Browsing by Author "Zampoli, Marco"
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- ItemOpen AccessAdenovirus-associated pneumonia in South African children : presentation, clinical course and outcome(2015) Mukuddem-Sablay, Zakira; Zampoli, MarcoBackground: Pneumonia is an important cause of morbidity and mortality in children. Viruses have emerged as important aetiological agents in childhood pneumonia. The aim of this study was to document the clinical presentation, severity and outcome of adenoviral-associated pneumonia (AVP) in children and identify risk factors associated with poor outcome. Methods: A retrospective study of laboratory-confirmed AVP cases was conducted between 1 January and 31 December 2011. The medical records of adenovirus PCR positive respiratory tract samples identified through the National Health Laboratory Service (NHLS) database were retrieved. Demographic, clinical and outcomes data of children with AVP were extracted and analysed. Outcome measures were death and development of chronic lung disease (CLD). Results: 1910 respiratory samples were submitted to the NHLS from which 206/1910 (11%) AVP cases were identified. The median age was 12 months (IQR 6-24), 70 (34%) children were malnourished and 14 (7%) HIV-infected. Fever was the commonest presenting symptom occurring in 159 (77%) of cases. Seventy six (37%) required intensive care unit (ICU) admission. There was a high prevalence of co-morbid conditions with 98 (47%) having at least one; cardiac disease was the most common (48 (23%). Twenty nine (14%) developed CLD which was associated with hypoxia at presentation (26/29, 90%, p = 0.01) and admission to ICU (18/29, 62%, p < 0.01). Eighteen (9%) children died. Admission to ICU (OR 8.3, 95% CI 2.3-29.0) and blood stream infection (OR 11.2; 95% CI 2.3-54.1) were independent risk factors for mortality. Conclusion: Adenoviral-associated pneumonia is an important cause of pneumonia and CLD in young children in South Africa. Admission to ICU and blood stream infection were associated with poor outcome
- ItemOpen AccessAetiology and presentation of childhood pleural infections in the post-pneumococcal conjugate vaccine era in South Africa(2021) Golden, Lauren; Zampoli, Marco; Chaya, ShaakiraComplications of respiratory infections include pleural effusion (PE), associated with a high morbidity. Differentiating between PE caused by bacterial infections and Mycobacterium tuberculosis (TB) in endemic areas is difficult in children, impacting treatment. We investigated the aetiology of PE and features distinguishing TB from bacterial PE in children. Methods In this prospective study, children with PE admitted to a tertiary hospital in Cape Town from December 2016 to December 2019 were enrolled. Clinical information and routine laboratory investigations were compared between children with bacterial, TB or unclassified PE, categorised according to study definitions. Results A total of 91 patients were included; their median age was 31 months (IQR 11.8–102.1). Aetiology was bacterial in 37 (40%), TB in 36 (39%) and unclassified in 18 (20%) patients. Staphylococcus aureus was the most common bacterial isolate, confirmed in 24/37 (65%) patients; and Streptococcus pneumoniae confirmed in only 3/37 patients (8%). TB was microbiologically confirmed in 12/36 (33%) patients. Patients with TB were older (median age 91.6 vs 11.8 months, p< 0.001), with more weight loss (28/36 (77.8%) vs 12/37 (32%) patients, p< 0.001), and longer cough duration (10 vs 4 days, p< 0.001) than those with bacterial PE. In contrast, the latter had significantly higher median values: serum C-reactive protein (250 vs 122 mg/L, p< 0.001), procalcitonin (11 vs 0.5 mg/L, p< 0.001) pleural fluid lactate dehydrogenase (7280 vs 544 U/L, p< 0.001), and adenosine deaminase levels (162 vs 48 U/L, p< 0.001) and lower glucose levels (1.3 vs 4 mmol/L, p< 0.001). Conclusion Post-PCV, S. aureus is the dominant cause of PE in children using traditional culture methods, while TB remains a common cause of PE in our setting. Useful clinical and laboratory differences between TB and bacterial PE were identified, but the cause of PE in 20% of children was underdetermined. Molecular testing of pleural fluid for respiratory pathogens may be useful in such children.
