Usa Thisyakorn

Activation of endothelial cells, coagulation and fibrinolysis in children with Dengue virus infection

Dengue virus causes a febrile illness: Dengue fever (DF), and less frequently a life-threatening illness: Dengue hemorrhagic fever (DHF). Although severe bleeding remains a major cause of death in DHF, the pathogenesis of bleeding is poorly understood. This prospective cohort study was designed to determine the extent of activation of endothelial cells and the hemostatic system in correlation with clinical severity, and also to detect the best prognostic factor(s) for DHF. Endothelial cell activation, coagulation, anticoagulant and fibrinolysis parameters were measured in 42 children with Dengue infections (20 with DF and 22 with DHF) during three phases of illness. In DHF patients, during the febrile phase, von Willebrand factor antigen (vWF:Ag), tissue factor (TF) and plasminogen activator inhibitor (PAI-1) were significantly elevated, while platelet counts and ADAMTS 13 (a disintegrin and metalloprotease with thrombospondin repeats) were significantly low compared to DF patients. During the toxic phase, soluble thrombomodulin (sTM), tissue plasminogen activator (t-PA) and PAI-1 were also significantly increased, while ADAMTS 13 and thrombin activatable fibrinolysis inhibitor (TAFIa) were significantly low compared to DF patients. Abnormal vWF multimers were seen only in DHF patients. For endothelial cell injury and release of procoagulant components, activation of the coagulation cascade with thrombin generation, increased antifibrinolytic factors and consumption of natural anticoagulants, each appeared to play an important role in the development of hemorrhage in Dengue patients. Using logistic regression analysis, we found plasma VWF:Ag to be the best indicator of progression to DHF.

Safety and Immunogenicity of a Single Administration of Live-attenuated Japanese Encephalitis Vaccine in Previously Primed 2- to 5-year-olds and Naive 12- to 24-month-olds: Multicenter Randomized Controlled Trial

Background: Safe and effective Japanese encephalitis (JE) vaccines are needed to protect populations living in or visiting endemic areas. A live-attenuated JE-chimeric virus vaccine (JE-CV) has been developed with a single-dose regimen. Methods: In an open-label, crossover study, 100 children aged 2 to 5 years with a history of 2-dose primary vaccination with mouse-brain derived inactivated JE vaccine according to the Thai Expanded Program for Immunization schedule, and 200 JE vaccination-naive 12- to 24-month-old toddlers were randomized 1:1 to receive JE-CV, containing ≥4 log10 plaque forming units, 1 month before or after hepatitis A control vaccine. Neutralizing antibody titers were assessed using PRNT50 (titers expressed in inverse of dilution) before and 28 days after JE-CV, and at months 7 and 12. Results: All 2- to 5-year-olds and 96% of 12- to 24-month-olds were seroprotected (titer ≥10) 28 days after JE-CV administration, and geometric mean titers (GMT) (95% confidence interval) in these age groups were 2634 (1928–3600) and 281 (219–362), respectively. One year later, seroprotection rates in the 2 age groups were 97% and 84% and GMTs were 454 and 62.3, respectively. Vaccine-induced antibodies neutralized a panel of wild-type JE isolates. There were no vaccine-related serious adverse events. Reactogenicity of JE-CV was comparable with that of the inactivated hepatitis A vaccine. Conclusions: A single administration of JE-CV has a good safety profile and elicits a protective immune response in both JE-naive toddlers and JE-primed young children.

Failure of Pre- and Postexposure Rabies Vaccinations in a Child Infected with HIV

We report the case of a 6-y-old HIV-infected girl with severe immune deficiency who failed to respond to intramuscular pre-exposure rabies vaccination using human diploid cell rabies vaccine on days 0, 7 and 28. She also failed to respond to an intradermal postexposure rabies regimen using purified verocell rabies vaccine at 4 sites on days 0, 3 and 7 and at 2 sites on days 30 and 90 (double the usual regimen). Sequentially monitored rabies neutralizing antibody titers were below the WHO minimum acceptable level (> 0.15 IU/ml) in all specimens. Rabies prevention in HIV-infected persons with severe immune suppression requires further study.We report the case of a 6-y-old HIV-infected girl with severe immune deficiency who failed to respond to intramuscular pre-exposure rabies vaccination using human diploid cell rabies vaccine on days 0, 7 and 28. She also failed to respond to an intradermal postexposure rabies regimen using purified verocell rabies vaccine at 4 sites on days 0, 3 and 7 and at 2 sites on days 30 and 90 (double the usual regimen). Sequentially monitored rabies neutralizing antibody titers were below the WHO minimum acceptable level (> 0.15 IU/ml) in all specimens. Rabies prevention in HIV-infected persons with severe immune suppression requires further study.

