Publications by authors named "Marco Zampoli"

29 Publications

  • Page 1 of 1

Cough augmentation techniques for people with chronic neuromuscular disorders.

Cochrane Database Syst Rev 2021 Apr 22;4:CD013170. Epub 2021 Apr 22.

Centre for Home Mechanical Ventilation and Specialized Centre for Neuromuscular Diseases, Inkendaal Rehabilitation Hospital, Vlezenbeek, Belgium.

Background: People with neuromuscular disorders may have a weak, ineffective cough predisposing them to respiratory complications. Cough augmentation techniques aim to improve cough effectiveness and mucous clearance, reduce the frequency and duration of respiratory infections requiring hospital admission, and improve quality of life.

Objectives: To determine the efficacy and safety of cough augmentation techniques in adults and children with chronic neuromuscular disorders.

Search Methods: On 13 April 2020, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and ClinicalTrials.gov for randomised controlled trials (RCTs), quasi-RCTs, and randomised cross-over trials.

Selection Criteria: We included trials of cough augmentation techniques compared to no treatment, alternative techniques, or combinations thereof, in adults and children with chronic neuromuscular disorders.

Data Collection And Analysis: Two review authors independently assessed trial eligibility, extracted data, and assessed risk of bias. The primary outcomes were the number and duration of unscheduled hospitalisations for acute respiratory exacerbations. We assessed the certainty of evidence using GRADE.

Main Results: The review included 11 studies involving 287 adults and children, aged three to 73 years. Inadequately reported cross-over studies and the limited additional information provided by authors severely restricted the number of analyses that could be performed. Studies compared manually assisted cough, mechanical insufflation, manual and mechanical breathstacking, mechanical insufflation-exsufflation, glossopharyngeal breathing, and combination techniques to unassisted cough and alternative or sham interventions. None of the included studies reported on the primary outcomes of this review (number and duration of unscheduled hospital admissions) or listed 'adverse events' as primary or secondary outcome measures. The evidence suggests that a range of cough augmentation techniques may increase peak cough flow compared to unassisted cough (199 participants, 8 RCTs), but the evidence is very uncertain. There may be little to no difference in peak cough flow outcomes between alternative cough augmentation techniques (216 participants, 9 RCTs). There was insufficient evidence to determine the effect of interventions on measures of gaseous exchange, pulmonary function, quality of life, general function, or participant preference and satisfaction.

Authors' Conclusions: We are very uncertain about the safety and efficacy of cough augmentation techniques in adults and children with chronic neuromuscular disorders and further studies are needed.
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http://dx.doi.org/10.1002/14651858.CD013170.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092569PMC
April 2021

COVID-19 and Pediatric Lung Disease: A South African Tertiary Center Experience.

Front Pediatr 2020 20;8:614076. Epub 2021 Jan 20.

Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa.

The COVID-19 pandemic led to rapid global spread with far-reaching impacts on health-care systems. Whilst pediatric data consistently shown a milder disease course, chronic lung disease has been identified as a risk factor for hospitalization and severe disease. In Africa, comprised predominantly of low middle-income countries (LMIC), the additional burden of HIV, tuberculosis, malnutrition and overcrowding is high and further impacts health risk. This paper reviewed the literature on COVID-19 and chronic lung disease in children and provides our experience from an African pediatric pulmonary center in Cape Town, South Africa. South African epidemiological data confirms a low burden of severe disease with children <18 years comprising 8% of all diagnosed cases and 3% of all COVID-19 admissions. A decrease in hospital admission for other viral lower respiratory tract infections was found. While the pulmonology service manages children with a wide range of chronic respiratory conditions including bronchiectasis, cystic fibrosis, asthma, interstitial lung disease and children with tracheostomies, no significant increase in COVID-19 admissions were noted and in those who developed COVID-19, the disease course was not severe. Current evidence suggests that pre-existing respiratory disease in children does not appear to be a significant risk factor for severe COVID-19. Longitudinal data are still needed to assess risk in children with immunosuppression and interstitial lung diseases. The indirect impacts of the pandemic response on child respiratory health are notable and still likely to be fully realized and quantified. Ensuring children have access to full preventive and care services during this time is priority.
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http://dx.doi.org/10.3389/fped.2020.614076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855972PMC
January 2021

Clinical characteristics of SARS-CoV-2 infection in children with cystic fibrosis: An international observational study.

J Cyst Fibros 2021 01 3;20(1):25-30. Epub 2020 Dec 3.

Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom; Paediatric Respiratory Medicine, Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom. Electronic address:

Background: The presence of co-morbidities, including underlying respiratory problems, has been identified as a risk factor for severe COVID-19 disease. Information on the clinical course of SARS-CoV-2 infection in children with cystic fibrosis (CF) is limited, yet vital to provide accurate advice for children with CF, their families, caregivers and clinical teams.

Methods: Cases of SARS-CoV-2 infection in children with CF aged less than 18 years were collated by the CF Registry Global Harmonization Group across 13 countries between 1 February and 7 August 2020.

Results: Data on 105 children were collated and analysed. Median age of cases was ten years (interquartile range 6-15), 54% were male and median percentage predicted forced expiratory volume in one second was 94% (interquartile range 79-104). The majority (71%) of children were managed in the community during their COVID-19 illness. Out of 24 children admitted to hospital, six required supplementary oxygen and two non-invasive ventilation. Around half were prescribed antibiotics, five children received antiviral treatments, four azithromycin and one additional corticosteroids. Children that were hospitalised had lower lung function and reduced body mass index Z-scores. One child died six weeks after testing positive for SARS-CoV-2 following a deterioration that was not attributed to COVID-19 disease.

