Tuberculosis (TB) remains a leading cause of death in children globally. It is recognized that human immunodeficiency virus (HIV) infection increases the risk of developing TB, but our understanding of the impact of HIV on risk of mortality for children treated for TB is limited. We aimed to identify predictors of mortality in children treated for drug-susceptible TB.A retrospective analysis of all children (<15 years of age) routinely treated between 2005 and 2012 for drug-susceptible TB in Cape Town was conducted using the programmatic electronic TB treatment database. Survival analysis using Cox regression was used to estimate hazard ratios for death. Logistic regression was used to estimate the odds of unfavorable outcomes.Of 29519 children treated for and notified with TB over the study period, <1% died during TB treatment and 89.5% were cured or completed treatment. The proportion of children with known HIV status increased from 13% in 2005 to 95% in 2012. Children aged <2 years had an increased hazard of death (adjusted hazard ratio [aHR], 3.13; 95% confidence interval [CI], 1.78-5.52) and greater odds of unfavorable outcome (adjusted odds ratio [aOR], 1.44; 95% CI, 1.24-1.66) compared with children aged 10-14 years. HIV-infected children had increased mortality compared to HIV-negative children (aHR, 6.85; 95% CI, 4.60-10.19) and increased odds of unfavorable outcome (aOR, 2.01; 95% CI, 1.81-2.23). Later year of TB treatment was a protective predictor for both mortality and unfavorable outcome.We demonstrate a dramatic improvement in HIV testing in children with TB over time and excellent overall treatment outcomes. HIV infection and young age were associated with increased risk of death and unfavorable outcome.
Treatment decision algorithms for childhood tuberculosis For most adults, the diagnosis of TB is made by the individual coughing sputum into a pot and with the sample then evaluated in a laboratory to look for the TB bacteria (or genetic components of the bacteria). However, because children tend to have forms of TB that have fewer bacteria, and because younger children are not able to cough up a sputum sample on demand, it is rare to diagnose TB in children using this approach. Instead, health workers must weigh up the clinical symptoms of the child, findings from the examination and impressions from the chest x-ray and make a decision. James Seddon, Reader in Global Child Health at Imperial College London, discusses the development of treatment decision algorithms for childhood tuberculosis.
"Making the Case for All-Oral, Shorter Regimens for Children with Drug-Resistant Tuberculosis." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Over the last 10 years, interest in pediatric tuberculosis (TB) has increased dramatically, together with increased funding and research. We have a better understanding of the burden of childhood TB as well as a better idea of how to diagnose it. Our appreciation of pathophysiology is improved and with it investigators are beginning to consider pediatric TB as a heterogeneous entity, with different types and severity of disease being treated in different ways. There have been advances in how to treat both TB infection and TB disease caused by both drug-susceptible as well as drug-resistant organisms. Two completely novel drugs, bedaquiline and delamanid, have been developed, in addition to the use of older drugs that have been re-purposed. New regimens are being evaluated that have the potential to shorten treatment. Many of these drugs and regimens have first been investigated in adults with children an afterthought, but increasingly children are being considered at the outset and, in some instances studies are only conducted in children where pediatric-specific issues exist.
Currently only limited data exist regarding the availability and clinical use of molecular and immunological tests for tuberculosis (TB) in the European setting.Web-based survey of Paediatric-Tuberculosis-Network-European-Trialsgroup (ptbnet) and Tuberculosis-Network-European-Trialsgroup (TBnet) members conducted June to December 2013. Both networks comprise clinicians, microbiologists, epidemiologists and researchers predominately based in Europe.191 healthcare professionals from 31 European countries participated. Overall, 26.8% of respondents did not have access to the Xpert MTB/RIF assay; only 44.6% had access to the assay in-house. However, a substantial proportion had access to other commercial and/or non-commercial PCR-based assays for TB (68.8% and 31.8%, respectively). Only 6.4% did not have access to any PCR-based assays for TB. A large proportion of participants with access to the Xpert MTB/RIF assay had used it for the analysis of non-respiratory samples [pleural fluid: 36.5%, gastric aspirates: 34.7%, cerebrospinal fluid: 34.7%, stool samples: 4.3%, blood/serum: 2.6%, 'other samples' (which included biopsy/tissue samples, lymph node aspirates, joint aspirates and urine samples): 16.5%]. Regarding interferon-gamma release assays, a greater proportion of respondents had access to the QuantiFERON-TB Gold assay (84.7%) than to the T-SPOT.TB assay (52.2%).Both immunological and molecular TB tests are widely available across Europe. The QuantiFERON-TB Gold assay is more widely used than the T-SPOT.TB assay, which may reflect the difficulties of integrating an ELISPOT assay into the routine laboratory setting. Although Xpert MTB/RIF assays are optimised and solely licensed for the analysis of sputum samples, in clinical practice they are commonly used for non-respiratory samples. Further research is needed to establish how current molecular TB tests impact on patient care and outcome in the routine clinical setting.
The number of children globally who develop drug-resistant tuberculosis is unclear, in part due to diagnostic challenges and limited resistance testing, and in part because recording and reporting is not comprehensive. Large numbers of children, however, are exposed to drug resistant bacilli each year and it is clear that the very young and those immune-compromised are vulnerable to developing disease. Few studies have looked at the progression from exposure to infection or from infection to disease in the child contacts of adults with drug-resistant tuberculosis. It is uncertain which factors influence this progression and also whether any interventions can prevent it. Finally, few studies have analysed the presentation, treatment and outcome of children with disease. This thesis starts by reviewing what is published regarding drug-resistant tuberculosis in children. This includes systematic reviews of the management of children exposed to drug resistant tuberculosis as well as the management of those with multi drug-resistant tuberculosis disease. It reviews what is known regarding the second-line tuberculosis drugs in children and then clarifies the definitions that are used throughout the rest of the work. The thesis then systematically examines each of the stages from infection to disease with a series of inter-related studies. The first study attempts to quantify the burden of drug resistance in the context that the work is carried out. The following study investigates the risk factors for infection and prevalent disease in children exposed to a multi drug-resistant tuberculosis source case. This is followed by two studies which explore the transmission of drug-resistant bacilli from adults to children. The identification and referral patterns and obstacles to referral for exposed children are examined through operational studies that include qualitative and quantitative components. A descriptive cohort study assesses the toxicity and efficacy of a standardised preventive treatment regimen given to child contacts. The final part of the thesis includes a series of studies to investigate the treatment of drug resistant tuberculosis disease in children and the adverse effects of the second-line medications.
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