8c

Viral infections: cz-viral arthropathy

P A U L E. M c G I L L

ARTHRITIS CAUSED BY MOSQUITO-BORNE VIRUSES

There are six viruses transmitted by mosquitoes known to cause arthritis in humans (Chikungunya, O'nyong-nyong, Sindbis, Ross River, Mayaro and Barmah Forest). The physical and antigenic properties of these viruses and the disorders they produce are similar. In this review the characteristics of the viruses and the diseases which they produce are summarized together and their epidemiology individually.

The viruses

All the spherical RNA-containing viruses and members of the family Togaviridae, genus or-virus. Intracerebral inoculation of o~-virus causes a fatal encephalitis in new-born mice. Following subcutaneous inoculation, a myositis and enthesitis have been observed, mimicking the clinical picture which occurs in humans.

CLINICAL FEATURES

A triad of fever, arthralgia and rash constitutes the main clinical features of persons affected with these oL-viruses. Arthralgia alone or fever and arthralgia without rash may occur, making isolated cases of o~-virus arthritis difficult to diagnose. Sporadic cases occur regularly in endemic areas but the majority are epidemic in nature, and seasonal depending on rainfall which enhances mosquito vector transmission. During epidemics, identification of classical cases should indicate the diagnosis. Most cases are diagnosed clinically without serological confirmation and it is likely that mild cases are missed. Other arthropod viral diseases such as dengue and West Nile fever may also present with arthralgia and rash. Arthritis, however, is a distinctive clinical feature of a-virus infection.

Fever

This is nearly always the first symptom preceding joint pains and rash. In Chikungunya (Chik) and Mayaro infection a high fever is accompanied by

Baillikre's Clinical Rheumatology-- Vol. 9, No. 1, February 1995 ISBN 0-7020-1946-1

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146 v.E. McGILL

conjunctivitis, headache, photophobia and myalgia. The fever lasts up to 10 days and may recur after an afebrile period. The other viruses cause a fever of a lower order, lasting 2-3 days only and associated constitutional symptoms are milder.

Arthralgia and arthritis

In nearly all cases fever is followed by joint pain. An exception may be Ross River virus (RRV) infection where in about one-half of patients arthritis may precede the rash for up to 15 days. In Sindbis virus infection myalgia and enthesitis are more prominent than arthritis. Otherwise, those afflicted experience severe, usually symmetrical peripheral polyarthritis affecting hands, feet, wrists, ankles, elbows and knees to a variable degree. Tender- ness and swelling, usually for several days, followed by complete recovery is the rule in most cases. A minority experience continuous pain and difficulty for several weeks whilst some develop a relapsing course over several months. An exception may be Chik; in a retrospective study of 107 cases of serological-proven infection, 3 years after contracting the disorder, 12% of patients had some form of joint stiffness and discomfort associated with very high titres of antibody (Brighton et al, 1983). Brighton and Simson (1984) describe a case of Chik arthritis, progressing to joint destruction of the feet and ankles, before ultimately subsiding after 15 years.

Rash

The rash is characteristically maculopapular and erythematous, occurring 2-5 days after the onset and lasts up to 10 days before fading, with some staining but no desquamation. A vesicular rash sometimes occurs in Sindbis, RRV and Barmah Forest virus (BFV). Bleeding into the papules may occur and a more extensive haemorrhagic state with haematemesis and melaena has been recorded in South-East Asia and India in some cases of Chik infection. Dengue virus is a more frequent cause of an haemorrhagic state in this region (Sarkar et al, 1965).

Tender cervical lymphadenopathy is common but generalized lymph- adenopathy and hepatosplenomegaly are rare. Conjunctivitis and pharyn- gitis may be observed. Some patients develop severe weakness and paraesthesiae, suggestive of neuropathy but no permanent neurological sequelae have been observed. Routine laboratory tests are usually normal with a normal sedimentation rate. Rheumatoid factor and other antibody tests are negative.

