Indoor air pollution and tobacco smoke exposure: impact on nasopharyngeal bacterial carriage in mothers and infants in an African birth cohort study.

Indoor air pollution (IAP) or environmental tobacco smoke (ETS) exposure may influence nasopharyngeal carriage of bacterial species and development of lower respiratory tract infection (LRTI). The aim of this study was to longitudinally investigate the impact of antenatal or postnatal IAP/ETS exposure on nasopharyngeal bacteria in mothers and infants. A South African cohort study followed mother-infant pairs from birth through the first year. Nasopharyngeal swabs were taken at birth, 6 and 12 months for bacterial culture. Multivariable and multivariate Poisson regression investigated associations between nasopharyngeal bacterial species and IAP/ETS. IAP exposures (particulate matter, carbon monoxide, nitrogen dioxide, volatile organic compounds) were measured at home visits. ETS exposure was measured through maternal and infant urine cotinine. Infants received the 13-valent pneumococcal and Haemophilus influenzae B conjugate vaccines. There were 881 maternal and 2605 infant nasopharyngeal swabs. Antenatal ETS exposure was associated with Streptococcus pneumoniae carriage in mothers (adjusted risk ratio (aRR) 1.73 (95% CI 1.03-2.92)) while postnatal ETS exposure was associated with carriage in infants (aRR 1.14 (95% CI 1.00-1.30)) Postnatal particulate matter exposure was associated with the nasopharyngeal carriage of H. influenzae (aRR 1.68 (95% CI 1.10- 2.57)) or Moraxella catarrhalis (aRR 1.42 (95% CI 1.03-1.97)) in infants. Early-life environmental exposures are associated with an increased prevalence of specific nasopharyngeal bacteria during infancy, which may predispose to LRTI.

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.

Specimen Pooling as a Diagnostic Strategy for Microbiologic Confirmation in Children with Intrathoracic Tuberculosis.

Three-hundred four young children with suspected pulmonary tuberculosis had a gastric aspirate, induced sputum and nasopharyngeal aspirate collected on each of 2 consecutive weekdays. Specimens collected on the second day were pooled in the laboratory for each child individually. The diagnostic yield by Xpert and culture from pooled specimens was not significantly different to a single gastric aspirate.

Lethal fibrosing mediastinitis in a child possibly due to Mycobacterium tuberculosis.

Fibrosing mediastinitis (FM) is a rare benign disease resulting from an excessive fibro-inflammatory reaction in the mediastinum that can compress and occlude mediastinal structures. There is a granulomatous and a diffuse non-granulomatous form of FM. We present a case of granulomatous FM following possible tuberculosis in a young child who presented with severe compression of the airways, pulmonary artery and the superior vena cava (SVC), unresponsive to treatment, resulting in death. Bronchoscopic findings included concentric narrowing and mucosal hyperaemia of the tracheobronchial airways. This case raises awareness of this rare complication and the limited treatment options available.

Early-life exposure to indoor air pollution or tobacco smoke and lower respiratory tract illness and wheezing in African infants: a longitudinal birth cohort study.

BACKGROUND: Indoor air pollution (IAP) and environmental tobacco smoke (ETS) are associated with lower respiratory tract illness (LRTI) or wheezing in children. However, the effect of the timing of these exposures, specifically antenatal versus postnatal, and of alternate fuel sources such as the increasingly used volatile organic compounds have not been well studied. We longitudinally investigated the effect of antenatal or postnatal IAP and ETS on LRTI or wheezing prevalence and severity in African infants. METHODS: Mother and infant pairs enrolled over a 3-year period in a birth cohort study in two centres in Paarl, South Africa, were followed for the first year of life for LRTI or wheezing illness. We measured exposure to IAP (particulate matter, nitrogen dioxide, sulphur dioxide, carbon monoxide, and volatile organic compounds benzene and toluene) using devices placed in homes, antenatally and postnatally. We measured ETS longitudinally by maternal self-report and by urine cotinine measures. Study staff trained in recognition of LRTI or wheeze documented all episodes, which were categorised according to WHO case definition criteria. We used multivariate logistic and Poisson regressions to explore associations. FINDINGS: Between March 1, 2012, and March 31, 2015, we enrolled 1137 mothers with 1143 livebirths. Of 1065 infants who attended at least one study visit, 524 episodes of LRTI occurred after discharge with a wheezing prevalence of 0·23 (95% CI 0·21-0·26) episodes per child year. Exposures associated with LRTI were antenatal maternal smoking (incidence rate ratio 1·62, 95% CI 1·14-2·30; p=0·004) or particulate matter (1·43, 1·06-1·95; p=0·008). Subanalyses of LRTI requiring hospitalisation (n=137) and supplemental oxygen (n=69) found antenatal toluene significantly increased the risk of LRTI-associated hospitalisation (odds ratio 5·13, 95% CI 1·43-18·36; p=0·012) and need for supplemental oxygen (13·21, 1·96-89·16; p=0·008). Wheezing illness was associated with both antenatal (incidence rate ratio 2·09, 95% CI 1·54-2·84; p<0·0001) and postnatal (1·27, 95% CI 1·03-1·56; p=0·024) maternal smoking. Antenatally, wheezing was associated with maternal passive smoke exposure (1·70, 1·25-2·31; p=0·001) and, postnatally, with any household member smoking (1·55, 1·17 -2·06; p=0·002). INTERPRETATION: Antenatal exposures were the predominant risk factors associated with LRTI or wheezing illness. Toluene was a novel exposure associated with severe LRTI. Urgent and effective interventions focusing on antenatal environmental factors are required, including smoking cessation programmes targeting women of childbearing age pre-conception and pregnant women. FUNDING: Bill & Melinda Gates Foundation, Discovery Foundation, South African Thoracic Society AstraZeneca Respiratory Fellowship, Medical Research Council South Africa, National Research Foundation South Africa, and CIDRI Clinical Fellowship.

