Many clinicians regard tuberculosis as an adult pulmonary disease, but tuberculosis (TB) is a major cause of disease, both pulmonary and extrapulmonary, and death in young children from TB-endemic countries, especially in areas affected by poverty, social disruption, and human immunodeficiency virus (HIV) infection. This article reviews the disease burden and the natural history of disease in children with TB. It also provides guidance regarding the diagnosis, treatment, and prevention of TB in children.

Background Multidrug-resistant tuberculosis (MDR-TB) threatens to reverse recent reductions in global tuberculosis (TB) incidence. Although children under 15 years of age constitute >25% of the worldwide population, the global incidence of MDR-TB disease in children has never been quantified. Methods Our approach for estimating regional and global annual incidence of MDR-TB in children required development of two models: one to estimate the setting-specific risk of MDR-TB among child TB cases, and a second to estimate the setting-specific incidence of TB disease in children. The model for MDR-TB risk among children with TB required a systematic literature review. We multiplied the setting-specific estimates of MDR-TB risk and TB incidence to estimate regional and global incidence of MDR-TB disease in children in 2010. Findings We identified 3,403 papers, of which 97 studies met inclusion criteria for the systematic review of MDR-TB risk. Thirty-one studies reported the risk of MDR-TB among both children and treatment-naïve adults with TB and were used for evaluating the linear association between MDR-TB risk in these two patient groups. We found that the setting-specific risk of MDR-TB was nearly identical in children and treatment-naïve adults with TB, consistent with the assertion that MDR-TB in both groups reflects the local risk of transmitted MDR-TB. Applying these calculated risks, we estimated that around 1,000,000 (95% Confidence Interval: 938,000 – 1,055,000) children developed TB disease in 2010, among whom 32,000 (95% Confidence Interval: 26,000 – 39,000) had MDR-TB. Interpretation Our estimates highlight a massive detection gap for children with TB and MDR-TB disease. Future estimates can be refined as more and better TB data and new diagnostic tools become available.

Background. Similar to poliovirus, enterovirus type 71 (EV71) causes severe disease, including aseptic meningitis, encephalitis, acute flaccid paralysis, and acute cardiopulmonary dysfunction. Large epidemics of EV71 infection have been reported worldwide.Methods. After recognition of a cluster of cases of EV71 disease, we reviewed records of patients with EV71 disease who required hospitalization at The Children's Hospital in Denver, Colorado, from 2003 through 2005. The presence of enterovirus was detected by reverse-transcriptase polymerase chain reaction (PCR) and/or viral culture of specimens from multiple sources, and the virus was typed as EV71 using genetic sequencing.Results. Eight cases of EV71 disease were identified in both 2003 and 2005. Fifty-six percent of patients with EV71 disease were р6 months of age (range, 4 weeks to 9 years). All 16 patients had EV71 central nervous system infection. Enterovirus PCR (EV-PCR) of cerebrospinal fluid specimens yielded positive results for only 5 (31.2%) of the 16 patients; all of these patients were !4 months of age and had less severe disease. However, EV-PCR of upper respiratory tract specimens yielded positive results for 8 (100%) of 8 patients, and EV-PCR of lower gastrointestinal tract specimens yielded positive results for 7 (87.5%) of 8 patients.Conclusions. An outbreak of neurologic EV71 disease occurred in Denver, Colorado, during 2003 and 2005. Likely, EV71 disease remains unrecognized in other parts of the United States, because EV-PCR of cerebrospinal fluid frequently yields negative results. EV-PCR of specimens from the respiratory and gastrointestinal tracts had higher diagnostic yields than did EV-PCR of cerebrospinal fluid. EV71 infection should be considered in young children presenting with aseptic meningitis, encephalitis, acute flaccid paralysis, or acute cardiopulmonary collapse. EV71 infection may be an underrecognized emerging disease in the United States.

The accurate diagnosis of tuberculosis (TB) in children remains challenging. A myriad of common childhood diseases can present with similar symptoms and signs, and differentiating between exposure and infection, as well as infection and disease can be problematic. The paucibacillary nature of childhood TB complicates bacteriological confirmation and specimen collection is difficult. In most instances intrathoracic TB remains a clinical diagnosis. TB infection and disease represent a dynamic continuum from TB exposure with/without infection, to subclinical/incipient disease, to non-severe and severe disease. The clinical spectrum of intrathoracic TB in children is broad, and the classification of clinical, radiological, endoscopic, and laboratory findings into recognized clinical syndromes allows a more refined diagnostic approach in order to minimize both under- and over-diagnosis. Bacteriological confirmation can be improved significantly by collecting multiple, high-quality specimens from the most appropriate source. Mycobacterial testing should include traditional smear microscopy and culture, as well as nucleic acid amplification testing. A systematic approach to the child with recent exposure to TB, or with clinical and radiological findings compatible with this diagnosis, should allow pragmatic classification as TB exposure, infection, or disease to facilitate timely and appropriate management. It is important to also assess risk factors for TB disease progression and to undertake follow-up evaluations to monitor treatment response and ongoing evidence supporting a TB, or alternative, diagnosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s41479-016-0023-9) contains supplementary material, which is available to authorized users.

An acquired immune deficiency due to interferon gamma (IFN-γ) autoantibodies was diagnosed in a 78-year-old Japanese man with treatment-refractory disseminated nontuberculous mycobacterial infection. In addition to standard antimycobacterial therapy, he was successfully treated with rituximab to eliminate B cells and thereby the autoantibody. Subsequently, he obtained a sustained remission from infection.

Few children with drug-resistant (DR) tuberculosis (TB) are identified, diagnosed, and given an appropriate treatment. The few studies that have described this vulnerable population have used inconsistent definitions. The World Health Organization (WHO) definitions used for adults with DR-TB and for children with drug-susceptible TB are not always appropriate for children with DR-TB. The Sentinel Project on Pediatric Drug-Resistant Tuberculosis was formed in 2011 as a network of experts and stakeholders in childhood DR-TB. An early priority was to establish standardized definitions for key parameters in order to facilitate study comparisons and the development of an evidence base to guide future clinical management. This consensus statement proposes standardized definitions to be used in research. In particular, it suggests consistent terminology, as well as definitions for measures of exposure, drug resistance testing, previous episodes and treatment, certainty of diagnosis, site and severity of disease, adverse events, and treatment outcome.

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