Clinical spectrum of disease and outcomes in children with Omicron SARS-COV-2 infection in Cape Town, South Africa.

INTRODUCTION: Children with underlying comorbidities and infants are most severely affected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including in low- and middle-income countries with a high prevalence of HIV and TB. We describe the clinical presentation of SARS-CoV-2 infection in children during the Omicron wave, in Cape Town, South Africa. METHODS: We analysed routine care data from a prospective cohort of children aged 0-13 years, with a positive SARS-CoV-2 real-time reverse-transcription polymerase chain reaction (rRT-PCR) or SARS-CoV-2 antigen test, admitted to Tygerberg Hospital between 1 November 2021 until 1 March 2022. Risk factors for severity of disease were assessed. RESULTS: Ninety-five children tested positive for SARS-CoV-2, of whom 87 (91.6%) were symptomatic. Clinical data were available for 86 children. The median age was 11 months (IQR 3.0-60.0), 37 (43.0%) were females, 21 (24.7%) were HIV-exposed and 7 (8.1%) were living with HIV (CLHIV). In total, 44 (51.2%) children had at least one underlying comorbidity. TB co-infection was seen in 11 children, 6 children were newly diagnosed and 5 children were already on TB treatment at the time of admission. CONCLUSION: There was no evidence of more severe disease in children living with HIV or TB.

INTRODUCTION: Les enfants et les nourrissons présentant des comorbidités sous-jacentes sont les plus gravement touchés par l'infection par le coronavirus-2 du syndrome respiratoire aigu sévère (SARS-CoV-2), y compris dans les pays à revenu faible ou intermédiaire où la prévalence du VIH et de la TB est élevée. Nous décrivons la présentation clinique de l'infection par le SARS-CoV-2 chez les enfants pendant la vague Omicron, au Cap, en Afrique du Sud. MÉTHODES: Nous avons analysé les données de soins de routine d'une cohorte prospective d'enfants âgés de 0 à 13 ans, avec un test positif de réaction en chaîne de la polymérase de transcription inverse en temps réel (rRT-PCR) ou d'antigène du SARS-CoV-2, admis à l'hôpital Tygerberg entre le 1er novembre 2021 et le 1er mars 2022. Les facteurs de risque de gravité de la maladie ont été évalués. RÉSULTATS: Quatre-vingt-quinze enfants ont été testés positifs au SARS-CoV-2, dont 87 (91,6%) étaient symptomatiques. Des données cliniques étaient disponibles pour 86 enfants. L'âge médian était de 11 mois (IQR 3,0­60,0), 37 (43,0%) étaient des filles, 21 (24,7%) étaient exposés au VIH et 7 (8,1%) vivaient avec le VIH (CLHIV). Au total, 44 (51,2%) enfants présentaient au moins une comorbidité sous-jacente. La co-infection par la TB a été observée chez 11 enfants, 6 enfants ont été nouvellement diagnostiqués et 5 enfants étaient déjà sous traitement antituberculeux au moment de l'admission. CONCLUSION: Il n'y a pas de preuve d'une maladie plus grave chez les enfants vivant avec le VIH ou la TB.

Endoscopic findings in children born with oesophageal atresia in an academic unit in South Africa.

BACKGROUND: Oesophageal atresia (OA) is one of the most common congenital gastrointestinal (GI) abnormalities. Due to advances in multidisciplinary care, early prognosis has improved with emphasis shifting to the long-term impact of this disease. Literature suggests a higher incidence of Barrett's and eosinophilic oesophagitis in these children, with an increased risk of oesophageal carcinoma. Guidelines for adults born with OA include routine endoscopy and lifelong screening of the upper gastrointestinal tract (GIT). Despite this, uncertainty remains regarding the necessity and frequency of endoscopic surveillance for children born with OA. We describe our endoscopic findings in children born with OA. METHODS: A prospective analytic cohort study was undertaken, which included all children born with OA, that were followed-up in our unit between 2020 and 2022. History regarding feeding and GI symptoms were documented after which an endoscopy was performed. RESULTS: During the study period, 37 endoscopies were performed in patients born with OA at a median age of 25 months. The most common clinical appearance on endoscopy was anastomotic strictures followed by oesophagitis. Twelve patients had biopsies taken, with abnormal histology in all but one patient. The most common histological finding was oesophagitis with lymphocytes and chronic gastritis. Two patients had Helicobacter Pylori infection, and one had findings suggestive of eosinophilic oesophagitis. CONCLUSION: All patients with a clinical indication for an endoscopy had abnormal clinical or histological findings, thus concurring with the literature in highlighting the need for regular endoscopy. We recommend regular clinical follow-up and endoscopic surveillance if clinically indicated for children born with OA.

