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Thomas Cherian

Publications and source records attributed to Thomas Cherian.

18 recordsLinked to original sources
PubMed2006

Animal models and antibody assays for evaluating candidate SARS vaccines: summary of a technical meeting 25-26 August 2005, London, UK.

Severe acute respiratory syndrome (SARS) emerged in the Guangdong province of China in late 2002 and spread to 29 countries. By the end of the outbreak in July 2003, the CDC and WHO reported 8437 cases with a 9.6% case fatality rate. The disease was caused by a previously unrecognized coronavirus, SARS-CoV. Drawing on experience with animal coronavirus vaccines, several vaccine candidates have been developed and evaluated in pre-clinical trials. Available data suggest that vaccines should be based on the the 180kDa viral spike protein, S, the only significant neutralization antigen capable of inducing protective immune responses in animals. In the absence of clinical cases of SARS, candidate vaccines should be evaluated for efficacy in animal models, and although it is uncertain whether the United States Food and Drug Administration's "animal rule" would apply to licensure of a SARS vaccine, it is important to develop standardized animal models and immunological assays in preparation for this eventuality. This report summarizes the recommendations from a WHO Technical Meeting on Animal Models and Antibody Assays for Evaluating Candidate SARS Vaccines held on 25-26 August 2005 in South Mimms, UK, provides guidance on the use of animal models, and outlines the steps to develop standard reagents and assays for immunological evaluation of candidate SARS vaccines.

Animals↗
PubMed2006

Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than 5 years of age for prevention of pneumonia: updated analysis using World Health Organization standardized interpretation of chest radiographs.

BACKGROUND: A World Health Organization (WHO) working group in 2001 developed a method for standardizing interpretation of chest radiographs in children for epidemiologic purposes. We reevaluated radiographs from the Kaiser Permanente Pneumococcal Efficacy trial using this method. METHODS: Seven-valent pneumococcal conjugate vaccine was evaluated in a randomized, controlled study including 37,868 infants. Effectiveness against pneumonia was previously evaluated using the original treating radiologist reading. There were 2841 sets of radiographs from this trial and all available radiographs were scanned and read blindly by 2 WHO crosstrained readers (A and B); discordance between the 2 primary readers was resolved through a consensus reading by an adjudicating panel of 2 radiologists. RESULTS: Of the 2841 radiographs, 2446 were available for scanning and were reviewed using WHO-defined descriptive categories. Two hundred fifty of the 2446 radiographs were read as positive by both readers. An additional 129 were read as positive by reader A only and 142 by reader B only for a total of 521 radiographs that were read as positive by one or both of the reviewers. The concordance rate between the 2 reviewers was 250 of 521 (48%). Of the 271 discordant radiographs, 45 of 129 (34.9%) of reader A and 66 of 142 (46.5%) for reader B were finalized as positive by the adjudicating panel. Overall, 361 radiographs were finalized as positive (12.7%). With these 361 images as the standard, the sensitivity and specificity of reader A were 82% and 97%, respectively, and for reader B, 88% and 97%, respectively. Kappa between the 2 readers was 0.58. Of 25 control radiographs read as positive by both A and B, 80% were also read as positive by the panel and all 25 control negative radiographs were read as negative by the panel. Using original readings by point-of-care radiologists, efficacy against first episode of radiograph confirmed pneumonia was 17.7% (95% confidence interval [CI] = 4.8-28.9%) in intent-to-treat and 20.5% (95% CI = 4.4-34%) in per protocol. Using the WHO method, the efficacy against first episode of radiograph confirmed pneumonia adjusting for age, gender and year of vaccination of 25.5% (95% CI = 6.5-40.7%, P = 0.011) for intent-to-treat and 30.3% (95% CI = 10.7-45.7%, P = 0.0043) for per protocol. CONCLUSION: Using WHO criteria for reading of radiographs increased point estimates of vaccine efficacy presumably as a result of improved specificity.

Child, Preschool↗
PubMed2006

Pneumococcal disease and vaccination in the Americas: an agenda for accelerated vaccine introduction.

