Children from Baffin Island have a disproportionate burden of tuberculosis in Canada: data from the Children's Hospital of Eastern Ontario (1998-2008)

<p>Abstract</p> <p>Background</p> <p>The Children's Hospital of Eastern Ontario (CHEO) provides services to children in Baffin Island, through the Baffin Island Pediatric Health Initiative. Tuberculosis (TB) remains a major public health problem in that region. The objective of our study was to describe the origin and clinical characteristics of patients with TB disease at CHEO, since the inception of the Baffin Island Pediatric Health Initiative.</p> <p>Methods</p> <p>All charts with a discharge diagnosis of TB disease during the first 10 years of the Baffin Island program were reviewed. Patients meeting a pre-determined case definition were included in analyses. A standard medical record abstraction form was used for patient data collection.</p> <p>Results</p> <p>Twenty patients met our case definition. Seven (35%) were Canadian-born children from Baffin Island. Seven resided in Ontario, 4 in Quebec, and 2 were visiting from other countries. All 7 children residing in Ontario were born in African countries. Endothoracic disease occurred in 16 patients (80%), including 9 with primary pulmonary TB, and 3 with sputum smear positive "adult-type" disease. Extrathoracic disease was present in 6 children (30%), including 3 with CNS disease. Three children had disease in 2 separate sites.</p> <p>Conclusions</p> <p>While Baffin Island makes up 1% of the hospital catchment population, they contributed 35% of TB patients, and the only TB death. While TB in foreign-born children is due in part to epidemics abroad, the problem in Baffin Island is a reflection of disease burden and transmission within Canada.</p

Preventing the spread of multidrug-resistant tuberculosis and protecting contacts of infectious cases

Prevention of multidrug-resistant and extensively drug-resistant tuberculosis (MDR/XDR-TB) is a top priority for global TB control, given the need to limit epidemic spread and considering the high cost, toxicity and poor treatment outcomes with available therapies. We performed a systematic literature review to evaluate the evidence for strategies to reduce MDR/XDR-TB transmission and disease progression. Rapid detection and timely initiation of effective treatment is critical to rendering MDR/XDR-TB cases non-infectious. The scale-up of rapid molecular testing has transformed the capacity of high-incidence settings to identify and treat patients with MDR/XDR-TB. Optimized infection control measures in hospitals and clinics are critical to protect other patients and healthcare workers, whereas creative measures to reduce transmission within community hotspots require consideration. Targeted screening of high-risk communities may enhance early case-detection and limit the spread of MDR/XDR-TB. Among infected contacts, preventive therapy promises to reduce the risk of disease progression. This is supported by observational cohort studies, but randomized trials are urgently needed to confirm these observations and guide policy formulation. Substantial investment in MDR/XDR-TB prevention and care will be critical if the ambitious global goal of TB elimination is to be realized

Tuberculosis among older adults in Zambia: Burden and characteristics among a neglected group

BACKGROUND: The 2010 Global Burden of Disease estimates show that 57% of all TB deaths globally occurred among adults older than 50 years of age. Few studies document the TB burden among older adults in Southern Africa. We focused on adults older than 55 years to assess the relative TB burden and associated demographic factors. METHODS: A cross sectional nationally representative TB prevalence survey conducted of Zambian residents aged 15 years and above from 66 clusters across all the 10 provinces of Zambia. Evaluation included testing for TB as well as an in-depth questionnaire. We compared survey data for those aged 55 and older to those aged 15-54 years. Survey results were also compared with 2013 routinely collected programmatic notification data to generate future hypotheses regarding active and passive case finding. RESULTS: Among older adults with TB, 30/ 54 (55.6%) were male, 3/27 (11.1%) were HIV infected and 35/54 (64.8%) lived in rural areas. TB prevalence was higher in those aged ≥55 (0.7%) than in the 15-54 age group (0.5%). Males had higher rates of TB across both age groups with 0.7% (15-54) and 1.0% (≥55) compared with females 0.4% (15-54) and 0.6% (≥55). In rural areas, the prevalence of TB was significantly higher among older than younger adults (0.7% vs 0.3%), while the HIV infection rate was among TB patients was lower (11.1% vs 30.8%). The prevalence survey detected TB in 54/7484 (0.7%) of older adults compared to 3619/723,000 (0.5% ) reported in 2013 programmatic data. CONCLUSION: High TB rates among older adults in TB endemic areas justify consideration of active TB case finding and prevention strategies

Adherence to isoniazid preventive therapy in Indonesian children: A quantitative and qualitative investigation

