Paediatrics (RCH) - Research Publications

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    Preventive therapy in children exposed to Mycobacterium tuberculosis: problems and solutions
    Rutherford, ME ; Hill, PC ; Triasih, R ; Sinfield, R ; van Crevel, R ; Graham, SM (WILEY, 2012-10)
    Young children living with a tuberculosis patient are at high risk of Mycobacterium tuberculosis infection and disease. WHO guidelines promote active screening and isoniazid (INH) preventive therapy (PT) for such children under 5 years, yet this well-established intervention is seldom used in endemic countries. We review the literature regarding barriers to implementation of PT and find that they are multifactorial, including difficulties in screening, poor adherence, fear of increasing INH resistance and poor acceptability among primary caregivers and healthcare workers. These barriers are largely resolvable, and proposed solutions such as the adoption of symptom-based screening and shorter drug regimens are discussed. Integrated multicomponent and site-specific solutions need to be developed and evaluated within a public health framework to overcome the policy-practice gap and provide functional PT programmes for children in endemic settings.
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    Use and Evaluation of Molecular Diagnostics for Pneumonia Etiology Studies
    Bhat, N ; O'Brien, KL ; Karron, RA ; Driscoll, AJ ; Murdoch, DR (OXFORD UNIV PRESS INC, 2012-04-01)
    Comprehensive microbiological testing will be a core function of the Pneumonia Etiology Research for Child Health (PERCH) project. The development stage of PERCH provided the time and resources necessary for us to conduct a comprehensive review of the current state of respiratory diagnostics. These efforts allowed us to articulate the unique requirements of PERCH, establish that molecular methods would be central to our testing strategy, and focus on a short list of candidate platforms. This process also highlighted critical challenges in the general design and interpretation of diagnostic evaluation studies, particularly in the field of respiratory infections. Although our final molecular diagnostic platform was ultimately selected on the basis of operational and strategic considerations determined by the specific context of PERCH, our review highlighted several conceptual and practical challenges in respiratory diagnostics that have broader relevance for the performance and interpretation of pneumonia research studies.
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    Childhood tuberculosis: progress requires an advocacy strategy now
    Sandgren, A ; Cuevas, LE ; Dara, M ; Gie, RP ; Grzemska, M ; Hawkridge, A ; Hesseling, AC ; Kampmann, B ; Lienhardt, C ; Manissero, D ; Wingfield, C ; Graham, SM (EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2012-08)
    Childhood tuberculosis (TB) is a preventable and curable infectious disease that remains overlooked by public health authorities, health policy makers and TB control programmes. Childhood TB contributes significantly to the burden of disease and represents the failure to control transmission in the community. Furthermore, the pool of infected children constitutes a reservoir of infection for the future burden of TB. It is time to prioritise childhood TB, advocate for addressing the challenges and grasp the opportunities in its prevention and control. Herein, we propose a scientifically informed advocacy agenda developed at the International Childhood TB meeting held in Stockholm, Sweden, from March 17 to 18, 2011, which calls for a renewed effort to improve the situation for children affected by Mycobacterium tuberculosis exposure, infection or disease. The challenges and needs in childhood TB are universal and apply to all settings and must be addressed more effectively by all stakeholders.
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    The Definition of Pneumonia, the Assessment of Severity, and Clinical Standardization in the Pneumonia Etiology Research for Child Health Study
    Scott, JAG ; Wonodi, C ; Moisi, JC ; Deloria-Knoll, M ; DeLuca, AN ; Karron, RA ; Bhat, N ; Murdoch, DR ; Crawley, J ; Levine, OS ; O'Brien, KL ; Feikin, DR (OXFORD UNIV PRESS INC, 2012-04-01)
    To develop a case definition for the Pneumonia Etiology Research for Child Health (PERCH) project, we sought a widely acceptable classification that was linked to existing pneumonia research and focused on very severe cases. We began with the World Health Organization's classification of severe/very severe pneumonia and refined it through literature reviews and a 2-stage process of expert consultation. PERCH will study hospitalized children, aged 1-59 months, with pneumonia who present with cough or difficulty breathing and have either severe pneumonia (lower chest wall indrawing) or very severe pneumonia (central cyanosis, difficulty breastfeeding/drinking, vomiting everything, convulsions, lethargy, unconsciousness, or head nodding). It will exclude patients with recent hospitalization and children with wheeze whose indrawing resolves after bronchodilator therapy. The PERCH investigators agreed upon standard interpretations of the symptoms and signs. These will be maintained by a clinical standardization monitor who conducts repeated instruction at each site and by recurrent local training and testing.
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    Specimen Collection for the Diagnosis of Pediatric Pneumonia
    Hammitt, LL ; Murdoch, DR ; Scott, JAG ; Driscoll, A ; Karron, RA ; Levine, OS ; O'Brien, KL (OXFORD UNIV PRESS INC, 2012-04-01)
    Diagnosing the etiologic agent of pneumonia has an essential role in ensuring the most appropriate and effective therapy for individual patients and is critical to guiding the development of treatment and prevention strategies. However, establishing the etiology of pneumonia remains challenging because of the relative inaccessibility of the infected tissue and the difficulty in obtaining samples without contamination by upper respiratory tract secretions. Here, we review the published and unpublished literature on various specimens available for the diagnosis of pediatric pneumonia. We discuss the advantages and limitations of each specimen, and discuss the rationale for the specimens to be collected for the Pneumonia Etiology Research for Child Health study.
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    Identification and Selection of Cases and Controls in the Pneumonia Etiology Research for Child Health Project
    Deloria-Knoll, M ; Feikin, DR ; Scott, JAG ; O'Brien, KL ; DeLuca, AN ; Driscoll, AJ ; Levine, OS (OXFORD UNIV PRESS INC, 2012-04-01)
    Methods for the identification and selection of patients (cases) with severe or very severe pneumonia and controls for the Pneumonia Etiology Research for Child Health (PERCH) project were needed. Issues considered include eligibility criteria and sampling strategies, whether to enroll hospital or community controls, whether to exclude controls with upper respiratory tract infection (URTI) or nonsevere pneumonia, and matching criteria, among others. PERCH ultimately decided to enroll community controls and an additional human immunodeficiency virus (HIV)-infected control group at high HIV-prevalence sites matched on age and enrollment date of cases; controls with symptoms of URTI or nonsevere pneumonia will not be excluded. Systematic sampling of cases (when necessary) and random sampling of controls will be implemented. For each issue, we present the options that were considered, the advantages and disadvantages of each, the rationale for the methods selected for PERCH, and remaining implications and limitations.
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    Contact Investigation of Children Exposed to Tuberculosis in South East Asia: A Systematic Review
    Triasih, R ; Rutherford, M ; Lestari, T ; Utarini, A ; Robertson, CF ; Graham, SM (HINDAWI LTD, 2012)
    Background. Screening of children who are household contacts of tuberculosis (TB) cases is universally recommended but rarely implemented in TB endemic setting. This paper aims to summarise published data of the prevalence of TB infection and disease among child contacts in South East Asia. Methods. Search strategies were developed to identify all published studies from South East Asia of household contact investigation that included children (0-15 years). Results. Eleven studies were eligible for review. There was heterogeneity across the studies. TB infection was common among child contacts under 15 years of age (24.4-69.2%) and was higher than the prevalence of TB disease, which varied from 3.3% to 5.5%. Conclusion. TB infection is common among children that are household contacts of TB cases in South East Asia. Novel approaches to child contact screening and management that improve implementation in South East Asia need to be further evaluated.