Shorter Treatment for Nonsevere Tuberculosis in African and Indian Children.

BACKGROUND: Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen. METHODS: We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment. RESULTS: From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, -0.4 percentage points; 95% confidence interval, -2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberculosis at baseline. A total of 95 participants (8%) had an adverse event of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, all but 2 of which occurred within the first 8 weeks, when the treatments were the same in the two groups). CONCLUSIONS: Four months of antituberculosis treatment was noninferior to 6 months of treatment in children with drug-susceptible, nonsevere, smear-negative tuberculosis. (Funded by the U.K. Medical Research Council and others; SHINE ISRCTN number, ISRCTN63579542.).

Pre-extensively Drug-Resistant Congenital Tuberculosis in an Extremely Premature Baby.

We describe a case of congenital tuberculosis in an extremely premature baby, with rapid molecular detection of a pre-extensively drug-resistant (XDR) pattern of drug resistance. The baby was treated successfully with a regimen including bedaquline and delamanid, drugs not previously described in the treatment of congenital tuberculosis (TB).

Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.

BACKGROUND: Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level. METHODS: We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve from 0 to 24 h post-dose (AUC0-24) and peak plasma concentration (C max) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC0-24 and C max were assessed with linear mixed-effects models. RESULTS: Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC0-24 were summarised for isoniazid (18.7 (95% CI 15.5-22.6) h·mg·L-1), rifampicin (34.4 (95% CI 29.4-40.3) h·mg·L-1), pyrazinamide (375.0 (95% CI 339.9-413.7) h·mg·L-1) and ethambutol (8.0 (95% CI 6.4-10.0) h·mg·L-1). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC0-24 for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC0-24 for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC0-24 and slow acetylators had higher isoniazid AUC0-24 than intermediate acetylators. Determinants of C max were generally similar to those for AUC0-24. CONCLUSIONS: This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring.

Detecting Mycobacterium tuberculosis Infection in Children Migrating to Australia.

In 2015, Australia updated premigration screening for tuberculosis (TB) disease in children 2-10 years of age to include testing for infection with Mycobacterium tuberculosis and enable detection of latent TB infection (LTBI). We analyzed TB screening results in children <15 years of age during November 2015-June 2017. We found 45,060 child applicants were tested with interferon-gamma release assay (IGRA) (57.7% of tests) or tuberculin skin test (TST) (42.3% of tests). A total of 21 cases of TB were diagnosed: 4 without IGRA or TST, 10 with positive IGRA or TST, and 7 with negative results. LTBI was detected in 3.3% (1,473/44,709) of children, for 30 applicants screened per LTBI case detected. LTBI-associated factors included increasing age, TB contact, origin from a higher TB prevalence region, and testing by TST. Detection of TB and LTBI benefit children, but the updated screening program's effect on TB in Australia is likely to be limited.

Evolution and spread of a highly drug resistant strain of Mycobacterium tuberculosis in Papua New Guinea.

BACKGROUND: Molecular mechanisms determining the transmission and prevalence of drug resistant tuberculosis (DR-TB) in Papua New Guinea (PNG) are poorly understood. We used genomic and drug susceptibility data to explore the evolutionary history, temporal acquisition of resistance and transmission dynamics of DR-TB across PNG. METHODS: We performed whole genome sequencing on isolates from Central Public Health Laboratory, PNG, collected 2017-2019. Data analysis was done on a composite dataset that also included 100 genomes previously sequenced from Daru, PNG (2012-2015). RESULTS: Sampled isolates represented 14 of the 22 PNG provinces, the majority (66/94; 70%) came from the National Capital District (NCD). In the composite dataset, 91% of strains were Beijing 2.2.1.1, identified in 13 provinces. Phylogenetic tree of Beijing strains revealed two clades, Daru dominant clade (A) and NCD dominant clade (B). Multi-drug resistance (MDR) was repeatedly and independently acquired, with the first MDR cases in both clades noted to have emerged in the early 1990s, while fluoroquinolone resistance emerged in 2009 (95% highest posterior density 2000-2016). We identified the presence of a frameshift mutation within Rv0678 (p.Asp47fs) which has been suggested to confer resistance to bedaquiline, despite no known exposure to the drug. Overall genomic clustering was significantly associated with rpoC compensatory and inhA promoter mutations (p < 0.001), with high percentage of most genomic clusters (12/14) identified in NCD, reflecting its role as a potential national amplifier. CONCLUSIONS: The acquisition and evolution of drug resistance among the major clades of Beijing strain threaten the success of DR-TB treatment in PNG. With continued transmission of this strain in PNG, genotypic drug resistance surveillance using whole genome sequencing is essential for improved public health response to outbreaks. With occurrence of resistance to newer drugs such as bedaquiline, knowledge of full drug resistance profiles will be important for optimal treatment selection.

