PubMed Health⌕ Search

Biomedical subjects

S Yoksan

Publications and source records attributed to S Yoksan.

At least 19 recordsLinked to original sources

A comparison of the age distributions in the dengue hemorrhagic fever epidemics in Santiago de Cuba (1997) and Thailand (1998).

The age profiles of the infected populations of two dengue hemorrhagic fever (DHF) epidemics, the 1997 epidemic, in Santiago de Cuba and the 1998 epidemic in Thailand, are compared. Using an age-structured model of disease transmission, the dependence of the forces of infection on age was determined for each epidemic. The difference in the behavior of the two epidemics and the role of primary and secondary infection in the development of DHF are discussed.

Adolescent↗

Viral etiologies of encephalitis in Thai children.

A prospective study of childhood encephalitis was performed in Bangkok from 1996 through 1998. The viral agents identifiable in 26 (65%) of 40 children were dengue virus (8), Japanese encephalitis (6), herpes simplex virus (4), human herpes virus type 6 (3), mumps (2), enterovirus (1), varicella-zoster virus (VZV) (1) and rabies (1).

Acyclovir↗

Dengue infection presenting with central nervous system manifestation.

The objective of this study was to investigate the possibility of dengue virus infection causing an abnormal neurologic presentation. Between 1996 and 1998, all pediatric patients with clinical manifestations of encephalitis-like illness who were admitted to the Department of Pediatrics, Siriraj Hospital were prospectively studied for any evidence of dengue virus infection. The diagnosis of dengue virus infection was based on mosquito viral isolation and serologic and polymerase chain reaction (PCR) evidence. Of 44 patients with the preliminary diagnosis of acute viral encephalitis, 8 were diagnosed with dengue infection. All of these 8 patients were diagnosed by serology. In addition to the serologic diagnosis, four also had positive PCR, one had positive viral isolation, and one had both positive PCR and viral isolation. Only two patients were diagnosed by serologic evidence alone. All except one had clinical courses and laboratory findings compatible with typical dengue infection. All had obvious encephalitic clinical manifestations with normal cerebrospinal fluid findings except one patient, who had mildly increased cerebrospinal fluid protein. All of these patients recovered completely and had benign clinical courses except one patient, who developed leakage symptoms. None had liver failure. Dengue virus can cause acute encephalopathy with fever. It can masquerade as other types of acute viral encephalitis. However, its clinical course and prognosis are usually favorable.

Acute Disease↗

Preliminary study on potential circulation of arenaviruses in the rodent population of Nakhon Pathom Province, Thailand and their medical importance in an evoluting environment.

Preliminary serological investigations were prefered to detect evidence of arenavirus infection in rodents. The study examined virus antibody in 367 rodents trapped in 6 different geographical areas of Nakhon Pathom Province, Thailand from February-March, 1998. The overall seroprevalence among rodents was 13.3%, mostly in Bandicota savilei (35.7%) and Rattus norvegicus (31.5%). Between ecology, behavior and sex of the rodents, seroprevalence was not significantly different (p>0.05), however the seroprevalence found among different geographical areas of Nakhon Pathom Province were significantly different (p<0.0001).

Animals↗

Serological study of hantavirus in the rodent population of Nakhon Pathom and Nakhon Ratchasima Provinces Thailand.

A serological survey has been carried out to detect evidence of hantavirus infection in rodents from two provinces of Thailand. This study aimed to examine virus antibody in 354 rodents trapped among 6 different villages of Nakhon Pathom Province (February-March, 1998) and in 326 rodents trapped among 14 villages of Nakhon Ratchasima Province (August-October, 1998). Seroprevalence among rodents from Nakhon Pathom Province (2.3%), was mostly find in Rattus norvegicus (3.8%) and Bandicota indica (2.6%). In Nakhon Ratchasima Province seroprevalence (4.0%) was mostly in Bandicota indica (19.1%) and Rattus exulans (3.5%).

Animals↗

Dengue virus specific T cell responses to live attenuated monovalent dengue-2 and tetravalent dengue vaccines.