Immunogenicity and safety study of a new DTaP–IPV–Hep B–PRP-T combined vaccine compared to a licensed DTaP–IPV–Hep B//PRP-T comparator, both concomitantly administered with a 7-valent pneumococcal conjugate vaccine at 2, 4, and 6 months of age in Thai infants

OBJECTIVE To assess a new, fully-liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine (diphtheria toxoid (D), tetanus toxoid (T), acellular pertussis (aP), inactivated poliovirus (IPV), hepatitis B (Hep B), and Haemophilus influenzae type b polysaccharide conjugated to tetanus protein (PRP-T) antigens) compared to a licensed DTaP-IPV-Hep B//PRP-T vaccine following primary series co-administration with a 7-valent pneumococcal conjugate vaccine (PCV7). METHODS This was a randomized, phase III, observer-blind study in Thai infants (N=412), who received DTaP-IPV-Hep B-PRP-T or DTaP-IPV-Hep B//PRP-T at 2, 4, and 6 months of age, co-administered with PCV7. All received Hep B at birth. Non-inferiority for Hep B ≥ 10 mIU/ml and PRP ≥0.15μg/ml was analyzed (DTaP-IPV-Hep B-PRP-T relative to DTaP-IPV-Hep B//PRP-T) at 1 month post-primary. Seroprotection/seroconversion and geometric mean titers (GMTs) were analyzed descriptively for all hexavalent components. Safety was evaluated from parental reports. RESULTS Anti-Hep B and anti-PRP antibody seroprotection rates were high for DTaP-IPV-Hep B-PRP-T (n=189) and DTaP-IPV-Hep B//PRP-T (n=190), and non-inferiority was demonstrated. Anti-D and anti-T ≥ 0.01 IU/ml, anti-polio types 1, 2, and 3 ≥ 8 (1/dil), and anti-PT and anti-FHA seroconversion were high and similar in each group. For DTaP-IPV-Hep B-PRP-T and DTaP-IPV-Hep B//PRP-T, anti-Hep B ≥ 100 mIU/ml was 98.4% and 99.5% (GMTs 2477 and 2442 mIU/ml), respectively; anti-PRP ≥ 1.0 μg/ml was 85.2% and 71.1% (GMTs 5.07 and 2.41 μg/ml), respectively. Safety profiles were comparable. There were no vaccine-related serious adverse events. CONCLUSIONS Following co-administration with PCV7 the investigational DTaP-IPV-Hep B-PRP-T vaccine was safe and immunogenic. Non-inferiority to DTaP-IPV-Hep B//PRP-T was shown for Hep B and PRP.

Safety, Humoral and Cell Mediated Immune Responses to Two Formulations of an Inactivated, Split-Virion Influenza A/H5N1 Vaccine in Children

Background Highly pathogenic influenza A/H5N1 has caused outbreaks in wild birds and poultry in Asia, Africa and Europe. It has also infected people, especially children, causing severe illness and death. Although the virus shows limited ability to transmit between humans, A/H5N1 represents a potential source of the next influenza pandemic. This study assesses the safety and immunogenicity of aluminium hydroxide adjuvanted (Al) and non adjuvanted influenza A/Vietnam/1194/2004 NIBRG-14 (H5N1) vaccine in children. Methods and Findings In a Phase II, open, randomised, multicentre trial 180 children aged 6 months to 17 years received two injections, 21 days apart, of vaccine containing either: 30 µg haemagglutinin (HA) with adjuvant (30 µg+Al) or 7.5 µg HA without adjuvant. An additional 60 children aged 6–35 months received two “half dose” injections (ie 15 µg+Al or 3.8 µg). Safety was followed for 21 days after vaccination. Antibody responses were assessed 21 days after each injection and cellular immune responses were explored. Vaccination appeared well tolerated in all age groups. The 30 µg+Al formulation was more immunogenic than 7.5 µg in all age groups: in these two groups 79% and 46% had haemagglutinination inhibition antibody titres ≥32 (1/dil). Among 6–35 month-olds, the full doses were more immunogenic than their half dose equivalents. Vaccination induced a predominantly Th2 response against H5 HA. Conclusions This influenza A(H5N1) vaccine was well tolerated and immunogenic in children and infants, with Al adjuvant providing a clear immunogenic advantage. These results demonstrate that an H5N1 Al-adjuvanted vaccine, previously shown to be immunogenic and safe in adults, can also be used in children, the group most at risk for pandemic influenza. Trial Registration ClinicalTrials.gov NCT00491985

