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Children had better treatment outcomes and lower mortality rates than adults., Extensively drug-resistant tuberculosis (XDR TB) has extremely poor treatment outcomes in adults. Limited data are available for children. We report on clinical manifestations, treatment, and outcomes for 37 children (

Background Urogenital tuberculosis (TB) is rare in children and usually develops due to reactivation of the foci in the genitourinary tract after the latency period following initial infection. Urogenital TB in children has no pathognomonic clinical features that can result in overlooking or misdiagnosing this clinical entity. Here, we report important findings regarding the pathogenesis and transmission of TB by using genotyping and whole-genome sequencing (WGS) in a study of renal TB case in a child. Case presentation A 13-year-old boy was admitted to the hospital because of high fever, severe dry cough, flank pain and painful urination. Abdominal ultrasonography and CT revealed an 8 mm calculus in the kidney, and clinical findings were initially interpreted as nephrolithiasis. Nevertheless, due to the atypical clinical presentation of kidney stone disease, additional investigations for possible TB were performed. The QuantiFERON®-TB Gold Plus test was positive, and the Mantoux test resulted in 15 mm of induration, confirming infection with Mycobacterium tuberculosis (Mtb). Chest X-ray was normal. Chest CT revealed calcified intrathoracic lymph nodes. The urine sample tested positive for acid-fast bacilli, and Mtb cultures were obtained from urine and bronchial aspirate samples, resulting in a final diagnosis of intrathoracic lymph node and renal TB. Contact investigation revealed that the child’s father was diagnosed with TB when the child was 1 year old. Genotyping and WGS analysis of Mtb isolates of the child and his father confirmed the epidemiological link and pointed to the latency of infection in the child. Conclusions This case report confirmed the development of active TB from calcified lesions in adolescent after 12 years of exposure, demonstrated the absence of microevolutionary changes in the Mtb genome during the period of latency, and proved the importance of appropriate evaluation and management to prevent the progression of TB infection to active TB disease. The use of WGS provided the ultimate resolution for the detection of TB transmission and reactivation events.

Background An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children. Methods and findings To inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged, In a systematic review and meta-analysis conducted to inform World Health Organization guidelines, Elizabeth Harausz and colleagues investigate different treatment regimens and outcomes for children with multidrug-resistant tuberculosis., Author summary Why was this study done? Treatment for multidrug-resistant tuberculosis (MDR TB) affects 32,000 children per year, requires longer treatment with much more toxic medications than drug-susceptible tuberculosis. Unfortunately, little is know about the optimal treatment for children with MDR TB. This study reviewed treatment and outcome data from children around the world in order to better understand the management of MDR-TB in children. This study also sought to understand the risk factors for poor treatment outcomes in children with MDR-TB. This study informed the World Health Organization guidelines on treatment of MDR-TB in children. What did the researchers do and find? We performed a systematic review and individual patient data meta-analysis on clinical characteristics and treatment outcomes on 975 children from across 18 countries. Children were analyzed in two separate groups, those with bacteriologically confirmed MDR-TB and those who were clinically diagnosed with MDR-TB. We found that, in general, children do well when treated with the second-line MDR-TB medications (78% overall had successful treatment outcomes), despite the fact that there was a high burden of severe disease. Malnutrition and not being treated for HIV (if the child was HIV-positive) during TB treatment significantly increased the risk of poor outcomes. Second-line injectable agents and high-dose isoniazid were associated with treatment success. However, a high proportion of children with non-severe disease who received no second-line injectable agents still did well; therefore, children with non-severe disease may be able to be spared from these toxic medications. What do these findings mean? Consideration should be given to using high-dose isoniazid in treatment regimens, and if children have non-severe disease, the possibility of excluding second-line injectable agents from the treatment regimen should be considered. HIV treatment should be started as soon as is possible, and malnutrition should be aggressively treated.

During last decades an incidence of chronic inflammatory diseases is on the rise in the world. There is an increasing need for drugs, including TNFα inhibitors, to help patients suffering from these diseases. However risk of TB infection and disease increases in patients receiving TNF α therapy. In Latvia there are national guidelines implemented, determining screening for TB infection and disease before initiation and during therapy with TNFα therapy. Aim: To evaluate the conformity of actions by health care providers with national guidelines. Material and methods: Retrospective descriptive cross-sectional study. The data was collected through questionnaires, sent out to all 40 TB/pneumonologists in Latvia. They contain information from patient records of those that were diagnosed with LTBI and/or active TB before or during TNFα therapy, for the period of time from 01.01.2014 to 30.09.2015. Data from questionnaires was abstratcted by coding using binary numbers and letters in the computer program Microsoft Excel. Results: Active TB developed in 4 (3%) out of 136 patients receiving TNFα treatment. TB contact history was identified in 2 of 30 patients diagnosed with LTBI. PPD test was performed in 67 (49%) and IGRA test in 104 (77%) of TNFα treatment candidates, respectively. Majority of latently infected patients (97%) had received preventive treatment with isoniazid, however only 4 (13%) of 30 patients received recomended 9 months therapy. Conclusion: The overall conformity with national guidelines was good. Mostly both tests were not performed due to the logistic difficulties. Improvement of algorythm should be discussed.

OBJECTIVE To perform a comprehensive analysis of case detection, diagnosis and treatment of tuberculosis (TB) in children and adolescents in Latvia, and to evaluate the utility of the current approach. DESIGN A retrospective study of all Latvian children and adolescents diagnosed with TB from 1 January 2011 to 31 December 2014. RESULTS Of 3081 patients diagnosed with TB during 2011-2014, 250 (8%) were aged

Setting: Drug-resistant tuberculosis (TB) is an important public health problem in Latvia. Objective: To document trends, characteristics and treatment outcomes of registered patients with multi-drug-resistant (MDR-) and extensively drug-resistant (XDR-) TB in Latvia from 2000 to 2010. Design: A retrospective national cohort study. Results: Of 1779 patients, 1646 (92%) had MDR- and 133 (8%) XDR-TB. Over 11 years, the proportion of XDR-TB among MDR-TB patients increased from 2% to 18%. Compared to MDR-TB patients, those with XDR-TB were significantly more likely to have failed MDR-TB treatment (OR 8.4, 95%CI 4.3–16.2), have human immunodeficiency virus infection (OR 3.2, 95%CI 1.8–5.7), be illegal drug users (OR 5.7, 95%CI 2.6–11.6) or have had contact with MDR-TB patients (OR 1.9, 95%CI 1.3–2.8). Cure rates for XDR-TB were 50%. Compared with MDR-TB patients, those with XDR-TB had a higher risk of treatment failure (29% vs. 8%, respectively, P < 0.001). Unfavourable treatment outcomes were significantly associated with being male; having smear-positive disease; pulmonary cavities; failure, default or relapse after previous MDR-TB treatment; and a history of incarceration. Conclusion: More MDR-TB in Latvia is now also XDR-TB. This study identified several risk factors for XDR-TB and, for unfavourable treatment outcomes, highlighting the importance of early diagnosis and appropriate management of MDR-/XDR-TB.