is confined to tropical forests of South America.
INVESTIGATIONS
The diagnosis, similar to other arboviruses, can be made via serology, reverse transcription polymerase chain reaction, or direct virus isolation.
Ross River virus infection
SIGNS / SYMPTOMS
The clinical presentation may be indistinguishable from chikungunya virus infection; however, Ross River virus infection is confined to Australia, particularly Queensland, the Northern Territory, and tropical Western Australia, New Guinea, and some islands of the South Pacific.
INVESTIGATIONS
The diagnosis is based on antibody detection
Barmah Forest virus
SIGNS / SYMPTOMS
The clinical presentation may be indistinguishable from chikungunya virus infection; however, Barmah Forest infection is confined to Queensland, Australia.
INVESTIGATIONS
The diagnosis is based on antibody detection.
O’nyong-nyong virus
SIGNS / SYMPTOMS
The clinical presentation may be indistinguishable from chikungunya virus infection; however, O’nyong-nyong infection has been described only in Kenya, Tanzania, Democratic Republic of Congo, and Mozambique.
INVESTIGATIONS
The diagnosis is based on antibody detection.
Sindbis virus infection
SIGNS / SYMPTOMS
The clinical presentation may be indistinguishable from chikungunya virus infection; however, clinical Sindbis infection in humans has almost exclusively been reported in northern Europe. Occasional cases have occurred in Australia, China, and South Africa.
INVESTIGATIONS
The diagnosis is based on antibody detection.
Hemorrhagic fevers
SIGNS / SYMPTOMS
This is an encompassing name that includes diseases caused by viruses from 4 distinct families: arenavirus, bunyavirus, filovirus (including Ebola) and flavivirus. The initial manifestations of these viruses may overlap with the clinical presentation of chikungunya virus infection; however, the progression to severe disease with bleeding from skin and mucosas and the relatively narrow geographic location of cases helps in the differential diagnosis.
INVESTIGATIONS
Diagnosis is based on antibody detection or molecular diagnosis. Direct isolation is recommended in biosafety level 4 laboratories.
West Nile virus infection
SIGNS / SYMPTOMS
The main difference with chikungunya virus infection is the lack of prominent joint symptoms and the presence of neurologic manifestations, including meningitis, encephalitis, and occasionally flaccid paralysis.
INVESTIGATIONS
Diagnosis is based on serologic detection of antibodies.
Rheumatoid arthritis
SIGNS / SYMPTOMS
Rheumatoid arthritis is not preceded by an acute febrile illness.
The chronic form of chikungunya virus infection can be difficult to differentiate from rheumatoid arthritis as cases have been described that fulfill the criteria proposed by the American College of Rheumatology, including arthritis of 3 or more joints, arthritis of hand joints, symmetric arthritis, erosions in radiological imaging, and even positive rheumatoid factor.
INVESTIGATIONS
Diagnosis of rheumatoid arthritis is based on clinical criteria, positive rheumatoid factor, and presence of bone erosions in radiologic evaluation. Anti-cyclic citrullinated peptide antibodies are less commonly positive in chikungunya virus infection.[60]
Seronegative spondyloarthropathy
SIGNS / SYMPTOMS
The disease is usually not preceded by a febrile illness.
Back pain is the main symptom, associated with prominent stiffness and decrease in spine range of motion. The pain is usually relieved with exercise.
INVESTIGATIONS
Diagnosis is based on clinical criteria. Imaging of the spine and testing for HLA-B27 may also be helpful.
Typhoid fever
SIGNS / SYMPTOMS
Pulse-temperature dissociation may occur in typhoid fever. The rash is macular and has a preference for the abdominal area.
Hepatosplenomegaly, gastrointestinal bleeding, abnormal mental status, and frank sepsis may occur after the third week of infection.
INVESTIGATIONS
Diagnosis is confirmed by isolation of Salmonella enterica in blood, urine, stool, or bone marrow cultures. Serologic antibody titers measured during acute and convalescing periods may also be used for diagnosis.
Leptospirosis
SIGNS / SYMPTOMS
Bone pain is less common. In severe cases, jaundice, renal failure, and bleeding can occur. There is usually a history of exposure to contaminated water or soil, or contact with infected animals or their depositions.
INVESTIGATIONS
Diagnosis depends on detection of antibodies, real-time polymerase chain reaction, or, less commonly, cultures of blood or urine.
Malaria
SIGNS / SYMPTOMS
Anemia and jaundice are more common with malaria. Also complications such as hypoglycemia, renal impairment, cerebral malaria, and pulmonary edema are not seen with chikungunya virus infection.
INVESTIGATIONS
Diagnosis is confirmed via direct identification of parasites in the blood smear, rapid antigen detection, or molecular testing.
Measles
SIGNS / SYMPTOMS
The exanthema starts in the face and extends centrifugally, then it darkens in 3 to 4 days and desquamates after a week or so. Koplick spots in the buccal mucosa are pathognomonic of measles. Pneumonia is a frequent complication.
INVESTIGATIONS
Diagnosis is made by detection of IgM antibodies, polymerase chain reaction, or viral culture.
Rubella
SIGNS / SYMPTOMS
Prominent lymphadenopathy affecting posterior cervical, posterior auricular, and suboccipital lymph nodes is common. Enanthema on the soft palate (Forchheimer spots) can occur. Orchitis can be a complication.
INVESTIGATIONS
Diagnosis is made by antibody detection or rarely via viral culture.
Rocky Mountain spotted fever
SIGNS / SYMPTOMS
The rash tends to evolve into a purpuric appearance. It classically affects palms and soles. Common complications include: encephalitis, adult respiratory distress syndrome, cardiac arrhythmias, coagulopathy, gastrointestinal bleeding, and skin necrosis.
INVESTIGATIONS
The diagnosis is made by detection of antibodies, direct immunofluorescence, or immunoperoxidase staining in skin biopsies. Polymerase chain reaction could be used, but sensitivity is low early in the course of the disease.
Epstein-Barr virus infection
SIGNS / SYMPTOMS
Maculopapular and pruritic rash may follow administration of ampicillin or amoxicillin. Complications such as airway obstruction from massive adenopathy and spleen rupture may occur.
INVESTIGATIONS
Diagnosis is made by detection of heterophile antibodies or Epstein-Barr virus-specific antibodies and by DNA detection.
Acute retroviral syndrome following HIV infection
SIGNS / SYMPTOMS
A history of recent sexual contact is usually obtained. During the acute retroviral syndrome pharyngitis can be prominent. The rash may affect the palms and soles.
INVESTIGATIONS
The best diagnosis method for acute retroviral syndrome is real-time polymerase chain reaction.
Coronavirus disease 2019 (COVID-19)
SIGNS / SYMPTOMS
Important to consider the current COVID-19 epidemiologic situation and any recent outbreaks. May give history of COVID-19 exposure. Not a known mosquito-borne disease. Respiratory symptoms may be prominent. Presence of anosmia or altered taste may help to differentiate but are less commonly features of infection with newer variants.
INVESTIGATIONS
Real-time reverse transcription polymerase chain reaction (RT-PCR): positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Rapid antigen tests may also be used.
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