Disease-specific quality of life as part of the long-term follow-up for children born with esophageal atresia in an academic unit in South Africa-a pilot study.

As neonatal mortality rates have decreased in esophageal atresia (EA), there is a growing focus on quality of life (QoL) in these children. No study from Africa has reported on this topic. This pilot study aimed to describe disease-specific QoL in EA children and its applicability as part of long-term follow-up in an academic facility in South Africa. Disease-specific QoL in children born with EA was assessed utilizing the EA-QoL questionnaire for children aged 2-17 years during a patient-encounter. The parent-report for children aged 2-7 years compromised 17 items categorized into three domains: eating, physical health and treatment, and social isolation/stress. The 24-item EA-QL questionnaire for children aged 8-18 (child- and parent-report) explored four domains: eating, body perception, social relationships, and health and well-being. A total of 13 questionnaires for children aged 2-7 years were completed by five parents. A negative perceived impact on their child's eating was reported by 46-92% of parents, and less impact in the other two domains. A total of 27 questionnaires were completed by eight children aged 8-17 years and 10 parents. Similar percentages children and parents reported a negative impact in the eating, social relationships, and body perception domains. More than half reported a negative impact on the child's health and well-being. This study supports the concept that assessment of disease-specific QoL should play a vital role in the comprehensive follow-up approach for children born with EA. We identified that parents of younger children were more likely to report eating disorders, whereas parents of older children were more likely to report health difficulties with different perceptions when it came to the child's scar.

Which side are they on? Diagnosing primary ciliary dyskinesias in low- or middle-income countries: A review and case series.

Background: Primary ciliary dyskinesia (PCD) is a rare genetic condition with a variable clinical presentation, making its diagnosis a challenge. We describe two unrelated sibling pairs with PCD: adult siblings in the first and perinatal/neonatal in the second. Both families highlight the more common and rarer clinical manifestations of PCD. We use these cases to highlight: (i) current understanding of the underlying genetic and pathophysiological mechanisms of PCD; (ii) the diversity of cardiac and respiratory features of PCD across a wide age range; (iii) aspects of the history and clinical examination that should raise suspicion of PCD; and (iv) the role of next-generation sequencing gene panel testing in confirmation of the diagnosis. We note genomic evidence predicting that PCD is relatively common in black African populations. Study synopsis: What the study adds. This review of two sibling pairs illustrates the variable histories, presentations, diagnostic processes and clinical courses of primary ciliary dyskinesia (PCD) in low- or middle-income countries (LMICs), highlighting the diagnostic challenges faced when encountering such patients in settings where there may not be access to specialised resources. Possible diagnostic tools that can be used are discussed, weighing up their pros and cons in an LMIC setting, and a potential diagnostic approach that can be adapted to the treating clinician's own context is provided.Implications of the findings. Confirmation of the diagnosis of primary ciliary dyskinesia is no longer limited to well-resourced institutions, but can be done in less specialised environments using novel, highly accurate next-generation sequencing gene panel testing, reducing the need to transport patients as well as the overall cost to the healthcare system. Well-resourced institutions that see high volumes of patients with PCD can invest in new highly sensitive diagnostic tools such as high-speed video microscopy. There is a need for research investigating the validity of tools such as ciliary immunofluorescence in the South African population.

Comparison of single coronal thick-slab minimum intensity projection with flexible bronchoscopy for airway compression in children with lymphobronchial tuberculosis.

