title: Can We Predict Oral Antibiotic Treatment Failure in Children with Fast-Breathing Pneumonia Managed at the Community Level? A Prospective Cohort Study in Malawi.
abstract: BACKGROUND
  Pneumonia is the leading cause of infectious death amongst children globally, with the highest burden in Africa. Early identification of children at risk of treatment failure in the community and prompt referral could lower mortality. A number of clinical markers have been independently associated with oral antibiotic failure in childhood pneumonia. This study aimed to develop a prognostic model for fast-breathing pneumonia treatment failure in sub-Saharan Africa.
  
  
  METHODS
  We prospectively followed a cohort of children (2-59 months), diagnosed by community health workers with fast-breathing pneumonia using World Health Organisation (WHO) integrated community case management guidelines. Cases were followed at days 5 and 14 by study data collectors, who assessed a range of pre-determined clinical features for treatment outcome. We built the prognostic model using eight pre-defined parameters, using multivariable logistic regression, validated through bootstrapping.
  
  
  RESULTS
  We assessed 1,542 cases of which 769 were included (32% ineligible; 19% defaulted). The treatment failure rate was 15% at day 5 and relapse was 4% at day 14. Concurrent malaria diagnosis (OR: 1.62; 95% CI: 1.06, 2.47) and moderate malnutrition (OR: 1.88; 95% CI: 1.09, 3.26) were associated with treatment failure. The model demonstrated poor calibration and discrimination (c-statistic: 0.56).
  
  
  CONCLUSIONS
  This study suggests that it may be difficult to create a pragmatic community-level prognostic child pneumonia tool based solely on clinical markers and pulse oximetry in an HIV and malaria endemic setting. Further work is needed to identify more accurate and reliable referral algorithms that remain feasible for use by community health workers.
authors: Institute for Global Health, University College London, London, United Kingdom.
authors: Carina
authors: C
authors: King
authors: 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: Eric D
authors: ED
authors: McCollum
authors: Parent and Child Health Initiative, Lilongwe, Malawi.
authors: Limangeni
authors: L
authors: Mankhambo
authors: Institute for Global Health, University College London, London, United Kingdom.
authors: Tim
authors: T
authors: Colbourn
authors: Institute for Global Health, University College London, London, United Kingdom.
authors: James
authors: J
authors: Beard
authors: Bill & Melinda Gates Foundation, Seattle, Washington, United States of America.
authors: Debbie C
authors: DC
authors: Hay Burgess
authors: Institute for Global Health, University College London, London, United Kingdom.
authors: Anthony
authors: A
authors: Costello
authors: Rasa
authors: R
authors: Izadnegahdar
authors: Bill & Melinda Gates Foundation, Seattle, Washington, United States of America.
authors: Raza
authors: R
authors: Izadnegahdar
authors: Acute Respiratory Infection Unit, Ministry of Health, Lilongwe, Malawi.
authors: Norman
authors: N
authors: Lufesi
authors: Parent and Child Health Initiative, Lilongwe, Malawi.
authors: Gibson
authors: G
authors: Masache
authors: Ministry of Health, Lilongwe, Malawi.
authors: Charles
authors: C
authors: Mwansambo
authors: Institute for Global Health, University College London, London, United Kingdom.
authors: Bejoy
authors: B
authors: Nambiar
authors: Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, United States of America.
authors: Eric
authors: E
authors: Johnson
authors: McGill University, Montreal, Canada.
authors: Robert
authors: R
authors: Platt
authors: Bill & Melinda Gates Foundation, Seattle, Washington, United States of America.
authors: David
authors: D
authors: Mukanga
mesh_terms: D000284:Administration, Oral; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002675:Child, Preschool; D015331:Cohort Studies; D003150:Community Health Workers; D006801:Humans; D007223:Infant; D008295:Malawi; D008954:Models, Biological; D010349:Patient Compliance; D011014:Pneumonia / Q000188:drug therapy*; D011446:Prospective Studies; D012119:Respiration; D017211:Treatment Failure; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination