Chikungunya virus (CHIKV) is a mosquito-borne alphavirus which causes epidemic fever, rash and polyarthralgia in Africa and Asia. Two outbreaks have been reported in Malaysia, in Klang, Selangor (1998) and Bagan Panchor, Perak (2006). It is not known if the outbreaks were caused by the recent introduction of CHIKV, or if the virus was already circulating in Malaysia. Seroprevalence studies from the 1960s suggested previous disease activity in certain parts of the country. In Asia, CHIKV is thought to be transmitted by the same mosquitoes as dengue, Aedes aegypti and Ae. albopictus. Due to similarities in clinical presentation with dengue, limited awareness, and a lack of laboratory diagnostic capability, CHIKV is probably often underdiagnosed or misdiagnosed as dengue. Treatment is supportive. The prognosis is generally good, although some patients experience chronic arthritis. With no vaccine or antiviral available, prevention and control depends on surveillance, early identification of outbreaks, and vector control. CHIKV should be borne in mind in sporadic cases, and in patients epidemiologically linked to ongoing local or international outbreaks or endemic areas.
A 55 year old female presented with fever, skin rash and subconjunctival hemorrhage. She also developed hepatitis. Fever and skin rash lasted for more than three weeks. This patient was diagnosed to have rubella, highlighting the fact that rubella can present with atypical features like prolonged fever and rash, subconjunctival hemorrhage and hepatitis, especially in adults.
The performance of a commercial rapid immunochromatographic dengue IgG/IgM assay device was evaluated against an in-place dengue IgM-capture ELISA in the National Public Health laboratory. Of the 239 serum samples from patients with clinical diagnosis of acute dengue illness, 140 and 99 samples were tested positive and negative respectively for anti-dengue IgM by the in-placed ELISA. Comparatively, 72 and 76 samples were tested positive and negative respectively, and 91 samples gave equivocal results by the rapid dengue test device. The rapid immunochromatographic assay device gave a relative sensitivity of 49.3% and a relative specificity of 62.6%. Though the rapid immunochromatographic assay device has the advantages of rapid testing which simultaneously detects both IgG and IgM and can also be performed with whole blood, serum or plasma, the user has to exercise extreme caution with the interpretation of the test result.
A serum survey of several characteristic groups of humans in urban, rural, and forested areas of Peninsular Malaysia for evidence of infection with three alphaviruses (Sindbis, getah, and chikungunya) was made on 4384 specimens collected between 1965 and 1969. Analysis of the serological results indicated that 1) persons residing in predominantly rural and forested areas have higher frequencies of specific alphavirus antibody of all three viruses than persons residing in urban areas, 2) human infection with chikungunya virus appears to be at a low level of activity but is widespread, although more common and recent in the northern part of the country, and 3) Sindbis and getah viruses probably do not represent a threat to the public health, but chikungunya virus remains a potential menance and may be responsible for future epidemics transmitted by A. aegypti and A. albopictus mosquitoes.
The first major Malaysian epidemic of dengue hemorrhagic fever with severe manifestations occurred in 1973, with 969 reported cases and 54 deaths. In a detailed study of 138 clinically diagnosed and laboratory confirmed cases at the General Hospital in Kuala Lumpur, hemorrhagic manifestations were observed in 68.7% and shock in 18.1% of the patients. The cases occurred mainly from May to September, largely in urban and suburban areas of the majority of the states in the country. A main focus of infection was Jinjang, a heavily populated outlying district of Kuala Lumpur, where unusually high incidences of morbidity, severe disease and mortality were seen. Severe disease was seen mostly in children under the age of 15 years, although a significant number of adults suffered milder illnesses. The Chinese population was chiefly affected, due to their living in crowded, low-income housing where the vector, Aedes aegypti, occurred in the greatest numbers. All four dengue types were recovered during the epidemic period, although dengue 3 (DEN-3) was incriminated as the major epidemic type. Entomological data revealed high indices of A. aegypti throughout the country and left little doubt that this epidemic was aegypti transmitted. Spraying and fogging operations were carried out in attempts to control vector populations.