Exploring Tuberculosis Riskscapes in a Papua New Guinean 'Hotspot'.

This article explores socio-spatial dimensions of risk and how they can enhance understanding of a high burden tuberculosis (TB) context in the South Fly District of Papua New Guinea. We report on select findings from a qualitative study that included 128 semi-structured in-depth interviews and 10 focus group discussions with a wide range of South Fly District community members. Using the conceptual framework of 'riskscapes' to examine emic perspectives on risk, space and practice, we map key elements of TB riskscapes on Daru Island, South Fly District, along with solutions for navigating through these riskscapes. Overcrowding, lack of water, sanitation and hygiene, as well as food insecurity and undernutrition, were identified as common elements within participants' riskscapes, that compounded upon each other to create the perception of an assemblage of risk favourable to TB transmission.

Predictors of Unlikely Bacterial Pneumonia and Adverse Pneumonia Outcome in Children Admitted to a Hospital in Central Vietnam.

BACKGROUND: Pneumonia is the leading cause of antibiotic use and hospitalization in Vietnam. There is a need for better prediction of unlikely bacterial pneumonia and adverse pneumonia outcome in order to guide hospital admission and improve rational antibiotic use. METHODS: All children under 5 admitted with pneumonia (per clinician assessment) to the Da Nang Hospital for Women and Children were prospectively enrolled. Children were classified as having likely or unlikely bacterial pneumonia and followed for outcome assessment. A Bayesian model averaging approach was used to identify predictors of unlikely bacterial pneumonia and adverse pneumonia outcome, which guided the development of a pragmatic management algorithm. RESULTS: Of 3817 patients assessed, 2199 (57.6%) met World Health Organization (WHO) pneumonia criteria. In total, 1594 (41.7%) children were classified as having unlikely and 129 (3.4%) as having likely bacterial pneumonia. The remainder (2399; 62.9%) were considered to have disease of uncertain etiology. Factors predictive of unlikely bacterial pneumonia were no fever, no consolidation on chest radiograph, and absolute neutrophil count <5 × 109/L at presentation, which had a negative predictive value (NPV) for likely bacterial pneumonia of 99.0%. Among those who met WHO pneumonia criteria, 8.6% (189/2199) experienced an adverse outcome. Not having any WHO danger sign or consolidation on chest radiograph had an NPV of 96.8% for adverse pneumonia outcome. CONCLUSIONS: An algorithm that screens for predictors of likely bacterial pneumonia and adverse pneumonia outcome could reduce unnecessary antibiotic use and hospital admission, but its clinical utility requires validation in a prospective study.

Characterisation of children hospitalised with pneumonia in central Vietnam: a prospective study.

Pneumonia is the most common reason for paediatric hospital admission in Vietnam. The potential value of using the World Health Organization (WHO) case management approach in Vietnam has not been documented.We performed a prospective descriptive study of all children (2-59 months) admitted with "pneumonia" (as assessed by the admitting clinician) to the Da Nang Hospital for Women and Children to characterise their disease profiles and assess risk factors for an adverse outcome. The disease profile was classified using WHO pneumonia criteria, with tachypnoea or chest indrawing as defining clinical signs. Adverse outcome was defined as death, intensive care unit admission, tertiary care transfer or hospital stay >10 days.Of 4206 admissions, 1758 (41.8%) were classified as "no pneumonia" using WHO criteria and only 252 (6.0%) met revised criteria for "severe pneumonia". The inpatient death rate was low (0.4% of admissions) with most deaths (11 out of 16; 68.8%) occurring in the "severe pneumonia" group. An adverse outcome was recorded in 18.7% of all admissions and 60.7% of the "severe pneumonia" group. Children were hospitalised for a median of 7 days at an average cost of 253 USD per admission. Risk factors for adverse outcome included WHO-classified "severe pneumonia", age <1 year, low birth weight, previous recent admission with an acute respiratory infection and recent tuberculosis exposure. Breastfeeding, day-care attendance and pre-admission antibiotic use were associated with reduced risk.Few hospital admissions met WHO criteria for "severe pneumonia", suggesting potential unnecessary hospitalisation and use of intravenous antibiotics. Better characterisation of the underlying diagnosis requires careful consideration.

