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Biomedical subjects

S Kalayanarooj

Publications and source records attributed to S Kalayanarooj.

29 records · Page 2Linked to original sources

Early clinical and laboratory indicators of acute dengue illness.

A prospective observational study was conducted to identify early indicators of acute dengue virus infection. Children with fever for <72 h without obvious cause were studied at hospitals in Bangkok and Kamphaeng Phet, Thailand, until resolution of fever. Of 172 evaluable subjects (91% of enrollees), 60 (35%) had dengue, including 32 with dengue fever (DF) and 28 with dengue hemorrhagic fever (DHF). At enrollment, children with dengue were more likely than children with other febrile illnesses (OFI) to report anorexia, nausea, and vomiting and to have a positive tourniquet test, and they had lower total white blood cell counts, absolute neutrophil and absolute monocyte counts, and higher plasma alanine and aspartate (AST) aminotransferase levels than children with OFI. Plasma AST levels were higher in children who developed DHF than in those with DF. These data identify simple clinical and laboratory parameters that help to identify children with DF or DHF.

Acute Disease↗

Dengue in the early febrile phase: viremia and antibody responses.

A multicenter effort was begun in 1994 to characterize the pathophysiology of dengue using a study design that minimized patient selection bias by offering enrollment to all children with undifferentiated fever for <72 h. In the first year, 189 children were enrolled (age range, 8 months to 14 years). Thirty-two percent of these children had dengue infections (60 volunteers). The percentage of children with a secondary dengue infection was 93%, with only 4 (7%) having a primary dengue infection. The virus isolation rate from the plasma of children with dengue was 98%. Viremia correlated highly with temperature. All four dengue virus serotypes were isolated at both study sites. This study demonstrates that all four serotypes of dengue virus can cause dengue hemorrhagic fever, that all dengue patients as defined by serology experience viremia during the febrile phase, and that as fever subsides, so does viremia.

Acute Disease↗

Rapid diagnosis of dengue viremia by reverse transcriptase-polymerase chain reaction using 3'-noncoding region universal primers.

A reverse transcriptase-polymerase chain reaction (RT-PCR) method was developed as a rapid diagnostic test of dengue viremia. To detect dengue viruses in serum or plasma specimens, a pair of universal primers was designed for use in the RT-PCR. Using these primers, the 3'-noncoding region of dengue virus types 1, 2, 3, and 4 could be amplified, but not those of other flaviviruses, such as West Nile virus, Japanese encephalitis virus, and yellow fever virus, or the alphavirus Sindbis virus. The sensitivity of the RT-PCR assay was similar to that of a quantitative fluorescent focus assay of dengue viruses in cell culture. Combining a silica method for RNA isolation and RT-PCR dengue virus could be detected in a 6-hr assay. In a preliminary study using this method, we detected dengue virus in 38 of 39 plasma specimens from which dengue virus had been isolated by mosquito inoculation. We then applied this method for detecting dengue viremia to 117 plasma samples from 62 children with acute febrile illnesses in a dengue-endemic area. We detected dengue viremia in 19 of 20 samples obtained on the day of presentation, which had been confirmed as acute dengue infection by mosquito inoculation and antibody responses. The overall sensitivity of this method was 91.4% (32 of 35; 95% confidence interval [CI] = 82.2-100%). The results from testing plasma samples from febrile nondengue patients showed a specificity of 95.4% (42 of 44; 95% CI = 89.3-100%).

Acute Disease↗

Possible occurrence of a genetic bottleneck in dengue serotype 2 viruses between the 1980 and 1987 epidemic seasons in Bangkok, Thailand.

Cocirculation of two genetic subtypes of dengue serotype 2 viruses was first observed in the 1980 epidemic season in Thailand. To further delineate the evolutionary history and the contribution of these subtypes to subsequent epidemics, we determined the envelope glycoprotein gene sequence of 20 dengue serotype 2 viruses isolated from infected patients during 1987 and compared them with those derived from earlier years. Subtype IIIa strains represented the majority (18 of 19) of dengue type 2 viruses derived from Bangkok metropolitan area, whereas all three strains from a province in the northeastern region belonged to subtype IIIb, indicating uneven local distribution of dengue subtypes within the same year. Three types of sequence variation were identified in both subtypes: substitutions that were unique to individual strains; substitutions that were shared among all subtype IIIa or IIIb viruses of both the 1980 and 1987 epidemics; and those that were shared only among all subtypes IIIa or IIlb viruses of the 1987 epidemic, but were absent from the corresponding subtypes of 1980. While the first and second types of substitution were indicative of the most recent random mutations and previous mutations that had been fixed in virus populations, respectively, the third type suggested possible occurrence of a genetic bottleneck and subsequent expansion of one or a limited number of subtype IIIa strains in Bangkok between 1980 and 1987. Immunoblot analysis of intracellular NS1 antigen with anti-NS1 monoclonal antibodies also revealed antigenic heterogeneity of the NS1 protein that correlated with the subdivision based on envelope protein variation.

Amino Acid Sequence↗

Protective antibody after a 'one dollar' hepatitis B vaccine.

The seropositivity rate of anti-HBs after hepatitis B vaccines, "Hepavax B", a one-dollar per dose vaccine produced by Korean Green Cross Corporation, Korea which were widely distributed and used for the first few years in the National Expanded Program on Immunization in Thailand were assessed in children who regularly came for immunization at the Well Baby Clinic at the Children's Hospital between June to December 1994. The schedule for hepatitis B immunization is at birth, 2 and 6 months of age. The seropositivity rate of anti-HBs at 6 months after the last dose were 86.3% and 87.7% at 12 months which was comparable to the seropositivity rate after other more expensive hepatitis B vaccines at 2 years (88.1%). This result should convince people that a one-dollar hepatitis B vaccine, "Hepavax" is immunogenic and expected to be as effective as other expensive hepatitis B vaccines. The marked reduce in the cost of hepatitis B vaccines will enable us to prevent and ultimately control of worldwide hepatitis B infections in the future.

