ALPHAVIRUSES

S.K. Lam and K.B. Chua, WHO Collaborating Centre for Arbovirus Reference and
Research (DF/DHF), Department of Medical Microbiology, Faculty of Medicine,
University of Malaya, 50603 Kuala Lumpur.

Alphaviruses are known to give rise to a spectrum of disease in humans, ranging from
silent asymptomatic infections to undifferentiated febrile illness to devastating
encephalitis. The following alphaviruses have been associated primarily with fever
and polyarthritis.

Chikungunya virus

CHIK is responsible for extensive Aedes aegypti-transmitted urban disease in cities in

Africa and major epidemics in Asia. The crippling arthralgia and frequent arthritis that
accompany the fever and other systemic symptoms are clinically distinct. Several
other togaviruses of the alphavirus genus (Ross River, O’nyong-nyong, etc) have been
associated with a similar syndrome. CHIK activity in Asia has been documented since
its isolation in Bangkok in 1958. Other countries which have reported CHIK activity
include Cambodia, Vietnam, Myanmar, Sri Lanka, India, Indonesia, and the
Philippines.

CHIK virus is transmitted in the savannahs and forests of tropical Africa by Aedes
mosquitoes of the subgenera Stegomyia and Diceromyia. Aedes aegypti is an
important vector in urban epidemics in both Africa and Asia.

Clinical Features

CHIK is an acute infection of abrupt onset, heralded by fever and severe arthralgia,
followed by other constitutional symptoms and rash, and lasting for a period of 1-7
days. The incubation period is usually 2-3 days, with a range of 1-12 days. Fever rises
abruptly, often reaching 39 to 40 degrees centigrade and accompanied by intermittent
shaking chills. This acute phase lasts 2-3 days. The temperature may remit for 1-2
days, resulting in a "saddle-back" fever curve.

The arthralgias are polyarticular, migratory, and predominantly affect the small joints
of the hands, wrists, ankles and feet, with lesser involvement of larger joints. Pain on
movement is worse in the morning, improved by mild exercise, and exacerbated by
strenous exercise. Swelling may occur, but fluid accumulation is uncommon. Patients
with milder articular manifestations are usually symptom-free within a few weeks, but
more severe cases require months to resolve entirely. Generalized myalgia, as well as
back and shoulder pain, is common.

Cutaneous manifestations are typical with many patients presenting with a flush over
the face and trunk. This is usually followed by a rash generally described as
maculopapular. The trunks and limbs are commonly involved, but face, palms and
soles may also show lesions. Pruritis or irritation may accompany the eruption.

During the acute disease, most patients will have headache, but it is not usually
severe. Photophobia and retroorbital pain also occur but not severe. Conjunctival
injection is present in some cases. Some patients will complain of sore throat and have
pharyngitis on examination.

CHIK infection has a somewhat different picture in younger patients. Arthralgia and
arthritis occur but are less prominent and last a shorter time. Rash may be less
frequent; but in infants and younger children, prominent flushing and early
appearance of maculopapular or urticarial eruption may be a useful indicator.

In Asia, several virus isolations have been made from severely ill children diagnosed
as having haemorrhagic fever, similar to DHF.

Treatment

Supportive care with rest is indicated during the acute joint symptoms. Movement and
mild exercise tend to improve stiffness and morning arthralgia, but heavy exercise
may exacerbate rheumatic symptoms. In unresolved arthritis refractory to aspirin and
nonsteroidal antiinflammatory drugs, chloroquine phosphate (250 mg/day) has given
promising results.

Diagnosis

The definitive diagnosis can only be made by laboratory means, but CHIK should be
suspected when epidemic disease occurs with the characteristic triad of fever, rash and
rheumatic manifestations.

Virus isolation is readily accomplished by inoculation of mosquito cell culture,

mosquito, mammalian cell culture or suckling mice. Viremia will be present in most
patients during the first 48 hours of disease and may be detected as late as day 4 in
some patients.

Virus-specific IgM antibodies are readily detected by capture ELISA in patients

recovering from CHIK infection and they persist in excess of 6 months.
Haemagglutination inhibition (HI) antibodies appear with the cessation of viremia. All
patients will be positive by day 5 to 7 of illness. Neutralization antibodies parallel HI
antibodies.

Chikungunya IgM serology test is available in University Malaya.

Ross River Virus (Epidemic Polyarthritis)

Striking epidemics of rash and fever were noted in rural Australia as early as 1928.
Both endemic and epidemic transmissions in Australia pose major public health
problems. Although never fatal, the discomfort and loss of productivity from joint
symptoms persist for weeks and occasionally even years. The isolation of Ross River
virus from mosquitoes and its serologic association with epidemic polyarthritis led to
better understanding of the disease.

RRV is endemic and epidemic in tropical and temperate regions of Australia. Large
epidemics have been reported from Northern Territory, Queensland, Victoria, South
Australia and New South Wales. Aedes mosquitoes such as Aedes vigilax and Aedes
camptorhynchites, Culex annulirostris and Mansonia uniformis have been implicated
as vectors.

Clinical Features

In Australian cases, the incubation period has been estimated to be 10-11 days. Onset
is relatively sudden and the first symptom is usually joint pain. Rash occurs in the
majority of patients, usually coincident with, or 1-2 days after, initial symptoms but in
some cases rash preceded joint pains by 11 days and followed them as much as 15
days. The eruption is usually macular, papular, or both and occasionally is
accompanied by vesiculation of the papules or petechiae. The eruption is typically
most prominent on the trunk and limbs and may involve the palms, soles, and face. In
a minority of patients it is itchy, and it fades within a few days. Constitutional
symptoms such as fatigue and lethargy occur in only half the patients. Body
temperature is normal, or in half the patients modestly elevated for 1-3 days. Myalgia,
headache, anorexia, and nausea are common.

Three-fourths of patients have joint manifestations and are incapacitated for

considerable periods of time. The severity of the pain interferes with sleeping,
walking or grasping everyday objects. Involvement of multiple joints, often
asymmetrical and usually migratory, occurs. Wrists, ankles, metacarpophalangeal,
interphalangeal, and knee joints are most common, although toes, shoulders, and
elbows are also targets. Joints of the spine, hip and jaws are least often affected.
Arthralgias are worse in the mornings or after immobilization; modest exercise may
improve them. About one-third of patients will have true arthritis. Periarticular
swelling and tenosynovitis are also common. 10-30% of patients will have
paresthesias and/or pain in the palms and soles.

Most patients will be unable to work or perform house work; but by 4 weeks, half will
be able to resume normal activities, albeit with residual arthralgia. About 10% will
still be limited by joint symptoms at 3 months. Occasional patients will continue to
have signs and symptoms of articular disease for 1-3 years.

Treatment and Prevention

Aspirin and, if no relief obtained, nonsteroidal antiinflammatory drugs should be used

for relief of joint pains. Because eventual complete recovery is always assured,
steroids should not be used.

A prototype inactivated vaccine has been produced in Australia.

SOURCE : FIELDS VIROLOGY (3RD EDITION)