This piece summarizes the presentations and discussions at a meeting on pneumococcal disease surveillance in the Americas that was held in Mexico City, Mexico, on 2 November 2004. This meeting was organized by the Pan American Health Organization (PAHO) and the Pneumococcal Vaccines Accelerated Development and Introduction Plan (PneumoADIP) of the Global Alliance for Vaccines and Immunization (GAVI). The meeting participants reviewed the status of pneumococcal disease surveillance in the Region of the Americas, estimates of the burden of pneumococcal disease, the distribution of Streptococcus pneumoniae serotypes that cause invasive disease, the status of pneumococcal vaccine introduction, health economic analyses, and financial issues related to vaccine introduction. The meeting participants also worked to identify the next steps for generating the critical information needed to help make decisions on pneumococcal vaccine introduction. Coordinated pneumococcal disease surveillance for the Region of the Americas dates back to the 1993 establishment by PAHO of the Regional System for Vaccines (RSV) project for surveillance of bacterial meningitis and pneumonia, including pneumococcal disease. Surveillance data from the RSV indicate that the distribution of major serotypes in the Americas has been stable over time (but that antibiotic resistance is increasing), with serotype 14 being the leading serotype isolated in most countries participating in RSV. Based on local serotype data from six of the RSV countries (Argentina, Brazil, Chile, Colombia, Mexico, and Uruguay), the 7-valent vaccine would cover 65% of serotypes, the 9-valent vaccine would cover 77%, and the 11-valent vaccine would cover 83%.

Health Promotion↗
PubMed2005

A review of vaccine research and development: human acute respiratory infections.

Worldwide, acute respiratory infections (ARIs) constitute the leading cause of acute illnesses, being responsible for nearly 4 million deaths every year, mostly in young children and infants in developing countries. The main infectious agents responsible for ARIs include influenza virus, respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV-3), Streptococcus pneumoniae and Haemophilus influenzae. While effective vaccines against influenza, H. influenzae type b (Hib) and S. pneumoniae infections have been available for several years, no vaccine is available at present against illnesses caused by RSV, PIV-3, metapneumovirus or any of the three novel coronaviruses. In addition, the threat constituted by the multiple outbreaks of avian influenza during the last few years is urgently calling for the development of new influenza vaccines with broader spectrum of efficacy, which could provide immunity against an avian influenza virus pandemic. This article reviews the state of the art in vaccine R&D against ARIs and attempts to address these basic public health questions.

Acute Disease↗
PubMed2005

Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies.

BACKGROUND: Although radiological pneumonia is used as an outcome measure in epidemiological studies, there is considerable variability in the interpretation of chest radiographs. A standardized method for identifying radiological pneumonia would facilitate comparison of the results of vaccine trials and epidemiological studies of pneumonia. METHODS: A WHO working group developed definitions for radiological pneumonia. Inter-observer variability in categorizing a set of 222 chest radiographic images was measured by comparing the readings made by 20 radiologists and clinicians with a reference reading. Intra-observer variability was measured by comparing the initial readings of a randomly chosen subset of 100 radiographs with repeat readings made 8-30 days later. FINDINGS: Of the 222 images, 208 were considered interpretable. The reference reading categorized 43% of these images as showing alveolar consolidation or pleural effusion (primary end-point pneumonia); the proportion thus categorized by each of the 20 readers ranged from 8% to 61%. Using the reference reading as the gold standard, 14 of the 20 readers had sensitivity and specificity of > 0.70 in identifying primary end-point pneumonia; 13 out of 20 readers had a kappa index of > 0.6 compared with the reference reading. For the 92 radiographs deemed to be interpretable among the 100 images used for intra-observer variability, 19 out of 20 readers had a kappa index of > 0.6. CONCLUSION: Using standardized definitions and training, it is possible to achieve agreement in identifying radiological pneumonia, thus facilitating the comparison of results of epidemiological studies that use radiological pneumonia as an outcome.

Child, Preschool↗
PubMed2004

Methodological and quality issues in epidemiological studies of acute lower respiratory infections in children in developing countries.

Acute respiratory infections are the most important single cause of global burden of disease in young children globally and a major cause of child mortality. A recent review of studies reporting the incidence of acute lower respiratory infections (ALRI) in young children in the developing world was carried out by the WHO Child Health Epidemiology Reference Group in order to inform global burden of disease estimates. The review highlighted the low number of community-based longitudinal studies of ALRI incidence in young children which met minimum quality criteria. It underscored the need to give attention to issues of study design and the reporting of a basic minimum dataset which describes circumstances under which the studies were being conducted and the key design features of the study which may influence the ALRI estimate. This paper aims to provide methodological guidelines for the design, conduct, and reporting of epidemiological studies of ALRI in under-5s in developing countries. It discusses determinants of study quality related to both study design and statistical analysis and also issues requiring further research. It is hoped that these guidelines will stimulate further work in this field and encourage the publication of reports which contain sufficient data to permit a meaningful meta-analysis of the data, thus forming the basis of more reliable future estimates of global burden of ALRI.

