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.

The association between environmental tobacco smoke exposure and childhood respiratory disease: a review.

INTRODUCTION: Childhood respiratory illness is a major cause of morbidity and mortality particularly in low and middle-income countries. Environmental tobacco smoke (ETS) exposure is a recognised risk factor for both acute and chronic respiratory illness. Areas covered: The aim of this paper was to review the epidemiology of ETS exposure and impact on respiratory health in children. We conducted a search of 3 electronic databases of publications on ETS and childhood respiratory illness from 1990-2015. Key findings were that up to 70% of children are exposed to ETS globally, but under-reporting may mask the true prevalence. Maternal smoking and ETS exposure influence infant lung development and are associated with childhood upper and lower respiratory tract infection, wheezing or asthma. Further, exposure to ETS is associated with more severe respiratory disease. ETS exposure reduces lung function early in life, establishing an increased lifelong risk of poor lung health. Expert commentary: Urgent and effective strategies are needed to decrease ETS exposure in young children to improve child and long-term lung health in adults especially in low and middle income countries where ETS exposure is increasing.

Antenatal and early life tobacco smoke exposure in an African birth cohort study.

BACKGROUND: Exposure to tobacco smoke in African infants has not been well studied, despite the high burden of childhood respiratory disease in these communities. OBJECTIVE: To investigate the prevalence of antenatal and early life tobacco smoke exposure and associations with infant birth outcomes in an African birth cohort, the Drakenstein Child Health Study. METHODS: Self-report questionnaires assessing maternal and household smoking were administered. Maternal and infant urine cotinine testing was conducted antenatally, at birth and at 6-10 weeks of life to measure tobacco smoke exposure. Multivariate regression models explored the associations between exposure to smoke and infant birth outcomes. RESULTS: Of 789 pregnant women included, 250 (32%) were active smokers on cotinine testing. At birth and at 6-10 weeks of life, respectively 135/241 (56%) and 154/291 (53%) infants had urine cotinine levels indicating tobacco smoke exposure. Household smoking was prevalent and was associated with positive infant cotinine test results. Antenatal maternal smoking was associated with decreased infant birthweight-for-age Z-score (0.3, 95%CI 0.1-0.5). CONCLUSION: Antenatal and early life tobacco smoke exposure is highly prevalent in this community, and may impact on birth outcomes and subsequent child health. Smoking cessation interventions are urgently needed to reduce tobacco smoke exposure in African communities.

The background and rationale for a new fixed-dose combination for first-line treatment of tuberculosis in children.

In 2010, the World Health Organization revised the recommendations for the treatment of tuberculosis (TB) in children. The major revision was to increase isoniazid, rifampicin and pyrazinamide dosages according to body weight in children. The recommendations for higher dosages are based on consistent evidence from 1) pharmacokinetic studies suggesting that young children require higher dosages than adolescents and adults to achieve desired serum concentrations; and 2) observational studies reporting that the higher dosages would not be associated with increased risk of toxicity in children. However, national tuberculosis programmes faced unforeseen challenges in implementing the revised recommendations. The main difficulty was to adapt the revised dosages for the treatment of children with drug-susceptible TB using available fixed-dose combinations (FDCs). A more suitable FDC for the intensive and continuation phases of treatment has now been developed for planned implementation in 2015. This paper explains the background and rationale for the development of a new FDC tablet for children with drug-susceptible TB.

Novel application of NIH case definitions in a paediatric tuberculosis contact investigation study.

BACKGROUND: International (National Institutes of Health [NIH]) case definitions have been proposed for paediatric tuberculosis (TB) diagnostic studies. The relevance of these definitions for contact tracing studies is unknown. METHODS: We developed case definitions for a community-based contact tracing diagnostic study. We compare disease certainty using protocol-defined and NIH case definitions and describe TB disease spectrum and severity. RESULTS: There were 111 potential disease episodes in 109 (21% human immunodeficiency virus [HIV] infected) of 1093 children enrolled. Based on NIH definitions, there were 8 confirmed, 12 probable, 17 possible and 3 unlikely TB and 2 non-TB episodes. Using protocol case definitions, there were 23 episodes of confirmed, 36 probable, 27 possible and 0 unlikely TB and 21 non-TB. Of 111 potential episodes, 69 were unclassifiable using the NIH definition, while 4 were unclassifiable using the protocol definition. Agreement between definitions was 0.30 (95%CI 0.23-0.38). There were 62 episodes (72%) of non-severe and 24 (28%) of severe TB. CONCLUSIONS: The NIH definition had limited applicability to household contact studies, despite the wide spectrum of disease observed. Further research is needed to develop case definitions relevant to different research settings, including contact investigation to capture the wide spectrum of paediatric TB in clinical research.

