Mycobacterium tuberculosis transmission is not related to household genotype in a setting of high endemicity.

Among the different strains of Mycobacterium tuberculosis, Beijing has been identified as an emerging genotype. Enhanced transmissibility provides a potential mechanism for genotype selection. This study evaluated whether the Beijing genotype is more readily transmitted than other prevalent genotypes to children in contact with an adult tuberculosis (TB) index case in the child's household. We conducted a prospective, community-based study at two primary health care clinics in Cape Town, South Africa, from January 2003 through December 2004. Bacteriologically confirmed new adult pulmonary TB cases were genotyped by IS6110 DNA fingerprinting; household contacts less than 5 years were traced and screened for M. tuberculosis infection and/or disease. A total of 187 adult index cases were identified from 174 households with children aged less than 5 years. Of 261 child contacts aged 0 to 5 years, 219 (83.9%) were completely evaluated and the isolate from the index case was successfully genotyped. M. tuberculosis infection (induration of >or=10 mm by Mantoux tuberculin skin test) was documented in 118/219 (53.9%) children; 34 (15.5%) had radiographic signs suggestive of active TB. There was no significant difference in the ratio of infected children among those exposed to the Beijing genotype (51/89; 57.3%) and those exposed to non-Beijing genotypes (55/115; 47.8%) (odds ratio, 1.5; 95% confidence interval, 0.8 to 2.7). Genotyping was successful for six children diagnosed with active TB; the isolates from only two children had IS6110 fingerprints that were identical to the IS6110 fingerprint of the isolate from the presumed index case. We found no significant association between the M. tuberculosis genotype and transmissibility within the household. However, undocumented M. tuberculosis exposure may have been a major confounding factor in this setting with a high burden of TB.

High prevalence of Mycobacterium tuberculosis infection and disease in children and adolescents with type 1 diabetes mellitus.

SETTING: Western Cape Province, South Africa. OBJECTIVES: To describe the prevalence of tuberculosis (TB) infection and disease in children with type 1 diabetes and to investigate the association between glycaemic control and prevalence of TB infection and disease. DESIGN: Cross-sectional hospital-based study conducted at two public referral hospitals. All children and adolescents (aged <21 years) with type 1 diabetes underwent a Mantoux tuberculin skin test (>or=10 mm classified as Mycobacterium tuberculosis infection), measurement of glycosylated haemoglobin and a chest radiograph. Patients with symptoms suggestive of TB were investigated using mycobacterial culture. Radiologically and/or bacteriologically confirmed disease was classified as TB disease. RESULTS: Of 291 eligible patients, 258 (88.7%) were included (58% female). The prevalence of M. tuberculosis infection was 29.8% (95%CI 24.2-35.4); nine patients were diagnosed with prevalent TB disease (point prevalence disease 3488 per 100,000 population). Poor glycaemic control (hazard ratio 1.39, 95%CI 1.18-1.63 per unit increase in glycated haemoglobin [HbA1c]) and contact with a TB source case (P = 0.0011) was associated with prevalent TB disease. CONCLUSIONS: There is a high prevalence of TB disease in diabetic children and adolescents in this setting. Routine TB screening of children with type 1 diabetes may be indicated in settings highly endemic for TB. Preventive treatment should be considered for diabetic children with proof of TB exposure and/or infection.

Consensus statement on the revised World Health Organization recommendations for BCG vaccination in HIV-infected infants.

This document outlines the consensus agreement from the Union's BCG Working Group regarding BCG vaccination in HIV-infected infants, in response to recently revised World Health Organization (WHO) guidelines, which make HIV infection in infants a full contraindication to bacille Calmette-Guérin (BCG) vaccination. BCG is one of the most widely given vaccines globally and is safe in immunocompetent individuals. Recent evidence shows that HIV-infected infants who were routinely vaccinated with BCG at birth, when asymptomatic, and who later developed AIDS, are at high risk of developing disseminated BCG disease (estimated incidence 407-1300 per 100 000). The document outlines requirements to implement selective BCG vaccination strategies in infants born to HIV-infected women and strategies to reduce the risk of vertical HIV transmission and disseminated BCG disease in infants.

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.

Esophageal stent improves ventilation in a child with a broncho-esophageal fistula caused by Mycobacterium tuberculosis.

The deployment of an esophageal stent to aid in the ventilation of a child who had developed an acquired broncho-esophageal fistula caused by Mycobacterium tuberculosis (MTB) is described. The 12-month-old boy presented with respiratory failure requiring ventilation. The air leak via the fistula led to inadequate mechanical ventilation. The deployment of the stent resulted in successful ventilation, closure of the fistula, and eventual successful treatment.

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.

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 bacteriologic yield in children with intrathoracic tuberculosis.

This report documents the bacteriologic yield in children who received treatment for intrathoracic tuberculosis in an area where it is highly endemic. A total of 307 children were included in the study, and bacteriologic confirmation was achieved in 122 (62.2%) of 196 children from whom specimens were collected. The lowest bacteriologic yield was recorded for the 69 children with uncomplicated lymph node disease (24 [34.8%] had bacteriologic confirmation). The high overall bacteriologic yield indicates the need to reassess the value of bacteriology-based approaches to diagnosis of intrathoracic tuberculosis in children, particularly in areas of endemicity where they frequently present with advanced disease.