Child, Preschool↗
PubMed2004

An outbreak of echovirus meningitis in children.

An outbreak of aseptic meningitis in children as evidenced by increase in the number of admissions in a tertiary care hospital is described. Clinical data and stool samples were collected from 25 hospitalized infants and young children. The stool samples were subjected to virological investigations. Fever and vomiting were the commonest symptoms. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis in majority of cases. Of the 25 stool samples, 14 showed an enterovirus specific cytopathogenic effect (CPE) in rhabdomyosarcoma (RD) cell line. All the 14 samples were positive for enterovirus RNA by reverse transcription-polymerase chain reaction (RT-PCR). Partial sequencing of the Virion protein 1 (VPI) region of the enterovirus genome carried out on the first 7 isolates revealed 5 isolates to be echovirus serotype 4 and one each to be echovirus serotypes 3 and 30. All children showed a rapid recovery and were discharged within 3 days of admission.

Child↗
PubMed2004

PneumoADIP: an example of translational research to accelerate pneumococcal vaccination in developing countries.

Historically, the introduction of new vaccines in developing countries has been delayed due to lack of a coordinated effort to address both demand and supply issues. The introduction of vaccines in developing countries has been plagued by a vicious cycle of uncertain demand leading to limited supply, which keeps prices relatively high and, in turn, further increases the uncertainty of demand. The Pneumococcal Vaccines Accelerated Development and Introduction Plan (PneumoADIP) is an innovative approach designed to overcome this vicious cycle and to help assure an affordable, sustainable supply of new pneumococcal vaccines for developing countries. Translational research will play an important role in achieving the goals of PneumoADIP by establishing the burden of pneumococcal disease and the value of pneumococcal vaccines at global and country levels. If successful, PneumoADIP will reduce the uncertainty of demand, allow appropriate planning of supply, and achieve adequate and affordable availability of product for the introduction of pneumococcal vaccines. This model may provide a useful example and valuable lessons for how a successful public-private partnership can improve global health.

Developing Countries↗
PubMed2003

Serological criteria for evaluation and licensure of new pneumococcal conjugate vaccine formulations for use in infants.

The World Health Organization (WHO) is undertaking a series of consultations on serological criteria for the evaluation and licensure of new formulations/combinations or different vaccination schedules of pneumococcal conjugate vaccines. The lack of a definitive serological correlate of protection and the multiplicity of antigens involved, especially since the clinical efficacy of most of the individual serotypes represented in the only licensed vaccine has not been established, are hindering the formulation of criteria for licensure of new formulations or combinations of the vaccine. This report analyses the various options with their relative merits and drawbacks and provides preliminary recommendations as guidance to regulatory agencies in evaluating these vaccines for the purposes of licensure. More detailed recommendations for production and control of pneumococcal conjugate vaccines, including criteria for evaluation for licensure, are currently being drafted.

Antibodies, Bacterial↗
PubMed2003

Effect of Vitamin A supplementation on the immune response to measles vaccination.

A randomized controlled trial was conducted in 395 infants aged 9-12 months to determine the effect of Vitamin A supplementation on concurrently administered measles vaccine. Antibody response was measured using the plaque reduction neutralization assay. No statistically significant differences were demonstrated between the immune response in Vitamin A supplemented and unsupplemented children. Unlike some recent studies, we were unable to demonstrate an immune enhancing effect of Vitamin A supplementation. On the contrary, among children who were given Vitamin A, a lower, but statistically non-significant, proportion had protective antibody levels 6 months after vaccination.

Antibodies, Viral↗
PubMed2002

Evaluation of a one-tube RT-PCR system for detection of enteroviruses.

BACKGROUND: A highly sensitive PCR assay for early and rapid detection of enteroviral (EV) RNA in CSF is necessary to investigate the role of EV in acute neurological illnesses. OBJECTIVES: To evaluate and compare two PCR protocols (Titan one-tube RT-PCR and random primed RT-PCR) for detection of enteroviral RNA in CSF. STUDY DESIGN: The PCR protocols were evaluated for lower limit of input detection using log dilutions of five stock EV strains and an isolate of enterovirus-71 in minimum essential medium and three EV stock strains in CSF. The tests were also applied on 77 CSF samples, 46 from patients with suspected acute EV neurological illness and 31 from 'disease controls'. RESULTS: Even though in the initial virus titration assays there was no statistically significant difference in the limit of input detection by Titan system and the random primed two-step PCR, the latter had a higher positivity rate when used on CSF samples from patients (20/46 vs. 10/46, P<0.01). CONCLUSIONS: Random primed RT-PCR assay is superior to Titan one-tube RT-PCR for detection of EV RNA in CSF.