EPIDEMIOLOGY

Chikungunya

The name chikungunya comes from the Swahili for 'he who walks doubled- up', describing the crippling joint pain encountered during the acute stage of

VIRAL INFECTIONS: iX-VIRAL A R T H R O P A T H Y 147

the illness. First described in the Newala province of Tanzania (Robinson, 1955), further outbreaks in Africa occurred in the eastern Transvaal (Gear, 1957), Zambia (Rodger, 1961) and Nigeria (Moore et al, 1969). There is evidence that the disease has occurred sporadically in India throughout the past 200 years (Carey et al, 1969) and extensive epidemics have been described in Thailand (Nummannity et al, 1969), Vietnam (Deller and Russel, 1968) and India (Jadhav et al, 1965; Ranitz et al, 1965).

In rural Africa the virus circulates in baboons and vervet monkeys, infecting forest Aedes mosquitoes (A. africanus, A. furcifer). By contrast, urban outbreaks of Chik infection are associated with Aedes aegypti and the virus may be maintained in a man-mosquito-man cycle. Chik tends to occur in epidemics where conditions favour the breeding of mosquitoes (e.g. wet season) and a sufficient proportion of the human population is susceptible to infection. In endemic areas sporadic cases occur regularly.

Serological surveys indicate that infection has occurred in Mozambique, Namibia, Botswana and Angola (McIntosh et al, 1963). In Uganda (Rodhain et al, 1987), and Burundi (Rodhain et al, 1989) antibodies against Chik virus were the most prevalent followed by flavivirus antibody probably due to West Nile virus. In Nigeria 52% of 477 human sera from a variety of locations were antibody-positive for Sindbis virus and 15% Chik virus (Adesina and Odelola, 1991).

O'nyong-nyong

Like Chik virus, this was isolated first in East Africa, in the northern province of Uganda in 1959 (Shore, 1961). The name means 'joint breaker', a description given to the disease by the Acholi tribe. Its epidemiology is poorly understood but the virus has been recovered in Uganda, Kenya, Tanzania, Malawi and Senegal (Berge, 1975). O'nyong-nyong is transmitted most probably by Anophelesfunestus and Anopheles gambiae. An extensive outbreak occurred in East Africa between 1959 and 1962 when an estimated 2 million people were affected (Haddow et al, 1960). In some areas, over 90% of the population had either clinical disease or inapparent infection. Chik and O'nyong-nyong occur in the same areas of Africa, are closely related antigenically and produce similar disease. They may be, therefore, difficult to differentiate. However, no large-scale outbreaks of O'nyong- nyong have been recorded since 1962.

Mayaro

Mayaro is known to occur in Trinidad, Brazil, Surinam, Colombia and Bolivia (Berge, 1975). Surveys for antibodies in sera of residents in Rio de Janeiro have shown one-third to be positive although clinical infection has been recorded only in those who inhabit or work in tropical forests (Causey and Maroja, 1957; Pinheiro et al, 1981). Mayaro infection has been reported in parallel with outbreaks of sylvan yellow fever; both diseases probably have the same mosquito vector.

148 P . E . M c G I L L

Sindbis

Sindbis is the name of the Egyptian village near Cairo where the first isolation was made in 1950 from a crow, reflecting its main reservoir in birds. It is the most widely distributed of the six human arthritogenic c~-viruses and studies by McIntosh et al (1964) in South Africa implicated Culex mosquitoes as the primary vector. Clinical disease is uncommon with reported cases usually being sporadic in occurrence. Culex mosquitoes feed mainly on birds and infrequently bite humans, explaining the relative infrequency of human disease in the presence of a very widely distributed virus recognized outside the tropics in Australia, the former USSR (Karelian fever), Sweden (okelbo disease), and Finland (pogosta disease).

RRV

From its first description in 1928 by Nimmo in Australia, where it was dubbed 'epidemic polyarthritis', RRV has continued to excite interest. Human infection has been reported in New Guinea and the Solomon Islands (Scrimgeour et al, 1987). In Australia the disease occurs in endemic and epidemic forms, mainly during the summer and autumn months among visitors to rural areas where the virus is probably maintained in an animal/ mosquito cycle with Culex annulirostris and Aedes vigilax being the principal vectors. Tai et al (1993) described an extensive outbreak in Australia's Northern Territory during a period of unusually high rainfall. From July 1990 to June 1991 368 cases were identified in a population of 150 000. Local variations in attack rate was related to the success of ground water and mosquito control measures. During 1979-1980 major epidemics of infection occurred on a number of isolated South Pacific islands (Thomson et al, 1979; Rosen et al, 1981; Tesh et al, 1981). The outbreaks were of sudden onset and affected a large percentage of a susceptible population, including a high proportion of American, Australian and New Zealand tourists. It is likely that the virus is maintained in a"man-mosquito-man cycle with Aedes polynesiensis the probable vector.

