Paediatric use of antibiotics in children with community acquired pneumonia: A survey from Da Nang, Vietnam.

AIM: To characterise paediatricians' antibiotic-prescribing behaviour when managing community acquired pneumonia. METHODS: We conducted a knowledge and attitudes survey of paediatric doctors practicing at a regional provincial hospital in central Vietnam over a 2-week period (from 12 December 2017 to 29 December 2017). RESULTS: Of 79 eligible paediatric doctors, 69 (87.3%) completed the questionnaire, of whom 65 (94.2%) thought that antibiotics were overused in Vietnam. Thirty-eight doctors (55.1%) indicated that they routinely hospitalised children with pneumonia to provide intravenous antibiotics. Most doctors reported discharging children with non-severe pneumonia after 5 days (76.9%) and those with severe pneumonia after 7-10 days (88.4%); older doctors generally continued intravenous antibiotics for longer. The two most important factors driving discharge decisions were clinical assessment (95.6%) and completion of the full course of intravenous antibiotics (80.0%). Antibiotic prescription was influenced by local guidelines (62.3%), drugs used before admission (50.0%) and the opinion of senior clinicians (37.7%). Most doctors believed antibiotic stewardship was necessary (98.6%) and that over-the-counter use of antibiotics should be restricted (97.1%). CONCLUSIONS: Paediatricians recognised an urgent need for more effective regulation and antibiotic stewardship in Vietnam. Routinely completing a full course of intravenous antibiotics leads to unnecessary and prolonged hospitalisation.

An Evaluation of Alternative Markers to Guide Initiation of Anti-retroviral Therapy in HIV-Infected Children in Settings where CD4 Assays are not Available.

OBJECTIVES: In settings where CD4 testing is not available, alternative markers to start paediatric anti-retroviral therapy (ART) could be used. A comprehensive evaluation of these markers has not been performed. METHODS: Prospective cross-sectional study of HIV-infected Malawian children not eligible for ART based on clinical criteria. Associations between CD4 and alternative markers [haemoglobin, total lymphocyte count (TLC), serum albumin, thrombocytes and growth parameters] were analysed, and accuracy of existing and new cut-offs were evaluated. RESULTS: In all, 417 children were enrolled. Of 261 children aged ≥5 years, 155 (59%) qualified to start ART using CD4. In this group, only TLC was associated with CD4 (p < 0.001). Sensitivity for TLC was 21% (95% CI: 15-29%), using World Health Organization cut-offs. Improved cut-offs increased sensitivity to 73% (95% CI: 65-80%), specificity 62% (95% CI: 52-72%). CONCLUSION: Clinical staging alone is an unreliable strategy to start ART in children. TLC is the only alternative marker for CD4, cut-offs need to be revised though.

A Blueprint to Address Research Gaps in the Development of Biomarkers for Pediatric Tuberculosis.

Childhood tuberculosis contributes significantly to the global tuberculosis disease burden but remains challenging to diagnose due to inadequate methods of pathogen detection in paucibacillary pediatric samples and lack of a child-specific host biomarker to identify disease. Accurately diagnosing tuberculosis in children is required to improve case detection, surveillance, healthcare delivery, and effective advocacy. In May 2014, the National Institutes of Health convened a workshop including researchers in the field to delineate priorities to address this research gap. This blueprint describes the consensus from the workshop, identifies critical research steps to advance this field, and aims to catalyze efforts toward harmonization and collaboration in this area.

Antibiotic use in children hospitalised with pneumonia in Central Vietnam.

BACKGROUND AND OBJECTIVES: Excessive use of antibiotics has been noted in children with respiratory tract infections in Vietnam, but antibiotic use in hospitalised children is poorly documented. Antibiotic use and direct healthcare costs in children hospitalised with pneumonia in central Vietnam were assessed. METHODS: A prospective descriptive study of children under 5 years old admitted with a primary admission diagnosis of 'pneumonia' to the Da Nang Hospital for Women and Children over 1 year. RESULTS: Of 2911 children hospitalised with pneumonia, 2735 (94.0%) were classified as 'non-severe' pneumonia by the admitting physician. In total, 2853 (98.0%) children received antibiotics. Intravenous antibiotics were given to 336 (12.3%) children with 'non-severe' and 157/176 (89.2%) children with 'severe' pneumonia; those with 'non-severe' pneumonia accounted for 68.2% (336/493) of intravenous antibiotics given. Only 19.3% (95/493) of children on intravenous antibiotics were stepped down to an oral antibiotic. Cefuroxime was the preferred oral agent, and ceftriaxone was the preferred injectable agent. Hospital admission for oral antibiotics in 'non-severe' pneumonia was a major cost driver, with an average direct cost of US$78.9 per patient, accounting for 54.0% of the total hospitalisation cost in the study cohort. In addition, 336 (12.3%) children with non-severe pneumonia received intravenous antibiotics without indication, accounting for a further 23.2% of hospitalisation costs. CONCLUSION: Limiting unnecessary hospitalisation and considering early intravenous to oral step down antibiotic will reduce direct health system costs and morbidity in children with respiratory tract infections in Vietnam.