- ItemOpen AccessAetiology of pleural effusions diagnosed by routine culture and molecular techniques in children living in a high tuberculosis-endemic setting(2025) Wordui, Seyram; Gray, Diane; Zampoli, MarcoBACKGROUND: Confirming aetiology of pleural effusion in children may be difficult in tuberculosis (TB)-endemic settings. We investigated the role of polymerase chain reaction (PCR) and routine biochemical tests in discriminating pleural effusion caused by bacteria from other aetiologies. METHODS: This is a post-hoc analysis of a cross-sectional study among children with pleural effusion in a tertiary hospital in South Africa, incorporating data from PCR testing of stored pleural fluid. Aetiological classification was defined by microbiological confirmation. RESULTS: Ninety-one children were enrolled, median age 31 months (IQR 12-102). Aetiology of pleural effusion was 40 % (n=36/91) bacteria, 11% (n=10/91) TB, 3% (n=3/91) viruses, 11% (n=10/91) polymicrobial and 35% (n=32/91) had no pathogen identified. The commonest pathogen was Staphylococcus aureus (n=27/91; 30%) with similar yields on culture and PCR, followed by Streptococcus pneumoniae (n=12/91; 13%), detected more commonly by PCR. PCR reduced the number of children with unconfirmed aetiologies from 48 to 32. Characteristics of children with no pathogen most resembled those with TB. Pleural fluid lactate dehydrogenase ≥1716 U/L best discriminated bacterial pleural effusion from other aetiologies (sensitivity of 86%; specificity 95%). CONCLUSION: PCR improved detection of pathogens and reduced number of children with unconfirmed aetiologies in presumed exudative pleural effusion.
- ItemOpen AccessAntiretroviral roll-out in South Africa: where do children feature?(Children's Institute, 2004) Shung King, Maylene; Zampoli, Marco
- ItemOpen AccessAntiretroviral treatment for children(Health and Medical Publishing Group, 2006) Eley, Brian; Davies, Mary-Ann; Apolles, Patti; Cowburn, Carol; Buys, Heloise; Zampoli, Marco; Finlayson, Heather; King, Spasina; Nuttall, JamesObjective: To describe the response of children during their first year on highly active antiretroviral therapy (HAART). Design: Retrospective, descriptive. Setting. Tertiary, referral hospital. Subjects: All HIV-infected children commenced on HAART from 1 August 2002 until 31 December 2004. Outcome measures: Children were retrospectively restaged using the WHO 4-stage clinical classification and CDC immunological staging system. After commencing HAART, patients were assessed at monthly intervals for the first 6 months and thereafter mostly 3-monthly. Baseline and 6- monthly CD4 counts and viral loads were performed. Results. Of 409 children commenced on HAART, 50.6% were < 2 years old, 62.7% had severe clinical disease and 76.6% had severe immune suppression. After 1 year, 65.8% were alive and continued HAART at the hospital, 11.2% had been transferred to another antiretroviral site, 15.4% had died, 4.6% were lost to follow-up and treatment had been discontinued in 2.9%. Kaplan-Meier survival estimate for 407 children at 1 year was 84% (95% confidence interval (CI) 80 - 87%). On multivariate analysis, survival was adversely affected in children with WHO stage 4 v. stage 2 and 3 disease (adjusted hazard ratio (HR): 5.26 (95% CI 2.25 - 12.32), p = 0.000), age < 12 months (adjusted HR: 2.46 (95% CI 1.48 - 4.09), p = 0.001) and CD4 absolute count (per 100 cell increase) (adjusted HR: 0.93 (95% CI 0.88 - 0.98), p = 0.013). In a separate multivariate model including only children with an initial viral load (N = 367), viral load r 1 million copies/ml (adjusted HR: 1.84 (95% CI 1.03 - 3.29)) and taking a protease inhibitor (PI)-based regimen (adjusted HR: 2.25 (95% CI 1.10 - 4.61)) were additionally independently associated with poorer survival; however, young age was not a significant predictor of mortality, after adjusting for viral load (p = 0.119). After 1 year of HAART 184/264 (69.7%) of children had a viral load < 400 copies/ml. Comparative analysis showed significant improvements in growth, immunological status and virological control. Conclusion: HAART can improve the health of many HIVinfected children with advanced disease, including those aged less than 2 years in resource-limited settings.
