Chikungunya Virus
Chikungunya virus belongs to the Alphavirus genus and causes a viral infection
characterized by fever and joint pain. The arthropod-borne (arbovirus) virus is
transmitted by mosquitoes (commonly Aedes albopictus and Aedes aegypti).
Symptoms usually appear within 1 week of infection. Additional manifestations of
chikungunya virus may include muscle pain, headache, maculopapular rash, and
lymphadenopathy. Most infected individuals recover, but chronic arthritis may
develop. Treatment is aimed at relieving symptoms. The disease is prevented by
mosquito avoidance, use of insect repellent, and protective clothing.
Last updated: October 10, 2022
CONTENTS
Classification
General Characteristics
Pathogenesis
Clinical Presentation
Diagnosis
Management
Comparisons of Species
Differential Diagnosis
References
Classification
RNA virus identification:
Viruses can be classified in many ways. Most viruses, however, will have a genome formed by
either DNA or RNA. RNA genome viruses can be further characterized by either a single- or
double-stranded RNA. "Enveloped" viruses are covered by a thin coat of cell membrane
(usually taken from the host cell). If the coat is absent, the viruses are called “naked” viruses.
Viruses with single-stranded genomes are “positive-sense” viruses if the genome is directly
employed as messenger RNA (mRNA), which is translated into proteins. “Negative-sense,”
single-stranded viruses employ RNA dependent RNA polymerase, a viral enzyme, to
transcribe their genome into messenger RNA.
Image by Lecturio. License: CC BY-NC-SA 4.0
General Characteristics
Basic features
Chikungunya virus:
Togaviridae family
Alphavirus genus
Genome:
Positive-sense, single-stranded RNA
Size: 11.8 kb
Properties:
Enveloped
Lipid-bilayer envelope has viral-encoded glycoproteins, which mediate
cell attachment and entry:
E1: consists of fusion peptides, which dissociate from E2 in low pH
and facilitate the release of nucleocapsids into the host cytoplasm
E2: binds to cellular receptors, resulting in receptor-mediated
endocytosis
Small, icosahedral capsid
Epidemiology
Geographic distribution:
Frequent outbreaks:
Africa
Southeast Asia
Indian subcontinent
South America and islands of the Caribbean
United States:
Cases reported from travelers to the above areas
Local transmission noted in Florida, Puerto Rico, and the United States
Virgin Islands
Pathogenesis
Vectors
Mosquitoes of the Aedes genus
Major vectors (also transmit Zika virus and dengue virus):
A. aegypti
A. albopictus
Reservoirs
Humans
Primates: The virus is seen in Africa and maintained in the sylvatic cycle (e.g.,
wild primates, monkeys, and mosquitoes).
Transmission
Transmitted from mosquitoes to humans
Vertical transmission (rare)
Blood transfusion (rare)
The life cycle of the chikungunya virus in Africa showing the interconnection between the
sylvatic cycle, involving primates and mosquitoes, and the urban cycle, involving humans and
mosquitoes.
Image: “Life cycle of Chikungunya virus” by Michelle M Thiboutot et al. License: CC BY 4.0
Host risk factors
Proximity to mosquito breeding sites
Severe disease can occur in:
Newborns
Adults ≥ 65 years of age
Individuals with underlying conditions such as diabetes or cardiovascular
disease
Pathophysiology
Chikungunya virus is introduced to the human skin and bloodstream via a
mosquito bite.
Viral replication occurs in the dermal fibroblasts, then the bloodstream:
The virus directly invades and replicates within the joints and muscles.
↑ In proinflammatory cytokines and inflammatory cells
Dissemination to and invasion of other organs may occur:
Liver (endothelial cells)
Brain (endothelial and epithelial cells)
Lymphoid tissue (lymph nodes and spleen)
Chronic joint disease is seen in up to 60% of patients and caused by:
Persistent viral replication
Continued immune response to remaining RNA
Autoimmunity
Clinical Presentation
Neonatal infection
Infection of newborns is seen within 1 week of delivery. Signs and symptoms
include:
Fever
Poor feeding
Edema
Rash
Thrombocytopenia
Neurologic disease (meningoencephalitis)
Infection of children and adults
The incubation period is 3–7 days. Symptoms of chikungunya fever appear
within 1 week of infection and include:
High-grade fever
Debilitating arthralgia and arthritis:
Bilateral and symmetric
Polyarticular: commonly involves the small joints of the hands, wrists, and
ankles
Patients are often in a flexed posture due to pain.
The development of chronic arthritis increases in those ≥ 45 years of age
and/or with preexisting osteoarthritis.
