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)

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Last Updated 11 May 2005


Article in Malaysian Medical Newsletter Cybermed column on Chikungunya virus.

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