[Consensus-Based Guidelines for Diagnosis, Prevention and Treatment of Tuberculosis in Children and Adolescents - A Guideline on Behalf of the German Society for Pediatric Infectious Diseases (DGPI)]. / S2k-Leitlinie zur Diagnostik, Prävention und Therapie der Tuberkulose im Kindes- und Jugendalter.

Recently, epidemiological data shows an increase of childhood tuberculosis in Germany. In addition to this, drug resistant tuberculosis becomes more frequent. Therefore, diagnosis, prevention and therapy in childhood and adolescence remain a challenge. Adult guidelines do not work for children, as there are age specific differences in manifestation, risk of progression and diagnostic as well as therapeutic pathways.The German Society for Pediatric Infectious Diseases (DGPI) has initiated a consensus-based (S2k) process and completed a paediatric guideline in order to improve and standardize care for children and adolescents with tuberculosis exposure, infection or disease.Updated dosage recommendations take age dependant pharmacokinetics in the treatment of drug sensitive but also drug resistant tuberculosis in account. In addition to this, there is a detailed chapter on perinatal exposure and disease as well as extrapulmonary manifestations.

Predictors of TB disease in HIV-exposed children from Southern Africa.

BACKGROUND: P1041 was a randomised, placebo-controlled isoniazid prophylaxis trial in South Africa. We studied predictors for TB in HIV-exposed children participating in the P1041 trial.METHODS: We included data from entry until Week 108. Predictors considered were type of housing, overcrowding, age, sex, ethnicity, tobacco exposure, weight-for-age percentile Z-score (WAZ), CD4%, viral load (VL), antiretroviral therapy (ART) and number of household smokers.RESULTS: Of 543 HIV-positive (HIV+) and 808 HIV-exposed uninfected (HEU) infants at entry, median age was 96 days (interquartile range: 92-105). Of 1,351 caregivers, 125 (9%) had a smoking history, and 62/1,351 reported current smoking. In 594/1,351 (44%) households, there was at least one smoker. Smoking caregivers consumed 1-5 cigarettes daily. In the HIV+ cohort, significant baseline TB predictors after adjusting covariates were as follows: WAZ (adjusted hazard ratio [aHR] 0.76, P = 0.002) and log10 HIV RNA copies/ml (aHR 1.50, P = 0.009). Higher CD4% (aHR 0.88, P = 0.002) and ART (aHR 0.50, P = 0.006) were protective. In the HEU cohort, smoking exposure was associated with reduced TB-free survival on univariate analysis, but not after adjustment in the multivariate model.CONCLUSION: Low WAZ and high VL were strong predictors of TB disease or death. Rising CD4 percentage and being on ART were protective in the HIV+ cohort.

Source case identification in HIV-exposed infants and tuberculosis diagnosis in an isoniazid prevention study.

BACKGROUND: Identifying source cases of children exposed to tuberculosis (TB) is challenging. We examined the time-point of obtaining contact information of TB source cases in human immunodeficiency virus (HIV) infected and HIV-exposed uninfected (HEU) children in a randomised, placebo-controlled trial of pre-exposure to isoniazid prophylaxis. METHODS: A total of 543 HIV-infected and 808 HEU infants without TB exposure aged 3-4 months were enrolled between 2004 and 2008. At 3-monthly follow-up, infants were evaluated for TB and care givers were asked about new TB exposure. RESULTS: In total, 128 cases of TB disease and 40 deaths were recorded among 19% (105/543) of the HIV-infected and 8% (63/808) of the HEU children; 229 TB contact occasions were reported in 205/1351 (15%) children, of which 83% (189/229) were in the household. Of the 189 household contacts, 108 (53%) underwent microbiological evaluations; 81% (87/108) were positive. HIV-infected and HEU infants had similar frequencies of TB contact: in 48% of infants with definite TB, 58% with probable TB and 43% with possible TB. Of 128 children diagnosed with TB, a TB contact was identified for 59. Of these, 29/59 (49%) were identified at or after the child's TB diagnosis. CONCLUSION: TB source cases are often identified at or after a child's TB diagnosis. More effort is required for earlier detection.