Headache
Muscle pain
Maculopapular rash (extremities and trunk)
Conjunctivitis
Lymphadenopathy
Severe symptoms may occur in those with risk factors:
Encephalitis
Myocarditis
Hepatitis
Renal failure
Hemorrhage
Symmetrical polyarthritis of the small joints in an individual with chikungunya fever in the
chronic stage
Image: “Symmetrical inflammatory polyarthritis of the small joints of the hands and tenosynovitis of the wrist
joints in a patient with chronic stage of Chikungunya fever” by Alladi Mohan et al. License: CC BY 2.0
Diagnosis
Diagnostics
Clinical history: fever, joint pain, and relevant exposure (i.e., travel to or living in
an endemic area)
Confirmatory tests:
Serology via ELISA or indirect fluorescent antibody (IFA):
IgM noted by the 5th day of symptom onset and may persist up to 3
months
IgG noted by 2 weeks after symptom onset
RT-PCR of chikungunya virus RNA
Viral culture
Additional tests
Because the symptom complexes are similar and patients may be coinfected
with more than 1 virus, the CDC and WHO recommend testing for chikungunya,
dengue, and Zika viruses in patients presenting with suspicious symptoms.
CBC:
Lymphopenia
Thrombocytopenia
Other findings:
↑ Hepatic transaminases
↑ Creatinine
Management
Acute disease
Treatment of chikungunya fever is symptomatic:
Analgesia:
Acetaminophen for pain and fever
Avoid NSAIDs and aspirin until dengue fever is ruled out (due to bleeding
risk).
Hydration
Rash spontaneously resolves and symptoms generally improve within 1 month.
Post-acute disease
Symptoms may persist or relapse, especially joint pain.
Analgesics such as acetaminophen and/or NSAIDs can be used.
For severe synovitis and continued elevation of inflammatory markers, a short
course of glucocorticoids can be given.
For symptoms ≥ 3 months, disease-modifying antirheumatic drugs (DMARDs)
such as methotrexate and sulfasalazine can be given.
Prevention
Avoid mosquito breeding areas by environment control (i.e., no standing water
in containers) and use personal protection:
Insect repellent
Wear protective clothing.
Sleep under a mosquito net.
Comparisons of Species
Chikungunya virus and the equine encephalitis virus belong to the Alphavirus
genus and are major etiologies of encephalitis in the United States.
Table: Comparison of chikungunya virus and equine encephalitis
virus
Organism Chikungunya virus Equine encephalitis virus
Family Togaviridae
Genus Alphavirus
Characteristics Enveloped, icosahedral capsid
Positive sense
ssRNA
Transmission Mosquito
Clinical Fever Fever
Headache Headache
Arthritis Nausea/vomiting
Rash Severe: encephalitis
Diagnosis Serology
RT-PCR
Management Symptomatic Supportive
Control of joint pain
Prevention Mosquito avoidance
Insect repellent
Protective clothing
Mosquito net
Differential Diagnosis
Conditions mimicking acute chikungunya fever, have a similar symptom
complex, and belong to the Flaviridae family and Flavivirus genus:
Dengue virus: a small, positive-sense, single-stranded RNA virus transmitted to
humans by the bite of a female Aedes mosquito. Most infections are
asymptomatic. Symptomatic individuals may progress through different stages.
The febrile phase includes fever, headache, retro-orbital pain, myalgias,
arthralgias, and maculopapular rash. More severe manifestations of capillary
leakage, hemorrhage, and shock may occur in the critical phase. Resolution of
signs and symptoms occur in the convalescent phase. Diagnostic tests include
serology, antigen testing, or PCR. Management is supportive.
Zika virus: a positive-sense, single-stranded RNA virus most commonly
transmitted by an A. aegypti mosquito. The virus can also be transmitted
sexually and transplacentally. Most infected patients are asymptomatic, but
some may present with low-grade fever, pruritic rash, and conjunctivitis.
Congenital Zika syndrome is a transplacental, fetal infection, which manifests
with ocular defects, microcephaly, spasticity, and seizures. The diagnosis is
made either by RT-PCR or serology. Treatment is mostly supportive. Prevention
includes control of the mosquito population with insect repellent, and
protective clothing.
Conditions presenting as chronic arthritis:
Seronegative rheumatoid arthritis: inflammatory arthritis in 3 or more joints,
which lasts for > 6 weeks. Rheumatoid factor and anti-cyclic citrullinated
peptide tests are negative and could present similarly to chikungunya infection.
Serology and history (including travel) distinguish seronegative rheumatoid
arthritis from chikungunya infection.
Reactive arthritis: arthritis occurring concomitantly with or after an
extraarticular infection. Characteristics include asymmetric oligoarthritis (often
involving the lower extremities), enthesitis, back pain, and dactylitis. Diagnosis
is made by history (GI or urinary infection is often noted) and ruling out other
arthritis etiologies with laboratory work-up and imaging.
References