Shigellosis in Thai children: epidemiologic, clinical and laboratory features.

Two hundred thirty cases of shigellosis in children managed at Chulalongkorn Hospital from 1984 to 1988 were reviewed. The most common presentation included diarrhea, most frequently with mucus and blood, and fever. There were no deaths. The most common species was Shigella flexneri (83.5%) which showed increasing resistance to trimethoprim-sulfamethoxazole.

Immunization for Persons Infected with Human Immunodeficiency Virus

Immunization is an important measure to protect HIV-infected children and adults against certain vaccine preventable diseases. However, the antibody response, which is associated with the level of CD4+ T cell count, is frequently impaired in this group of patients. Certain vaccines enhance virus replication and transiently increase HIV viral load. Theoretically, vaccination should be given before the immune status of the patients is suppressed. Inactivated vaccines are generally safe and are beneficial for HIV-infected patients. These vaccines should be administered at appropriate age recommended for immunocompetent individuals. Live vaccines should be used with caution since some of the vaccines may be harmful to patients with severe immunologic suppression. Recommendations for immunization in HIV-infected patients may differ from country to country, depending on the availability and affordability of each vaccine, and the prevalence of each preventable disease. Vaccine trial in HIV-infected patients is needed in order to establish the most appropriate vaccine recommendation for this group of patients.

Measles-Associated Appendicitis: Two Case Reports and Literature Review

We report 2 cases of appendicitis associated with measles. Four previously reported cases are reviewed. In all 6 patients typical measles rash appeared after removal of the appendix, which showed Warthin-Finkelday giant cells.We report 2 cases of appendicitis associated with measles. Four previously reported cases are reviewed. In all 6 patients typical measles rash appeared after removal of the appendix, which showed Warthin?Finkelday giant cells.

Persistence of Wild-Type Japanese Encephalitis Virus Strains Cross-Neutralization Five Years following JE-CV Immunization

Background The live-attenuated Japanese encephalitis (JE) vaccine (JE-CV; IMOJEV) induces a protective response in children. A shift in circulating JE virus strains suggests that a genotype shift phenomenon may occur throughout Southeast Asia. We assessed the neutralization of wild-type (WT) JE virus isolates at distal time points after vaccination. Methods We analyzed serum samples from a subset of 47 children who had received a JE-CV booster after an inactivated JE vaccine primary immunization. We measured antibody titers (50% plaque reduction neutralization test) using a panel of WT JE strains at baseline, then after the booster at 28 days and 6 months in all subjects present at the time points and in a subset at year 5. Three additional recent isolates were tested at year 5. Results Of 47 subjects, 43 (91.5%) subjects had JE neutralizing antibody titers ≥10 (reciprocal serum dilution) against the homologous strain before JE-CV boost; all were seroprotected up to year 5 after the JE-CV boost. Baseline WT seroprotection ranged between 78.7% and 87.2%; all subjects were seroprotected against the 4 WT strains at 28 days and 6 months; year 5 seroprotection ranged between 95.7% and 97.9%. Similar rates of protection against 3 additional WT isolates were observed at year 5. Conclusions The long-term immune responses induced after a JE-CV booster dose in toddlers were able to neutralize WT viruses from various genotypes circulating in Southeast Asia and India. Clinical Trials Registration NCT00621764.

Ten-year-old boy with hemangiopericytoma and human immunodeficiency virus infection

This report documents the first case of hemangiopericytoma in an HIV-infected child who is most likely a case of vertical transmission of HIV with slow progression to AIDS. We also raise the possibility that there is a causal relationship between HIV and hemangiopericytoma.