Bacille Calmette-Guérin vaccine-induced disease in HIV-infected and HIV-uninfected children.

BACKGROUND: Bacille Calmette-Guérin (BCG)--a live, attenuated vaccine--is routinely given to neonates in settings where tuberculosis is endemic, irrespective of human immunodeficiency virus (HIV) exposure. HIV-infected infants and other immunodeficient infants are at risk of BCG-related complications. We report the presentation, treatment, and mortality of children who develop BCG disease, with emphasis on HIV-infected children. In addition, we present a revised classification of BCG disease in children and propose standard diagnostic and management guidelines. METHODS: This retrospective, hospital-based study was conducted in the Western Cape Province, South Africa. Mycobacterium tuberculosis complex isolates recovered from children aged <13 years during the period of August 2002 through January 2005 were speciated by polymerase chain reaction to confirm Mycobacterium bovis BCG. Clinical data were collected through medical file review. BCG disease was classified according to standard and revised disease classifications. Mortality was assessed at the end of the study period. RESULTS: BCG disease was diagnosed in 25 children; 22 (88%) had local disease, and 8 (32%) had distant or disseminated disease; 5 children (20%) had both local and distant or disseminated disease. Seventeen children were HIV infected; 2 children had other immunodeficiencies. All 8 children with distant or disseminated disease were immunodeficient; 6 were HIV infected. The mortality rate was 75% for children with distant or disseminated disease. CONCLUSIONS: BCG vaccination poses a risk to infants perinatally infected with HIV and to other primary immunodeficient children. The proposed pediatric BCG disease classification reflects clinically relevant disease categories in HIV-infected children. The suggested diagnostic and treatment guidelines should improve existing case management and surveillance. Prospective evaluation of management strategies for BCG disease in HIV-infected and HIV-uninfected children is essential.

Management of childhood asthma.

The guidelines for the management of childhood asthma have evolved from recommendations by experts to being evidence-based as a result of better understanding of the pathophysiology of asthma, awareness of the heterogeneity and early onset of childhood asthma and a new approach to the pharmacological management. While there are reasonably good evidence-based guidelines for the treatment of asthma in children aged over 5 years, there is a paucity of data for preschool children for the most appropriate management. Most guidelines include recommendations on diagnosis of asthma in children and pharmacological treatment according to the severity of the asthma. Environmental control is an important cornerstone of care, and allergen avoidance should be recommended for children with asthma who are known to be sensitised to the allergen. Environmental tobacco smoke remains an important trigger for worsening asthma in all children, and their parents must be encouraged to give up the habit. Educating children with asthma and their care givers on the disease and proper treatment is another vital element in the management of asthma. There remains a major problem with ensuring the implementation of guidelines in most countries. A care gap thus exists between best practice and common practice. The impact on asthma morbidity of developing and implementing guidelines requires appropriate study.

The spectrum of disease in children treated for tuberculosis in a highly endemic area.

BACKGROUND: Children contribute a substantial proportion of the global tuberculosis (TB) caseload, particularly in endemic areas, where little is known about their spectrum of disease. OBJECTIVE: To document the complete disease spectrum, with relevant age- and HIV-related differences, in children treated for TB in a highly endemic community. METHODS: A prospective descriptive study was conducted from February 2003 to October 2004 at five primary health care clinics in Cape Town, South Africa, including all children (< 13 years of age) treated for TB. RESULTS: In total, 439 children received anti-tuberculosis treatment. The spectrum of disease included 85 (19.4%) 'not TB', 307 (86.7%) intra-thoracic TB and 72 (20.3%) extra-thoracic TB (25 [5.7%] with co-existing intra- and extra-thoracic disease were included in both groups). In non-HIV-infected children, disseminated (miliary) disease (9/11, 81.8%) and tuberculous meningitis (TBM) (10/13, 76.9%) were predominantly documented in children < 3 years of age. In HIV-infected children, complicated Ghon focus and disseminated (miliary) disease were significantly more common (6/25, 24.0%) than in non-HIV-infected children (12/414, 2.9%) (OR 10.9, 95% CI 3.2-35.9). CONCLUSION: This study describes the complete disease spectrum observed in children treated for TB in a highly endemic area. Children suffered significant morbidity, with most severe disease recorded in very young and/or HIV-infected children.

Adherence to anti-tuberculosis chemoprophylaxis and treatment in children.