Enterovirus↗
PubMed2002

Comparison of molecular and conventional methods for typing of enteroviral isolates.

Twenty-eight enteroviral isolates obtained from various clinical specimens were typed by Lim-Benyesh-Melnick (LBM) pool-based neutralization, PCR-restriction fragment length polymorphism (RFLP), and partial sequencing of the VP1 region of the enteroviral genome. Sequencing was found to be a good alternative to LBM typing, while PCR-RFLP was inadequate for identification of enteroviral isolates.

Bacterial Typing Techniques↗
PubMed2002

Safety and immunogenicity of Haemophilus influenzae type B vaccine given in combination with DTwP at 6, 10 and 14 weeks of age.

OBJECTIVE: To assess the immunogenicity and reactogenicity of a tetanus conjugate Haemophilus influenzae type b vaccine (Act-Hib) when extemporaneously mixed and administered as a DTwP-Hib combination using an Indian DTwP vaccine (BE DTwP) in comparison with a licensed DTwP-Hib combination vaccine. METHODS: 378 healthy infants were enrolled and randomly allocated to receive either three doses, at 6, 10 and 14 weeks of age, of Act-Hib in combination with BE DTwP (Group A, n = 160), TetrAct-Hib (Group B, n = 160), or BE DTwP and Act-Hib as separate injections (Group C, n = 58). Sera collected before the first dose and one month after the third dose were tested for antibodies to vaccine antigens. Safety was determined using parental diary cards. RESULTS: Anti-Hib antibody concentrations indicative of short-term protection (> 0.15 g/ml) were elicited in all but one subject in Group A (99.3%), and all subjects in Groups B and C. The concentration of 1 g/ml, considered to provide long-term protection, was achieved in 96.7%, 100% and 98.2% of the infants in Groups A, B and C, respectively. All children displayed satisfactory responses to the three DTwP component antigens, TetrAct-Hib eliciting higher titers against diphtheria and tetanus than BE DTwP. No vaccine-associated serious adverse events occurred. The BE DTwP vaccine was associated with more reports of fever than TetrAct-Hib, but most symptoms were regarded as mild and all resolved without sequelae. CONCLUSIONS: Combining Act-Hib and a local DTwP vaccine did not affect the anti-Hib response. In countries where DTwP vaccine available for use in the EPI program is manufactured by a local or other developing country manufacturer, mixing it with lyophilised Act-Hib is a reasonable option though the immunogenicity may have to be documented before routine use. However, use of TetrAct-Hib combination vaccine would be preferable in view of its lower reactogenicity and superior immunogenicity with respect to diphtheria and tetanus.

Diphtheria Toxoid↗
PubMed2002

A pilot study on the seroprevalence of parvovirus B19 infection.

BACKGROUND & OBJECTIVES: Human parvovirus B 19 (PVB 19) causes aplastic crisis in children with congenital haemolytic anaemia, erythema infectiosum, abortion and stillbirth. Since data on PVB 19 prevalence is lacking in India, a pilot study was undertaken to estimate the prevalence of IgG antibody in children and adults. METHODS: The samples were obtained from children attending our hospital and from volunteer blood donors, majority of whom were from south India. They included 45 children aged 1-5 yr, 39 aged 6-10 yr, 42 aged 11-15 yr and 100 healthy blood donors > 15 yr of age. Sera were tested for the presence of antibody to PVB 19 using a commercial enzyme immuno assay (EIA). RESULTS: Of 226 samples tested, 113 (50%) were positive for PVB 19 IgG. The prevalence of antibody increased from 8.9 per cent at 1-5 yr to 70 per cent in those > 15 yr: the median age of infection was between 6 and 15 yr. Sex and domiciliary status did not have significant effect on the prevalence of antibody. The IgG antibody index increased significantly with age, suggesting repeated exposure to the virus. INTERPRETATION & CONCLUSION: This seroprevalence study indicates that large numbers of individuals show exposure to PVB 19 virus. The exposure as indicated by IgG positivity is seen to increase with age. The IgG negative individuals may be considered to be at risk of developing infections due to PVB 19.

Adolescent↗