- ItemOpen AccessBuilding capacity for diagnosis of Primary Ciliary Dyskinesia in South Africa: a descriptive study(2025) Eze, Joy Nkiru; Zampoli, Marco; Gray DianeBackground: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by abnormal cilia motility. Diagnostic capacity for PCD in sub-Saharan Africa (sSA) is limited; and incidence of PCD and genotype in sSA is unknown. Objectives: To determine the prevalence of PCD in children and adults with suspected PCD using a range of specialized diagnostic tests; and inform the development of local guidelines for PCD diagnosis. Methods: A prospective cross-sectional study in Cape Town, SA. Diagnostic tests performed included: nasal nitric oxide (nNO), nasal brushings for video microscopy of ciliary beat; transmission electron microscopy (TEM), immunofluorescence (IF) of ciliary protein antigens and genotyping. Results: Thirty-three participants (31 children; 2 adults) were enrolled July 2022 to July 2023 [median (IQR) age 5.6 years (3.8, 8.2); 16 (49%) males; 22 (66.7%) non-Caucasian]. The most frequent clinical characteristics were upper respiratory disease with or without hearing impairment (91%, n=30), chronic wet cough (73%, n=24), bronchiectasis (36%, n=12), neonatal respiratory distress (48%, n= 16), and situs inversus (36%, n=12); 7/17 (41%) participants recorded nNO <77nl/. Ciliary beat pattern and TEM were abnormal in 55% (n=18) and 6.1% (n=2) of the participants respectively; PCD was confirmed genetically in 5/24 (21%), of which two had abnormal IF. Two unrelated black Africans were homozygous for the same pathogenic variant in DNAAF3. Conclusion: Using a range of diagnostic modalities, the study has identified PCD cases who would have otherwise been missed or incorrectly diagnosed
- ItemOpen AccessClinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?(Multidisciplinary Digital Publishing Institute, 2023-08-01) Warner, Sherridan; Blaxland, Anneliese; Counoupas, Claudio; Verstraete, Janine; Zampoli, Marco; Marais, Ben J.; Fitzgerald, Dominic A.; Robinson, Paul D.; Triccas, James A.Mycobacterium abscessus is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Guérin (BCG) vaccination may impact NTM infection, using a murine model of Mycobacterium abscessus infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD up sup T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with M. abscessus afforded the highest level of protection against M. abscessus challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4 T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for M. abscessus. This study provides evidence that routine BCG vaccination may reduce M. abscessus colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4T cells recognising M. abscessus in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF.
- ItemOpen AccessCystic fibrosis in black African children in South Africa: a case control study(2020) Kwarteng, Owusu Sandra; Zampoli, Marco; Vanker, Aneesa; Gray, DianeBackground Cystic fibrosis (CF) is described more commonly in Caucasian populations in whom p.Phe508del is the most common mutation. There is a paucity of data of CF in black African children. The aim of this study was to describe and compare the presentation and outcomes of black African children with CF to those with p.Phe508del genotype. Methods A retrospective case-controlled study was conducted from January 2000 – March 2018 of children with CF attending two CF centres in South Africa. Presentation, genotype, nutrition and pulmonary function outcomes of black African children were compared to matched controls with the p.Phe508del mutation. Results Thirty-four black African children (cases) with median age of diagnosis (5.5 months, IQR 2.0- 15.0) were matched to 34 controls. Among cases, 3120+1G->A CFTR mutation was most commonly identified; homozygous n=22 (64.7%) and heterozygous=7(20.5%). Compared to controls, cases at diagnosis were more malnourished and fewer presented with neonatal bowel obstruction [cases n=2 (5.9%) vs. controls n=10 (29.4%); p = 0.03]. Nutrition and pulmonary function (FEV1 in children ≥ 6 years) outcomes and changes over time from ages 3-16 years were similar in both groups; median FEV1 z-score at age 6,10 and 14 years was -0.9 (±1.5), -1.8 (±2.0) and -1.8 (±1.9) respectively for all patients. Deaths were recorded in three cases (8.8%) and one control (2.9%) (p = 0.6). Conclusion Black African children with CF were more malnourished at diagnosis, and fewer presented with neonatal bowel obstruction. Cases and controls had comparable nutritional, pulmonary function and early mortality outcomes.