The incidence of tuberculosis among adolescents and young adults: a global estimate.

Historical data show that the risk of tuberculosis increases dramatically during adolescence, and young people face unique challenges in terms of case detection and effective treatment. However, little is known about the burden of tuberculosis among young people in the modern era. This study aimed to provide the first estimates of the global and regional incidence of tuberculosis among young people aged 10-24 years.Using the World Health Organization (WHO) database of tuberculosis notifications for 2012, we estimated the burden of tuberculosis among young people by WHO region. Adjustments were made for incomplete age disaggregation and underreporting, using supplementary data from several countries representing diverse tuberculosis epidemics.We estimate that 1.78 million (uncertainty interval (UI) 1.23-3.00 million) young people developed tuberculosis in 2012, accounting for 17% of all new tuberculosis cases globally. Young people in the WHO South East Asian Region (721 000, UI 473 000-1.35 million) and the WHO African Region (534 000, UI 359 000-912 000) experienced the greatest number of tuberculosis episodes.Young people suffer a considerable burden of tuberculosis. Age-specific burden of disease estimation for this age group is complicated by incomplete age disaggregation of tuberculosis data, highlighting the importance of continued surveillance system strengthening.

Incidence and prevalence of bacteriologically confirmed pulmonary tuberculosis among adolescents and young adults: a systematic review.

The burden of tuberculosis (TB) among adolescents and young adults in endemic settings is poorly characterised. This study aimed to review published and unpublished estimates of the incidence and prevalence of bacteriologically confirmed TB among young people aged 10-24 years. We searched PubMed and World Health Organization archives for publications and unpublished data from population-based epidemiologic studies reporting confirmed pulmonary TB among young people, conducted from January 2000 onwards. We identified 27 publications and unpublished data from two national surveys, representing a total of 26 studies in 19 countries. The prevalence of bacteriologically confirmed TB ranged from 45 to 799 per 100 000 in the Asia-Pacific region and from 160 to 462 per 100 000 in African settings. We did not identify any epidemiologic studies of confirmed TB among adolescents living with human immunodeficiency virus (HIV). Many studies were excluded due to absent or inadequately reported age-specific data. Adolescents and young adults living in many endemic settings appear to be at substantial risk of developing active TB. There is a pressing need to improve the routine reporting of age in epidemiologic studies of TB, and to generate high-quality epidemiologic data regarding TB among adolescents living with HIV.

New and Repurposed Drugs for Pediatric Multidrug-Resistant Tuberculosis. Practice-based Recommendations.

It is estimated that 33,000 children develop multidrug-resistant tuberculosis (MDR-TB) each year. In spite of these numbers, children and adolescents have limited access to the new and repurposed MDR-TB drugs. There is also little clinical guidance for the use of these drugs and for the shorter MDR-TB regimen in the pediatric population. This is despite the fact that these drugs and regimens are associated with improved interim outcomes and acceptable safety profiles in adults. This review fills a gap in the pediatric MDR-TB literature by providing practice-based recommendations for the use of the new (delamanid and bedaquiline) and repurposed (linezolid and clofazimine) MDR-TB drugs and the new shorter MDR-TB regimen in children and adolescents.

Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: an open, randomised controlled trial.

