Global respiratory syncytial virus–related infant community deaths

Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines

Viral and bacterial pathogens identification in children hospitalised for severe pneumonia and parapneumonic empyema

Pneumonia is caused by respiratory bacteria and/or viruses. Little is known if co-infections are an aggravating factor in hospitalised children with severe pneumonia. We studied the impact of respiratory pathogens on the severity of pneumonia. Between 2007 and 2009, 52 children hospitalised with a well-documented diagnosis of communityacquired pneumonia (CAP), with or without parapneumonic empyema (PPE), were enrolled in the study. The patients were classified into 2 groups: CAP + PPE (n = 28) and CAP (n = 24). The identification of respiratory viruses and bacteria in nasopharyngeal aspirates and pleural effusion samples were performed using conventional bacterial techniques and molecular assays. Using real-time multiplex PCR and antigen detection, Streptococcus pneumoniae was the main agent identified in 76% of the cases by molecular tests and BinaxNOW® in pleural fluid. A total of 8% of pleural fluid samples remained undiagnosed. In nasopharyngeal aspirates, rhinovirus, parainfluenza viruses, human metapneumovirus, and respiratory syncytial virus were detected in both CAP and CAP + PPE populations; however, the percentage of viral co-detection was significantly higher in nasopharyngeal aspirates from CAP + PPE patients (35%) compared with CAP patients (5%). In conclusion, viral co-detection was observed mainly in patients with more severe pneumonia. Molecular biology assays improved the pathogens detection in pneumonia and confirmed the S. pneumoniae detection by BinaxNOW® in pleural effusion samples. Interestingly, the main S. pneumoniae serotypes found in PPE are not the ones targeted by the heptavalent pneumococcal conjugate vaccine

The Relevance of a Novel Quantitative Assay to Detect up to 40 Major Streptococcus pneumoniae Serotypes Directly in Clinical Nasopharyngeal and Blood Specimens

International audienceFor epidemiological and surveillance purposes, it is relevant to monitor the distribution and dynamics of Streptococcus pneumoniae serotypes. Conventional serotyping methods do not provide rapid or quantitative information on serotype loads. Quantitative serotyping may enable prediction of the invasiveness of a specific serotype compared to other serotypes carried. Here, we describe a novel, rapid multiplex real-time PCR assay for identification and quantification of the 40 most prevalent pneumococcal serotypes and the assay impacts in pneumonia specimens from emerging and developing countries. Eleven multiplex PCR to detect 40 serotypes or serogroups were optimized. Quantification was enabled by reference to standard dilutions of known bacterial load. Performance of the assay was evaluated to specifically type and quantify S. pneumoniae in nasopharyngeal and blood samples from adult and pediatric patients hospitalized with pneumonia (n = 664) from five different countries. Serogroup 6 was widely represented in nasopharyngeal specimens from all five cohorts. The most frequent serotypes in the French, South African, and Brazilian cohorts were 1 and 7A/F, 3 and 19F, and 14, respectively. When both samples were available, the serotype in blood was always present as carriage with other serotypes in the nasopharynx. Moreover, the ability of a serotype to invade the bloodstream may be linked to its nasopharyngeal load. The mean nasopharyngeal concentration of the serotypes that moved to the blood was 3 log-fold higher than the ones only found in the nasopharynx. This novel, rapid, quantitative assay may potentially predict some of the S. pneumoniae serotypes invasiveness and assessment of pneumococcal serotype distribution

Database_BMJ_Open_25Jul2014

Data spreadshee

Primers/Probes Sequences and Concentration Used in Each Pool for the <i>S</i>. <i>pneumoniae</i> Serotype Identification and Quantification Assay.

<p>Primers/Probes Sequences and Concentration Used in Each Pool for the <i>S</i>. <i>pneumoniae</i> Serotype Identification and Quantification Assay.</p

<i>S</i>. <i>pneumoniae</i> serotypes distribution determined by the 40 <i>S</i>. <i>pneumoniae</i> serotype real-time PCR typing assay (40-PCR).

<p>(A) in NP samples (n = 562) of patients from Cambodia (n = 149), France (n = 45), South Africa (n = 227), Mali (n = 86) and Brazil (n = 55), (B) in WB samples (n = 102) of patients from France (n = 5), Mali (n = 16) and South Africa (n = 81). Each column represents the cumulative number of patients for a given serotype.</p

Serotype-Dependent Detection Limits and Linear Equation Values.

<p>Serotype-Dependent Detection Limits and Linear Equation Values.</p

Pneumococcal load distribution in NP samples from the South African cohort.