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.

Teaching chest X-ray reading for child tuberculosis suspects.

SETTING: Cape Town, South Africa. OBJECTIVE: To improve the reading of chest X-rays (CXRs) in child tuberculosis (TB) suspects. DESIGN: We designed a reporting and recording form to assist in the diagnosis of childhood TB from CXRs. We then developed an image bank of antero-posterior and lateral CXR pairs, with each image pair assigned to one of four diagnostic categories. Finally, we designed and carried out a 1-day training course to teach clinicians how to read paediatric CXRs, with pre- and post-course assessments. RESULTS: Of the 27 participants included, 17 (63%) were women. The median age was 38 years (interquartile range [IQR] 32.5-43.5). The median pre-training score was 16.0/30 (IQR 13.0-18.0) and the median post-training score was 17.0 (IQR 13.5-21.0). Sensitivity (P = 0.09) and specificity (P = 0.06) to detect TB did not change as a result of the course; however, the Wilcoxon signed ranks paired-sample test indicated an increase in the participants' overall ability to read CXRs (P = 0.017). CONCLUSIONS: Teaching clinicians with a 1-day training course using a systematic approach and a standardised form led to a limited improvement in CXR reading ability.

Left main bronchus compression as a result of tuberculous lymphnode compression of the right-sided airways with right lung volume loss in children.

RATIONALE: The superior mediastinal space is confined by the sterno-manubrium anteriorly and the vertebral column posterior. An abnormal relationship between the superior mediastinal structures may result in compression of the left main bronchus. In patients with right-sided pneumonectomy an exaggerated compensatory response may lead to stretching and compression of the remainder of the intra-thoracic airway. Lymphobronchial TB mimics pneumonectomy when it causes compression of the bronchus intermedius, between nodal lymphnode groups with resultant volume loss in the right lung and displacement of the mediastinum to the right. The left main bronchus may be at risk of compression due to rotation and displacement of the major vessels. AIM: To report pediatric cases of right-sided lymphobronchial TB with volume loss, demonstrate the use of angle measurements to quantify mediastinal dynamics and support a pathogenetic theory for left main bronchus compression. MATERIALS AND METHODS: CT scans in children with TB and right lung volume loss, were compared retrospectively with controls using angle measurements based on descriptions of the aorta-carinal syndrome and the post-pneumonectomy syndrome. The Mann-Whitney U-test was used to compare groups. RESULTS: The "Pulmonary bifurcation angle" between the main pulmonary arteries reached statistical significance (P = 0.025). The "Pulmonary outflow tract rotation" angle (pulmonary trunk with the mid sagittal plane) approached statistical significance (P = 0.078). The left main bronchus ranged from complete obliteration in two patients to 0.7 cm. In 16 of 30 patients the size was reduced to less than 75% of expected. CONCLUSION: In children with right lung volume loss from TB, the compression of the contralateral bronchus is due to narrowing of the pulmonary artery bifurcation angle as the main trunk rotates towards the midline. This is comparable to the post-pneumonectomy syndrome.

Guideline for the management of acute asthma in children: 2013 update.