BFV

BFV was first isolated in 1974 from the mosquito Culex annulirostris in the Murray River basin, Australia, and subsequently in most states of Australia (Anon, 1991). Cases of human infection were first identified in 1988 followed by a series of 29 cases in 1990 (Phillips et al, 1990). BFV infection is probably under-diagnosed because of its clinical similarity to the RRV and Sindbis infection, their shared geographical distribution and the small number of laboratories offering a diagnostic service (Boughton et al, 1984). Clinical features observed in the above study were polyarthritis (79%), arthralgia and myalgia (74%) and fever (63%). A rash, often vesicular, was found in half the patients in this study. The illness is relatively mild. There is a high rate of sub-clinical infection, especially in New South Wales and Queensland where an estimated 2.3% of the resident population may be

VIRAL INFECTIONS: OL-VIRAL ARTHROPATHY 149

infected each year (Hawkes et al, 1987; Phillips et al, 1990). Both RRV and BFV are transmitted by similar mosquitoes and simultaneous infection has been reported (Phillips et al, 1990). It is not yet known whether BFV is present in other countries but the potential for spread in the fashion of RRV must surely exist.

SUMMARY

Six different mosquito-borne viruses (Chikungunya, O'nyong-nyong, Mayaro, Ross River, Sindbis and Barrnah Forest) have been associated with arthritis in humans. These viruses are prevalent in the tropics and subtropics and they produce similar symptoms, consisting of fever, joint pains and rash. The symptoms are usually of short duration, around 1 week; complete recovery is the rule apart from exceptional cases of Chik infection.

Precise diagnosis requires a serological service which is not available in many parts of the tropics these days. Treatment is symptomatic and there is no vaccine currently available. With an increasing number of visitors to the tropics being exposed to potential infection and with rapid air transport it is possible that visitors may return home during the viraemic incubation stage, infect the local mosquito populations and then develop clinical disease.

REFERENCES

Adesina OA & Odelola HA (1991) Ecological distribution of chikungunya haemaglutination inhibition antibodies in human and domestic animals in Nigeria. Tropical and Geo- graphical Medicine 43: 271-275.

Anon (1991) Barmah Forest virus. Lancet 337: 948-949. Berge TO (1975) International Catalogue ofArboviruses (2nd edn) United States Department

of Health Education and Welfare, Public Health Service, DHEW Publication No. (CDC) 75-8301.

Boughton CR, Hawkes RA, Naim HL et al (1984) Arbovirus infection in humans in New South Wales. Medical Journal of Australia 141: 700-704.

Brighton SW & Simson IW (1984) A destructive arthropathy following chikungunya virus arthritis: a possible association. Clinical Rheumatology 3: 253-258,

Brighton SW, Prozesky OW & Harpe AL de la (1983) Chikungunya virus infection. A retrospective study of 107 cases. South African Medical Journal 63: 313--315.

Carey DE, Myers RM, DeRanitz CM et al (1969) The 1964 chikungunya epidemic at Vellore, South India, including observations on concurrent dengue. Transactions of the Royal Society of Tropical Medicine and Hygiene 63: 434-445.

Causey OR & Maroja OM (1957) Mayaro virus: A new human disease agent III. Investigation of an epidemic of acute febrile illness on the river Guama in Para, Brazil, and isolation of Mayaro virus as causative agent. American Journal of Tropical Medicine and Hygiene 6: 1017-1023.

Deller JJ Jr & Russel PK (1968) Chikungunya disease. American Journal of Tropical Medicine and Hygiene 17: 107-111.

Fourie ED & Morrison JGL (1979) Rheumatoid arthritic syndrome after chikungunya fever. South African Medical Journal 56: 130-132.