AIM: To generate standardised coronal minimum intensity projection (MinIP) computed tomography (CT) reconstructions, and compare these with flexible bronchoscopy in children with lymphobronchial tuberculosis (LBTB). MATERIALS AND METHODS: Standardised coronal MinIP reconstructions were performed from CT images in children with LBTB and the findings of three readers were compared with the reference standard, flexible bronchoscopy (FB), regarding airway narrowing. Intraluminal lesions, the site of the stenosis, and the degree of stenosis were also evaluated. The length of stenosis was evaluated by CT MinIP only. RESULTS: Sixty-five children (38 males; 58.5% and 27 females; 41.5%), with ages ranging from 2.5 to 144 months were evaluated. Coronal CT MinIP demonstrated a sensitivity of 96% and specificity of 89% against FB. The most common site of stenosis was the bronchus intermedius (91%), followed by the left main bronchus (85%), the right upper lobe bronchus RUL (66%), and the trachea (60%). CONCLUSION: Coronal CT MinIP reconstruction is useful in demonstrating airway stenosis in children with lymphobronchial TB, with high sensitivity and specificity. CT MinIP had additional advantages over FB in that it allowed objective measurement of the diameter of stenosis, measurement of the length of stenosis, and evaluation of post-stenotic segments of the airways and lung parenchymal abnormalities.

Post-TB health and wellbeing.

TB affects around 10.6 million people each year and there are now around 155 million TB survivors. TB and its treatments can lead to permanently impaired health and wellbeing. In 2019, representatives of TB affected communities attending the '1st International Post-Tuberculosis Symposium´ called for the development of clinical guidance on these issues. This clinical statement on post-TB health and wellbeing responds to this call and builds on the work of the symposium, which brought together TB survivors, healthcare professionals and researchers. Our document offers expert opinion and, where possible, evidence-based guidance to aid clinicians in the diagnosis and management of post-TB conditions and research in this field. It covers all aspects of post-TB, including economic, social and psychological wellbeing, post TB lung disease (PTLD), cardiovascular and pericardial disease, neurological disability, effects in adolescents and children, and future research needs.

Cytomegalovirus viral load as predictor of the clinical course of hypoxic pneumonia in children.

BACKGROUND: Children under 1 year of age with hypoxic pneumonia regularly have concurrent cytomegalovirus (CMV) viremia. In these children, the diagnosis of CMV-associated pneumonia and the prediction of an outcome are difficult. It is unclear whether quantification of blood CMV viral load (CMV-VL) can predict outcomes in these children.METHODS: This was a retrospective study including children (1-12 months of age), with detectable CMV-VL and hypoxic pneumonia admitted to the paediatric intensive care unit of Tygerberg Hospital, Cape Town, South Africa between 1 January 2014 and 31 December 2015. Clinical, radiological and biochemical data were collected.RESULTS: Of the 87 participants included (median age: 3.9 months, IQR 2.2-4.8), 35 were (40%) born prematurely. The median weight-for-age Z-score was -2.68 (IQR -3.0 to -0.83); 37 (43%) were severely underweight for age; 27 (31%) were HIV-positive, 3 were on ART. The median CMV-VL was log 4.0 (IQR 3.3-4.79); CMVhigh was defined as CMV-VL > median; CMV-VL < median was classified as CMVlow. Overall survival was 90%; 12 (15.4%) remained oxygen-dependent at Day 28 post-admission. There was no difference in survival, 24-h post-admission ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2:FiO2), oxygen dependence or ventilation duration between CMVlow and CMVhigh. High-frequency oscillation ventilation duration was longer (P = 0.005) and Pneumocystis jirovecii (PJP) co-infection more frequent (P = 0.018) in CMVhigh.CONCLUSION: CMV-VL is unable to predict the clinical outcome in children with hypoxic pneumonia. Specific treatment for CMV should be considered in all children at risk of CMV-associated pneumonia with detectable CMV-VL.

Caregivers' perspectives on health-related quality of life in young children with TB and respiratory illnesses.