Conclusions: SARS-CoV-2 infection in children with CF is usually associated with a mild illness in those who do not have pre-existing severe lung disease.
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http://dx.doi.org/10.1016/j.jcf.2020.11.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713571PMC
January 2021

The global impact of SARS-CoV-2 in 181 people with cystic fibrosis.

J Cyst Fibros 2020 11 4;19(6):868-871. Epub 2020 Nov 4.

Instituto da Criança HCFMUSP, São Paulo, Brazil.

With the growing SARS-CoV-2 pandemic, we need to better understand its impact in specific patient groups like those with Cystic Fibrosis (CF). We report on 181 people with CF (32 post-transplant) from 19 countries diagnosed with SARS-CoV-2 prior to 13 June 2020. Infection with SARS-CoV-2 appears to exhibit a similar spectrum of outcomes to that seen in the general population, with 11 people admitted to intensive care (7 post-transplant), and 7 deaths (3 post-transplant). A more severe clinical course may be associated with older age, CF-related diabetes, lower lung function in the year prior to infection, and having received an organ transplant. Whilst outcomes in this large cohort are better than initially feared overall, possibly due to a protective effect of the relatively younger age of the CF population compared to other chronic conditions, SARS-CoV-2 is not a benign disease for all people in this patient group.
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http://dx.doi.org/10.1016/j.jcf.2020.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641525PMC
November 2020

Cystic fibrosis in low and middle-income countries (LMIC): A view from four different regions of the world.

Paediatr Respir Rev 2021 Jun 30;38:37-44. Epub 2020 Jul 30.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Cystic fibrosis (CF) has been shown to affect people all over the world. While life expectancy for people with CF has increased substantially, CF is still associated with death in infants and young children in many regions, particularly in low and middle-income countries (LMIC). These countries face significant challenges to promote CF diagnosis and improvements to CF care due to financial constraints and a significant burden of other diseases. In this review, we describe the status of CF diagnosis and care in different LMIC settings, from four different parts of the world (Brazil, South Africa, Israel and India). We highlight challenges and opportunities for CF practitioners in LMIC to improve CF care and outcomes. While early CF diagnosis is the key to optimising outcomes, newborn screening may not be feasible for countries with lower CF incidence and higher birth rates, such as India or South Africa. CF therapies and care in LMIC need to be adapted to available resources of these countries. Collaboration initiatives of the global CF community with LMIC may improve CF care in these countries. Most individuals with CF in LMIC are not benefiting from CFTR modulator treatments due to the prohibitive cost of these drugs.
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http://dx.doi.org/10.1016/j.prrv.2020.07.004DOI Listing
June 2021

Lung function determinants and mortality of children and adolescents with cystic fibrosis in South Africa 2007-2016.

Pediatr Pulmonol 2020 06 16;55(6):1381-1387. Epub 2020 Mar 16.

Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.

Objectives: Forced expiratory volume in 1 second (FEV1) is an important predictor of outcome in cystic fibrosis (CF). This study aimed to describe the change in lung function, nutritional status, and mortality of children with CF at a single center in Cape Town, South Africa, and identify factors associated with poor lung function and mortality.

Methods: A retrospective study was conducted of children aged between 5 and 18 years between January 2007 and December 2016. At least two separate best annual FEV1 measurements were required for inclusion in the study.

Results: A total of 143 children were followed up from which 107 study participants (median diagnosis age 5.5 months) were included. There was no statistically significant improvement from 2007 to 2016 in population mean FEV1 (2.5 ± 1.70 to -1.9 ± 1.70 [P = .1]) and body mass index (-0.7 ± 1.2 to -0.4 ± 1.2 [P = .3]) Z scores. FEV1 Z score declined by 0.17 per year. No significant correlation between FEV1 and age of diagnosis, sex, ethnicity, genotype, geographical location, pancreatic status, or infections was identified. On multiple stepwise regression analysis, FEV1 at age 6 was found to be the only independent predictor of mortality (adjusted odds ratio [95% CI] 0.5 [0.3-0.8]; P = .005).

Conclusion: FEV1 at age 6 was an independent predictor for CF-related mortality. Measurement of lung function in preschool children in SA with CF using more sensitive methods than spirometry is important to identify children at risk of poor outcomes.
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http://dx.doi.org/10.1002/ppul.24726DOI Listing
June 2020

Cystic fibrosis in black African children in South Africa: a case control study.

J Cyst Fibros 2020 07 31;19(4):540-545. Epub 2019 Oct 31.

Division of Paediatric Pulmonology, Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, South Africa. Electronic address:

Background: 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.
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http://dx.doi.org/10.1016/j.jcf.2019.09.007DOI Listing
July 2020

The future of cystic fibrosis care: a global perspective.

Lancet Respir Med 2020 01 27;8(1):65-124. Epub 2019 Sep 27.

Queen's University of Belfast, Belfast, UK.