Gear J (1957) The occurrence of a Dengue-like fever in the north-eastern Transvaal. Clinical features and isolation of virus. South African Medical Journal 31: 253-257.

Haddow A J, Davies CW & Walker AJ (1960) O'nyong-nyong fever: an epidemic virus disease in East Africa. Transactions of the Royal Society of Tropical Medicine and Hygiene 54: 517-522.

150 P . E . McGILL

Hawkes RA, Boughton CR, Naim HM et al (1987) Barmah forest virus infections in humans in New South Wales. Medical Journal of Australia 146: 569-573.

Jadhav M, Namboodripad M, Carman RH et al (1965) Chikungunya disease in infants and children in Vellore: A report of clinical and haematological features of virologically proved cases. Indian Journal of Medical Research 53: 764-774.

McIntosh BM, Harwin RM, Paterson HE & Westwater ML (1963) An epidemic of chikungunya in south-eastern Rhodesia. Central African Journal of Medicine 9:351-359.

McIntosh BM, McGillivray GM, Dickinson DB & Malherbe H (1964) Illness caused by Sindbis and West Nile viruses in South Africa. South African Medical Journal 38" 291-294.

Nimmo JR (1928) An unusual epidemic. Medical Journal of Australia 1: 549-550. Nummannitya S, Halstead SB, Cohen SN & Margiotta MR (1969) Dengue and chikungunya

virus infection in man in Thailand 1962-64. American Journal of Tropical Medicine and Hygiene 18: 954-971.

Phillips DA, Murray JR, Aaskov JG & Weimers MA (1990) Clinical and sub-clinical Barmah forest virus infection in Queensland. Medical Journal of Australia 152: 463-466.

Pinheiro FP, Freitas RB, Rosa da JFT et al (1981) An outbreak of Mayaro virus disease in Belterra, Brazil. American Journal of Tropical Medicine and Hygiene 30: 674-681.

Ranitz CM de, Myers RM, Varkey MJ et al (1965) Clinical impressions of chikungunya in Vellore gained from study of adult patients. Indian Journal of Medical Research 53: 756-763.

Robinson MC (1955) An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. Transactions of the Royal Society of Tropical Medicine and Hygiene 49: 28-32.

Rodhain F, Carteron B, Laroche R & Hannoun C (1987) Human arbovirus infection in Burundi: results of a sero-epidemiological survey 1980-82. Bulletin de la Societe de Pathologie Exotique Filiares 80: 155-161.

Rodhain F, Gonzales JP, Mercier E et al (1989) Arbovirus infections and viral haemorrhagic fevers in Uganda: a serological survey in Karamoja district. Transactions of the Royal Society of Tropical Medicine and Hygiene 83: 851-854.

Rosen L, Gubler DJ & Bennett PH (1981) Epidemic polyarthritis: (Ross River Virus infection) in the Cook Islands. American Journal of Tropical Medicine and Hygiene 30: 1294-1302.

Sarkar JK, Chatterjee SN, Chakravarti SK & Mitra AC (1965) Chikungunya virus infection with haemorrhagic manifestations. Indian Journal of Medical Research 53: 921-925.

Scrimgeour EM, Aaskov JG & Matz LR (1987) Ross River virus arthritis in Papua, New Guinea. Transactions of the Royal Society of Tropical Medicine and Hygiene 81: 833-834.

Shore H (1961) O'nyong-nyong fever: Transactions of the Royal Society of Tropical Medicine and Hygiene 55: 361-373.

Tesh RB, McLean RG, Scroyer DA et al (1981) Ross River virus infection (epidemic poly- arthritis) in America Samoa. Transactions of the Royal Society of Tropical Medicine and Hygiene 75: 426-431.

Thomson KDB, Austin FJ, Macguire T & Miles AR (1979) Epidemic polyarthritis in Fiji and New Zealand. New Zealand Medical Journal 90: 31-32.

Tai KS, Whelan P, Patel MS & Currie B (1993) An outbreak of Epidemic Polyarthritis (Ross River Virus Disease) in the Northern Territory during the 1990-1991 wet season. Medical Journal of Australia 158: 522-525.