BACKGROUND: There is a lack of holistic health-related quality of life (HRQoL) measures for young children with respiratory disease, especially in low- and middle-income countries (LMICs). We aimed to understand caregivers' perceptions of the relevance of common HRQoL domains for children with respiratory diseases, including TB. METHODS: This study was nested in a prospective observational cohort of children presenting with respiratory symptoms presumptive of pulmonary TB. We conducted 10 semi-structured interviews to explore caregivers' perceptions of the five commonly measured HRQoL domains: physical health, social support, emotional and psychological wellbeing, and schooling. We used case descriptive analysis and thematic coding. RESULTS: Caregivers considered all five domains to be relevant. The socio-economic context framed their responses, with QoL requiring sufficient basic resources for children. HRQoL experiences varied according to the severity of the child's symptoms, but not between TB and non-TB illnesses. Manifestations in the psychological domain were difficult to distinguish from the emotional domain. Social support included broad support for family members, indirectly benefiting the children. Caregivers were concerned about their children's early developmental milestones and future schooling. CONCLUSION: This exploratory study shows that HRQoL domains are relevant but require adaptation to be applicable for young children affected by respiratory illnesses living in LMICs.

CONTEXTE: Il existe un manque de mesures holistiques de la qualité de vie liée à la santé (HRQoL) pour les jeunes enfants atteints de maladies respiratoires, en particulier dans les pays à revenu faible ou intermédiaire (LMIC). Nous avons cherché à comprendre la perception qu'ont les soignants de la pertinence des domaines communs de la HRQoL pour les enfants atteints de maladies respiratoires, dont la TB. MÉTHODES: Cette étude était imbriquée dans une cohorte observationnelle prospective d'enfants présentant des symptômes respiratoires présomptifs de TB pulmonaire. Nous avons mené 10 entretiens semi-structurés pour explorer les perceptions des soignants sur les cinq domaines de la HRQoL communément mesurés : santé physique, soutien social, bien-être émotionnel et psychologique, et scolarité. Nous avons utilisé une analyse descriptive des cas et un codage thématique. RÉSULTATS: Les soignants considèrent que les cinq domaines sont pertinents. Le contexte socio-économique encadrait leurs réponses, la QoL nécessitant des ressources de base suffisantes pour les enfants. Les expériences de QoL variaient en fonction de la gravité des symptômes de l'enfant, mais pas entre les maladies TB et non TB. Les manifestations dans le domaine psychologique étaient difficiles à distinguer du domaine émotionnel. Le soutien social comprenait un large soutien aux membres de la famille, ce qui profitait indirectement aux enfants. Les soignants étaient préoccupés par les premiers stades de développement de leurs enfants et par leur future scolarité. CONCLUSION: Cette étude exploratoire montre que les domaines de la QoL sont pertinents mais nécessitent une adaptation pour être applicables aux jeunes enfants atteints de maladies respiratoires vivant dans les LMIC.

Pediatric bronchoscopy: recent advances and clinical challenges.

Introduction: During the last 40 years equipment has been improved with smaller instruments and sufficient size working channels. This has ensured that bronchoscopy offers therapeutic and interventional options.Areas covered: We provide a review of recent advances and clinical challenges in pediatric bronchoscopy. This includes single-use bronchoscopes, endobronchial ultrasound, and cryoprobe. Bronchoscopy in persistent preschool wheezing and asthma is included. The indications for interventional bronchoscopy have amplified and included balloon dilatation, endoscopic intubation, the use of airway stents, whole lung lavage, closing of fistulas and air leak, as well as an update on removal of foreign bodies. Others include the use of laser and microdebrider in airway surgery. Experience with bronchoscope during the COVID-19 pandemic has been included in this review. PubMed was searched for articles on pediatric bronchoscopy, including rigid bronchoscopy as well as interventional bronchoscopy with a focus on reviewing literature in the past 5 years.Expert opinion: As the proficiency of pediatric interventional pulmonologists continues to grow more interventions are being performed. There is a scarcity of published evidence in this field. Courses for pediatric interventional bronchoscopy need to be developed. The COVID-19 experience resulted in safer bronchoscopy practice for all involved.

Horseshoe lung in a young child at Tygerberg Hospital, South Africa.