Healthy Malaysians from various parts of Peninsular Malaysia were examined for CF antibodies against cytomegalovirus (CMV) and herpes simplex virus (HSV) type 2. CMV antibodies were detected in 1114 out of 1556 persons (71.6%) and HSV antibodies were detected in 954 persons out of 1554 (61.4%). The age distribution patterns were similar for the two infections, with maximum prevalence at 5 - 14 years of age. Prevalence was higher in women than in men. There were no significant differences among the Malay, Chinese, and Indian groups of the population with respect to CMV, 72 - 78% possessing antibodies, but in the case of HSV, 76% of the Chinese had antibodies, compared with 57 - 60% of the Malays and Indians. More than 90% of newborn infants had CMV and HSV CF antibodies, confirming the highly immune status of childbearing women in Malaysia. No CMV-specific IgM was detected in the Malaysian neonates examined but this does not exclude the possibility of congenital infection.
A total of 234 sera from healthy Malaysians of diverse ethnic origins were tested for antibody to the Z29 and prototype GS strains of HHV-6. The prevalence in the races ranged from 58 to 80% for the GS strain and 49 to 76% for the Z29 strain. The highest prevalence was in Malays with semi-urban cultural lifestyles and lowest was in the indigenous rural tribes (Ibans, Kadazans, Bidayuhs, and Orang Asli). The antibody titres to GS and Z29 virus capsid antigens differed in 11 (4.7%) samples by more than 2 dilutions. In 9 of the 11 sera the titres to GS strain were higher than to the Z29 strain. The differences in the antibody titres between strains of HHV-6 may reflect subtle changes in antigen structure of the virus recognised by some individuals.
The prevalence of antibody to human herpesvirus type 6 (HHV-6) and Epstein-Barr virus (EBV) viral capsid antigens (VCA) were analysed in sera from Kadazans of Sabah, North Borneo. At a serum dilution of 10, about 34% were positive for HHV-6 antibody but in contrast all 95 individuals studied were positive for EBV VCA antibody. The study shows that HHV-6 and EBV infection occur independently. The low frequency of seropositive individuals in this community suggests that other than socioeconomic factors are responsible for the spread of the virus.
The prevalence of hepatitis B virus markers in 121 men and 239 women prostitutes was studied. Of 33 (9.7%) with hepatitis B surface antigen (HBsAg), nine (27.3%) also had hepatitis Be antigen, which was more prevalent in men than women. Antibodies to HBsAg (anti-HBs) and to hepatitis B core antigen (anti-HBc) were found in about 71% of men and women prostitutes. Hepatitis B virus markers were more prevalent in men than in women prostitutes. Compared with other people, prostitutes had a significantly greater prevalence of hepatitis B virus markers. This study strongly suggested the importance of sexual transmission of infection with hepatitis B virus in a country where infection is endemic.
A survey of the activity of three alphaviruses (Sindbis, getah and chikungunya) in Peninsular Malaysia was conducted between 1962 and 1970. Serum samples were examined from 3,917 vertebrates representing a wide variety of wild and domestic animals throughout the peninsula for hemagglutination-inhibiting and neutralizing antibodies. A total of 548,939 mosquitoes were collected from different habitats, including jungle, rural, suburban and urban areas, and the majority of the females taken were examined for the presence of virus. Two strains of Sindbis virus and one strain of getah virus were isolated from pools of Culex mosquitoes collected in and around domestic animal shelters. Analysis of the serological results indicated that, 1) getah virus is associated principally with large domestic animals, particularly swine, 2) Sindbis virus is associated with large domestic animals and birds, especially domestic ducks, and 3) chikungunya virus, which has not yet been isolated in Malaysia, appeared to be present at a very low level of activity, probably with wild monkeys as the vertebrate hosts.
Studies were carried out into the immunopathogenesis and laboratory diagnosis of dengue virus infections. Using an experimental system it was shown that cell-mediated immunity (CMI), as measured by delayed-type hypersensitivity (DTH) was induced in mice infected with dengue virus. The nature of the DTH response satisfies most criteria for a classical DTH reaction. In addition, it was also shown that infection with dengue virus causes a transient immunosuppression as measured by the immune response to other, unrelated antigens. With regard to the laboratory diagnosis of dengue infections, it was found that mosquito cells were a sensitive system for the isolation of dengue viruses and that the success of isolation was related to the antibody content of the serum. A new method for the rapid isolation of dengue viruses was also developed involving the intracerebral inoculation of mosquito larvae. By the use of this method viral antigens can be detected as early as 2-3 days after specimen inoculation. The significance of these findings in relation to the immunopathogenesis, prevention and control of disease syndromes due to dengue viruses is discussed.