- ItemOpen AccessCystic fibrosis in South Africa: spectrum of disease, diagnosis, and determinants of outcome(2023) Zampoli, Marco; Morrow, BrendaCystic fibrosis (CF) occurs with varying incidence in all populations throughout the world but much less is known about the epidemiology and outcomes of CF in low-or-middle income countries (LMIC) compared with high income settings. Continued improvement in CF-related outcomes and survival witnessed in the past decades is attributed to multiple factors yet sub-optimal quality of CF care, and limited CF diagnosis capacity continue to exist in most LMIC, including South Africa (SA). CF treatment and prognosis have been transformed by the recent introduction of highly effective cystic fibrosis transmembrane conductance regulator modulator drugs (CFTRm). However, access to these transformative drugs for those with eligible genotypes is currently limited to high-income countries. Understanding the clinical spectrum of CF in SA and investigating novel techniques to diagnose CF is important to advocate for improved quality of CF care including CFTRm drugs. The overall aim of this work was to document the spectrum and outcomes of CF in South Africans and to investigate more sensitive measures to diagnose CF and CFTR-related disorders in this population. The studies included in this thesis are divided into two components. This first component comprises observational cohort studies derived from a single-centre CF clinic dataset in Cape Town, SA, and the nation-wide South African CF registry, which was established in 2018 in preparation for this thesis. The CF registry cohort in SA was then compared in a cross-sectional study to a matched Canadian CF registry cohort, and differences in lung function and nutrition outcomes adjusted for known factors. The second component was a prospective study investigating the feasibility and diagnostic utility of the novel β-adrenergic sweat test in a cohort of South Africans with inconclusive CF diagnosis. The chapters of this thesis are presented as published manuscripts, which collectively address the overall aim of this body of work. The SA CF registry in its first year of inception captured a total of 447 people with CF across both private and public health sectors. Summary demographic descriptions of the cohort include median age of 14.7 years with self-identified White race making up 70% of the CF population, followed by Mixed-race ancestry (19%) and Black Africans (10%). Genotype pattern mirrored ancestry with F508del is the most common variant in Whites and people with Mixed-race ancestry, and 3120+1G>A (class I) the most common variant in Black Africans. Overall, 81% of people with CF (pwCF) in SA have at least one copy of F508del and are, thus, eligible for elexacaftor/tezacaftor/ivacaftor. A key finding of the registry-based studies was that lung function and nutrition outcomes in SA were significantly lower across all ages compared with Canada, attributed to differences in the quality of CF care and social determinants of CF health between the two countries. In SA, poor nutrition was the strongest factor independently associated with severe lung disease and was more prevalent in people living in lower 10 socioeconomic conditions, including people who were not White. Another key finding was despite significant improvement in overall CF survival at a single centre in Cape Town over the past 40 years, disparities between race groups still exist in SA with increased risk of mortality observed in young children who were not White. People with Black African ancestry, who form the majority of the SA population, are likely to be underrepresented in the SA CF registry, raising concern that CF is being missed or underdiagnosed in the majority of South Africans. Furthermore, the genotype of Black Africans means that none are eligible for CFTRm, which has serious implications for future treatment. These registry-based studies highlight disparities in CF care and outcomes both within SA and compared with a high-income setting – novel findings because SA is one of only a few LMIC with CF registries. Addressing these disparities affecting people with CF in SA will require interventions such as greater awareness of CF in SA, universal newborn screening for CF, focused attention on improving nutrition and overall improvement in the quality of essential CF care, especially as LMIC have disproportionally more pwCF who are ineligible for CFTRm drugs. The diagnosis of CF using standard approaches may remain inconclusive in a small proportion of individuals, which leads to unnecessary anxiety for families and inappropriate treatment where people do not actually have CF or a CFTR-related disorder. Furthermore, accurate diagnosis of CF is important for research and submission of registry data. The β-adrenergic sweat test was proposed as an easier alternative to other electrophysiological measurements of CFTR function such as nasal potential difference and intestinal current measurements, which are not available in SA. We therefore conducted a study evaluating this hypothesis in adult subject controls, and 32 individuals (mostly children) whose CF diagnosis was inconclusive. Key findings of this study were that the β-adrenergic sweat was superior to sweat chloride test in excluding CF in the majority of subjects and that βadrenergic sweat secretion in children was lower compared to adults. Implications and novelty of this research are that existing reference ranges for this test may not be applicable in children, and confirmation that the β-adrenergic sweat test is a viable alternative for measuring CFTR function. A number of families benefited from this study by reversal of their incorrect CF diagnosis. The overriding finding and impact of this work has been to highlight disparities in diagnosis, treatment, and outcomes of CF within SA and in the global context. The current status of CF care in SA mirrors many other LMIC that share similar challenges and barriers to improving CF care, including access to affordable CFTRm drugs. The findings of this thesis have made valuable contributions to local and global advocacy initiatives to improve CF care and access to CFTR drugs for many thousands of pwCF living in LMIC who are being left behind in this new era of CF treatment.