The proliferative T cell responses to dengue vaccines were studied using the parental strains of dengue vaccines as antigens in 26 dengue immune individuals who resided in Bangkok which is the endemic area of dengue infection. The magnitude of the T cell responses in subjects with flavivirus cross-reactive neutralizing antibody was much higher and the cross-reactivity was broader than in those with dengue serotype-specific neutralizing antibodies, Japanese encephalitis (JE) specific antibodies or dengue cross-reactive antibodies. The T cell response in those with neutralizing antibody against a single serotype or in those who had dengue cross-reactive neutralizing antibody was relatively low, independent of the level or degree of cross-reactivity of the antibody. Evaluation of the proliferative T cell responses in 8 recipients of the monovalent dengue-2 (16681-PDK53) or the tetravalent dengue vaccines demonstrated that both vaccines induced high levels of neutralizing antibody as well as high levels of T cell responses to all serotypes of dengue virus. These results indicate that the evaluated dengue vaccines efficiently induced humoral and cell mediated immunity comparable to natural infection with dengue virus.

Adolescent↗

The use of Toxorhynchites splendens for identification and quantitation of serotypes contained in the tetravalent live attenuated dengue vaccine.

Assurance of identity and quantity is an indispensable part of quality control in the manufacture of vaccines. Dengue-1 PDK13, dengue-2 PDK53, dengue-3 PGMK30F3 and dengue-4 PDK48 in the live attenuated tetravalent dengue vaccine were assayed by identification and quantitation in a mosquito system (Toxorhynchites splendens). Each serotype of dengue virus was identified by dengue specific monoclonal antibodies in the indirect fluorescent antibody test. Virus content was estimated by calculating the 50% mosquito infectious dose (MID50). Differences from 0 to +/-0.5 log10 were observed between the original monovalent titer and that from the blend which showed no significant difference at 95% confidence limit (P < 0.05). This result indicates that there is no interference between dengue serotypes in mosquitoes infected by intrathoracic inoculation with the virus mixture. It can be also concluded that this mosquito system can be used as an effective measure for infectivity titration of each component in the tetravalent dengue vaccine.

Animals↗

Dynamics of susceptibility and transmissibility of the live, attenuated, candidate vaccines dengue-1 PDK13, dengue-3 PGMK30F3, and dengue-4 PDK48 after oral infection in Aedes aegypti.

Dengue-1 virus PDK13 and isolates from vaccinees (dengue-1 Ib1 and dengue-1 Ib 10), dengue-3 PGMK30F3, and dengue-4 PDK48 were studied for their abilities to infect, disseminate, and replicate in Aedes aegypti mosquitoes by the oral route. In general, infection and dissemination rates were poorer for the vaccine compared with the parent viruses. The transmissibility was also lower for dengue-1 PDK13 than the parent virus, whereas it was not detected for isolates from vaccinees and dengue-3 PGMK30F3. Transmissibility of dengue-4 PDK48 was not determined because no dissemination occurred. Replication rates of vaccine strains were also found to be less efficient than the parent viruses. These imply that vaccination with the candidate vaccine is safe. Moreover, vector attenuation of vaccine viruses was consistent with its phenotypic markers of attenuation, which remained stable after a mosquito passage or after human and mosquito passage.

Administration, Oral↗

Dengue viruses induce cell proliferation and morphological changes of endothelial cells.

Replication of dengue viruses (type 1, 2, 3 and 4) in vitro in endothelial cells from human umbilical cord vein was demonstrated by virus titers and immunofluorescent antibody studies. Both showed highest peak at Day 6 after inoculation and declined to origin at Day 14. Some of the cultured endothelial cells detached from the culture well. Most of these floating cells were rarely viable as shown by failure in trypan blue exclusion whereas the adhering cells are mostly viable. More frequent and higher intensity of immunofluorescent positive cells were found in the detached cells as compared to adhering cells. The virus titers in the supernatant and in the adhering cell population were comparable, although floating cells were maximally 26.2% of the total cultured endothelial cells. Many floating cells and occasional adhering cells had numerous blebs on their surface. Endothelial cell proliferation was markedly increased after virus inoculation as compared with the control. Increased number of mitotic cells was also observed in the dengue virus-endothelial cell culture. Comparing among the four types, dengue type 4 induced highest peaks of cell proliferation and cell mitosis at Day 10 after inoculation. Dengue type 2 had the highest virus titers both in adhering cells and in supernatant at Day 6 as compared with other types.

