The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule

<p>Abstract</p> <p>Background</p> <p>Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and <it>Haemophilus influenzae </it>type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib_2.5[Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib_2.5[Kft] was not inferior to the licensed DTPw-HBV/Hib (<it>Tritanrix</it>(tm)-HepB/<it>Hiberix</it>(tm)) vaccine or the DTPw-HBV/Hib_2.5vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age.</p> <p>Methods</p> <p>299 healthy infants were randomised to receive either DTPw-HBV/Hib_2.5[Kft] DTPw-HBV/Hib_2.5or DTPw-HBV/Hib according to the 6-10-14 week EPI schedule. Blood samples were analysed prior to the first dose of study vaccine and one month after the third vaccine dose for the analysis of immune responses. Solicited local and general symptoms such as pain, redness and swelling at the injection site and drowsiness and fever, unsolicited symptoms (defined as any additional adverse event) and serious adverse events (SAEs) were recorded up to 20 weeks of age.</p> <p>Results</p> <p>One month after the third vaccine dose, 100% of subjects receiving DTPw-HBV/Hib_2.5[Kft] or DTPw-HBV/Hib and 98.8% of subjects receiving DTPw-HBV/Hib_2.5vaccine had seroprotective levels of anti-PRP antibodies (defined as anti-PRP antibody concentration ≥0.15 μg/ml). Seroprotective antibody concentrations were attained in over 98.9% of subjects for diphtheria, tetanus and hepatitis B. The vaccine response rate to pertussis antigen was at least 97.8% in each group. Overall, the DTPw-HBV/Hib_2.5[Kft] vaccine was well tolerated in healthy infants; no SAEs were reported in any group.</p> <p>Conclusions</p> <p>The DTPw-HBV/Hib_2.5[Kft] vaccine was immunogenic and well-tolerated when administered according to the EPI schedule to Indian infants.</p> <p>Trial registration</p> <p><url>http://www.clinicaltrials.gov</url> NCT00473668</p

A Comparison of Clinical and Epidemiological Characteristics of Fatal Human Infections with H5N1 and Human Influenza Viruses in Thailand, 2004–2006

BACKGROUND: The National Avian Influenza Surveillance (NAIS) system detected human H5N1 cases in Thailand from 2004-2006. Using NAIS data, we identified risk factors for death among H5N1 cases and described differences between H5N1 and human (seasonal) influenza cases. METHODS AND FINDINGS: NAIS identified 11,641 suspect H5N1 cases (e.g. persons with fever and respiratory symptoms or pneumonia, and exposure to sick or dead poultry). All suspect H5N1 cases were tested with polymerase chain reaction (PCR) assays for influenza A(H5N1) and human influenza viruses. NAIS detected 25 H5N1 and 2074 human influenza cases; 17 (68%) and 22 (1%) were fatal, respectively. We collected detailed information from medical records on all H5N1 cases, all fatal human influenza cases, and a sampled subset of 230 hospitalized non-fatal human influenza cases drawn from provinces with ≥1 H5N1 case or human influenza fatality. Fatal versus non-fatal H5N1 cases were more likely to present with low white blood cell (p = 0.05), lymphocyte (p<0.02), and platelet counts (p<0.01); have elevated liver enzymes (p = 0.05); and progress to circulatory (p<0.001) and respiratory failure (p<0.001). There were no differences in age, medical conditions, or antiviral treatment between fatal and non-fatal H5N1 cases. Compared to a sample of human influenza cases, all H5N1 cases had direct exposure to sick or dead birds (60% vs. 100%, p<0.05). Fatal H5N1 and fatal human influenza cases were similar clinically except that fatal H5N1 cases more commonly: had fever (p<0.001), vomiting (p<0.01), low white blood cell counts (p<0.01), received oseltamivir (71% vs. 23%, p<.001), but less often had ≥1 chronic medical conditions (p<0.001). CONCLUSIONS: In the absence of diagnostic testing during an influenza A(H5N1) epizootic, a few epidemiologic, clinical, and laboratory findings might provide clues to help target H5N1 control efforts. Severe human influenza and H5N1 cases were clinically similar, and both would benefit from early antiviral treatment

Preexisting Japanese Encephalitis Virus Neutralizing Antibodies and Increased Symptomatic Dengue Illness in a School-Based Cohort in Thailand

Dengue viruses (DENVs) and Japanese encephalitis virus (JEV) have significant cross-reactivity in serological assays, but the possible clinical implications of this remain poorly understood. Interactions between these flaviviruses are potentially important for public health because wild-type JEV continues to co-circulate with DENV in Southeast Asia, the area with the highest burden of DENV illness, and JEV vaccination coverage in this region is high. In this study, we examined how preexisting JEV neutralizing antibodies (NAbs) influenced the clinical severity of subsequent DENV infection using data from a prospective school-based cohort study in Thailand that captured a wide range of clinical severities, including asymptomatic, non-hospitalized, and hospitalized DENV infections. We found that the prior existence of JEV NAbs was associated with an increased occurrence of symptomatic versus asymptomatic DENV infection. This association was most notable in DENV-naives, in whom the presence of JEV NAbs was also associated with an illness of longer duration. These findings suggest that the issue of heterologous flavivirus immunity and DENV infection merits renewed attention and interest and that DENV vaccine developers might incorporate detailed assessments of preexisting immunity to non-DENV flaviviruses and histories of vaccination against non-DENV flaviviruses in evaluating DENV vaccine safety and efficacy

Evidence and rationale for the World Health Organization recommended standards for Japanese encephalitis surveillance