Costs and Cost Analysis↗

Antibodies that block virus attachment to Vero cells are a major component of the human neutralizing antibody response against dengue virus type 2.

Epidemiological data strongly implicate a role for the host humoral immune response in both protection against and exacerbation of dengue virus-caused disease. In an effort to characterize elements of the normal human immune response against dengue virus we have addressed the issue of antibody-mediated neutralization of dengue virus. We show here the ability of both mouse monoclonal antibody 3H5 and human anti-dengue neutralizing sera to block binding of dengue-2 virus to monkey kidney (Vero) cells. Since Vero cells possess virus receptors but not Fc receptors we conclude that the major effect of host neutralizing antibodies is to block virus attachment to Vero cell dengue virus receptors. Analysis of 61 patient antisera yielded good correlation (Pearson's coefficient = 0.90; P < 0.001) between neutralizing activity and ability to block virus-cell attachment suggesting that antibody-mediated neutralization of dengue virus occurs primarily extracellularly and less by a postattachment mechanism as has been described for certain other viruses.

Adolescent↗

A field study on Nakayama and Beijing strains of Japanese encephalitis vaccines.

A field study to compare the immune response of children aged 1-6 years to Nakayama and Beijing strains JE vaccines was carried out in Mae Hong Son Province, northwest Thailand, where there was low incidence of JEV infection. The first and second dose of each vaccine was given 1-2 weeks apart and the third dose was 1 year after the second dose. Seroconversion rate was similarly high, about 94% in both groups of vaccinees. At 6 and 12 months after 2 doses of vaccines, the seroconversion rates dropped in both groups of vaccinees, so there were 10-20% of children (50-65% if cross protection was considered) susceptible to JEV infections during this period. After the third dose of vaccine, the seroconversion rate rose to 100% in both groups. The GMT in Bejing strain vaccinees were slightly higher than Nakayama strain JE vaccines. To reduce the number of susceptible children during 6-12 months after the second dose and for longer protection, the primary JE immunization should be 3 doses and the timing for the third dose should be at 6 months after the second dose. Either Nakayama or Beijing strain vaccine could be used in Thailand.

Antibodies, Viral↗

Age-specific prevalence of hepatitis A antibody in Thai children.

Age-specific prevalence of anti-HAV was determined for 3 groups of children whose mean ages were 12.6, 20.7 and 52.5 months. There were 41, 43 and 99 children in the respective age groups. All children were healthy, from middle to low socioeconomic families in Bangkok and vicinity. None of the children in the two younger age groups had anti-HAV antibody while 2 of 99 children in the oldest age group did. One of them resided in central Bangkok (Amphoe Dusit) and the other in Nonthaburi Province. The overall prevalence of anti-HAV in children under 5 years old was 1.1%. This demonstrates that hepatitis A transmission rates in Bangkok are very low when compared to ten years ago when prevalence rates were as high as 50-65%. From this study hepatitis A vaccine is recommended for 4-5 years old children in Bangkok. We need more epidemiologic data concerning hepatitis A transmission in Thailand before we can consider hepatitis A immunization for the whole country.

Age Distribution↗

A study of erythrocyte sedimentation rate in dengue hemorrhagic fever.

Erythrocyte sedimentation rate (ESR) was determined in 180 DHF patients and 70 patients with various viral and bacterial infections using the Winthrobe method. Seventy-seven percent of DHF patients had normal ESR (less than 20 mm/hour) and 15% had slightly elevated ESR value (between 21-30 mm/hour). The other 8% had ESR in the range of 31-49 mm/hour. Among 7 patients in the latter group, one had definite evidence of complicating urinary tract infection while the other 6 cases had anemia and severe bleeding. The mean ESR in DHF patients (10.71 mm/hour) was significantly lower than the mean values in other groups of patients with viral infection (20.46 mm/hour), bacterial infection (34.81 mm/hour) and miscellaneous illnesses (35.29 mm/hour). The mean ESR in shock cases was 7.63 mm/hour while in non-shock cases it was 13.87 mm/hour and they are statistically different (p less than 0.05). The mean ESR during the time of shock was lower than in the pre-shock and post-shock period. Hemoconcentration, low level of albumin and fibrinogen and the presence of disseminated intravascular clotting (DIC) in a majority of DHF patients are most likely responsible to this observed lower ESR especially during shock period. The determination of ESR, which is simple, is therefore useful in differentiating DHF from bacterial infections and dengue shock syndrome from septic shock.

Bacterial Infections↗

T cell receptor Vbeta gene usage in Thai children with dengue virus infection.

T lymphocyte activation during dengue is thought to contribute to the pathogenesis of dengue hemorrhagic fever (DHF). We examined the T cell receptor Vbeta gene usage by a reverse transcriptase-polymerase chain reaction assay during infection and after recovery in 13 children with DHF and 13 children with dengue fever (DF). There was no deletion of specific Vbeta gene families. We detected significant expansions in usage of single Vbeta families in six subjects with DHF and three subjects with DF over the course of infection, but these did not show an association with clinical diagnosis, viral serotype, or HLA alleles. Differences in Vbeta gene usage between subjects with DHF and subjects with DF were of borderline significance. These data suggest that the differences in T cell activation in DHF and DF are quantitative rather than qualitative and that T cells are activated by conventional antigen(s) and not a viral superantigen.

Adolescent↗