SETTING: Limited data exist on adherence to anti-tuberculosis treatment and chemoprophylaxis in children in high-burden settings. OBJECTIVE: To determine the adherence to anti-tuberculosis chemoprophylaxis and treatment in children evaluated as household contacts of adult pulmonary tuberculosis (PTB) cases. METHODS: A retrospective study, conducted from January 1996 to September 2003, in suburban Cape Town, South Africa, with a high TB incidence. A folder search was done on all children <5 years of age identified as household contacts of adult PTB cases between 1996 and 2003. Data on screening for TB and adherence to prescribed therapy in child contacts were analysed. RESULTS: Three hundred and sixty-one contact episodes with 243 adult PTB cases were identified in 335 children. The median age was 25 months. Adherence to anti-tuberculosis treatment was significantly better than adherence to chemoprophylaxis (82.6% vs. 44.2%; OR 6.83; 95%CI 3.6-12.96). Adherence to a 3-month chemoprophylaxis regimen of isoniazid and rifampicin (3HR) was significantly better than adherence to a 6-month chemoprophylaxis regimen of isoniazid only (69.6% vs. 27.6%; OR 4.97; 95%CI 2.40-10.36). CONCLUSIONS: Although adherence to treatment was good, adherence to unsupervised chemoprophylaxis was poor. We recommend that shorter chemoprophylaxis regimens such as 3HR should be considered to improve adherence, but further studies are required.

The burden of childhood tuberculosis and the accuracy of community-based surveillance data.

BACKGROUND: Inadequate surveillance and diagnostic difficulties compromise the quality of epidemiological data on childhood tuberculosis (TB). OBJECTIVE: To document the incidence of childhood TB and to evaluate the accuracy of community-based surveillance data in a high-burden setting. METHODS: This prospective observational study was conducted from February 2003 to October 2004 at five primary health care clinics in Cape Town, South Africa. Comprehensive surveillance was done to ensure that all children <13 years of age treated for TB were included. RESULTS: During the study period, 443 children (<13 years of age) received anti-tuberculosis treatment, of whom 389 (87.8%) were recorded in the TB treatment register. The TB incidence calculated from the TB treatment register was 441/100,000/year amongst children and 845/100,000/year amongst adults. Fifty-four children treated for TB were not recorded in the TB treatment register, including 21/28 (75%) children with severe disease. DISCUSSION: Children <13 years of age contributed 13.7% of the total TB burden, but experienced more than half (52.2%) the TB incidence recorded in adults. Community-based surveillance data excluded the majority of children with severe disease. The accuracy of surveillance data is an important consideration when describing the epidemiology of childhood TB or measuring the success of public health interventions.

Pasteurella multocida lung and liver abscess in an immune-competent child.

We report on a 20-month-old infant with a complicated lung and liver abscess caused by Pasteurella multocida after the child had been in close contact with a domestic cat. Surgical drainage confirmed lung and liver abscesses connected to each other, with involvement of the diaphragm.

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.

Criteria used for the diagnosis of childhood tuberculosis at primary health care level in a high-burden, urban setting.

BACKGROUND: Children contribute a significant proportion of the total tuberculosis (TB) case load in high-burden settings and present a major diagnostic challenge. OBJECTIVE: To document the criteria used at primary health care level to diagnose childhood TB in a high-burden, urban setting. METHODS: This retrospective descriptive study was conducted at two primary health care clinics in Cape Town, South Africa. Information on all children (<15 years of age) entered into the TB register from January 2002 through December 2003 was retrieved for analysis. RESULTS: During the study period, 1277 cases of TB were entered into the TB register, of which 268 (21.0%) were children. Information on 256 (95.5%) children was available for analysis. The majority (206, 80.5%) had intrathoracic TB, of whom 107 (51.5%) had uncomplicated lymph node disease, 79 (38.3%) complicated lymph node disease, 8 (3.9%) a pleural effusion and 12 (5.8%) adult-type cavitating disease. According to modified WHO criteria, the diagnosis of TB was confirmed in 27 (10.5%), probable in 193 (75.4%) and suspect in 36 (14.1%). DISCUSSION: The diagnostic criteria used at primary health care level demonstrated good agreement with current guidelines, but depended heavily on chest radiograph interpretation.

The burden of childhood tuberculosis: a public health perspective.

The burden of childhood tuberculosis (TB) reflects recent transmission within a community and the level of TB control achieved within the adult (maintenance host) population. Children contribute little to the maintenance of the TB epidemic, but they may suffer severe TB-related morbidity and mortality. This review describes the main determinants of the burden of childhood TB within a particular community. Basic infectious disease principles identify the community, and not the individual, as the central entity that sustains an epidemic. The prevalence of TB is determined by the community's exposure to Mycobacterium tuberculosis, and their vulnerability to developing disease following exposure. The main variables that influence both exposure and vulnerability are discussed. Multiple variables are linked to poverty, and it is their cumulative effect, rather than the exact degree of poverty, that seems most important. Diligent contact tracing and the use of preventive chemotherapy will reduce the TB-related suffering of children. The burden of childhood TB, however, is a reflection of our ability to control the epidemic; this remains the ultimate challenge. Current efforts to control the TB epidemic aim to reduce transmission by treating sputum smear-positive adults, while very little emphasis is placed on reducing the vulnerability of high-burden communities. Successful control of the epidemic is the most effective way to reduce the burden of childhood TB, but this will require a holistic approach that acknowledges the importance of sustainable poverty alleviation.

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.

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.