Cell Division↗

Testing of a dengue 2 live-attenuated vaccine (strain 16681 PDK 53) in ten American volunteers.

A live-attenuated dengue 2 vaccine (strain 16681 PDK 53) developed at Mahidol University, Thailand was evaluated for safety and immunogenicity by administering 10(4) p.f.u. subcutaneously to ten flavivirus non-immune American volunteers. The vaccine was safe; there were no serious adverse reactions. Eight recipients experienced no or mild side effects. One recipient reported headaches on 7 separate days. One volunteer, who had a fracture of the humerus 1 day after vaccination requiring surgical repair, experienced generalized malaise with fever (maximum temperature = 38.9 degrees C), headache, eye pain and myalgia lasting less than 24 h. The vaccine was highly immunogenic; all recipients developed neutralizing antibody that persisted for two years.

Adolescent↗

Langerhans cell density and serological changes following intradermal immunisation of mice with dengue 2 virus.

After the introduction of the dengue-2 (16681) virus by intradermal (i.d.) injection into the footpads of mice, Langerhans cells (LCs) increased in numbers within 24 h at the site of injection and neutralising antibody developed. On comparing the i.d. and intramuscular (i.m.) routes, antibody was produced more rapidly and at higher levels when the virus was injected by the i.d. route. Subsequent re-challenge by the i.d. route produced an even more rapid serological response with all mice producing significant neutralising titres within 12 h. Numbers of ATPase-positive LCs varied with time. A significant sharp drop in LC densities in the early post-injection phase directly correlated with the increased numbers of dendritic cells in the superficial dermis and interfollicular sinuses of draining lymph nodes (LN). Immunofluorescence showed the presence of viral antigen in the footpad epidermis and draining LN within minutes or within 2 h of challenge, respectively.

Animals↗

In vivo and in vitro studies on the morphological change in the monkey epidermal Langerhans cells following exposure to dengue 2 (16681) virus.

A direct comparison of skin Langerhans cell (LC) morphologic change following in vivo and in vitro exposure to dengue-2 (DEN-2) virus (16681) was performed in the monkey to investigate any differences in functional activity profiles. Time-lapse study of skin biopsy at the intradermal (id) virus injection sites, and thin skin sheets removed from the monkey with exposure to virus in culture medium, revealed a highly active migration of epidermal LCs in both sets of experimental specimens. The migration led to a relatively higher number of dendritic cells (DC) which appeared in active migrational profiles, in the superficial dermis. Moreover, obvious cytoplasmic structural changes, corresponding to their immunologic function, were observed in these superficial dermal DCs 2 hours after exposure. Despite their similar changes, early and late endosomes with degraded virus-like particles could be seen in the skin sheets owing to lagging in cellular physiological process in vitro, but none in the skin biopsies. Existence of these endosomes, which was extremely difficult to visualize in vivo, highlighted the mode of antigen processing by the endocytic pathway. The present study showed that the epidermal LC was a potent antigen-presenting cell for eliciting the success of id immunization and carried out the immunological activity in vivo or in vitro in the like manner, in respect to the physiological conditions.

Animals↗

Dengue virus-specific memory T cell responses in human volunteers receiving a live attenuated dengue virus type 2 candidate vaccine.

A live attenuated dengue virus type 2 candidate vaccine (16681-PDK53) was evaluated in a phase I trial in 10 nonimmune adult volunteers. The dengue virus-specific memory T cell responses were analyzed as part of this study. Dengue virus-specific T cell proliferative responses were observed in all subjects after stimulating their peripheral blood mononuclear cells with live viruses or noninfectious viral antigens. The highest proliferative response was against dengue virus type 2, although cross-reactivity with other flaviviruses was detected to a lesser degree in some subjects. Dengue virus type 2-specific CD4+ and CD8+ cytotoxic T lymphocytes were generated in all vaccinees. This study investigated whether the candidate vaccine was efficacious in inducing dengue virus-specific CD4+ and CD8+ T cell memory after a single immunization in nonimmune recipients.

Adult↗

Infection, dissemination, transmission, and biological attributes of dengue-2 PDK53 candidate vaccine virus after oral infection in Aedes aegypti.

