Pneumocystis pneumonia in South African children diagnosed by molecular methods

BMC Research Notes, Dec 2014

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.

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Pneumocystis pneumonia in South African children diagnosed by molecular methods

BMC Research Notes Pneumocystis pneumonia in South African children diagnosed by molecular methods Brenda M Morrow 0 2 Catherine M Samuel 1 Marco Zampoli 0 2 Andrew Whitelaw 1 Heather J Zar 0 2 0 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 1 Division of Medical Microbiology, National Health Laboratory Services, University of Cape Town , Cape Town , South Africa 2 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 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. Pneumocystis pneumonia; HIV; Children; Prophylaxis; PCR; Diagnosis; Incidence Background Pneumocystis pneumonia (PCP) is a major cause of morbidity and mortality in HIV infected infants [ 1-5 ]. Approximately 29 – 67% of respiratory related deaths among African HIV infected children have been associated with PCP [ 6-8 ], and in-hospital case-fatality rates range from 20 – 63% [ 1,2,9-11 ]. South African studies have reported that the prevalence of PCP ranges from 10% to 49% among antiretroviral naïve HIV infected children hospitalized with pneumonia [ 9-11 ]. PCP has also been shown to occur in HIV uninfected infants, mostly with an underlying predisposing factor such as HIV exposure or malnutrition [ 2,4,12-16 ]. The use of highly active antiretroviral therapy (HAART) has dramatically reduced the incidence of PCP in developed countries [ 17-19 ]. However PCP remains a common cause of hospitalization and mortality in HIV-infected South African children [ 2,4 ]. In a recent study, 21% of children admitted to a tertiary paediatric hospital with acute severe hypoxic pneumonia were found to have PCP despite a well- functioning paediatric HIV program [2]. In previous studies, immunofluorescence (IF) or silver staining of respiratory secretions have been used for the diagnosis of PCP. Such methods have been reported to be insensitive for diagnosis, potentially leading to under recognition of PCP [ 20-24 ].We recently reported that real-time polymerase chain reaction (PCR) is more sensitive than IF for the diagnosis of PCP when used on lower [induced sputum (IS) or non-bronchoscopic broncho-alveolar lavage (BAL)] or upper respiratory tract [nasopharyngeal aspirate (NPA)] specimens. The yield for PCP from upper and lower respiratory tract specimens was similar by PCR [ 20 ]. The aim of this study was to describe the incidence, clinical features and outcome of PCP in children when diagnosed with PCR. Methods This was a prospective study of consecutive children hospital (...truncated)


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Brenda M Morrow, Catherine M Samuel, Marco Zampoli, Andrew Whitelaw, Heather J Zar. Pneumocystis pneumonia in South African children diagnosed by molecular methods, BMC Research Notes, 2014, pp. 26, Volume 7, Issue 1, DOI: 10.1186/1756-0500-7-26