Horseshoe lung is a very rare congenital malformation in which the bases of the right and left lung are fused to each other by a narrow isthmus. Although rare, a hyperlucent area in the lower left lung, close to the vertebral column, may represent a horseshoe lung. Horseshoe lung is often associated with scimitar syndrome. Here, we present a case of a 2-year-old girl who presented with recurrent chest infections and wheezing associated with horseshoe lung. The right lung appeared to be hypoplastic.

Tonsillar hypertrophy and prolapse in a child - is epiglottitis a predisposing factor for sudden unexpected death?

BACKGROUND: Tonsillitis, with associated tonsillar hypertrophy, is a common disease of childhood, yet it is rarely associated with sudden death due to airway obstruction. Lethal complications involving the inflamed tonsils include haemorrhage, retropharyngeal abscess and disseminated sepsis. CASE PRESENTATION: We report on a case of sudden and unexpected death in an 8-year-old female who was diagnosed with and treated for tonsillitis. The child was diagnosed with acute tonsillitis 2 days prior to her collapse and was placed on a course of oral antibiotics. There were no signs of upper or lower airway obstruction. She was found to be unresponsive by her caregiver and gasping for air in her bed in the early hours of the second morning after the start of treatment. Autopsy showed massive and symmetrically enlarged palatine tonsils. The tonsils filled the pharynx almost completely. The epiglottis and laryngeal mucosa at the base of the epiglottis in the vicinity of the aryepiglottic membrane and the superior aspect of the larynx displayed red-purple discoloration, with mucosal swelling and edema. Histological examination of the palatine tonsils revealed prominent lymphoid hyperplasia, but no evidence of acute inflammation. CONCLUSION: Palatine tonsillar hypertrophy in infants is a common feature of both viral and bacterial tonsillitis and has been postulated as a possible risk factor for Sudden and Unexplained Death in Infancy (SUDI), based on the theory of mechanical impediment of breathing by narrowing of the upper airway. The rounded shape of the tonsils may facilitate some airflow past the enlarged structures and hence protect against asphyxial death when the enlarged tonsils fill the laryngo-pharynx. Epiglottal and proximal laryngeal edema may play a more significant role in asphyxial unexpected deaths in cases of tonsillitis with tonsillar hypertrophy than previously suspected. This focusses the importance of careful examination of the epiglottis and proximal laryngeal mucosa, as part of a thorough examination of the laryngo-pharynx in cases of sudden death associated with tonsillar hypertrophy.

Empyema necessitans in a six-month-old girl.

Empyema necessitans is a rare complication of acute bacterial pneumonia, especially in children. It is a complication of empyema characterised by the extension of pus from the pleural cavity into the thoracic wall to form a mass of purulent fluid in the adjacent soft tissue. An inflammatory chest wall mass following pneumonia caused by Streptococcus pneumonia in a six-month-old infant is reported. The case emphasises that children presenting with persistent fever and a painful chest wall mass following pneumonia should be investigated immediately as there might be an urgent need for surgery.

Mycobacterium tuberculosis, a cause of necrotising pneumonia in childhood: a case series.

SETTING: Tertiary care hospital, Western Cape, South Africa. DESIGN: Retrospective descriptive study of a case series of necrotising pneumonia (NP) in children associated with Mycobacterium tuberculosis presenting over a 4-year period in a country with high human immunodeficiency virus (HIV) and tuberculosis (TB) prevalence. OBJECTIVE: To describe the clinical and radiological features of, and treatment regimens and outcomes in, children with NP. RESULTS: Of 32 children (median age 16.5 months, interquartile range 10-33), 8 (25%) (median age 49 months) had NP associated with M. tuberculosis, 6 of whom were HIV-infected. Chest computed tomography (CT) was diagnostic in all cases: no radiological signs were suggestive of TB. There was no difference in the clinical picture, chest radiography or CT scan between M. tuberculosis-associated and bacterial NP. M. tuberculosis was cultured in 75% of cases; pleural fluid acid-fast bacilli was positive in an additional two cases. Surgery was required in 46% of the M. tuberculosis cases. At follow-up, 50% of these cases had complete radiological resolution similar to bacterial NP. CONCLUSION: This series highlights the fact that M. tuberculosis not only causes acute pneumonia in children, it also results in numerous complications. M. tuberculosis should be considered as a cause of NP in all children, especially HIV-infected children, living in high TB prevalence regions.