BACKGROUND: Acute asthma exacerbations remain a common cause of hospitalisation and healthcare utilisation in South African children. AIM: To update the South African paediatric acute asthma guidelines according to current evidence, and produce separate recommendations for children above and below 2 years of age. METHODS: A working group of the South African Childhood Asthma Group was established to review the published literature on acute asthma in children from 2000 to 2012, and to revise the South African guidelines accordingly. RECOMMENDATIONS: Short-acting inhaled bronchodilators remain the first-line treatment of acute asthma. A metered-dose inhaler with spacer is preferable to nebulisation for bronchodilator therapy to treat mild to moderate asthma. Two to four puffs of a short-acting bronchodilator given every 20 - 30 minutes, depending on clinical response, should be given for mild attacks; up to 10 puffs may be needed for more severe asthma. Children with severe asthma or oxygen saturation (SpO2) <92% should receive oxygen and frequent doses of nebulised beta-2-agonists, and be referred to hospital. Nebulised ipratropium bromide (via nebulisation or multidosing via pMDI-spacer combination) should be added if there is a poor response to three doses of ß2-agonist or if the symptoms are severe. Early use of corticosteroids reduces the need for hospital admission and prevents relapse; oral therapy is preferable. Assessment of acute asthma in children below the age of 2 years can be difficult, and other causes of wheezing must be excluded. Treatment of acute asthma in this age group is similar to that of older children. CONCLUSION: Effective therapy for treatment of acute asthma - primarily inhaled short-acting ß2-agonists, oral corticosteroids and oxygen with appropriate delivery systems - should be available in all healthcare facilities and rapidly instituted for treatment of acute asthma in children. ENDORSEMENT: The guideline document was endorsed by the Allergy Society of South Africa (ALLSA), the South African Thoracic Society (SATS), the National Asthma Education Programme (NAEP), the South African Paediatric Association (SAPA) and the South African Academy of Family Practice.

Well-quantified tuberculosis exposure is a reliable surrogate measure of tuberculosis infection.

SETTING: Cape Town, South Africa. OBJECTIVE: To develop a standardized, reliable measure of household tuberculosis (TB) exposure that considers child-specific risk factors. DESIGN: We assessed TB exposure in 536 children. Children were considered Mycobacterium tuberculosis infected if two of three tests of infection were positive. Principal component analysis identified a discrete set of components that collectively described exposure and contributed to a composite contact score. Logistic regression assessed the odds of having M. tuberculosis infection given increasing contact score while controlling for age and past TB treatment. RESULTS: Four components described 68% of data variance: 1) maternal TB and sleep proximity, 2) index case infectivity, 3) duration of exposure, and 4) exposure to multiple index cases. Components were derived from 10 binary questions that contributed to a contact score (range 1-10, median 5, 25th-75th interquartile range [IQR] 4-7). Among children aged 3 months to 6 years with household exposure, the odds of being M. tuberculosis-infected increased by 74% (OR 1.74, 95%CI 1.42-2.12) with each 1-point increase in the contact score. CONCLUSIONS: Well-quantified TB exposure is a good surrogate measure of M. tuberculosis infection in child household contacts in a high-burden setting, and could guide targeted preventive treatment in children at highest risk of M. tuberculosis infection.

Tuberculosis contact investigation in a high-burden setting: house or household?

SETTING: A high tuberculosis (TB) burden setting, South Africa. Two frequently used definitions for 'household' are 1) 'all dwellings on the same plot of land that share the same residential address'; and 2) 'a group of persons who live together in the same dwelling unit and who have the same eating arrangements'. OBJECTIVE: To characterise a household and the outcome of investigations in household child contacts using definition 1 compared to definition 2 during a TB contact investigation. DESIGN: Access to a household (definition 1) was gained via an adult TB case. Children were assessed for TB infection and disease. RESULTS: Household enumeration indicated 25 members of three families living in a main house and a fourth family living in an adjacent structure. Three children were diagnosed with TB and two referred for isoniazid preventive therapy. Families living in the main house shared the main kitchen, while the yard house family used its own kitchen. This household would have been classified as two separate households if definition 2 had been used, and children with TB disease and infection would have been missed. CONCLUSION: The definition of household in TB contact investigation should provide a framework that is broad enough to capture the majority of children at risk.

Tracheostomy home care: in a resource-limited setting.

INTRODUCTION: Home tracheostomy care for children in South Africa dates back to 1989. OBJECTIVE: This study aimed to describe the tracheostomy home programme at Tygerberg Children's Hospital (TCH), situated in a resource-limited setting in Cape Town, South Africa. DESIGN: Retrospective descriptive study. SETTING: Tracheostomy home programme at TCH. The primary care giver is trained by nurses. RESULTS: Fifty-six children (29 girls) were discharged to the home programme (47 to home and 9 to institutions). The median age at tracheostomy was 3 months, mainly for airway obstruction. The mean duration of home care was 26.6 months. Twenty-seven children (43%) were successfully decannulated. Seven children lived in informal housing. The 56 children generated 745 social work contacts. The overall survival was 82%. CONCLUSION: Children with tracheostomies can be safely cared for at home, even in a resource-constrained environment, provided training, appropriate technology and social support services are available.

