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      Epidemiology of Viral-associated Acute Lower Respiratory Tract Infection Among Children <5 Years of Age in a High HIV Prevalence Setting, South Africa, 2009–2012

      research-article

      , MD , *† , , MD *† , , MD *† , , MD ‡§ , , PhD ¶‖ , , MSc * , , MSc * , , MD **†† , , MD ‡‡ , , MD ‡‡ , , MD §§ , , MD ¶¶‖‖ , , MD ***†††‡‡‡ , , MD ‡§ , , BSc * , , MD *‡ , , PhD *‡ , , MD ¶‖ , , PhD * , , PhD *§§§ , , PhD *‡§

      The Pediatric Infectious Disease Journal

      Williams & Wilkins

      pneumonia, HIV, AIDS, children, lower respiratory tract infection, South Africa

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          Abstract

          Supplemental Digital Content is available in the text.

          Abstract

          Background:

          Data on the epidemiology of viral-associated acute lower respiratory tract infection (LRTI) from high HIV prevalence settings are limited. We aimed to describe LRTI hospitalizations among South African children aged <5 years.

          Methods:

          We prospectively enrolled hospitalized children with physician-diagnosed LRTI from 5 sites in 4 provinces from 2009 to 2012. Using polymerase chain reaction (PCR), nasopharyngeal aspirates were tested for 10 viruses and blood for pneumococcal DNA. Incidence was estimated at 1 site with available population denominators.

          Results:

          We enrolled 8723 children aged <5 years with LRTI, including 64% <12 months. The case-fatality ratio was 2% (150/8512). HIV prevalence among tested children was 12% (705/5964). The overall prevalence of respiratory viruses identified was 78% (6517/8393), including 37% rhinovirus, 26% respiratory syncytial virus (RSV), 7% influenza and 5% human metapneumovirus. Four percent (253/6612) tested positive for pneumococcus. The annual incidence of LRTI hospitalization ranged from 2530 to 3173/100,000 population and was highest in infants (8446–10532/100,000). LRTI incidence was 1.1 to 3.0-fold greater in HIV-infected than HIV-uninfected children. In multivariable analysis, compared to HIV-uninfected children, HIV-infected children were more likely to require supplemental-oxygen [odds ratio (OR): 1.3, 95% confidence interval (CI): 1.1–1.7)], be hospitalized >7 days (OR: 3.8, 95% CI: 2.8–5.0) and had a higher case-fatality ratio (OR: 4.2, 95% CI: 2.6–6.8). In multivariable analysis, HIV-infection (OR: 3.7, 95% CI: 2.2–6.1), pneumococcal coinfection (OR: 2.4, 95% CI: 1.1–5.6), mechanical ventilation (OR: 6.9, 95% CI: 2.7–17.6) and receipt of supplemental-oxygen (OR: 27.3, 95% CI: 13.2–55.9) were associated with death.

          Conclusions:

          HIV-infection was associated with an increased risk of LRTI hospitalization and death. A viral pathogen, commonly RSV, was identified in a high proportion of LRTI cases.

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          Most cited references 38

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          Viral pneumonia.

          About 200 million cases of viral community-acquired pneumonia occur every year-100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient's age, speed of onset of illness, symptoms, biomarkers, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            Evaluation and improvement of real-time PCR assays targeting lytA, ply, and psaA genes for detection of pneumococcal DNA.

            The accurate diagnosis of pneumococcal disease has frequently been hampered not only by the difficulties in obtaining isolates of the organism from patient specimens but also by the misidentification of pneumococcus-like viridans group streptococci (P-LVS) as Streptococcus pneumoniae. This is especially critical when the specimen comes from the respiratory tract. In this study, three novel real-time PCR assays designed for the detection of specific sequence regions of the lytA, ply, and psaA genes were developed (lytA-CDC, ply-CDC, and psaA, respectively). These assays showed high sensitivity (<10 copies for lytA-CDC and ply-CDC and an approximately twofold less sensitivity for psaA). Two additional real-time PCR assays for lytA and ply described previously for pneumococcal DNA detection were also evaluated. A panel of isolates consisting of 67 S. pneumoniae isolates (44 different serotypes and 3 nonencapsulated S. pneumoniae isolates from conjunctivitis outbreaks) and 104 nonpneumococcal isolates was used. The 67 S. pneumoniae isolates were reactive in all five assays. The new real-time detection assays targeting the lytA and psaA genes were the most specific for the detection of isolates confirmed to be S. pneumoniae, with lytA-CDC showing the greatest specificity. Both ply PCRs were positive for all isolates of S. pseudopneumoniae, along with 13 other isolates of other P-LVS isolates confirmed to be non-S. pneumoniae by DNA-DNA reassociation. Thus, the use of the ply gene for the detection of pneumococci can lead to false-positive reactions in the presence of P-LVS. The five assays were applied to 15 culture-positive cerebrospinal fluid specimens with 100% sensitivity; and serum and ear fluid specimens were also evaluated. Both the lytA-CDC and psaA assays, particularly the lytA-CDC assay, have improved specificities compared with those of currently available assays and should therefore be considered the assays of choice for the detection of pneumococcal DNA, particularly when upper respiratory P-LVS might be present in the clinical specimen.
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              Viral etiology of severe pneumonia among Kenyan infants and children.