A case of haemorrhagic fever with renal syndrome that originated in Malaysia is reported. The patient presented with clinical symptoms which were not typical of the disease as seen in endemic regions. Renal involvement, which is characteristic of haemorrhagic fever with renal syndrome, was mild, and the predominant symptom was a persistently marked elevation of serum transaminase levels that was suggestive of hepatitis. Liver involvement has not been described in the Asian form of haemorrhagic fever with renal syndrome. The patient developed a petechial skin rash and had severe thrombocytopenia. Serological confirmation of the diagnosis of haemorrhagic fever with renal syndrome was obtained by the demonstration of significant antibody rises to hantaviruses in the patient's acute- and convalescent-phase sera.
A study of race-related distribution of hepatitis B markers was conducted in 458 children admitted consecutively to Singapore General Hospital. The positive rates for hepatitis B surface antigen (HBsAg) in Chinese, Malays and Indians were 11.2, 8.0 and 12.2% respectively and the corresponding figures for anti-HBs were 30.2, 12.0 and 14.6%. In Chinese children HBsAg prevalence was shown to be sex-related, being higher in males than females. The percentages of Chinese children positive for anti-HBs and anti-HBc were also higher than those of the Indians. This study confirmed that Singapore children were exposed to hepatitis B infection from early life. All three races were equally susceptible to this infection.
Sera from cynomolgus monkeys from Malaysia, from Indian rhesus monkeys, from various species of monkeys from Africa and from South America have been examined for neutralizing antibody to Tanapox and Yaba viruses. No antibody was found to either virus in the sera of rhesus monkeys or South American monkeys. A certain proportion of sera from cynomolgus monkeys and various species of African monkey showed antibody to one or other of the viruses, but few of the positive sera showed antibody to both. The results would seem to suggest that infection with the two viruses is endemic in African and Malaysian monkeys but does not occur or is very rare in Indian rhesus and New World monkeys.
449 human sera collected in a Land Dyak village were tested for antibodies to 11 arboviruses. Japanese encephalitis and dengue virus antibodies were particularly prevalent. The rates of infection with these viruses were estimated to be 5-2% per annum for Japanese encephalitis, 8-8% for dengue 1 and 4-3% for dengue 2. Chikungunya virus antibodies were quite common with an annual infection rate of the order of 5% per annum. Infections with other Group A and B and Bunyamwera group viruses were generally at a low level.
The passive transfer of convalescent sera did not protect the majority of mice against challenge with the homologous strain and was completely ineffective against challenge with strains unrelated by fluorescent antibody techniques. When the immune sera was incubated with the rickettsia in vitro and then inoculated into the mice a dramatic increase occurred in the number of surviving mice. The importance of these data in relation to published results with other species of rickettsia is discussed.
Plaque reduction neutralization tests, using five group A arboviruses (chikungunya, Ross River, Getah, Bebaru and Sindbis), were done on sera from human populations in 44 Southeast Asia and Pacific island localities. Specificity of the plaque neutralization test was determined by examining convalescent sera from patients with known alphavirus infections. Chikungunya-specific neutralizing antibodies were demonstrated in sera of persons living in South Vietnam, Northern Malaysia, Indonesia (Kalimantan and Sulawesi), as well as Luzon, Marinduque, Cebu and Mindanao islands in the Philippines. Evidence of Ross River virus infection was found among populations living in West New Guinea and Papua New Guinea mainland, the Bismark Archipelago, Rossel Island and the Solomon Islands. There appeared to be no geographic overlap in the distribution of chikungunya and Ross River viruses, with the separation in their distribution corresponding with Weber's line in the Pacific. Sindbis neutralizing antibodies were found in 7 of 21 populations sampled, but in general the prevalence of infection was low. Four sera, from Vietnam, Malaysia and Mindanao gave monospecific reactions with Getah virus. No evidence of specific Bebaru virus infection was detected. The epidemiology of these five alphaviruses in Southeast Asia and the Pacific islands is discussed.