Bacteriologically confirmed tuberculosis in HIV-infected infants: disease spectrum and survival.

BACKGROUND: The human immunodeficiency virus (HIV) has resulted in epidemiological shifts with an emergence of tuberculosis (TB) amongst HIV-infected women and infants. There are limited data on the TB disease spectrum and outcome amongst HIV-infected infants. OBJECTIVES: We describe the clinical characteristics, treatment and survival of HIV-infected infants with culture-confirmed TB. METHODS: This retrospective hospital-based study from Cape Town, South Africa, used routine laboratory-based surveillance among infants diagnosed with culture-confirmed TB from 1 January 2004 to 31 December 2006. Folder and chest radiographic review were completed and vitality status established. TB was classified as pulmonary, extra-pulmonary or disseminated disease. RESULTS: Of 52 infants, 37 (71.1%) had pulmonary, 2 (3.9%) extra-pulmonary only, 7 (13.5%) pulmonary and extra-pulmonary and 6 (11.5%) disseminated TB. Forty-six (88.5%) were started anti-tuberculosis therapy; 37 (71.2%) received antiretroviral therapy (ART) and 17 (32.7%) died, 10 (19.2%) of whom never started ART. HIV stage 4 disease was associated with death. TB treatment outcome was poorly documented. CONCLUSIONS: TB is associated with advanced HIV disease and high mortality in HIV-infected infants. Missed opportunities for initiation of ART were frequent. Although the effects of young age, TB disease spectrum and HIV co-infection are difficult to distinguish, our findings support the initiation of early ART in HIV-infected infants with TB.

Value of bone marrow biopsy in children with suspected disseminated mycobacterial disease.

BACKGROUND: Disseminated tuberculosis (TB) is a severe form of disease that can be difficult to diagnose or exclude. The diagnostic role of bone marrow biopsy and culture in children with suspected disseminated TB is not clearly defined. METHODOLOGY: In a prospective hospital-based study conducted from November 2007 to October 2008, bone marrow biopsy and culture were performed in all children referred with possible disseminated TB; relevant clinical and laboratory data were reviewed. RESULTS: Thirty-five children were included in the study. An alternative diagnosis was established in 10 (29%) and mycobacterial disease confirmed or probable in 25 (71%). Among those with mycobacterial disease, multiple respiratory specimens provided the best yield (17/25; 68%). Bone marrow histology and/or culture were positive in 5/25 (20%), but were frequently collected after initiation of TB treatment. Blood cultures were positive in only one patient. Mycobacterium tuberculosis accounted for 16/19 (84%) confirmed cases, M.bovis bacille Calmette-Guérin for one, M. avium complex for one, and one was culture-negative. Histology results were available within 24 hours; TB was confirmed exclusively by bone marrow in two cases. CONCLUSION: Bone marrow biopsy is a valuable diagnostic procedure in children with suspected disseminated mycobacterial disease. Ideally, patients should be referred prior to treatment initiation.

The diagnostic value and safety of transbronchial needle aspiration biopsy in children with mediastinal lymphadenopathy.

INTRODUCTION: Anterior mediastinal masses in children can have different causes which includes, Mycobacterium tuberculosis (MTB) or malignant lymphadenopathy. Transbronchial needle aspiration (TBNA) has been described as a safe and effective diagnostic procedure in adult patients with lung cancer. AIM: To describe the use of TBNA as a diagnostic test in children with large subcarinal lymphadenopathy and to determine the safety of the procedure in children. PATIENTS AND METHODS: Prospective descriptive study of children with subcarinal mediastinal lymph nodes who underwent TBNA. The majority of the children were referred due to treatment failure. Children were enrolled if the diagnosis remained unclear after computer tomography of the chest. RESULTS: Thirty patients were enrolled in this study; TBNA was done in 28 patients. A definitive diagnosis was made by TBNA in 54% (n = 15) of patients; MTB lymphadenopathy (n = 13), metastatic nephroblastoma (n = 1), and fibrosing mediastinitis (n = 1). In seven (25%) cases the TBNA was the sole source of the specimens from which the definitive diagnosis was made. No serious complications were encountered during or after the procedure. CONCLUSION: TBNA is a safe procedure in children with mediastinal lymphadenopathy of unknown cause resulting in a definitive diagnosis in 57% of cases. TBNA adds additional value to flexible bronchoscopy in the diagnosis of mediastinal lymphadenopathy in children.