<p>Comparison between invasive (present in both NP and WB samples of the same patient; n = 36) and non-invasive serotypes (present in NP samples only; n = 145). Each plot represents a sample. The bold bars indicate the mean bacterial concentration for each group (Student's <i>t</i>-test, <i>P</i><0.001).</p

Multicenter case–control study protocol of pneumonia etiology in children: Global Approach to Biological Research, Infectious diseases and Epidemics in Low-income countries (GABRIEL network)

Made available in DSpace on 2015-06-17T12:05:23Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) patricia_barretoetal_IOC_2014.pdf: 442142 bytes, checksum: dfb79e91e1be1c313d56b6e04b7de26f (MD5) Previous issue date: 2014Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France.Hospices Civils de Lyon. Edouard Herriot Hospital. Infection Control and Epidemiology Unit. Lyon, Grance / Universit of Lyon 1, Epidemiology and Public Health Unit. Lyon, France.Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France.Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France.University of Health Sciences. Faculty of Pharmacy. Phnom Penh, Cambodia.National Pediatric Hospital. Department of Pneumology. Phnom Penh, Cambodia.MOH Key Laboratory of Systems Biology of Pathogens. Dr. Christophe Mérieux Laboratory. Fondation Mérieux. Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College. Beijing, China.Capital Medical University. Key Laboratory of Major Diseases in Children. National Key Discipline of Pediatrics. Ministry of Education. Beijing Pediatric Research Institute. Beijing Children’s Hospital. Capital Medical University, Beijing, China.GHESKIO (Groupe Haïtien d’Etude du Sarcome de Kaposi et des Infections Opportunistes) Centers. Port au Prince, Haiti.GHESKIO (Groupe Haïtien d’Etude du Sarcome de Kaposi et des Infections Opportunistes) Centers. Port au Prince, Haiti.Chatrapati Shahuji Maharaj University. Lucknow, India.Chatrapati Shahuji Maharaj University. Lucknow, India.KEM Hospital Research Center. Pune, India.KEM Hospital Research Center. Pune, India.Hôpital Femme-Mère-Enfant. Antananarivo, Madagascar.Fondation Mérieux. Centre d’Infectiologie Charles Mérieux (CICM); Antananarivo, Madagascar.Fondation Mérieux. Centre d’Infectiologie Charles Mérieux (CICM); Antananarivo, Madagascar.Gabriel Touré Hospital. Bamako, Mali.Centre d`Infectiologie Charles Mérieux (CICM). Bamako, Mali.Mongolian Academy of Medical Sciences. Ulaanbaatar, Mongolia.Bayanzurkh District General Hospital. Ulaanbaatar, Mongolia.Research Institute of health. Asuncion, Paraguay.Hospital Pediátrico ! Niños de Acosta ¨Nu". San Lorenzo, Paraguay.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e Sarampo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e Sarampo. Rio de Janeiro, RJ, Brasil.Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France.Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France.Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France.Hospices Civils de Lyon. Edouard Herriot Hospital. Infection Control and Epidemiology Unit. Lyon, Grance / Universit of Lyon 1, Epidemiology and Public Health Unit. Lyon, France.Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France.Background: Data on the etiologies of pneumonia among children are inadequate, especially in developing countries. The principal objective is to undertake a multicenter incident case–control study of <5-year-old children hospitalized with pneumonia in developing and emerging countries, aiming to identify the causative agents involved in pneumonia while assessing individual and microbial factors associated with the risk of severe pneumonia. Methods/design: A multicenter case–control study, based on the GABRIEL network, is ongoing. Ten study sites are located in 9 countries over 3 continents: Brazil, Cambodia, China, Haiti, India, Madagascar, Mali, Mongolia, and Paraguay. At least 1,000 incident cases and 1,000 controls will be enrolled and matched for age and date. Cases are hospitalized children <5 years with radiologically confirmed pneumonia, and the controls are children without any features suggestive of pneumonia. Respiratory specimens are collected from all enrolled subjects to identify 19 viruses and 5 bacteria. Whole blood from pneumonia cases is being tested for 3 major bacteria. S. pneumoniae-positive specimens are serotyped. Urine samples from cases only are tested for detection of antimicrobial activity. The association between procalcitonin, C-reactive protein and pathogens is being evaluated. A discovery platform will enable pathogen identification in undiagnosed samples. Discussion: This multicenter study will provide descriptive results for better understanding of pathogens responsible for pneumonia among children in developing countries. The identification of determinants related to microorganisms associated with pneumonia and its severity should facilitate treatment and prevention