The past six decades have seen remarkable improvements in health outcomes for people with cystic fibrosis, which was once a fatal disease of infants and young children. However, although life expectancy for people with cystic fibrosis has increased substantially, the disease continues to limit survival and quality of life, and results in a large burden of care for people with cystic fibrosis and their families. Furthermore, epidemiological studies in the past two decades have shown that cystic fibrosis occurs and is more frequent than was previously thought in populations of non-European descent, and the disease is now recognised in many regions of the world. The Lancet Respiratory Medicine Commission on the future of cystic fibrosis care was established at a time of great change in the clinical care of people with the disease, with a growing population of adult patients, widespread genetic testing supporting the diagnosis of cystic fibrosis, and the development of therapies targeting defects in the cystic fibrosis transmembrane conductance regulator (CFTR), which are likely to affect the natural trajectory of the disease. The aim of the Commission was to bring to the attention of patients, health-care professionals, researchers, funders, service providers, and policy makers the various challenges associated with the changing landscape of cystic fibrosis care and the opportunities available for progress, providing a blueprint for the future of cystic fibrosis care. The discovery of the CFTR gene in the late 1980s triggered a surge of basic research that enhanced understanding of the pathophysiology and the genotype-phenotype relationships of this clinically variable disease. Until recently, available treatments could only control symptoms and restrict the complications of cystic fibrosis, but advances in CFTR modulator therapies to address the basic defect of cystic fibrosis have been remarkable and the field is evolving rapidly. However, CFTR modulators approved for use to date are highly expensive, which has prompted questions about the affordability of new treatments and served to emphasise the considerable gap in health outcomes for patients with cystic fibrosis between high-income countries, and low-income and middle-income countries (LMICs). Advances in clinical care have been multifaceted and include earlier diagnosis through the implementation of newborn screening programmes, formalised airway clearance therapy, and reduced malnutrition through the use of effective pancreatic enzyme replacement and a high-energy, high-protein diet. Centre-based care has become the norm in high-income countries, allowing patients to benefit from the skills of expert members of multidisciplinary teams. Pharmacological interventions to address respiratory manifestations now include drugs that target airway mucus and airway surface liquid hydration, and antimicrobial therapies such as antibiotic eradication treatment in early-stage infections and protocols for maintenance therapy of chronic infections. Despite the recent breakthrough with CFTR modulators for cystic fibrosis, the development of novel mucolytic, anti-inflammatory, and anti-infective therapies is likely to remain important, especially for patients with more advanced stages of lung disease. As the median age of patients with cystic fibrosis increases, with a rapid increase in the population of adults living with the disease, complications of cystic fibrosis are becoming increasingly common. Steps need to be taken to ensure that enough highly qualified professionals are present in cystic fibrosis centres to meet the needs of ageing patients, and new technologies need to be adopted to support communication between patients and health-care providers. In considering the future of cystic fibrosis care, the Commission focused on five key areas, which are discussed in this report: the changing epidemiology of cystic fibrosis (section 1); future challenges of clinical care and its delivery (section 2); the building of cystic fibrosis care globally (section 3); novel therapeutics (section 4); and patient engagement (section 5). In panel 1, we summarise key messages of the Commission. The challenges faced by all stakeholders in building and developing cystic fibrosis care globally are substantial, but many opportunities exist for improved care and health outcomes for patients in countries with established cystic fibrosis care programmes, and in LMICs where integrated multidisciplinary care is not available and resources are lacking at present. A concerted effort is needed to ensure that all patients with cystic fibrosis have access to high-quality health care in the future.
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http://dx.doi.org/10.1016/S2213-2600(19)30337-6DOI Listing
January 2020

Tuberculosis in children presenting with chylothorax - Report of two cases and review of the literature.

Respir Med Case Rep 2019 17;27:100848. Epub 2019 Apr 17.

Division of Paediatric Pulmonology, Department of Paediatrics and Child Health and MRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town and Red Cross War Memorial Children's Hospital, South Africa.

One third of the world's population is estimated to be infected with . Tuberculosis (TB) is endemic in many sub-Saharan African counties. The burden is further made worse by the HIV scourge. The number of children with TB and its attendant complications, is equally on the rise. TB can mimic many diseases ranging from infections to malignancies. Among pleuro-pulmonary TB complications, exudative effusion is more common while chylothorax is rare and thus easily missed especially if not the classical milky appearance. We present two children from a TB endemic region, with microbiologically-confirmed TB presenting with chylothoraces that were initially misdiagnosed as pleural empyema. Tuberculosis in children presenting as chylothorax is uncommon. These cases are instructive as they bring to the fore the importance of a full investigation of pleural effusions in children, to ensure a correct diagnosis and prompt effective management.
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http://dx.doi.org/10.1016/j.rmcr.2019.100848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479155PMC
April 2019

Exogenous lipoid pneumonia in children: A systematic review.

Paediatr Respir Rev 2020 Feb 20;33:45-51. Epub 2019 Jan 20.

Division of Paediatric Pulmonology, Department of Paediatrics and Child Health and Medical Research Council Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.

Objectives: To describe the clinical-radiological-pathological characteristics and treatment outcomes of children with suspected exogenous lipoid pneumonia (ELP).

Design: Systematic review. We searched electronic databases and reference lists published between 1967 and 2018, restricted to non-accidental cases.

Results: Forty-four studies including 489 participants aged 1 day to 17 years from 13 countries were included. Cultural, medical, and behavioural rationale for oil-use was described. The clinical-radiological presentation varied widely. Diagnostic certainty was deemed highest if ELP was confirmed on bronchoalveolar lavage/frozen section lung biopsy with documented extracellular lipid on cytological staining and/or fat analysis. Non-tuberculous mycobacteria infection was identified in six studies: Mycobacterium fortuitum/chelonei, Mycobacterium smegmatis and Mycobacterium abscessus. Treatment comprised supportive therapy, corticosteroids, stopping oil, therapeutic lung-lavage and surgical resection. Outcomes were reported inconsistently.

Conclusion: Paediatric ELP resulting from cultural and medical practices continues to be described globally. Preventive interventions, standardized reporting, and treatment efficacy studies for cases not averted, are lacking. Protocol registration: PROSPERO CRD42017068313.
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http://dx.doi.org/10.1016/j.prrv.2019.01.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106224PMC
February 2020

Nebulized gentamicin in combination with systemic antibiotics for eradicating early Pseudomonas aeruginosa infection in children with cystic fibrosis.

Pediatr Pulmonol 2019 04 18;54(4):393-398. Epub 2019 Jan 18.

Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.

Objectives: Chronic Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) can be prevented with early eradication treatment. In resource-constrained environments, low-cost, off-label nebulized antibiotics, including intravenous gentamicin solution, are often used for eradication therapy. This study aimed to describe the characteristics and clinical course of children with CF and early Pa infection, treated with a Pa eradication protocol combining inhaled gentamicin and systemic antibiotics.

Study Design: Retrospective descriptive study.

Patient-subject Selection: All children (0-18 years) attending a CF clinic in South Africa, with early Pa infections between January 2005 and March 2015, who received nebulized gentamicin-based Pa eradication treatment.

Methodology: Data were described and compared between those with successful versus unsuccessful eradication, using descriptive and inferential statistics appropriate to normality of distribution.

Results: One hundred and forty-nine children were managed in the CF Clinic over the study period, of whom 44 (29.5%; 28 [63.6%] male) had early Pa infections treated with a gentamicin-based eradication regimen. Thirty-nine (88.6%) patients had successful Pa eradication at 12 months follow-up; of which 28 (71.8%) had Pa reinfection at a median of 37.0 (21.0-101.0) months after initial treatment. Six patients (13%) acquired chronic Pa infection during the median follow-up period of 77 months. Older age was associated with Pa eradication failure and chronic Pa infection. There were no clinically significant adverse events associated with gentamicin inhalational therapy.

Conclusions: Nebulized gentamicin solution combined with systemic antibiotics appears to be safe and has comparable efficacy to other strategies in eradicating early Pa infections in children with CF.
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http://dx.doi.org/10.1002/ppul.24254DOI Listing
April 2019

Exogenous lipoid pneumonia: an important cause of interstitial lung disease in infants.

Respirol Case Rep 2018 Oct 7;6(7):e00356. Epub 2018 Aug 7.

Division of Paediatric Pulmonology, Department of Paediatrics and Child Health and Medical Research Council Unit on Child and Adolescent Health University of Cape Town Cape Town South Africa.

Exogenous lipoid pneumonia (ELP), an important cause of interstitial lung disease, often goes unrecognized. We conducted a retrospective study of children with histologically confirmed ELP at Red Cross Children's Hospital, South Africa. 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 of 11 caregivers. Cough (12/12), tachypnoea (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). Bronchoalveolar lavage specimens appeared cloudy/milky, with abundant lipid-laden macrophages and extracellular lipid on Oil-Red-O staining (12/12), with polymicrobial (6/12) and Mycobacterium abscessus (2/12) co-infection. Antibiotics, systemic corticosteroids, and therapeutic lavage were interventions in all eight and five patients, respectively. Clinicians should consider ELP in children with non-resolving pneumonia in settings with similar practices.
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http://dx.doi.org/10.1002/rcr2.356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079933PMC
October 2018

The First Case of Riboflavin Transporter Deficiency in sub-Saharan Africa.

Semin Pediatr Neurol 2018 07 4;26:10-14. Epub 2017 Apr 4.

Division of Paediatric Neurology, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.

This report describes the first case of a child with genetically confirmed Brown-Vialetto-van Laere syndrome in sub-Saharan Africa. This is an extremely rare clinical condition that presents with an auditory neuropathy, bulbar palsy, stridor, muscle weakness, and respiratory compromise that manifests with diaphragmatic and vocal cord paralysis. It is an autosomal recessive condition for which the genetic mutation has only recently been linked to a riboflavin transporter deficiency. We describe an 11-month-old affected male infant. He has required long-term respiratory support and a gastrostomy tube to support feeding. With high-dose riboflavin supplementation, he had limited recovery of motor function. His respiratory chain enzyme studies were abnormal suggestive of mitochondrial (mt) dysfunction. In the setting of limited resources, recognition of this striking clinical phenotype is important to highlight, specifically regarding the genetic implications of the condition and the potentially remedial response to vitamin supplementation.
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http://dx.doi.org/10.1016/j.spen.2017.03.002DOI Listing
July 2018

Acute flaccid paralysis in South African children: Causes, respiratory complications and neurological outcome.

J Paediatr Child Health 2018 Mar 28;54(3):247-253. Epub 2017 Sep 28.

Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.

Aim: To describe the causes, clinical presentation and neurological outcome of acute flaccid paralysis in children.

Methods: A retrospective study in a tertiary paediatric hospital in South Africa. Data on clinical presentation, respiratory complications and long-term neurological outcomes of children presenting with acute flaccid paralysis were collected. Logistic regression analysis was applied to determine predictors for the need of mechanical ventilation.

Results: The study included 119 patients, 99 of whom had Guillain-Barré syndrome (GBS); 47 patients (39.5%) required mechanical ventilation. Backward logistic regression analysis revealed that bulbar dysfunction (P < 0.001), autonomic dysfunction (P = 0.003) and upper limb paralysis (P = 0.038) significantly predicted the need for mechanical ventilation. EuroQol-5D scores of self-care problems and usual activities after discharge significantly declined over time.

Conclusions: In this large series from Africa, GBS was the main cause of acute flaccid paralysis in children and was associated with significant morbidity. Other causes of acute flaccid paralysis mimicking GBS were not uncommon and should be excluded in this setting.
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http://dx.doi.org/10.1111/jpc.13709DOI Listing
March 2018

The African Pediatric Fellowship Training Program in Pediatric Pulmonology: A Model for Growing African Capacity in Child Lung Health.

Ann Am Thorac Soc 2017 Apr;14(4):500-504

1 Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, and University of Cape Town, and.

Childhood respiratory diseases are the major cause of mortality and morbidity in African children. However, there is limited expertise in pediatric pulmonology in Africa. The African Pediatric Fellowship Program (APFP) was developed in the Department of Paediatrics and Child Health at the University of Cape Town in partnership with African academic institutions beyond South Africa to promote training of African child health professionals and to build capacity. From 2008 to 2016, 11 fellows have completed APFP training in pediatric pulmonology. Fellows have come from Kenya, Nigeria, Ghana, and Uganda. All but one returned to their home institutions, where they are building academic departments, improving clinical service delivery, growing research capacity, and advancing advocacy and policies to improve child lung health. In parallel, training of South African pediatric pulmonologists has been strengthened with a further nine South African fellows trained during this period. The African Pediatric Pulmonology program provides a highly successful model, with high retention of graduates in their home countries. The long-term goal is to grow African clinical capacity and strengthen services, research, training, and advocacy for child lung health in Africa.
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http://dx.doi.org/10.1513/AnnalsATS.201612-953PSDOI Listing
April 2017

Paediatric tracheostomy and ventilation home care with challenging socio-economic circumstances in South Africa.

Int J Pediatr Otorhinolaryngol 2016 May 19;84:161-5. Epub 2016 Mar 19.

Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.

Background: Children discharged home with a tracheostomy need a safe home environment and access to health care. We described the indications, clinical characteristics, socio-economic circumstances and outcomes of children enroled in a tracheostomy home care programme in South Africa.

Methods: We performed a retrospective chart review of children receiving a tracheostomy and enroled in the Breatheasy programme at the Red Cross War Memorial Children's Hospital, Cape Town. Medical and background characteristics were recorded. Influences of socio-economic variables and underlying medical conditions on length of hospital stay, unplanned readmissions and mortality in the first year after discharge were evaluated.

Results: In the period 2008-2012, 157 patients were discharged home with a tracheostomy. Median hospital stay after tracheostomy insertion was significantly longer when parents had incomplete schooling compared to completed secondary school or higher education; 30 days (IQR 21-53) versus 23 days (IQR 16-33), respectively. Unplanned readmissions in the first year were documented for 72 patients (45.9%). The risk for unplanned readmission was 2.6 times higher in families with substance abuse the risk of respiratory infections was two-fold in case of household cigarette smoke exposure (OR 2.3.) Tracheostomy-related mortality was low (1.2%). An underlying medical condition was the only independent significant risk factor for mortality (OR 5.1, 95% CI 1.8-14.3).

Conclusion: This study demonstrates that despite difficult socio-economic circumstances, home ventilation of children with a tracheostomy is safe, provided caregivers are adequately trained and supported.
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http://dx.doi.org/10.1016/j.ijporl.2016.03.013DOI Listing
May 2016

Microbiological yield from induced sputum compared to oropharyngeal swab in young children with cystic fibrosis.

J Cyst Fibros 2016 09 26;15(5):605-10. Epub 2016 Jan 26.

Department of Paediatrics and Child Health, Division of Pediatric Pulmonology, University of Cape Town, Red Cross War Memorial Children's Hospital, Cape Town, South Africa. Electronic address:

Background: Standard respiratory sampling in young children with cystic fibrosis (CF) is by oropharyngeal swab (OPS) as they cannot spontaneously expectorate. Sputum induction (IS) has been poorly investigated in this population. We aimed to compare the bacteriological yield of OPS vs. IS in young children with CF.

Methods: Sequentially paired OPS followed by IS samples was collected in children <5years of age attending a CF clinic in Cape Town, South Africa.

Results: IS was successfully paired with OPS in 98/113 (85%) attempts in 32 children (mean±SD 19±16months), with no serious adverse events. IS culture yield for any CF-associated bacteria from IS was 46% vs. 28% from OPS (p=0.01). The sensitivity, specificity, PPV and NPV of OPS compared to IS in isolating CF-associated bacteria were 56%, 96%, 93%, and 72% respectively.

Conclusion: Sputum induction is feasible, safe and superior to OPS for detecting CF-associated bacteria in young children with CF.
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http://dx.doi.org/10.1016/j.jcf.2016.01.001DOI Listing
September 2016

Impact of fibrinolytics on the outcome of empyema in South African children.

S Afr Med J 2015 Sep 21;105(7):549-53. Epub 2015 Sep 21.

Division of Paediatric Pulmonology, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of Cape Town, South Africa.

Background: Childhood pneumonia is common in all countries, and empyema is one of the commonest complications. The role of routine intrapleural fibrinolytics in the management of childhood empyema is not well established in low- and middle-income countries.

Methods: We did a prospective observational study of children sequentially hospitalised with empyema between December 2006 and December 2011 in South Africa (SA). Intrapleural tissue plasminogen activator (TPA), administered according to a standard protocol, was introduced in September 2009. Outcomes in children treated with TPA after 2009 were compared with the historical cohort not treated with TPA who met the treatment criteria.

Results: One hundred and forty-two children with empyema, median age 17 months (interquartile range 8-43), were admitted during the study period. Excluding children who did not have a chest tube inserted and those in whom fibrinolysis was contraindicated, there were 99 patients, 52 of whom received fibrinolytics. Clinical characteristics and empyema aetiology were similar in those who received fibrinolysis and those who did not. Eighteen children (38.3%) not treated with TPA required surgery v. 5 (9.6%) treated with TPA (relative risk 0.25; 95% confidence interval 0.1-0.6). The median duration of hospitalisation was similar in both groups. Complications occurred rarely and with a similar incidence in both groups. In-hospital mortality was low, with two deaths in each group.

Conclusion: Intrapleural TPA resulted in a four-fold reduction in surgery. Fibrinolytics should be used for management of empyema in children in SA.
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http://dx.doi.org/10.7196/SAMJnew.7796DOI Listing
September 2015

Etiology and Incidence of Pleural Empyema in South African Children.

Pediatr Infect Dis J 2015 Dec;34(12):1305-10

From the *Division of Pediatric Pulmonology, Department of Pediatrics and Child Health, University of Cape Town, Cape Town, South Africa; †Centre for Respiratory Diseases and Meningitis, National Institute for Communicable Diseases of the National Health Laboratory Service and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; ‡Department of Pediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; and §MRC Unit on Child & Adolescent Health, Cape Town, South Africa.

Background: South Africa introduced the 7-valent pneumococcal conjugate vaccine (PCV7) in 2009 and PCV13 in 2011. The etiology and incidence of childhood empyema in an 8-year period overlapping the introduction of PCV was investigated.

Methods: Children younger than 12 years admitted with empyema at a tertiary pediatric hospital in Cape Town, South Africa, from December 2006 to December 2011 (cohort A) and January 2012 to December 2014 (cohort B) were investigated. Pathogens were identified by culture of pleural fluid and blood. In addition, polymerase chain reaction targeting bacterial pathogens and Streptococcus pneumoniae serotypes was conducted on pleural fluid in a subset of patients enrolled 2009-2011.

Results: Cohort A: 142 children were prospectively enrolled, with a median age of 17 months (interquartile range 8-43). Most (92%) children were unimmunized with PCV. S. pneumoniae and Staphylococcus aureus were the most common culture-identified pathogens (each 25 of 142; 18%); polymerase chain reaction of pleural fluid increased yield of S. pneumoniae detection by 31% [26 of 54 (48%) vs. 9 of 54 (17%), P < 0.001]. Serotypes were identified for 24 of 26 (92%) patients with S. pneumoniae, of which 22 of 24 (92%) were included in PCV13. Cohort B: 22 patients were retrospectively identified. No pathogen was found in 12 of 22 (54.5%) patients and S. pneumoniae in 1 patient (4.5%). Empyema incidence declined by 50% in cohort B compared with that of cohort A (4.2 vs. 10.4 cases per 1000 pneumonia admissions; risk ratio: 0.5; 95% confidence incidence: 0.3-0.7).

Conclusion: S. pneumoniae is the commonest cause of childhood empyema in South Africa. PCV has been highly effective at reducing empyema incidence in South African children.
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http://dx.doi.org/10.1097/INF.0000000000000880DOI Listing
December 2015

Pneumocystis pneumonia in South African children diagnosed by molecular methods.

BMC Res Notes 2014 Jan 10;7:26. Epub 2014 Jan 10.

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.
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http://dx.doi.org/10.1186/1756-0500-7-26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3892044PMC
January 2014

Mechanical insufflation-exsufflation for people with neuromuscular disorders.

Cochrane Database Syst Rev 2013 Dec 30(12):CD010044. Epub 2013 Dec 30.

Department of Paediatrics, University of Cape Town, 5th Floor ICH Building, Red Cross Memorial Children's Hospital, Klipfontein Road, Rondebosch, 7700, Cape Town, South Africa.

Background: People with neuromuscular disorders (NMDs) may have weak respiratory (breathing) muscles which makes it difficult for them to effectively cough and clear mucus from the lungs. This places them at risk of recurrent chest infections and chronic lung disease. Mechanical insufflation-exsufflation (MI-E) is one of a number of techniques available to improve cough efficacy and mucus clearance.

Objectives: To determine the efficacy and safety of MI-E in people with NMDs.

Search Methods: On 7 October 2013, we searched the following databases from inception: the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (The Cochrane Library), MEDLINE, and EMBASE. We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform for ongoing trials. We conducted handsearches of reference lists and conference proceedings.

Selection Criteria: We considered randomised or quasi-randomised clinical trials, and randomised cross-over trials of MI-E used to assist airway clearance in people with a NMD and respiratory insufficiency. We considered comparisons of MI-E with no treatment, or alternative cough augmentation techniques.

Data Collection And Analysis: Two authors independently assessed trial eligibility, extracted data, and assessed risk of bias in included studies according to standard Cochrane methodology. The primary outcome was mortality throughout follow-up or at six months follow-up.

Main Results: Five studies with a total of 105 participants were found to be eligible for inclusion in this review. All included trials were short-term studies (two days or less), measuring immediate effects of the interventions. There was insufficient detail in the reports to assess methods of randomisation and allocation concealment. All five studies were at a high risk of bias from lack of blinding. The studies did not report on mortality, morbidity, quality of life, serious adverse events or any of the other prespecified outcomes. One study was a randomised cross-over trial conducted over two days, in which investigators applied two interventions twice daily in randomly assigned order, with a reverse cross-over the following day. Four studies applied multiple interventions for cough augmentation to each participant, in random order. One study reported fatigue as an adverse effect of MI-E, using a visual analogue scale. Peak cough expiratory flow (PCEF) was the most common outcome measure and was reported in four studies. Based on three studies, MI-E may improve PCEF compared to an unassisted cough. All interventions increased PCEF to the critical level necessary for mucus clearance. The included studies did not clearly show that MI-E improves cough expiratory flow more than other cough augmentation techniques. Based on one study, which was at risk of assessor bias, the addition of MI-E may reduce treatment time when added to a standard airway clearance regimen with manually assisted cough. MI-E appeared to be as well tolerated as other cough augmentation techniques, based on three studies which reported comfort visual analogue scores.

Authors' Conclusions: The results of this review do not provide sufficient evidence on which to base clinical practice as we were unable to address important short- and long-term outcomes, including adverse effects of MI-E. There is currently insufficient evidence for or against the use of MI-E in people with NMDs. Further randomised controlled clinical trials are needed to test the safety and efficacy of MI-E.
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http://dx.doi.org/10.1002/14651858.CD010044.pub2DOI Listing
December 2013

Cytomegalovirus viraemia in HIV exposed and infected infants: prevalence and clinical utility for diagnosing CMV pneumonia.

J Clin Virol 2013 Sep 31;58(1):74-8. Epub 2013 May 31.

Division of Medical Virology, National Health Laboratory Service and University of Cape Town, Anzio Road, Observatory 7925, South Africa.

Background: Human cytomegalovirus (HCMV) is an important pathogen in HIV exposed infants with pneumonia. However, the diagnosis of HCMV pneumonia in this setting is challenging due to limited access to bronchoscopy, lung biopsy and direct sampling of the lower respiratory tract. HCMV viraemia is more accessible, but their diagnostic performance in this context has not been studied.

Objective: To describe the prevalence of HCMV viraemia and evaluate its clinical utility in HIV exposed infants.

Study Design: In this cross-sectional study, we performed qualitative and quantitative PCR to detect HCMV viraemia in HIV exposed asymptomatic infants and in infants with severe pneumonia in the Western Cape province of South Africa.

Results: 283 asymptomatic HIV exposed infants and 142 HIV exposed infants with severe pneumonia were studied. Infants with pneumonia had a higher prevalence of HCMV viraemia compared to asymptomatic infants (68% vs 24% OR 6.7, 95% CI 4.2-10.8). This increased prevalence remained significant (OR 4.3 95% CI 2.6-7.0) after adjusting for HIV infection. Of the infants with pneumonia, the level of HCMV viraemia was significantly higher in a subset of infants diagnosed with HCMV pneumonia (median HCMV viral load 4.6 vs 2.5 log copies/ml p<0.001). Receiver operator characteristic (ROC) analysis showed the area under the curve was 0.78 (95% CI 0.71-0.86) and a threshold of 4.1 log copies/ml was able to correctly identify 70% of HCMV pneumonia cases.

Conclusion: Prevalence and level of HCMV viraemia in sub-Saharan HIV-exposed and infected infants peaks at 3-4 months of age. Quantitative HCMV PCR may be useful in diagnosing HCMV pneumonia.
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http://dx.doi.org/10.1016/j.jcv.2013.05.002DOI Listing
September 2013

Infective dermatitis associated with human T-cell lymphotropic virus type 1 in a child with bronchiectasis.

Pediatr Infect Dis J 2013 Jun;32(6):690-3

Department of Paediatric Rheumatology, Red Cross War Memorial Children's Hospital and University of Cape Town, Cape Town, South Africa.

We report a case of infective dermatitis associated with human T lymphocyte virus type 1 in a South African child with associated stunting, anaemia and chronic lung disease. human T lymphocyte virus type 1 should always be considered in a patient with unexplained recurrent dermatitis. Chronic lung disease is a rare association.
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http://dx.doi.org/10.1097/INF.0b013e3182882aa2DOI Listing
June 2013

Improved detection of Pneumocystis jirovecii in upper and lower respiratory tract specimens from children with suspected pneumocystis pneumonia using real-time PCR: a prospective study.

BMC Infect Dis 2011 Nov 28;11:329. Epub 2011 Nov 28.

Division of Medical Microbiology, University of Cape Town and National Health Laboratory Service, Cape Town, South Africa.

Background: 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.
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http://dx.doi.org/10.1186/1471-2334-11-329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3254081PMC
November 2011

Prevalence and outcome of cytomegalovirus-associated pneumonia in relation to human immunodeficiency virus infection.

Pediatr Infect Dis J 2011 May;30(5):413-7

Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.

Aim: To investigate the antemortem prevalence and outcome of cytomegalovirus (CMV)-associated pneumonia in African children.

Methods: A total of 202 children (median age, 3.2 months; 124 human immunodeficiency virus [HIV]-infected, 62%; 87 severely malnourished, 43%) sequentially hospitalized for severe pneumonia were prospectively investigated. In addition to routine microbiologic investigations, respiratory tract secretions and blood were submitted for CMV culture and qualitative and quantitative CMV polymerase chain reaction.

Results: CMV-associated pneumonia was common (28%, 47/169) and more prevalent in HIV-infected than uninfected children (36% vs. 15%; odds ratio [OR], 3.0; 95% confidence interval, 1.3-7.4). CMV-associated pneumonia was more common than Pneumocystis pneumonia (27%) and other viral-associated pneumonia (19%) in HIV-infected children. In-hospital mortality was 25% (51/202) with increased mortality in HIV-infected compared with uninfected children (43/124 [35%] vs. 8/76 [11%]; OR, 4.5; 1.9-11.8). Increased mortality occurred in HIV-infected children with CMV-associated pneumonia (OR, 2.5; 1.04-6.5) but this association was not evident after adjusting for CD4 <15% (adjusted OR, 1.78; 0.6-4.6).

Conclusions: CMV-associated pneumonia is common and associated with a poor outcome in children with advanced HIV disease. Improved diagnostic testing and increased access to antiviral therapy might improve the outcome of HIV-infected children with CMV-associated pneumonia.
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May 2011

Pneumocystis pneumonia in South African children with and without human immunodeficiency virus infection in the era of highly active antiretroviral therapy.

Pediatr Infect Dis J 2010 Jun;29(6):535-9

Department of Paediatics and Child Health, University of Cape Town, Cape Town, South Africa.

Background: Pneumocystis pneumonia (PCP) is a major cause of hospitalization and mortality in human immunodeficiency virus (HIV)-infected African children.

Aim: The aim of this study was to investigate the incidence and outcome of PCP in South African children living in a high HIV-prevalence area in the context of a free, available antiretroviral therapy program.

Methods: Sequential children hospitalized with hypoxic pneumonia were prospectively enrolled from November 2006 to August 2008. Sociodemographic, historical, clinical, and outcome data were collected. A nasopharyngeal aspirate and lower respiratory tract sample (induced sputum or bronchoalveolar lavage) were submitted for PCP immunofluorescence. Lower respiratory tract samples were also investigated for bacterial, mycobacterial, and viral pathogens.

Results: A total of 202 children were enrolled; 124 (61.4%) were HIV-infected; 34 (16.8%) were HIV-exposed but uninfected and 44 (21.8%) were HIV-unexposed. Among HIV-exposed children, 70 (44.3%) had participated in the Prevention of Mother to Child Transmission program, but only 18.4% were taking trimethoprim-sulfamethoxazole prophylaxis. PCP occurred in 43 children (21.3%) of whom 33 (76.7%) were HIV-infected. The case fatality of children with PCP was higher than those without PCP (39.5% vs. 21.4%; relative risk, 1.85; 95% confidence interval, 1.15-2.97; P = 0.01).

Conclusions: PCP is a common cause of hypoxic pneumonia and mortality in HIV-infected South African infants. Underuse of the Prevention of Mother to Child Transmission program and failure to institute trimethoprim-sulfamethoxazole prophylaxis in HIV-exposed children identified through the program are important obstacles to reducing PCP incidence.
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http://dx.doi.org/10.1097/INF.0b013e3181ce871eDOI Listing
June 2010

Immune reconstitution inflammatory syndrome after initiating highly active antiretroviral therapy in HIV-infected children.

Pediatr Radiol 2009 Jun 10;39(6):569-74. Epub 2009 Mar 10.

Department of Paediatric Radiology, Red Cross War Memorial Children's Hospital, Rondebosch 7925, Cape Town, South Africa.

The outcome of HIV infection has improved since the widespread availability of highly active antiretroviral therapy (HAART). Some patients, however, develop a clinical and radiological deterioration following initiation of HAART due to either the unmasking of occult subclinical infection or an enhanced inflammatory response to a treated infection. This phenomenon is believed to result from the restored ability to mount an immune response and is termed immune reconstitution inflammatory syndrome (IRIS) or immune reconstitution disease. IRIS is widely reported in the literature in adult patients, most commonly associated with mycobacterial infections. There is, however, a paucity of data documenting the radiological findings of IRIS in children. Radiologists need to be aware of this entity. As a diagnosis of exclusion it is essential that the radiological findings be assessed in the context of the clinical presentation. This article reviews the common clinical and radiological manifestations of IRIS in HIV-infected children.
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http://dx.doi.org/10.1007/s00247-009-1192-yDOI Listing
June 2009

Antiretroviral treatment for children.

S Afr Med J 2006 Sep;96(9 Pt 2):988-93

Red Cross War Memorial Children's Hospital, Rondebosch, Cape Town, South Africa.

Objective: 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 > or = 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 HIV-infected children with advanced disease, including those aged less than 2 years in resource-limited settings.
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September 2006
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