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Global health: tuberculosis
Though the WHO endorsed gold standard for diagnosing tuberculosis in all age groups is positive microbiology, this is notoriously difficult to achieve in children. If all else fails and the infrastructure allows, bronchoscopy is an option, but is rarely available in low and middle income country settings which shoulder the vast majority of the global burden of TB disease. In non-expectorating children, the alternatives are induced sputum (IS), nasopharyngeal aspiration and gastric aspirate. Which though performs best? Bonnet and colleagues undertook a systematic review of detection yields of mycobacterial culture and Xpert MTB/RIF from each of these methods and included 30 studies involving 11, 554 children. Detection yields for culture ranged between 1% and 30% for IS, 1% and 45% for GA and 4% and 24% for NPA and for Xpert MTB/RIF between 2% and 17% (IS), 5% to and 51% (GA) and between 3% and 8% for NPA. There was a trend to better yields with IS when the pretest probability of ITB was low and to GA when high but, the wide ranges in detection re-emphasises the imperfections inherent to each. See page 629 .
Treatment in household contacts
The surveillance and management of child contacts of adult multidrug resistant TB is controversial. Sanchez-Padilla longitudinally evaluated the evolution of tuberculin reactivity in household contacts of MDR TB in Armenia. Children were screened using tuberculin skin test, interferon-gamma release assay and chest X-ray at the initial consultation and were reassessed every 3–6 months for a period of 24 months. They received no receive preventive treatment. At the start, 3 of the 150 children included were diagnosed with TB disease (2.0%) with a prevalence of latent TB of close to 60%. This increased most rapidly during the first 6 months of follow-up but there were no additional cases with incident disease. After adjustment, LTBI was significantly associated with the child’s age, sleeping in the same house, household density, the index case’s age, positive smear result and presence of lung cavities. These data add backing to regular surveillance rather than active treatment in this high risk hard to treat group. See page 622 .
As part of primary vaccination against invasive pneumococcal disease (IPD), the WHO recommends either a ‘3+0’ (6 weeks, 3 to 4 months and 4 to 6 months) or ‘2+1’ (2 doses before 6 months and a third at 9 to 15 months) schedule. However, IPD remains prevalent and little is known about persistence of effect of the early (‘3+0’) schedule, In addition, antibody titres required for protection against nasopharyngeal carriage, disease type and cross-protection between serotypes are different.
Zimmerman assessed the pneumococcal antibody concentrations to all 13 antigens included in the 13-valent pneumococcal conjugate vaccine (PCV13) after 3+0 vaccination in 91 infants at 7 months and in 311 infants at 13 months of age and calculated geometric mean concentrations (GMCs) and the proportion of infants with an antibody concentration above the standard protection threshold. At 7 months of age, seroprotection rates varied between 69% and 100%, but, by 13 months, were below 90% for most serotypes, with lowest rates for serotype 4, 19A, 23F and 6B. The clear inference of the findings, although from a small group, is that for long term seroprotection, a booster dose in infancy might be required. See page 680 .
A group of papers revisit Kawasaki’s Disease (KD) from several different angles. Treatment resistance remains enigmatic and Shimizu’s study from a metropolitan are in Japan (Kitakyushu City) followed the courses of 715 patients who were initially treated with intravenous immunoglobulin (IVIG) with respect to response by season. Though incidence was higher in the cold months, the proportion of patients with resistance to the initial IVIG therapy was significantly higher (OR 1.49, 95% CI 1.02 to 2.17, p=0.038) during the warm period. There was, however, no difference in coronary artery aneurysm (CAA) rates. They hypothesise that infection burden and immune triggers might vary by season. Tulloh and colleagues report the latest British Paediatric Surveillance Unit (BPSU) KD and show a winter peak with higher rates in children in rural areas, later treatment predicting poorer outcome in terms of CAAs. Editorials by Burns and Cornish respectively comment on these findings and implications for practice. See pages 640, 615 and 616 .
It’s hard to think of a single area in paediatric which has seen a faster rise in research than that of the gut microbiome which is why Ryan’s review of this bewilderingly rapidly evolving area is so welcome. In terms of direct relevance to child health the follow areas are identified: the infant microbiome is vulnerable, programmes the immune system and might contribute to atopic and autoimmune disease; though (through monozygotic twin studies) it appears that the initial microbiome is largely genetically based, divergence is rapid; a diverse microbiome predicts metabolic ‘well being’ and that certain probiotics protect against necrotizing enterocolitis. So, how do we best nurture young children’s microbiome? Simply, advocate for full term, normal deliveries, for breastfeeding and for the judicious use of antibiotics. See page 701 .
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.
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