Monoclonal antibody-escape variant of dengue virus serotype 1: Genetic composition and envelope protein expression

Monoclonal antibody-escape variant of dengue virus type 1 (MabEV DEN-1) was discovered and isolated in an outbreak of dengue in Klang Valley, Malaysia from December 2004 to March 2005. This study was done to investigate whether DEN152 (an isolate of MabEV DEN-1) is a product of recombination event or not. In addition, the non-synonymous mutations that correlate with the monoclonal antibody-escape variant were determined in this study. The genomes of DEN152 and two new DEN-1 isolates, DENB04 and DENK154 were completely sequenced, aligned, and compared. Phylogenetic tree was plotted and the recombination event on DEN152 was investigated. DEN152 is sub-grouped under genotype I and is closely related genetically to a DEN-1 isolated in Japan in 2004. DEN152 is not a recombinant product of any parental strains. Four amino acid substitutions were unique only to DEN 152. These amino acid substitutions were Ser[326]Leu, Ser[340]Leu at the deduced E protein, Ile[250]Thr at NS1 protein, and Thr[41]Ser at NS5 protein. Thus, DEN152 is an isolate of the emerging monoclonal antibody-escape variant DEN-1 that escaped diagnostic laboratory detection.

Serological evidence of hantavirus infections in Malaysia.

Hantaviruses are primarily rodent-borne and transmission is by inhalation of virus-contaminated aerosols of rodent excreta, especially urine and saliva. The genus Hantavirus, family Bunyaviridae, comprises at least 14 serotypes and the symptoms of clinical illness range from mild fever to severe hemorrhagic manifestations with renal complications. Many countries in Southeast Asia are unaware of the importance of hantavirus infections and give them low priority. Malaysia, like other countries in the region, has conducted very few studies on the epidemiology of hantaviruses - and even these were conducted in the 1980s. Using a more extensive range of hantavirus antigens, we conducted a seroprevalence study of rodents and humans and found further evidence of hantavirus infections. Moreover, the data from the antibody profiles strongly suggest the presence of different hantaviruses at the study sites.

Chikungunya infection--an emerging disease in Malaysia.

Many countries neighboring Malaysia have reported human infections by chikungunya virus, a mosquito-borne togavirus belonging to the genus Alphavirus. However, although there is serological evidence of its presence in Malaysia, chikungunya virus has not been known to be associated with clinical illness in the country. An outbreak of chikungunya virus occurred in Klang, Malaysia, between December 1998 and February 1999. The majority of the cases were in adults and the clinical presentation was similar to classical chikungunya infections. Malaysia is heavily dependent on migrant workers from countries where chikungunya is endemic. It is speculated that the virus has been re-introduced into the country through the movement of these workers.

Seroepidemiology of human herpesvirus 6 in a population seen in the University Hospital, Kuala Lumpur, Malaysia.

Sera from healthy donors and patients stored over a period of 2 years, aged 1 to 83 years, were examined for reactivity to human herpes virus 6 (HHV-6) by the standard indirect immunofluorescence assay (IFA). Of the 600 serum specimens screened, 502 showed positive reactivity to HHV-6. This gives an overall seropositive rate of 83.7%. There is no significant difference in the overall positive rate between the ethnic groups (Chinese, Malays, Indians) (chi 2 = 0.35 df = 2 p > 0.05). However, there is significant difference in the positive rates at the extreme age groups of 1 year as well as 61 years and above. From birth up to below 1 year of age, the seroprevalence rate was 82%. At one year of age the positive rate decreased to 66% before gradually rising so that the percentage seropositivity of 6 to 10 years old becomes similar to that in older children and adults (11 to 40 years). The positive rate then starts to decline after 40 years of age. Using a standardized scoring system, the corresponding antibody titer was found to be high in the very young population and starts to decline after the age of 15 years. This suggests that in our population group, primary infection occurs mainly in the pediatric age group. It also accounts for the low positive rate in the age group of 61 years and above, as by then the titer had fallen to the level below the detection limits of the assay system.