- ItemOpen AccessExogenous Lipoid Pneumonia in Children: A Systematic Review and Case Series from South Africa(2018) Marangu, Diana Mwendwa; Zampoli, Marco; Gray, Diane; Vanker, AneesaBackground and objective: To describe the clinical-radiological-pathological characteristics and treatment outcomes of childhood exogenous lipoid pneumonia (ELP) and elucidate oil administration practices. Methods: A retrospective study of children with histologically-confirmed ELP at Red Cross Children’s Hospital, South Africa. Caregivers were interviewed to understand oil administration practices. Results: Twelve children of Zimbabwean heritage aged 2.1-10.8 months were identified between 2012 and 2017. Repeated oral administration of plant-based oil for cultural reasons was reported by 10/11 caregivers. Cough (12/12), tachypnea (11/12), hypoxia (9/12) and diffuse alveolar infiltrates on chest radiography (12/12) were common at presentation. Chest computed tomography revealed ground glass opacification with lower zone predominance (9/9) and interlobular septal thickening (8/9). All bronchoalveolar lavage specimens appeared cloudy/milky, with abundant lipid laden macrophages and extracellular lipid on Oil-Red-O staining and documented polymicrobial (6/12) and Mycobacterium abscessus (2/12) co-infection. Antibiotics, systemic corticosteroids and therapeutic partial lung lavage were interventions in all, 8 and 5 patients respectively. Median time to clinical resolution was 1.1 months IQR (0.5-8.0) with radiological resolution only in 2/12 cases. Conclusions: Paediatric ELP resembles pulmonary alveolar proteinosis. Health workers should explicitly probe for a history of oil administration in children with non-resolving pneumonia and consider the diagnosis of ELP in settings where this is a common practice.
- ItemOpen AccessImproved detection of Pneumocystis jirovecii in upper and lower respiratory tract specimens from children with suspected pneumocystis pneumonia using real-time PCR: a prospective study(BioMed Central Ltd, 2011) Samuel, Catherine M; Whitelaw, Andrew; Corcoran, Craig; Morrow, Brenda; Hsiao, Nei-Yuan; Zampoli, Marco; Zar, HeatherBACKGROUND: Pneumocystis pneumonia (PCP) is a major cause of hospitalization and mortality in HIV-infected African children. Microbiologic diagnosis relies predominantly on silver or immunofluorescent staining of a lower respiratory tract (LRT) specimens which are difficult to obtain in children. Diagnosis on upper respiratory tract (URT) specimens using PCR has been reported useful in adults, but data in children are limited. The main objectives of the study was (1) to compare the diagnostic yield of PCR with immunofluorescence (IF) and (2) to investigate the usefulness of upper compared to lower respiratory tract samples for diagnosing PCP in children. METHODS: Children hospitalised at an academic hospital with suspected PCP were prospectively enrolled. An upper respiratory sample (nasopharyngeal aspirate, NPA) and a lower respiratory sample (induced sputum, IS or bronchoalveolar lavage, BAL) were submitted for real-time PCR and direct IF for the detection of Pneumocystis jirovecii. A control group of children with viral lower respiratory tract infections were investigated with PCR for PCP. RESULTS: 202 children (median age 3.3 [inter-quartile range, IQR 2.2 - 4.6] months) were enrolled. The overall detection rate by PCR was higher than by IF [180/349 (52%) vs. 26/349 (7%) respectively; p < 0.0001]. PCR detected more infections compared to IF in lower respiratory tract samples [93/166 (56%) vs. 22/166 (13%); p < 0.0001] and in NPAs [87/183 (48%) vs. 4/183 (2%); p < 0.0001]. Detection rates by PCR on upper (87/183; 48%) compared with lower respiratory tract samples (93/166; 56%) were similar (OR, 0.71; 95% CI, 0.46 - 1.11). Only 2/30 (6.6%) controls were PCR positive. CONCLUSION: Real-time PCR is more sensitive than IF for the detection of P. jirovecii in children with PCP. NPA samples may be used for diagnostic purposes when PCR is utilised. Wider implementation of PCR on NPA samples is warranted for diagnosing PCP in children.
