title: Pneumocystis pneumonia in South African children diagnosed by molecular methods.
abstract: BACKGROUND
  Pneumocystis pneumonia (PCP) is an important cause of hospitalization and mortality in HIV-infected children. However, the incidence of PCP has been underestimated due to poor sensitivity of diagnostic tests. The use of polymerase chain reaction (PCR) for pneumocystis has enabled more reliable diagnosis. This study describes the incidence, clinical features and outcome of PCP in South African children diagnosed using PCR.
  
  
  METHODS
  A prospective study of children hospitalised in South Africa with suspected PCP was done from November 2006 to August 2008. Clinical, laboratory and radiological information were collected. Lower respiratory tract specimens were obtained for PCP immunofluorescence (IF), real- time PCR for pneumocystis, bacterial and mycobacterial culture. Nasopharyngeal aspirates were taken for immunofluorescence (IF), real-time PCR for pneumocystis and PCR for respiratory viruses. A blood specimen for bacterial culture and for cytomegalovirus PCR was taken. Children were followed for the duration of their hospitalisation and the outcome was recorded.
  
  
  RESULTS
  202 children [median (interquartile range, IQR) age 3.2 (2.1- 4.6) months] were enrolled; 124 (61.4%) were HIV infected. PCP was identified in 109 (54%) children using PCR, compared to 43 (21%) using IF and Grocott staining (p < 0.0001). Most PCP cases (88, 81%) occurred in HIV-infected children. All 21 cases (19%) occurring in HIV- negative children had another risk factor for PCP. On logistic regression, predictive factors for PCP were HIV infection, lack of fever, high respiratory rate and low oxygen saturation whilst cotrimoxazole prophylaxis was protective (OR 0.24; 95% CI 0.1 to 0.5; p < 0.002). The case fatality of children with PCP was higher than those without PCP (32.1% versus 17.2%; relative risk 1.87; 95% confidence interval (CI) 1.11 - 3.15). Amongst HIV-infected children, a CD4 less than 15% was the only independent predictor of mortality.
  
  
  CONCLUSIONS
  The diagnostic yield for PCP is more than 2.5 times higher on PCR than other detection methods. PCP is a very common cause of severe hypoxic pneumonia and is associated with high mortality in HIV-infected African infants.
authors.affiliation: Department of Paediatics and Child Health, Red Cross War Memorial Children's Hospital (RCWMCH), University of Cape Town, 5th Floor Institute of Child Health Building, Klipfontein Road, Rondebosch 7700, Cape Town, South Africa. Brenda.morrow@uct.ac.za.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Morrow
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Samuel
authors.forename: Marco
authors.initials: M
authors.lastname: Zampoli
authors.forename: Andrew
authors.initials: A
authors.lastname: Whitelaw
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Zar
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D023241:Antiretroviral Therapy, Highly Active; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D018791:CD4 Lymphocyte Count; D003586:Cytomegalovirus Infections / Q000188:drug therapy; D005260:Female; D005455:Fluorescent Antibody Technique; D018023:HIV Seronegativity; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D009305:Nasopharynx / Q000382:microbiology; D010100:Oxygen / Q000097:blood; D011010:Pneumocystis / Q000254:growth & development; D011020:Pneumonia, Pneumocystis / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality; D011024:Pneumonia, Viral / Q000188:drug therapy; D011237:Predictive Value of Tests; D011241:Prednisone / Q000627:therapeutic use; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods*; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
chemical_list: D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D010100:Oxygen; D011241:Prednisone