<p>Abstract</p> <p>Background</p> <p>It is recommended that young child contacts of sputum smear positive tuberculosis cases receive isoniazid preventive therapy (IPT) but reported adherence is low and risk factors for poor adherence in children are largely unknown.</p> <p>Methods</p> <p>We prospectively determined rates of IPT adherence in children < 5 yrs in an Indonesian lung clinic. Possible risk factors for poor adherence, defined as ≤3 months prescription collection, were calculated using logistic regression. To further investigate adherence barriers in-depth interviews were conducted with caregivers of children with good and poor adherence.</p> <p>Results</p> <p>Eighty-two children eligible for IPT were included, 61 (74.4%) of which had poor adherence. High transport costs (OR 3.3, 95% CI 1.1-10.2) and medication costs (OR 20.0, 95% CI 2.7-414.5) were significantly associated with poor adherence in univariate analysis. Access, medication barriers, disease and health service experience and caregiver TB and IPT knowledge and beliefs were found to be important determinants of adherence in qualitative analysis.</p> <p>Conclusion</p> <p>Adherence to IPT in this setting in Indonesia is extremely low and may result from a combination of financial, knowledge, health service and medication related barriers. Successful reduction of childhood TB urgently requires evidence-based interventions that address poor adherence to IPT.</p

High caseload of childhood tuberculosis in hospitals on Java Island, Indonesia: a cross sectional study

Background Childhood tuberculosis (TB) has been neglected in the fight against TB. Despite implementation of Directly Observed Treatment Shortcourse (DOTS) program in public and private hospitals in Indonesia since 2000, the burden of childhood TB in hospitals was largely unknown. The goals of this study were to document the caseload and types of childhood TB in the 0-4 and 5-14 year age groups diagnosed in DOTS hospitals on Java Island, Indonesia. Methods Cross-sectional study of TB cases recorded in inpatient and outpatient registers of 32 hospitals. Cases were analyzed by hospital characteristics, age groups, and types of TB. The number of cases reported in the outpatient unit was compared with that recorded in the TB register. Results Of 5,877 TB cases in the inpatient unit and 15,694 in the outpatient unit, 11% (648) and 27% (4,173) respectively were children. Most of the childhood TB cases were under five years old (56% and 53% in the inpatient and outpatient clinics respectively). The proportion of smear positive TB was twice as high in the inpatient compared to the outpatient units (15.6% vs 8.1%). Extra-pulmonary TB accounted for 15% and 6% of TB cases in inpatient and outpatient clinics respectively. Among children recorded in hospitals only 1.6% were reported to the National TB Program. Conclusion In response to the high caseload and gross under-reporting of childhood TB cases, the National TB Program should give higher priority for childhood TB case management in designated DOTS hospitals. In addition, an international guidance on childhood TB recording and reporting and improved diagnostics and standardized classification is require

Risk of latent tuberculosis infection in children living in households with tuberculosis patients: a cross sectional survey in remote northern Lao People's Democratic Republic

ABSTRACT: BACKGROUND: Tuberculosis is highly prevalent in Laos (289 per 100,000). We evaluated the risk of latent tuberculosis infection (LTBI) among children (0-15 years) living with tuberculosis patients in rural northern Laos. METHODS: In a cross sectional survey of 30 randomly selected villages, 72 tuberculosis patients were traced and their 317 contacts (148 were children) investigated using a questionnaire, a tuberculin skin tests (positive: <= 10mm), a 3-day sputum examination for acid-fast bacilli (AFB), and chest radiography. RESULTS: None of the 148 contact-children received prophylaxis, one had cervical tuberculosis; the risk for LTBI was 31.0%. Awareness of the infectiousness of tuberculosis was low among patients (31%) and their contacts (31%), and risky behavior was common. After multivariate logistic analysis, increased LTBI was found in children with contact with sputum positive adults (OR: 3.3, 95% CI: 1.4-7.7), patients highly positive sputum prior to treatment (AFB <2+; OR: 4.7, 95% CI: 1.7-12.3), and living in ethnic minorities (OR: 5.4, 95% CI: 2.2-13.6). CONCLUSION: The study supports the importance of contact tracing in remote settings with high TB prevalence. Suggestions to improve the children's detection rate, the use of existing guidelines, chemoprophylaxis of contact-children and the available interventions in Laos are discussed. Improving education and awareness of the infectiousness of TB in patients is urgently needed to reduce TB transmissio

Clinical presentation and outcome of Tuberculosis in Human Immunodeficiency Virus infected children on anti-retroviral therapy

<p>Abstract</p> <p>Background</p> <p>The tuberculosis (TB) and human immunodeficiency virus (HIV) epidemics are poorly controlled in sub-Saharan Africa, where highly active antiretroviral treatment (HAART) has become more freely available. Little is known about the clinical presentation and outcome of TB in HIV-infected children on HAART.</p> <p>Methods</p> <p>We performed a comprehensive file review of all children who commenced HAART at Tygerberg Children's Hospital from January 2003 through December 2005.</p> <p>Results</p> <p>Data from 290 children were analyzed; 137 TB episodes were recorded in 136 children; 116 episodes occurred before and 21 after HAART initiation; 10 episodes were probably related to immune reconstitution inflammatory syndrome (IRIS). The number of TB cases per 100 patient years were 53.3 during the 9 months prior to HAART initiation, and 6.4 during post HAART follow-up [odds ratio (OR) 16.6; 95% confidence interval (CI) 12.5–22.4]. A positive outcome was achieved in 97/137 (71%) episodes, 6 (4%) cases experienced no improvement, 16 (12%) died and the outcome could not be established in 18 (13%). Mortality was less in children on HAART (1/21; 4.8%) compared to those not on HAART (15/116; 12.9%).</p> <p>Conclusion</p> <p>We recorded an extremely high incidence of TB among HIV-infected children, especially prior to HAART initiation. Starting HAART at an earlier stage is likely to reduce morbidity and mortality related to TB, particularly in TB-endemic areas. Management frequently deviated from standard guidelines, but outcomes in general were good.</p