Diagnosing diffuse lung disease in children in a middle-income country: the role of open lung biopsy.

SETTING: A tertiary care hospital situated in a middle-income country with a high burden of tuberculosis (TB) and human immunodeficiency virus (HIV) infection. OBJECTIVE: To determine the diagnostic yield of open lung biopsy (OLB) in children with diffuse lung disease (DLD), comparing findings in HIV-infected and non-HIV-infected children. DESIGN: This 9-year retrospective study included 51 children with DLD (oxygen-dependent or on artificial ventilation), who required an OLB where the diagnosis remained uncertain after extensive investigations. RESULTS: The median age was 7 months, median body weight was 6.6 kg (61% were severely malnourished) and 30% were HIV-infected (62% on antiretroviral treatment). The diagnostic yield of the OLB was 86% (n = 44) and was significantly higher in HIV-infected (77%) than in non-HIV-infected (48%) children (P = 0.01). Pneumonia was the most common diagnosis (n = 25, 57%), with common agents being cytomegalovirus (CMV), viruses other than CMV, Pneumocystis jiroveci pneumonia and previously undiagnosed TB (10%). Mycobacterium tuberculosis as a cause of DLD was not suspected before the OLB, as all investigations for TB were negative. Non-infectious causes of DLD were established in 10% of cases. CONCLUSION: The OLB is a useful diagnostic tool to diagnose idiopathic DLD, including TB, in young children.

Chest radiograph findings in children with tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is diagnosed based on a combination of clinical, laboratory and radiological findings, including signs suggestive of tuberculosis (TB) on a standard chest X-ray (CXR). METHODS: We describe the radiological features suggestive of intrathoracic TB in children diagnosed with TBM during a prospective evaluation of TBM suspects seen at Tygerberg Children's Hospital, Cape Town, South Africa. RESULTS: Of 84 children treated for TBM, 31 (37%) had 'definite' TBM, 45 (55%) 'probable' TBM and 8 (9%) 'possible' TBM. In total, 37 (44%) TBM patients had CXR findings suggestive of TB, 9 (11%) with disseminated (miliary) TB. Only 1 in 4.39 children aged ≤3 years with TBM had suggestive CXR findings. The presence of complicated intrathoracic lymph node disease was significantly higher in children aged ≤3 years (OR 21.69, 95%CI 2.73-172.67, P < 0.01). Among 6 human immunodeficiency virus infected children, 3 (50%) had intrathoracic lymphadenopathy. CONCLUSION: The majority of the children with TBM, including the very young, did not have signs suggestive of TB on CXR.

Uveal melanoma hepatic metastases mutation spectrum analysis using targeted next-generation sequencing of 400 cancer genes.

AIMS: Uveal melanoma (UM) is the most common malignant tumour of the eye. Diagnosis often occurs late in the course of disease, and prognosis is generally poor. Recently, recurrent somatic mutations were described, unravelling additional specific altered pathways in UM. Targeted next-generation sequencing (NGS) can now be applied to an accurate and fast identification of somatic mutations in cancer. The aim of the present study was to characterise the mutation pattern of five UM hepatic metastases with well-defined clinical and pathological features. METHODS: We analysed the UM mutation spectrum using targeted NGS on 409 cancer genes. RESULTS: Four previous reported genes were found to be recurrently mutated. All tumours presented mutually exclusive GNA11 or GNAQ missense mutations. BAP1 loss-of-function mutations were found in three UMs. SF3B1 missense mutations were found in the two UMs with no BAP1 mutations. We then searched for additional mutation targets. We identified the Arg505Cys mutation in the tumour suppressor FBXW7. The same mutation was previously described in different cancer types, and FBXW7 was recently reported to be mutated in UM exomes. CONCLUSIONS: Further studies are required to confirm FBXW7 implication in UM tumorigenesis. Elucidating the molecular mechanisms underlying UM tumorigenesis holds the promise for novel and effective targeted UM therapies.