<p>Abstract</p> <p>Background</p> <p>Japanese encephalitis (JE) is the most important form of viral encephalitis in Asia. Surveillance for the disease in many countries has been limited. To improve collection of accurate surveillance data in order to increase understanding of the full impact of JE and monitor control programs, World Health Organization (WHO) Recommended Standards for JE Surveillance have been developed. To aid acceptance of the Standards, we describe the process of development, provide the supporting evidence, and explain the rationale for the recommendations made in the document.</p> <p>Methods</p> <p>A JE Core Working Group was formed in 2002 and worked on development of JE surveillance standards. A series of questions on specific topics was initially developed. A literature review was undertaken and the findings were discussed and documented. The group then prepared a draft document, with emphasis placed on the feasibility of implementation in Asian countries. A field test version of the Standards was published by WHO in January 2006. Feedback was then sought from countries that piloted the Standards and from public health professionals in forums and individual meetings to modify the Standards accordingly.</p> <p>Results</p> <p>After revisions, a final version of the JE surveillance standards was published in August 2008. The supporting information is presented here together with explanations of the rationale and levels of evidence for specific recommendations.</p> <p>Conclusion</p> <p>Provision of the supporting evidence and rationale should help to facilitate successful implementation of the JE surveillance standards in JE-endemic countries which will in turn enable better understanding of disease burden and the impact of control programs.</p

Incidence, Seasonality and Mortality Associated with Influenza Pneumonia in Thailand: 2005–2008

Data on the incidence, seasonality and mortality associated with influenza in subtropical low and middle income countries are limited. Prospective data from multiple years are needed to develop vaccine policy and treatment guidelines, and improve pandemic preparedness.During January 2005 through December 2008, we used an active, population-based surveillance system to prospectively identify hospitalized pneumonia cases with influenza confirmed by reverse transcriptase–polymerase chain reaction or cell culture in 20 hospitals in two provinces in Thailand. Age-specific incidence was calculated and extrapolated to estimate national annual influenza pneumonia hospital admissions and in-hospital deaths.Influenza was identified in 1,346 (10.4%) of pneumonia patients of all ages, and 10 influenza pneumonia patients died while in the hospital. 702 (52%) influenza pneumonia patients were less than 15 years of age. The average annual incidence of influenza pneumonia was greatest in children less than 5 years of age (236 per 100,000) and in those age 75 or older (375 per 100,000). During 2005, 2006 and 2008 influenza A virus detection among pneumonia cases peaked during June through October. In 2007 a sharp increase was observed during the months of January through April. Influenza B virus infections did not demonstrate a consistent seasonal pattern. Influenza pneumonia incidence was high in 2005, a year when influenza A(H3N2) subtype virus strains predominated, low in 2006 when A(H1N1) viruses were more common, moderate in 2007 when H3N2 and influenza B co-predominated, and high again in 2008 when influenza B viruses were most common. During 2005–2008, influenza pneumonia resulted in an estimated annual average 36,413 hospital admissions and 322 in-hospital pneumonia deaths in Thailand.Influenza virus infection is an important cause of hospitalized pneumonia in Thailand. Young children and the elderly are most affected and in-hospital deaths are more common than previously appreciated. Influenza occurs year-round and tends to follow a bimodal seasonal pattern with substantial variability. The disease burden varies significantly from year to year. Our findings support a recent Thailand Ministry of Public Health (MOPH) decision to extend annual influenza vaccination to older adults and suggest that children should also be targeted for routine vaccination

Prospective population-based incidence of Haemophilus influenzae type b meningitis in Thailand

C1 - Journal Articles RefereedThere are limited prospective data for Haemophilus influenzae type b (Hib) disease in Asia, where some countries are considering vaccine introduction. A prospective population-based study was conducted to measure the incidence of Hib meningitis in children in two northern provinces of Thailand. Children <5 years with symptoms consistent with bacterial meningitis were enrolled in the study if inclusion criteria were met. The study enrolled 598 children with clinical meningitis, 76% of whom received lumbar puncture. The rate of probable bacterial meningitis was 26.6/100,000 children <5 years per year. There were four cases of laboratory confirmed Hib meningitis (rate 3.8/100,000 children <5 years per year). These findings suggest a relatively low incidence of Hib meningitis. However, additional data from studies of pneumonia are needed to define the Hib disease burden in Thailand

Human metapneumovirus reinfection among children in Thailand determined by ELISA using purified soluble fusion protein

BACKGROUND: Human metapneumovirus (hMPV) is a newly discovered paramyxovirus that causes acute respiratory illness. Despite apparent near-universal exposure during early childhood, immunity is transient. METHODS: An indirect screening enzyme-linked immunosorbent assay using a recombinant soluble fusion (F) glycoprotein derived from hMPV was used to test for anti-F IgG in 1,380 pairs of acute- and convalescent-stage serum samples collected from children in Kamphaeng Phet, Thailand. RESULTS: Of the 1,380 serum sample pairs tested, 1,376 (99.7%) showed evidence of prior infection with hMPV. Sixty-six paired specimens demonstrated a \u3e or=4-fold rise in titer, for an overall reinfection rate of 4.9%. Two children demonstrated evidence of an initial infection. Forty-eight of the 68 new infections or reinfections occurred in 2000, accounting for 13.2% of all nonflaviviral febrile illnesses in the study population in that year. Of 68 positive cases, 85.3% complained of cough and 66.2% complained of rhinorrhea, compared with 61.4% and 49.0% of negative cases, respectively (P \u3c .01). All positive samples were also tested for an increase in titer of antibodies to respiratory syncytial virus F, and 27% exhibited a \u3e or=4-fold rise. CONCLUSION: These results demonstrate that hMPV reinfections cause illness at a rate equal to that seen for initial infections. hMPV may have a more significant impact in older children than previously realized and may be the cause of significant outbreaks in this population