              Pneumonia is the leading cause of childhood death in sub-Saharan Africa. Comparative estimates of the contribution of causative pathogens to the burden of disease are essential for targeted vaccine development. To determine the viral etiology of severe pneumonia among infants and children at a rural Kenyan hospital using comprehensive and sensitive molecular diagnostic techniques. Prospective observational and case-control study during 2007 in a rural Kenyan district hospital. Participants were children aged 1 day to 12 years, residing in a systematically enumerated catchment area, and who either were admitted to Kilifi District Hospital meeting World Health Organization clinical criteria for severe pneumonia or very severe pneumonia; (2) presented with mild upper respiratory tract infection but were not admitted; or (3) were well infants and children attending for immunization. The presence of respiratory viruses and the odds ratio for admission with severe disease. Of 922 eligible admitted patients, 759 were sampled (82% [median age, 9 months]). One or more respiratory viruses were detected in 425 of the 759 sampled (56% [95% confidence interval {CI}, 52%-60%]). Respiratory syncytial virus (RSV) was detected in 260 participants (34% [95% CI, 31%-38%]) and other respiratory viruses were detected in 219 participants (29%; 95% CI, 26%-32%), the most common being Human coronavirus 229E (n = 51 [6.7%]), influenza type A (n = 44 [5.8%]), Parainfluenza type 3 (n = 29 [3.8%]), Human adenovirus (n = 29 [3.8%]), and Human metapneumovirus (n = 23 [3.0%]). Compared with well control participants, detection of RSV was associated with severe disease (5% [corrected] in control participants; adjusted odds ratio, 6.11 [95% CI, 1.65-22.6]) while collectively, other respiratory viruses were not associated with severe disease (23% in control participants; adjusted odds ratio, 1.27 [95% CI, 0.64-2.52]). In a sample of Kenyan infants and children admitted with severe pneumonia to a rural hospital, RSV was the predominant viral pathogen.
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                Author and article information

                Journal
                Pediatr Infect Dis J
                Pediatr. Infect. Dis. J
                INF
                The Pediatric Infectious Disease Journal
                Williams & Wilkins
                0891-3668
                1532-0987
                January 2015
                11 December 2014
                : 34
                : 1
                : 66-72
                Affiliations
                From the [* ]Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service; []School of Public Health, Faculty of Health Sciences, University of the Witwatersrand; []Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, Faculty of Health Sciences, University of the Witwatersrand; [§ ]Department of Science and Technology/National Research Foundation, Vaccine Preventable Diseases, University of the Witwatersrand, Johannesburg, South Africa; []Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA; []Influenza Programme, Centers for Disease Control and Prevention–South Africa, Pretoria; [* ]*Department of Medicine, Pietermaritzburg Metropolitan Hospital; []†Department of Medicine, University of KwaZulu Natal; []‡Department of Paediatrics, Pietermaritzburg Metropolitan Hospital [§§ ]School of Pathology, University of KwaZulu Natal, Pietermaritzburg; []¶Department of Medicine, Klerksdorp Tshepong Hospital, Klerksdorp; []‖Department of Medicine, Faculty of Health Sciences, University of the Witwatersrand; [* ]**MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; []††Centre for Global Health Research, Umeå University, Umeå, Sweden; []‡‡INDEPTH Network, Accra, Ghana; and [§ ]§§Zoonoses Research Unit, Department of Medical Virology, University of Pretoria, Gauteng, South Africa
                Author notes
                Address for correspondence: Cheryl Cohen, MD, Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases, Private Bag X4, Sandringham 2131, Gauteng, South Africa. E-mail: cherylc@ 123456nicd.ac.za .
                Article
                00014
                10.1097/INF.0000000000000478
                4276570
                25093972
                696a18d9-5f04-4be2-bca5-96831108b99e
                Copyright © 2014 by Lippincott Williams & Wilkins

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

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