title: Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Clinical and Hypoxemic Childhood Pneumonia over Three Years in Central Malawi: An Observational Study.
abstract: BACKGROUND
  The pneumococcal conjugate vaccine's (PCV) impact on childhood pneumonia during programmatic conditions in Africa is poorly understood. Following PCV13 introduction in Malawi in November 2011, we evaluated the case burden and rates of childhood pneumonia.
  
  
  RESULTS
  Between January 1, 2012-June 30, 2014 we conducted active pneumonia surveillance in children <5 years at seven hospitals, 18 health centres, and with 38 community health workers in two districts, central Malawi. Eligible children had clinical pneumonia per Malawi guidelines, defined as fast breathing only, chest indrawing +/- fast breathing, or, ≥1 clinical danger sign. Since pulse oximetry was not in the Malawi guidelines, oxygenation <90% defined hypoxemic pneumonia, a distinct category from clinical pneumonia. We quantified the pneumonia case burden and rates in two ways. We compared the period immediately following vaccine introduction (early) to the period with >75% three-dose PCV13 coverage (post). We also used multivariable time-series regression, adjusting for autocorrelation and exploring seasonal variation and alternative model specifications in sensitivity analyses. The early versus post analysis showed an increase in cases and rates of total, fast breathing, and indrawing pneumonia and a decrease in danger sign and hypoxemic pneumonia, and pneumonia mortality. At 76% three-dose PCV13 coverage, versus 0%, the time-series model showed a non-significant increase in total cases (+47%, 95% CI: -13%, +149%, p = 0.154); fast breathing cases increased 135% (+39%, +297%, p = 0.001), however, hypoxemia fell 47% (-5%, -70%, p = 0.031) and hospital deaths decreased 36% (-1%, -58%, p = 0.047) in children <5 years. We observed a shift towards disease without danger signs, as the proportion of cases with danger signs decreased by 65% (-46%, -77%, p<0.0001). These results were generally robust to plausible alternative model specifications.
  
  
  CONCLUSIONS
  Thirty months after PCV13 introduction in Malawi, the health system burden and rates of the severest forms of childhood pneumonia, including hypoxemia and death, have markedly decreased.
authors.affiliation: Institute for Global Health, University College London, London, United Kingdom.|Department of Pediatrics, Division of Pulmonology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Eric D
authors.initials: ED
authors.lastname: McCollum
authors.affiliation: Institute for Global Health, University College London, London, United Kingdom.
authors.forename: Bejoy
authors.initials: B
authors.lastname: Nambiar
authors.affiliation: Parent and Child Health Initiative Trust, Lilongwe, Malawi.
authors.forename: Rashid
authors.initials: R
authors.lastname: Deula
authors.affiliation: Parent and Child Health Initiative Trust, Lilongwe, Malawi.
authors.forename: Beatiwel
authors.initials: B
authors.lastname: Zadutsa
authors.affiliation: Parent and Child Health Initiative Trust, Lilongwe, Malawi.
authors.forename: Austin
authors.initials: A
authors.lastname: Bondo
authors.affiliation: Institute for Global Health, University College London, London, United Kingdom.
authors.forename: Carina
authors.initials: C
authors.lastname: King
authors.affiliation: Institute for Global Health, University College London, London, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Beard
authors.affiliation: Parent and Child Health Initiative Trust, Lilongwe, Malawi.
authors.forename: Harry
authors.initials: H
authors.lastname: Liyaya
authors.affiliation: Parent and Child Health Initiative Trust, Lilongwe, Malawi.
authors.forename: Limangeni
authors.initials: L
authors.lastname: Mankhambo
authors.affiliation: WHO Collaborating Centre for Maternal and Child Health, Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Lazzerini
authors.affiliation: Parent and Child Health Initiative Trust, Lilongwe, Malawi.
authors.forename: Charles
authors.initials: C
authors.lastname: Makwenda
authors.affiliation: Parent and Child Health Initiative Trust, Lilongwe, Malawi.
authors.forename: Gibson
authors.initials: G
authors.lastname: Masache
authors.affiliation: Malawi-Liverpool-Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.|Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Naor
authors.initials: N
authors.lastname: Bar-Zeev
authors.affiliation: Baylor College of Medicine Children's Foundation, Lilongwe, Malawi.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Kazembe
authors.affiliation: Ministry of Health, Lilongwe, Malawi.
authors.forename: Charles
authors.initials: C
authors.lastname: Mwansambo
authors.affiliation: Community Health Sciences Unit, Ministry of Health, Lilongwe, Malawi.
authors.forename: Norman
authors.initials: N
authors.lastname: Lufesi
authors.affiliation: Institute for Global Health, University College London, London, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Costello
authors.affiliation: Department of Social and Environmental Health Research, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Ben
authors.initials: B
authors.lastname: Armstrong
authors.affiliation: Institute for Global Health, University College London, London, United Kingdom.
authors.forename: Tim
authors.identifier: http://orcid.org/0000-0002-6917-6552
authors.initials: T
authors.lastname: Colbourn
mesh_terms: D002648:Child; D046688:Child Mortality; D017281:Cost of Illness; D004306:Dose-Response Relationship, Immunologic; D005843:Geography; D006801:Humans; D000860:Hypoxia / Q000150:complications*; D008295:Malawi / Q000453:epidemiology; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000150:complications* / Q000276:immunology* / Q000401:mortality; D013997:Time Factors; D018074:Vaccines, Conjugate / Q000276:immunology*
chemical_list: C538862:13-valent pneumococcal vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate