Aetiology of pleural effusions in children living in a high TB endemic setting.

Confirming the aetiology of pleural effusion in children may be difficult in 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.This is a cross-sectional post-hoc analysis among children with pleural effusion in a tertiary hospital in South Africa, incorporating new data from PCR testing of stored pleural fluid. Aetiological classification was defined by microbiological confirmation.Ninety-one children were enrolled; the median age 31 months (IQR 12-102). The aetiology of pleural effusion was 40% (36/91) bacteria, 11% (10/91) TB, 3% (3/91) viruses, 11% (10/91) polymicrobial and 35% (32/91) had no pathogen identified. The most common pathogen was Staphylococcus aureus (27/91, 30%) with similar yields on culture and PCR, followed by Streptococcus pneumoniae (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 ≥1,716 U/L best discriminated bacterial pleural effusion from other aetiologies (sensitivity of 86%; specificity 95%).PCR improved detection of pathogens and reduced number of children with unconfirmed aetiologies in presumed exudative pleural effusion..

Case report: a giant cell-rich gnathic bone lesion in a child with pycnodysostosis.

Pycnodysostosis is a skeletal dysplasia characterized by short stature, generalized osteosclerosis, acro-osteolysis, and recognizable facial features. Oral manifestations are commonly described and include a high-arched palate with dental crowding and malocclusion, hypoplastic enamel, and retained deciduous teeth with impacted permanent teeth, and there is an increased risk of developing osteomyelitis of the jaw. We report here the history of a 9-year-old male with the typical facial and skeletal phenotype of pycnodysostosis but novel oral features. He presented with bilateral progressive facial swelling, which caused functional impairment with chewing and contributed to his severe obstructive sleep apnea (OSA). The severity of his OSA required surgical intervention, and the lesions were resected. Extensive bone remodeling and replacement by fibrous tissue were noted on submucosal dissection, and bilateral subtotal maxillectomies were required. The histopathology of the biopsied lesion was consistent with a giant cell-rich lesion. Genetic testing identified a pathogenic homozygous variant in the CTSK gene, c.953G > A, p. (Cys318Tyr). The proband had a good postsurgical response with sustained improvement in his sleep OSA. We present here the history and clinical characteristics of a patient with typical features of pycnodysostosis and an unusual presentation and histopathology of gnathic bone lesions. This report adds to the body of literature on this rare condition and also highlights the finding of giant cell-rich lesions of the gnathic bones. Giant cell-rich lesions in pycnodysostosis have previously been reported in two cases in the literature. While there is not enough evidence to support a certain association with pycnodysostosis, it is prudent to consider regular oral dental reviews in affected individuals to identify pathology early and avoid such life-threatening complications.

Real-world disparities and ethical considerations with access to CFTR modulator drugs: Mind the gap!

The third Sustainable Development Goal (SDG), to ensure healthy lives and promote well-being for all at all ages, has particular relevance and implementation challenges amongst people living with rare diseases such as cystic fibrosis (CF). Although the treatment and projected outcome of CF has significantly improved with the advent of CF transmembrane conductance regulator protein modulator (CFTRm) therapy, there remains significant global inequality with regards to access to these life-saving and life-altering drugs. Elexacaftor, tezacaftor, and ivacaftor (ETI) triple combination therapy, first licensed in the United States in 2019, has rapidly become the standard of care for children aged 6 years and older in most high-income countries for individuals with CFTR variants responsive to ETI. Negotiated agreements for access to ETI are currently in place in North America,Europe, Israel ,Australia and New Zealand. However, less priority has been given to negotiate agreements for access to CFTRm in low-middle income countries(LMIC) with significant CF populations such as Central and South America, India, the Middle East, and Southern Africa. These countries and individuals living with CF are therefore effectively being left behind, in direct conflict with the stated principle of the 2030 SDGs. In this review, we highlight the current global inequity in access to CFTRm drugs and its impact on widening disparities between high-income countries and LMIC in CF outcomes and survival. We further discuss the reasons for this inequity and explore the ethical- and human rights-based principles and dilemmas that clinicians, families, governments, and healthcare funders must consider when prioritizing fair and affordable access to expensive CFTRm drugs. Lastly, we propose possible solutions to overcoming the barriers to accessing affordable CFTRm drugs in LMIC and illustrate with examples how access to drug therapies for other conditions have been successfully negotiated in LMIC through innovative partnerships between governments and pharmaceutical industries.

Aetiology and presentation of childhood pleural infections in the post-pneumococcal conjugate vaccine era in South Africa.

Background: Complications of respiratory infections including pleural effusion (PE) are associated with a high morbidity. Differentiating between PE caused by Mycobacterium tuberculosis (Mtb) infection and other bacterial infections in endemic areas is difficult in children, thus, impacting treatment. Objectives: To investigate the aetiology of PE and features distinguishing tuberculosis (TB) from bacterial PE in children. Methods: We conducted a prospective study in children with PE admitted to a tertiary hospital in Cape Town from December 2017 to December 2019. Clinical information and routine laboratory investigations were compared between children with bacterial, Mtb or unclassified PE, categorised according to study definitions. Results: A total of 91 patients were included in the present study and their median age was 31 months (interquartile range (IQR) 11.8 - 102.1). The aetiology was bacterial in 40% (n=37), Mtb in 39% (n=36) and unclassified in 20% (n=18) of patients. Staphylococcus aureus was the most common bacterial isolate, confirmed in 65% (n=24/37) patients, and Streptococcus pneumoniae was confirmed in only 8% of patients. TB was microbiologically confirmed in 33% (n=12/36) of patients. Patients with TB were older (91.6 v. 11.8 months; p<0.001), with more weight loss (28 v. 12 patients; p<0.001), and longer cough duration (10 v. 4 days; p<0.001) than those with other bacterial PE. In contrast, the latter had significantly higher serum C-reactive protein (median 250 v. 122 mg/L; p<0.001), procalcitonin (11 v. 0.5 mg/L; p<0.001), pleural fluid lactate dehydrogenase (7 280 v. 544 U/L; p<0.001), and adenosine deaminase levels (162 v. 48 U/L; p<0.001) and lower glucose levels (1.3 v. 4 mmol/L; p<0.001). Conclusion: Post 13-valent pneumococcal conjugate vaccine, S. aureus is the dominant cause of PE in children using traditional culture methods, while Mtb remains a common cause of PE in our setting. Useful clinical and laboratory differences between Mtb and other 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.

Overnight oximetry as a screening tool for moderate to severe obstructive sleep apnoea in South African children.

BACKGROUND: Obstructive sleep apnoea (OSA) is common in children yet often overlooked, as symptom-based screening is unreliable. Polysomnography is regarded as the gold standard for the diagnosis of OSA, but is not widely available in South Africa (SA). Overnight oximetry is a validated screening tool for OSA. OBJECTIVES: To describe the impact and utility of overnight oximetry at a tertiary children's hospital in SA. METHODS: A retrospective descriptive study was conducted of patients screened for OSA by overnight oximetry at a paediatric referral hospital from December 2012 to December 2014. Clinical data were retrieved from the oximetry database and medical records. Recordings of ≥6 hours were considered adequate and included in the study. OSA severity was determined using the McGill score. Details on management and outcome were documented. RESULTS: Oximetry studies in 137 of 153 patients were suitable for analysis (88 males (64.2%), median age 31.4 months (interquartile range (IQR) 15.8 - 65.8). Adenotonsillar hypertrophy was common (n=97, 70.8%), and 65 children (47.4%) had two or more underlying OSA risk factors. McGill's score classified patients as follows: no/mild OSA n=55 (40.1%), moderate OSA n=23 (16.8%), severe OSA n=23 (16.8%) and very severe OSA n=36 (26.3%). Male gender, adenotonsillar hypertrophy and a lower weight-for-age z-score (-1.3 v. -0.7; p=0.038) were associated with severe to very severe OSA. Seventy-eight children (56.9%) were referred for surgery, 33 (24.1%) receiving urgent surgery within a median of 6 days (IQR 4 - 12). In contrast, 59 children (43.1%) with suspected OSA did not require surgical intervention. CONCLUSIONS: Overnight oximetry is a simple low-cost tool to assess severity of OSA and prioritise appropriate OSA management in resource-constrained settings such as SA.

An unusual cause of haemoptysis in childhood: A case report and literature review.

Haemoptysis is uncommon in children and the diagnosis is challenging. We describe a 14-year-old child who presented with haemoptysis secondary to a suspected congenital broncho-oesophageal fistula. This is a rare condition and the symptoms are insidious, occasionally beginning in childhood but may present only in adulthood. The case report describes the presentation, diagnosis and management of broncho-oesophageal fistulas, with a review of the current literature.

Adenovirus-associated pneumonia in South African children: Presentation, clinical course and outcome.

BACKGROUND: Viruses have emerged as important aetiological agents of childhood pneumonia. OBJECTIVE: To investigate the clinical presentation, severity and outcome of adenovirus-associated pneumonia (AVP) in children. METHODS: A retrospective analysis of AVP cases over 12 months was performed, including demographic, clinical course and outcome (death, persistent lung disease (PLD)) data. RESULTS: Two hundred and six AVP cases (median age 12 months, interquartile range 6 - 24) were identified; 70 children (34.0%) were malnourished and 14 (6.8%) were HIV-infected. Twenty-nine children (14.1%) developed PLD, which was associated with hypoxia at presentation in 26 cases (89.7%; p=0.01) and necessitated admission to the intensive care unit (ICU) in 18 (62.1%; p<0.01); 18/206 children (8.7%) died. Admission to the ICU (odds ratio (OR) 8.3, 95% confidence interval (CI) 2.3 - 29.0) and a positive blood culture (OR 11.2, 95% CI 2.3 - 54.1) were independent risk factors for mortality. CONCLUSIONS: Adenovirus is a potential cause of pneumonia and PLD in young children in South Africa. ICU admission and a positive blood culture were associated with poor outcome.

Adenovirus-associated pneumonia in South African children: Presentation, clinical course and outcome

Background. Viruses have emerged as important aetiological agents of childhood pneumonia.Objective. To investigate the clinical presentation, severity and outcome of adenovirus-associated pneumonia (AVP) in children.Methods. A retrospective analysis of AVP cases over 12 months was performed, including demographic, clinical course and outcome (death, persistent lung disease (PLD)) data.Results. Two hundred and six AVP cases (median age 12 months, interquartile range 6 - 24) were identified; 70 children (34.0%) were malnourished and 14 (6.8%) were HIV-infected. Twenty-nine children (14.1%) developed PLD, which was associated with hypoxia at presentation in 26 cases (89.7%; p=0.01) and necessitated admission to the intensive care unit (ICU) in 18 (62.1%; p<0.01); 18/206 children (8.7%) died. Admission to the ICU (odds ratio (OR) 8.3, 95% confidence interval (CI) 2.3 - 29.0) and a positive blood culture (OR 11.2, 95% CI 2.3 - 54.1) were independent risk factors for mortality.Conclusions. Adenovirus is a potential cause of pneumonia and PLD in young children in South Africa. ICU admission and a positive blood culture were associated with poor outcome

Phenotypic expression of the 3120+1G>A mutation in non-Caucasian children with cystic fibrosis in South Africa.

INTRODUCTION: Cystic fibrosis (CF) is the most common genetic disorder in Caucasians. Presentation of CF in non-Caucasians is less well studied. OBJECTIVE: This audit was undertaken to determine the phenotypic expression of the 3120+1G>A mutation in black and mixed race children in South Africa. METHODS: A multi-centre retrospective chart review of clinical, laboratory and spirometry data of non-Caucasian CF patients in four CF centres in South Africa was collected. Data was collected at diagnosis and after a five-year follow-up period. Ethical approval was granted for the study. RESULTS: A total of 30 participants were enrolled of whom 14 (47%) were homozygous and 16 (53%) heterozygous for the 3120+1G>A mutation. The mean age of diagnosis was 13 months. Twenty-four (80%) patients had malnutrition (mean weight z-score -3.6) or failure to thrive (77%) at presentation. Twenty (67%) presented with non-specific abdominal symptoms, whilst fifteen (50%) had recurrent respiratory tract infections. Pseudomonas aeruginosa was detected at a mean age of 21 months. The mean FEV1 was 73% predicted (95% CI 54.0-91.1) at study entry and 68% predicted (95% CI 49.74-87.06) at follow-up. CONCLUSION: Failure to thrive and a diagnosis of protein energy malnutrition (kwashiorkor) are the common presenting features of CF in children with the 3120+1G>A mutation. Meconium ileus is a rare presenting feature of CF in black and mixed race children with this deletion in South Africa.

Conservative management of a ruptured pulmonary hydatid cyst.

Pulmonary hydatid cysts in children frequently develop complications such as infection and air leaks. Surgery combined with medical therapy remains the standard form of treatment. We report a 7-year-old child who developed rupture of a large pulmonary hydatid cyst following chest trauma; conservative management resulted in successful expulsion of the cyst.

Tuberculosis during early antiretroviral-induced immune reconstitution in HIV-infected children.

SETTING: Referral paediatric hospital, Cape Town, South Africa. OBJECTIVE: To describe the clinical manifestations of Mycobacterium tuberculosis (TB) associated disease in human immunodeficiency virus (HIV) infected children during early antiretroviral-induced immune reconstitution. DESIGN: Case series. RESULTS: Eleven patients with probable or culture confirmed TB were identified. Seven presented after a median 25 (range 8-54) days on highly active antiretroviral therapy (HAART) with pulmonary TB and one also had extra-pulmonary disease. Three of the patients had a prior history of TB and presented with relapse or recurrent disease. Four patients with TB developed a tuberculous paradoxical reaction; one died of suspected tuberculous immune reconstitution pneumonitis. The duration of pre-HAART anti-tuberculosis treatment and antiretroviral treatment ranged from 21 to 59 and 6 to 105 days, respectively, when they presented with a paradoxical reaction. Drug-resistant (isoniazid and rifampicin) TB was cultured from one patient with relapse disease. Chest radiograph features present during immune reconstitution were increasing or new intrathoracic lymphadenopathy, parenchymal infiltrates and pleural effusions. CONCLUSION: This report documents the clinical presentation of TB during the early phase of HAART which may be attributed to HAART-mediated immune reconstitution. More research is needed to improve the accuracy of TB diagnosis in HIV-infected children.

Empyema and parapneumonic effusions in children: an update

Childhood empyema is an important complication of bacterial pneumonia. The incidence of empyema is increasing worldwide. Streptococcus pneumoniae and Staphylococcus aureus are the most common aetiologies in high and low-income countries respectively. The diagnosis is based on clinical; radiographic and pleural fluid examination. Tuberculosis (TB) is an important cause of a pleural effusion in high TB prevalence areas. There is controversy about the optimal treatment for empyema in children. Sepsis should be controlled with antibiotics and drainage of the pleural cavity. Intrapleural fibrinolysis and Video Assisted Thorascopic Surgery (VATS) are modern interventions widely used in high-income countries but mostly unavailable in the developed world. There are however few properly conducted studies that would support one therapeutic approach over the other. Despite this; the clinical outcome of paediatric empyema is usually good regardless of therapeutic approach. This review summarises aetiology; pathogenesis and clinical presentation of childhood empyema and discusses the various treatment modalities with an emphasis on clinical practice in developing countries