Adolescent tuberculosis.

Adolescence is characterised by a substantial increase in the incidence of tuberculosis, a known fact since the early 20th century. Most of the world's adolescents live in low-income and middle-income countries where tuberculosis remains common, and where they comprise a quarter of the population. Despite this, adolescents have not yet been addressed as a distinct population in tuberculosis policy or within tuberculosis treatment services, and emerging evidence suggests that current models of care do not meet their needs. This Review discusses up-to-date information about tuberculosis in adolescence, with a focus on the management of infection and disease, including HIV co-infection and rifampicin-resistant tuberculosis. We outline the progress in vaccine development and highlight important directions for future research.

Levofloxacin versus placebo for the treatment of latent tuberculosis among contacts of patients with multidrug-resistant tuberculosis (the VQUIN MDR trial): a protocol for a randomised controlled trial.

INTRODUCTION: Treatment of latent tuberculosis infection (LTBI) plays a substantial role in the prevention of drug-susceptible tuberculosis (TB). However, clinical trials to evaluate the efficacy of preventive therapy for presumed multidrug-resistant (MDR) LTBI are lacking. This trial aims to evaluate the efficacy of the antibiotic levofloxacin in preventing the development of active TB among latently infected contacts of index patients with MDR-TB. METHODS AND ANALYSIS: A double-blind placebo-controlled parallel group randomised controlled trial will be conducted in 10 provinces of Vietnam. Household contacts living with patients with bacteriologically confirmed rifampicin-resistant or MDR-TB will be eligible for recruitment if they have a positive tuberculin skin test or are known to be immunosuppressed, and do not have active TB. Participants will be randomised to receive either levofloxacin or placebo tablets once per day for 6 months. Screening for incident TB will be performed at 6 months intervals. The primary study outcome is the incidence of bacteriologically confirmed TB within 30 months after randomisation. Analysis will be by intention to treat, using Poisson regression. ETHICS: Ethical approval from the University of Sydney Human Research Ethics Committee was obtained on 29 April 2015 (2014/929), and from the Vietnam Ministry of Health Institutional Review Board on 30 September 2015 (4040/QD-BYT). DISSEMINATION: Findings of the study will be published in peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12616000215426.

Evaluation of an interferon-gamma release assay in children with suspected tuberculosis in Papua New Guinea.

There are few data from tuberculosis (TB) endemic settings of the performance and outcome predictors of the QuantiFERON-TB Gold in Tube assay (QFT) in children with suspected TB. A prospective cross-sectional study was conducted in Papua New Guinea children with suspected TB evaluated at Port Moresby General Hospital (Port Moresby, Papua New Guinea). Two hundred sixteen children were enrolled including 106 probable TB, 87 possible TB and 23 without TB. Concordance between QFT and tuberculin skin test results was 86% (P < 0.001, κ = 0.70). QFT was significantly more likely to be positive than tuberculin skin test, overall and within the probable or possible TB categories, with no difference in prevalence of positivity between these 2 categories. The role of QFT in supporting the clinical diagnosis of TB in endemic settings, where resources are limited, remains uncertain especially as cost and technical requirements remain considerable.

Guidance for National Tuberculosis Programmes on the management of tuberculosis in children - an update.

About one million children develop tuberculosis (TB) annually worldwide. Childhood TB is common in Malawi accounting for about 12% of all TB cases. Childhood TB differs from TB in adults in ways that have important implications for the prevention, diagnosis and treatment of TB in children. Young children living in close contact with a case of smear-positive pulmonary TB are at particular risk of infection and TB disease. Screening of the household contacts of an infectious source case is therefore recommended to identify children with TB and enable their prompt treatment, and to provide children who do not have TB with isoniazid preventive treatment. It is recognised that there is a need to improve the diagnosis and management of children with TB, the prevention of TB in children and to ensure their inclusion under the implementation of the Stop TB strategy by National TB Programmes. A subgroup of the WHO DOTS Expansion Working Group called the Stop TB Partnership Childhood TB Subgroup published guidelines for the management of child TB in 2006. The guidelines are designed to complement current national and international guidelines on the implementation of the Stop TB Strategy and existing guidelines, but also to fill existing gaps to ensure that children with M. tuberculosis infection and TB disease are identified early and managed effectively. This paper summarises some of the most important information and recommendations put forward in those guidelines.

Poor potential coverage for 7-valent pneumococcal conjugate vaccine, Malawi.

Streptococcus pneumoniae infections can be prevented by using new conjugate vaccines, but these vaccines have limited serogroup coverage. We report the first serogrouping data from carried and invasive isolates obtained from children and adults in Malawi. The 7-valent vaccine would cover 41% of invasive isolates from children and 25% from adults. A 9-valent vaccine, including types 1 and 5, would cover 66% of invasive isolates from children and 55% from adults.