- ItemOpen AccessLung function determinants and mortality of children and adolescents with cystic fibrosis in South Africa 2007-2016(2019) Vandenbroucke, Natalie Joëlle; Morrow, Brenda; Zampoli, MarcoObjectives: Cystic fibrosis (CF) is one of the commonest inherited disorders in South Africa, affecting all population groups. Progressive pulmonary disease with declining forced expiratory volume in one second (FEV1) is the main predictor of morbidity and mortality in individuals with CF. This study aimed to describe the change in lung function, nutritional status and mortality of children and adolescents with CF, attending the Red Cross War Memorial Children’s Hospital (RCWMCH) CF Clinic and to identify factors associated with poor pulmonary function outcomes and mortality. Methods: A retrospective study was conducted of the clinical records and annual pulmonary function tests, with matched body mass index (BMI), of children between 5 and 18 completed years of age attending the RCWMCH CF clinic in Cape Town, South Africa, between January 2007 and December 2016. Results: A total of 143 study participants (51.4% male; median age at diagnosis 5.5 months) were included. Population mean FEV1 and body mass index (BMI) Z scores improved from -2.5 1.70 to -1.9 1.70 (p = 0.1) and from -0.7 1.2 to -0.4 1.2 (p = 0.3) respectively from 2007 to 2016. FEV1 Z score declined by an average of 0.17 per year of age and this was mirrored by an average decline in BMI Z scores of 0.07 for each year of advancing age. FEV1 decline was greater in patients who died compared to those who survived (p = 0.03). Of the factors postulated to influence lung function decline, there was no significant correlation between FEV1 at any age and age of diagnosis, sex, ethnicity, genotype, geographical location, pancreatic status, or Methicillinresistant S. aureus or Aspergillus spp. infection. Participants who were ever infected or colonised with P. Aeruginosa had consistently lower FEV1, however this difference only became significant at certain ages. On multiple stepwise regression analysis, only FEV1 at age 6 was found to be a significant independent predictor of mortality (adjusted odds ratio (95% CI) 0.5 (0.3 – 0.8); p = 0.005). Conclusion: Pulmonary function of children with cystic fibrosis improved non-significantly over the 10-year study period. FEV1 at age 6 was identified as an independent predictor for CF-related mortality. Early diagnosis and measurement of pulmonary function in young children with CF is essential to identify children at risk of poor outcomes.
- ItemOpen AccessPneumocystis pneumonia in South African children diagnosed by molecular methods(BioMed Central, 2014-01-10) Morrow, Brenda M; Samuel, Catherine M; Zampoli, Marco; Whitelaw, Andrew; Zar, Heather JBackground: 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.
- ItemOpen AccessThe Management of Asymptomatic Congenital Pulmonary Airway Malformation: Results of a European Delphi Survey(Multidisciplinary Digital Publishing Institute, 2022-07-30) Kersten, Casper M.; Hermelijn, Sergei M.; Mullassery, Dhanya; Muthialu, Nagarajan; Cobanoglu, Nazan; Gartner, Silvia; Bagolan, Pietro; Mesas Burgos, Carmen; Sgrò, Alberto; Heyman, Stijn; Till, Holger; Suominen, Janne; Schurink, Maarten; Desender, Liesbeth; Losty, Paul; Steyaert, Henri; Terheggen-Lagro, Suzanne; Metzelder, Martin; Bonnard, Arnaud; Sfeir, Rony; Singh, Michael; Yardley, Iain; Rikkers-Mutsaerts, Noor R. V. M.; van der Ent, Cornelis K.; Qvist, Niels; Cox, Des W.; Peters, Robert; Bannier, Michiel A. G. E.; Wessel, Lucas; Proesmans, Marijke; Stanton, Michael; Hannon, Edward; Zampoli, Marco; Morini, Francesco; Tiddens, Harm A. W. M.; Wijnen, René M. H.; Schnater, Johannes M.Consensus on the optimal management of asymptomatic congenital pulmonary airway malformation (CPAM) is lacking, and comparison between studies remains difficult due to a large variety in outcome measures. We aimed to define a core outcome set (COS) for pediatric patients with an asymptomatic CPAM. An online, three-round Delphi survey was conducted in two stakeholder groups of specialized caregivers (surgeons and non-surgeons) in various European centers. Proposed outcome parameters were scored according to level of importance, and the final COS was established through consensus. A total of 55 participants (33 surgeons, 22 non-surgeons) from 28 centers in 13 European countries completed the three rounds and rated 43 outcome parameters. The final COS comprises seven outcome parameters: respiratory insufficiency, surgical complications, mass effect/mediastinal shift (at three time-points) and multifocal disease (at two time-points). The seven outcome parameters included in the final COS reflect the diversity in priorities among this large group of European participants. However, we recommend the incorporation of these outcome parameters in the design of future studies, as they describe measurable and validated outcomes as well as the accepted age at measurement.