QuantiFERON®-TB gold in-tube performance for diagnosing active tuberculosis in children and adults in a high burden setting.

To determine whether QuantiFERON®-TB Gold In-Tube (QFT) can contribute to the diagnosis of active tuberculosis (TB) in children in a high-burden setting and to assess the performance of QFT and tuberculin skin test (TST) in a prospective cohort of TB suspect children compared to adults with confirmed TB in Tanzania. Sensitivity and specificity of QFT and TST for diagnosing active TB as well as indeterminate QFT rates and IFN-γ levels were assessed in 211 TB suspect children in a Tanzanian district hospital and contrasted in 90 adults with confirmed pulmonary TB. Sensitivity of QFT and TST in children with confirmed TB was 19% (5/27) and 6% (2/31) respectively. In adults sensitivity of QFT and TST was 84% (73/87) and 85% (63/74). The QFT indeterminate rate in children and adults was 27% and 3%. Median levels of IFN-γ were lower in children than adults, particularly children <2 years and HIV infected. An indeterminate result was associated with age <2 years but not malnutrition or HIV status. Overall childhood mortality was 19% and associated with an indeterminate QFT result at baseline. QFT and TST showed poor performance and a surprisingly low sensitivity in children. In contrast the performance in Tanzanian adults was good and comparable to performance in high-income countries. Indeterminate results in children were associated with young age and increased mortality. Neither test can be recommended for diagnosing active TB in children with immature or impaired immunity in a high-burden setting

Characteristics and Programme-Defined Treatment Outcomes among Childhood Tuberculosis (TB) Patients under the National TB Programme in Delhi

Childhood tuberculosis (TB) patients under India's Revised National TB Control Programme (RNTCP) are managed using diagnostic algorithms and directly observed treatment with intermittent thrice-weekly short-course treatment regimens for 6–8 months. The assignment into pre-treatment weight bands leads to drug doses (milligram per kilogram) that are lower than current World Health Organization (WHO) guidelines for some patients.The main aim of our study was to describe the baseline characteristics and treatment outcomes reported under RNTCP for registered childhood (age <15 years) TB patients in Delhi. Additionally, we compared the reported programmatic treatment completion rates between children treated as per WHO recommended anti-TB drug doses with those children treated with anti-TB drug doses below that recommended in WHO guidelines.For this cross-sectional retrospective study, we reviewed programme records of all 1089 TB patients aged <15 years registered for TB treatment from January to June, 2008 in 6 randomly selected districts of Delhi. WHO disease classification and treatment outcome definitions are used by RNTCP, and these were extracted as reported in programme records.Among 1074 patients with records available, 651 (61%) were females, 122 (11%) were <5 years of age, 1000 (93%) were new cases, and 680 (63%) had extra-pulmonary TB (EP-TB)—most commonly peripheral lymph node disease [310 (46%)]. Among 394 pulmonary TB (PTB) cases, 165 (42%) were sputum smear-positive. The overall reported treatment completion rate was 95%. Similar reported treatment completion rates were found in all subgroups assessed, including those patients whose drug dosages were lower than that currently recommended by WHO. Further studies are needed to assess the reasons for the low proportion of under-5 years of age TB case notifications, address challenges in reaching all childhood TB patients by RNTCP, the accuracy of diagnosis, and the clinical validity of reported programme defined treatment completion

Standardized methods for enhanced quality and comparability of tuberculous meningitis studies

Tuberculous meningitis remains a major cause of death and disability in tuberculosis endemic areas, especially in young children and immunocompromised adults. Research aimed at improving outcomes is hampered by poor standardization, which limits study comparison and the generalizability of results. We propose standardized methods for the conduct of tuberculous meningitis clinical research that were drafted at an international tuberculous meningitis research meeting organized by the Oxford University Clinical Research Unit in Vietnam. We propose a core dataset including demographic and clinical information to be collected at study enrolment, important aspects related to patient management and monitoring, and standardized reporting of patient outcomes. The criteria proposed for the conduct of observational and intervention tuberculous meningitis studies should improve the quality of future research outputs, facilitate multi-centre studies and meta-analyses of pooled data, and could provide the foundation for a global tuberculous meningitis data repository