Stool Culture for Diagnosis of Pulmonary Tuberculosis in Children.

Bacteriological confirmation of Mycobacterium tuberculosis is achieved in the minority of young children with tuberculosis (TB), since specimen collection is resource intensive and respiratory secretions are mostly paucibacillary, leading to limited sensitivity of available diagnostic tests. Although molecular tests are increasingly available globally, mycobacterial culture remains the gold standard for diagnosis and determination of drug susceptibility and is more sensitive than molecular methods for paucibacillary TB. We evaluated stool culture as an alternative to respiratory specimens for the diagnosis of suspected intrathoracic TB in a subgroup of 188 children (median age, 14.4 months; 15.4% HIV infected) enrolled in a TB diagnostic study at two local hospitals in Cape Town, South Africa. One stool culture was compared to overall bacteriological confirmation by stool Xpert and by Xpert and culture of multiple respiratory specimens. After decontamination/digestion with NALC (N-acetyl-l-cysteine)-NaOH (1.25%), concentrated fluorescent smear microscopy, Xpert MTB/RIF, and liquid culture were completed for all specimens. Culture contamination of stool specimens was high at 41.5%. Seven of 90 (7.8%) children initiating TB treatment were stool culture positive for M. tuberculosis Excluding contaminated cultures, the sensitivity of stool culture versus confirmed TB was 6/25 (24.0%; 95% confidence interval [CI] = 9.4 to 45.1%). In addition, stool culture detected TB in 1/93 (1.1%) children with "unconfirmed TB." Testing the same stool by Xpert increased sensitivity to 33.3% (95% CI = 18.0 to 51.8%). In conclusion, stool culture had low sensitivity for M. tuberculosis detection in children with intrathoracic TB. Reducing culture contamination through improved laboratory protocols may enable more reliable estimates of its diagnostic utility.

HIV-related chronic lung disease in adolescents: are we prepared for the future?

INTRODUCTION: Chronic lung diseases (CLD) are the most chronic disease occurring in adolescents living with human immunodeficiency virus (ALHIV). In ALHIV who received antiretroviral therapy (ART) late in childhood, bronchiectasis, bronchiolitis obliterans and interstitial pneumonitis are common. In adolescents who received ART early in life the spectrum of CLD has changed with asthma and chronic obstructive pulmonary disease being common. Areas covered: The aim of this paper was to review CLD in ALHIV. We conducted a literature review of electronic databases focusing on CLD that were common prior to the introduction of ART (1996-2004), the present situation where ART is widely available (2005 to 2016), and articles which aided us speculating on the impact of HIV-related CLD in adolescents transitioning to adult HIV-clinics. Amongst the approximately 2.1 million adolescents living with HIV, CLD commonly occurs. Awareness of the CLD amongst ALHIV needs to be raised to ensure that disease appropriate treatment is available to these vulnerable adolescents. Expert commentary: As adolescents' transition from pediatric HIV-clinics to adult HIV-clinics the evidence shows that adolescents might not receive optimal care if adult pulmonologists are not aware of the CLD that commonly occur in ALHIV.

Xpert MTB/RIF on Stool Is Useful for the Rapid Diagnosis of Tuberculosis in Young Children With Severe Pulmonary Disease.

