title: Early use of corticosteroids in infants with a clinical diagnosis of Pneumocystis jiroveci pneumonia in Malawi: a double-blind, randomised clinical trial.
abstract: BACKGROUND
  Pneumocystis jiroveci pneumonia (PJP) is the most common opportunistic infection in infants with vertically acquired HIV infection and the most common cause of death in HIV-infected infants.
  
  
  OBJECTIVE
  To determine whether early administration of adjuvant corticosteroids in addition to standard treatment reduces mortality in infants with vertically acquired HIV and clinically diagnosed PJP when co-infection with cytomegalovirus and other pathogens cannot be excluded.
  
  
  METHODS
  A double-blind placebo-controlled trial of adjuvant prednisolone treatment in HIV-exposed infants aged 2-6 months admitted to Queen Elizabeth Central Hospital, Blantyre who were diagnosed clinically with PJP was performed. All recruited infants were HIV-exposed, and the HIV status of the infant was confirmed by DNA-PCR. HIV-exposed and infected infants as well as HIV-exposed but non-infected infants were included in the study. The protocol provided for the addition of prednisolone to the treatment at 48 h if there was clinical deterioration or an independent indication for corticosteroid therapy in any patient not receiving it. Oral trimethoprim-sulfamethoxazole (TMP/SMX) therapy and full supportive treatment were provided according to established guidelines. Primary outcomes for all patients included survival to hospital discharge and 6-month post-discharge survival.
  
  
  RESULTS
  It was planned to enroll 200 patients but the trial was stopped early because of recruitment difficulties and a statistically significant result on interim analysis. Seventy-eight infants were enrolled between April 2012 and August 2014; 36 infants (46%) were randomised to receive corticosteroids plus standard treatment with TMP/SMX, and 42 infants (54%) received the standard treatment plus placebo. In an intention-to treat-analysis, the risk ratio of in-hospital mortality in the steroid group compared with the standard treatment plus placebo group was 0.53 [95% CI 0.29-0.97, p = 0.038]. The risk ratio of mortality at 6 months was 0.63 (95% CI 0.41-0.95, p = 0.029). Two children who received steroids developed bloody stools while in hospital.
  
  
  CONCLUSIONS
  In infants with a clinical diagnosis of PJP, early use of steroids in addition to conventional TMP/SMX therapy significantly reduced mortality in hospital and 6 months after discharge.
authors.affiliation: a College of Medicine, University of Malawi , Blantyre , Malawi.|b Queen Elizabeth Central Hospital , Blantyre , Malawi.
authors.forename: Laura
authors.initials: L
authors.lastname: Newberry
authors.affiliation: a College of Medicine, University of Malawi , Blantyre , Malawi.|b Queen Elizabeth Central Hospital , Blantyre , Malawi.|c Global Health Implementation Group , University of St Andrews , Fife , Scotland.
authors.forename: Bernadette
authors.initials: B
authors.lastname: O'Hare
authors.affiliation: a College of Medicine, University of Malawi , Blantyre , Malawi.|b Queen Elizabeth Central Hospital , Blantyre , Malawi.|d Department of Paediatrics , Queen's University Belfast , Belfast , Northern Ireland.
authors.forename: Neil
authors.initials: N
authors.lastname: Kennedy
authors.affiliation: a College of Medicine, University of Malawi , Blantyre , Malawi.|b Queen Elizabeth Central Hospital , Blantyre , Malawi.
authors.forename: Andrew
authors.initials: A
authors.lastname: Selman
authors.affiliation: a College of Medicine, University of Malawi , Blantyre , Malawi.|b Queen Elizabeth Central Hospital , Blantyre , Malawi.
authors.forename: Sofia
authors.initials: S
authors.lastname: Omar
authors.affiliation: a College of Medicine, University of Malawi , Blantyre , Malawi.|b Queen Elizabeth Central Hospital , Blantyre , Malawi.
authors.forename: Pamela
authors.initials: P
authors.lastname: Dawson
authors.affiliation: a College of Medicine, University of Malawi , Blantyre , Malawi.|b Queen Elizabeth Central Hospital , Blantyre , Malawi.
authors.forename: Kim
authors.initials: K
authors.lastname: Stevenson
authors.affiliation: a College of Medicine, University of Malawi , Blantyre , Malawi.|b Queen Elizabeth Central Hospital , Blantyre , Malawi.
authors.forename: Yo
authors.initials: Y
authors.lastname: Nishihara
authors.affiliation: a College of Medicine, University of Malawi , Blantyre , Malawi.|b Queen Elizabeth Central Hospital , Blantyre , Malawi.
authors.forename: Samantha
authors.initials: S
authors.lastname: Lissauer
authors.affiliation: a College of Medicine, University of Malawi , Blantyre , Malawi.|b Queen Elizabeth Central Hospital , Blantyre , Malawi.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Molyneux
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007223:Infant; D008295:Malawi; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D045363:Pneumocystis carinii / Q000302:isolation & purification*; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D011239:Prednisolone / Q000008:administration & dosage*; D055502:Secondary Prevention; D016019:Survival Analysis; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage
chemical_list: D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D010919:Placebos; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D011239:Prednisolone
keywords: HIV; Pneumocystis jiroveci pneumonia; infant