The capacity for oral infection, dissemination, and transmission of the dengue-2 candidate vaccine virus DEN-2 PDK53 and an isolate from a vaccinate individual, DEN-2 Ia8, were compared with the parent strain DEN-2 16681. Capacity for oral infection and dissemination to the brain and salivary gland tissues were significantly lower in the first two than in the parent strain (P < 0.001). Replication was more than 100 times higher for the parent strain when compared with the dengue-2 candidate vaccine virus. Transmission was not demonstrated in the mosquitoes orally infected with DEN-2 PDK53 and DEN-2 Ia8, whereas transmission was achieved in 57% (8 of 14) of mosquitoes infected with the parent virus strain. Using immunofluorescence, viral antigen was detected in the mosquitoes infected with DEN-2 PDK53 and DEN-2 Ia8. It was seen mainly in the form of specks scattered in some parts of the tissues, and was strikingly different from that seen in the parent strain, in which major parts of the tissues contained viral antigen in the form of rings and specks. The biological markers of DEN-2 PDK53 and DEN-2 Ia8 retained the biological characteristic of the vaccine after a mosquito passage and a human and mosquito passage, respectively.

Aedes↗

Dengue-3 (16562) PGMK 33 vaccine: neurovirulence, viremia and immune responses in Macaca fascicularis.

Investigation of monkey neurovirulence of dengue-3 viruses (DEN-3, 16562) was undertaken to provide an evaluation of the relative safety of virus strain attenuated for potential use of live virus vaccine. Ten flavivirus-negative, cynomolgus monkeys (Macacafascicularis) were used in the test. The animals were inoculated intrathalamically, intraspinally and intramuscularly with DEN-3 PGMK 33 attenuated live virus vaccine (6 monkeys): parent virus (2) and control cell culture fluid (2). Blood samples were collected on days 0, 1, 2, 4, 6, 8, 10, 12 and 21 for virus isolation and days 0 and 21 or 22 for serologic testing. One monkey with DEN-3 (16562) PGMK 33 candidate vaccine had detectable viremia on day 10. By day 21, all recipients of PGMK 33 and both monkeys with DEN-3 parent virus developed serum neutralizing antibodies to DEN-3 titers ranged from 56-320. The monkeys showed no evidence of illness and none died of dengue infection. Histopathological examination of tissue collected on day 21 or 22 revealed only minimal neurovirulence lesions as scored by the routine grading system. No differences were observed between the DEN-3 parent and vaccine viruses and it is concluded that neither virus is neurovirulent for cynomolgus monkeys.

Animals↗

Comparison of a dengue-2 virus and its candidate vaccine derivative: sequence relationships with the flaviviruses and other viruses.

A comparison of the sequence of the dengue-2 16681 virus with that of the candidate vaccine strain (16681-PDK53) derived from it identified 53 of the 10,723 nucleotides which differed between the strains. Nucleotide changes occurred in genes coding for all virion and nonvirion proteins, and in the 5' and 3' untranslated regions. Twenty-seven of the nucleotide changes resulted in amino acid alterations. The greatest amino acid sequence differences in the virion proteins occurred in prM (2.20%; 2/91 amino acids) followed by the M protein (1.33%; 1/75 amino acids), the C protein (0.88%; 1/114 amino acid), and the E protein (0.61%; 3/495 amino acids). Differences in the amino acid sequence of nonvirion proteins ranged from 1.51% (6/398 amino acids) in NS4 to 0.33% (3/900 amino acids) in NS5. The encoded protein sequences of 16681-PDK53 were also compared with the published sequences of other flaviviruses to obtain a detailed classification of 17 flaviviruses using the neighbor-joining tree method. The analyses of the sequence data produced dendrograms which supported the traditional groupings based on serological evidence, and they suggested that the flaviviruses have evolved by divergent mutational change and there was no evidence of genetic recombination between members of the group. Comparisons of the sequences of the flavivirus polymerase and helicase-like proteins (NS5 and NS3, respectively) with those from other viruses yielded a classification of the flaviviruses indicating that the primary division of the flaviviruses was between those transmitted by mosquitoes and those transmitted by ticks.

Amino Acid Sequence↗