BACKGROUND: Tuberculosis (TB) continues to result in high morbidity and mortality in children from resource-limited settings. Diagnostic challenges, including resource-intense sputum collection methods and insensitive diagnostic tests, contribute to diagnostic delay and poor outcomes in children. We evaluated the diagnostic utility of stool Xpert MTB/RIF (Xpert) compared with bacteriologic confirmation (combination of Xpert and culture of respiratory samples). METHODS: In a hospital-based study in Cape Town, South Africa, we enrolled children younger than 13 years of age with suspected pulmonary TB from April 2012 to August 2015. Standard clinical investigations included tuberculin skin test, chest radiograph and HIV testing. Respiratory samples for smear microscopy, Xpert and liquid culture included gastric aspirates, induced sputum, nasopharyngeal aspirates and expectorated sputum. One stool sample per child was collected and tested using Xpert. RESULTS: Of 379 children enrolled (median age, 15.9 months, 13.7% HIV infected), 73 (19.3%) had bacteriologically confirmed TB. The sensitivity and specificity of stool Xpert versus overall bacteriologic confirmation were 31.9% [95% confidence interval (CI): 21.84%-44.50%] and 99.7% (95% CI: 98.2%-100%), respectively. A total of 23/51 (45.1%) children with bacteriologically confirmed TB with severe disease were stool Xpert positive. Cavities on chest radiograph were associated with Xpert stool positivity regardless of age and other relevant factors [odds ratios (OR) 7.05; 95% CI: 2.16-22.98; P = 0.001]. CONCLUSIONS: Stool Xpert can rapidly confirm TB in children who present with radiologic findings suggestive of severe TB. In resource-limited settings where children frequently present with advanced disease, Xpert on stool samples could improve access to rapid diagnostic confirmation and appropriate treatment.

The indications and role of paediatric bronchoscopy in a developing country, with high prevalence of pulmonary tuberculosis and HIV.

BACKGROUND: Bronchoscopy, an important investigation for the diagnosis and management of respiratory diseases, is widely used in high income countries. There is limited information on value of paediatric bronchoscopy in low and middle income countries (LMIC). AIMS AND OBJECTIVES: Aim was to describe the indications, findings and complications of bronchoscopy in a middle income country with a high prevalence of tuberculosis and HIV. METHODOLOGY: A retrospective analysis of a database over a 3.5 year period. RESULTS: A total of 509 bronchoscopies were performed on neonates (2.3%) and children (median age = 18 months) of which 5.1% were HIV-infected. The main indications were: possible large airway compression 40%, complicated pneumonia (25%) and persistent stridor (15%). Pathology was observed in 64% of bronchoscopies. The most findings were lymph node compression of the airways (21%), and upper airway pathology (12%). Interventional procedures were performed in 112 cases (22%), the commonest being foreign bodies removal (30%), endobronchial lymph node enucleation (30%) and transbronchial needle aspiration (20%). No major complications. CONCLUSION: The diagnostic yield of paediatric bronchoscopy did not differ from high income countries emphasising the importance of paediatric bronchoscopy in the management of childhood lung disease in LMICs.

Socioeconomic factors associated with asthma prevalence and severity among children living in low-income South African communities.

BACKGROUND: Rates of asthma, poverty and social deprivation are high among young people in South Africa (SA), yet asthma interventions largely remain focused on biomedical factors. OBJECTIVE: To investigate associations between socioeconomic factors and childhood asthma. METHODS: We recruited 6 002 children aged 10 - 17 years from six low-income urban and rural sites in three SA provinces. Self-report questionnaires measured health status, sociodemographics and socioeconomic factors. Logistic regression and mediation analyses were used to test models of risk factors for asthma prevalence and severity (frequency of attacks). RESULTS: Child anxiety (odds ratio (OR) 1.08; 95% confidence interval (CI) 1.04 - 1.12) and community violence (OR 1.14; 95% CI 1.00 - 1.30) were associated with increased odds of having asthma. Children doing more outdoor housework (OR 0.83; 95% CI 0.71 - 0.98) and living in greater poverty (OR 0.93; 95% CI 0.88 - 0.99) had lower odds of having asthma. Severe asthma was predicted by child depression (OR 1.14; 95% CI 1.03 - 1.26) and greater household poverty (OR 1.14; 95% CI 1.01 - 1.28). Most socioeconomic factors operated in 'risk pathways', wherein structural factors (e.g. urban living) were associated with individual factors (e.g. fewer outdoor tasks), which predicted greater odds of having asthma or severe exacerbations. CONCLUSIONS: This study suggests the need to consider the context of childhood asthma in SA for improved prevention and treatment. A multidisciplinary approach may be more effective than a biomedical model, given the plausible effects of psychosocial stress and poverty on asthma outcomes.

Outcome of Children Admitted to a General Highcare Unit in a Regional Hospital in the Western Cape; South Africa

Background. Critically ill children are often managed in non-tertiary general intensive care units admitting both adults and children; but few data are currently available regarding paediatric outcomes in these general units.Objective. To determine the outcome of critically ill neonates and children admitted to a general high-care unit in a large regional hospital in the Western Cape; South Africa.Methods. This was a retrospective descriptive analysis of outcome of all neonatal and paediatric (13 years of age) patients admitted with non-surgical disease; during a 1-year period; to a general high-care unit at a large regional hospital in Worcester; South Africa. Data included demography; admission time; length of stay; diagnoses; HIV status; therapeutic interventions and outcome. The primary outcome was defined as successful discharge; transfer to a central hospital or death.Results. There were 185 admissions; with the majority (83%) 12 months of age (median age 3.7 months; range 0 - 151 months) and a male:female ratio of 1.3:1. The majority (70%) were successfully discharged; while 24% were transferred to a tertiary paediatric intensive care unit (PICU) and only 6% died. Causes of death included acute lower respiratory tract infections (33%); acute gastroenteritis (33%); birth asphyxia (16%) and complications of prematurity (16%). Nasal continuous positive airway pressure (p0.001); ventilation (p0.001) and HIV infection (p

The simple bread tag - a menace to society?

Foreign bodies are potentially life-threatening when inhaled by a child, depending on where they lodge. Symptoms can range from acute upper airway obstruction to mild, vague respiratory complaints. Between 80% and 90% of inhaled foreign bodies occlude the bronchi, while the larynx is a less common site. The commonest inhaled paediatric foreign bodies are organic, e.g. seeds or nuts. Plastic foreign bodies are less common and more difficult to diagnose. They are generally radiolucent on lateral neck radiographs and are often clear and thin. We report three cases of an unusual plastic laryngeal foreign body, the bread tag. Plastic bread tags were first reported in the medical literature as an ingested gastrointestinal foreign body in 1975. Since then, over 20 cases of gastrointestinal complications have been described. We report what is to our knowledge the first paediatric case of an inhaled bread tag, and also the first case series, briefly discuss the symptoms and options for removal of laryngeal foreign bodies, and highlight the dangers of the apparently harmless bread tag. Images of the bread tags in situ and after their removal are included.

Potentially Modifiable Factors Associated with Death of Infants and Children with Severe Pneumonia Routinely Managed in District Hospitals in Malawi.

OBJECTIVE: To investigate recognised co-morbidities and clinical management associated with inpatient pneumonia mortality in Malawian district hospitals. METHODS: Prospective cohort study, of patient records, carried out in Malawi between 1st October 2000 and 30th June 2003. The study included all children aged 0-59 months admitted to the paediatric wards in sixteen district hospitals throughout Malawi with severe and very severe pneumonia. We compared individual factors between those that survived (n = 14 076) and those that died (n = 1 633). RESULTS: From logistic regression analysis, predictors of death in hospital, adjusted for age, sex and severity grade included comorbid conditions of meningitis (OR =2.49, 95% CI 1.50-4.15), malnutrition (OR =2.37, 95% CI 1.94-2.88) and severe anaemia (OR =1.41, 95% CI 1.03-1.92). Requiring supplementary oxygen (OR =2.16, 95% CI 1.85-2.51) and intravenous fluids (OR =3.02, 95% CI 2.13-4.28) were associated with death while blood transfusion was no longer significant (OR =1.10, 95% CI 0.77-1.57) when the model included severe anaemia. CONCLUSIONS: This study identified a number of challenges to improve outcome for Malawian infants and children hospitalised with pneumonia. These included improved assessment of co-morbidities and more rigorous application of standard case management.

Home environment and indoor air pollution exposure in an African birth cohort study.

BACKGROUND: Household indoor air pollution (IAP) is a global health problem and a risk factor for childhood respiratory disease; the leading cause of mortality in African children. This study aimed to describe the home environment and measure IAP in the Drakenstein Child Health Study (DCHS), an African birth cohort. METHODS: An antenatal home visit to assess the home environment and measure IAP (particulate matter, sulphur dioxide, nitrogen dioxide, carbon monoxide and volatile organic compounds (VOCs)) was done on pregnant women enrolled to the DCHS, in a low-socioeconomic, peri-urban South African community. Urine cotinine measured maternal tobacco smoking and exposure. Dwellings were categorised according to 6 household dimensions. Univariate and multivariate analysis explored associations between home environment, seasons and IAP levels measured. RESULTS: 633 home visits were completed, with IAP measured in 90% of homes. Almost a third of participants were of the lowest socio-economic status and the majority of homes (65%) lacked 2 or more of the dwelling category dimensions. Most households had electricity (92%), however, fossil fuels were still used for cooking (19%) and heating (15%) in homes. Antenatal maternal smoking prevalence was 31%; 44% had passive smoke exposure. Of IAP measured, benzene (VOC) was significantly above ambient standards with median 5.6 µg/m3 (IQR 2.6-17.1). There were significant associations between the use of fossil fuels for cooking and increased benzene [OR 3.4 (95% CI 2.1-5.4)], carbon monoxide [OR 2.9 (95% CI 1.7-5.0)] and nitrogen dioxide [OR 18.6 (95% CI 3.9-88.9)] levels. A significant seasonal association was found with higher IAP levels in winter. CONCLUSION: In this low-socioeconomic African community, multiple environmental factors and pollutants, with the potential to affect child health, were identified. Measurement of IAP in a resource-limited setting is feasible. Recognising and quantifying these risk factors is important in effecting public health policy changes.

Decompression of enlarged mediastinal lymph nodes due to mycobacterium tuberculosis causing severe airway obstruction in children.

BACKGROUND: Large airway compression by enlarged tuberculosis (TB) lymph nodes results in life-threatening airway obstruction in a small proportion of children. The indications, safety, and efficacy of TB lymph node decompression are inadequately described. This study aims to describe the indications and efficacy of TB lymph node decompression in children with severe airway compression and investigate variables influencing outcome. METHODS: A prospective cohort of children (aged 3 months to 13 years) with life-threatening airway obstruction resulting from TB lymph node compression of the large airways were enrolled. The site and degree of airway obstruction were assessed by bronchoscopy and chest computed tomography scan. RESULTS: Of the 250 children enrolled, 34% (n = 86) required transthoracic lymph node decompression, 29% as an urgent procedure and 71% (n = 63) after failing 1 month of antituberculosis treatment that included glucosteroids. Compression (less than 75%) of the bronchus intermedius (odds ratio 2.28, 95% confidence interval: 1.29 to 4.02) and left main bronchus (odds ratio 3.34, 95% confidence interval: 1.73 to 6.83) were the best predictors for lymph node decompression. Human immunodeficiency virus status, drug resistance, and malnutrition were not associated with decompression. Few complications (self-limiting, 8%) or treatment failures (2%) resulted from the decompression. There were no deaths. CONCLUSIONS: In one third of children with TB, severe airway obstruction caused by enlarged lymph nodes requires decompression. Transthoracic decompression can be safely performed with low complication, failure, and fatality rates.

Optimizing the detection of recent tuberculosis infection in children in a high tuberculosis-HIV burden setting.

RATIONALE: Children who are young, malnourished, and infected with HIV have significant risk of tuberculosis (TB) morbidity and mortality following TB infection. Treatment of TB infection is hindered by poor detection and limited pediatric data. OBJECTIVES: Identify improved testing to detect pediatric TB infection. METHODS: This was a prospective community-based study assessing use of the tuberculin skin test and IFN-γ release assays among children (n = 1,343; 6 mo to <15 yr) in TB-HIV high-burden settings; associations with child characteristics were measured. MEASUREMENTS AND MAIN RESULTS: Contact tracing detects TB in 8% of child contacts within 3 months of exposure. Among children with no documented contact, tuberculin skin test and QuantiFERON-TB Gold In-Tube positivity was greater than T-SPOT.TB. Nearly 8% of children had IFN-γ release assay positive and skin test negative discordance. In a model accounting for confounders, all tests correlate with TB contact, but IFN-γ release assays correlate better than the tuberculin skin test (P = 0.0011). Indeterminate IFN-γ release assay results were not associated with age. Indeterminate QuantiFERON-TB Gold In-Tube results were more frequent in children infected with HIV (4.7%) than uninfected with HIV (1.9%), whereas T-SPOT.TB indeterminates were rare (0.2%) and not affected by HIV status. Conversion and reversion were not associated with HIV status. Among children infected with HIV, tests correlated less with contact as malnutrition worsened. CONCLUSIONS: Where resources allow, use of IFN-γ release assays should be considered in children who are young, recently exposed, and infected with HIV because they may offer advantages compared with the tuberculin skin test for identifying TB infection, and improve targeted, cost-effective delivery of preventive therapy. Affordable tests of infection could dramatically impact global TB control.