BACKGROUND: In developing countries, mortality in children with very severe pneumonia is high, even with the provision of appropriate antibiotics, standard oxygen therapy, and other supportive care. We assessed whether oxygen therapy delivered by bubble continuous positive airway pressure (CPAP) improved outcomes compared with standard low-flow and high-flow oxygen therapies. METHODS: This open, randomised, controlled trial took place in Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. We randomly assigned children younger than 5 years with severe pneumonia and hypoxaemia to receive oxygen therapy by either bubble CPAP (5 L/min starting at a CPAP level of 5 cm H2O), standard low-flow nasal cannula (2 L/min), or high-flow nasal cannula (2 L/kg per min up to the maximum of 12 L/min). Randomisation was done with use of the permuted block methods (block size of 15 patients) and Fisher and Yates tables of random permutations. The primary outcome was treatment failure (ie, clinical failure, intubation and mechanical ventilation, death, or termination of hospital stay against medical advice) after more than 1 h of treatment. Primary and safety analyses were by intention to treat. We did two interim analyses and stopped the trial after the second interim analysis on Aug 3, 2013, as directed by the data safety and monitoring board. This trial is registered at ClinicalTrials.gov, number NCT01396759. FINDINGS: Between Aug 4, 2011, and July 17, 2013, 225 eligible children were recruited. We randomly allocated 79 (35%) children to receive oxygen therapy by bubble CPAP, 67 (30%) to low-flow oxygen therapy, and 79 (35%) to high-flow oxygen therapy. Treatment failed for 31 (14%) children, of whom five (6%) had received bubble CPAP, 16 (24%) had received low-flow oxygen therapy, and ten (13%) had received high-flow oxygen therapy. Significantly fewer children in the bubble CPAP group had treatment failure than in the low-flow oxygen therapy group (relative risk [RR] 0·27, 99·7% CI 0·07-0·99; p=0·0026). No difference in treatment failure was noted between patients in the bubble CPAP and those in the high-flow oxygen therapy group (RR 0·50, 99·7% 0·11-2·29; p=0·175). 23 (10%) children died. Three (4%) children died in the bubble CPAP group, ten (15%) children died in the low-flow oxygen therapy group, and ten (13%) children died in the high-flow oxygen therapy group. Children who received oxygen by bubble CPAP had significantly lower rates of death than the children who received oxygen by low-flow oxygen therapy (RR 0·25, 95% CI 0·07-0·89; p=0·022). INTERPRETATION: Oxygen therapy delivered by bubble CPAP improved outcomes in Bangladeshi children with very severe pneumonia and hypoxaemia compared with standard low-flow oxygen therapy. Use of bubble CPAP oxygen therapy could have a large effect in hospitals in developing countries where the only respiratory support for severe childhood pneumonia and hypoxaemia is low-flow oxygen therapy. The trial was stopped early because of higher mortality in the low-flow oxygen group than in the bubble CPAP group, and we acknowledge that the early cessation of the trial reduces the certainty of the findings. Further research is needed to test the feasibility of scaling up bubble CPAP in district hospitals and to improve bubble CPAP delivery technology. FUNDING: International Centre for Diarrhoeal Disease Research, Bangladesh, and Centre for International Child Health, University of Melbourne.

Mycobacteria-Specific Cytokine Responses Detect Tuberculosis Infection and Distinguish Latent from Active Tuberculosis.

RATIONALE: Current immunodiagnostic tests for tuberculosis (TB), including the tuberculin skin test and IFN-γ release assay (IGRA), have significant limitations, which include their inability to distinguish between latent TB infection (LTBI) and active TB, a distinction critical for clinical management. OBJECTIVES: To identify mycobacteria-specific cytokine biomarkers that characterize TB infection, determine their diagnostic performance characteristics, and establish whether these biomarkers can distinguish between LTBI and active TB. METHODS: A total of 149 children investigated for TB infection were recruited; all participants underwent a tuberculin skin test and QuantiFERON-TB Gold assay. In parallel, whole-blood assays using early secretory antigenic target-6, culture filtrate protein-10, and PPD as stimulatory antigens were undertaken, and cytokine responses were determined by xMAP multiplex assays. MEASUREMENTS AND MAIN RESULTS: IFN-γ, interferon-inducible protein-10 (IP-10), tumor necrosis factor (TNF)-α, IL-1ra, IL-2, IL-13, and MIP-1ß (macrophage inflammatory protein-1ß) responses were significantly higher in LTBI and active TB cases than in TB-uninfected individuals, irrespective of the stimulant. Receiver operating characteristic analyses showed that IP-10, TNF-α, and IL-2 responses achieved high sensitivity and specificity for the distinction between TB-uninfected and TB-infected individuals. TNF-α, IL-1ra, and IL-10 responses had the greatest ability to distinguish between LTBI and active TB cases; the combinations of TNF-α/IL-1ra and TNF-α/IL-10 achieved correct classification of 95.5% and 100% of cases, respectively. CONCLUSIONS: We identified several mycobacteria-specific cytokine biomarkers with the potential to be exploited for immunodiagnosis. Incorporation of these biomarkers into future immunodiagnostic assays for TB could result in substantial gains in sensitivity and allow the distinction between LTBI and active TB based on a blood test alone.

Childhood tuberculosis: A roadmap towards zero deaths.

'Every day, more than 200 children under the age of 15 die needlessly from tuberculosis (TB) - a disease that is preventable and curable. The World Health Organization estimates that as many as 1 in 10 TB cases globally (6-10% of all TB cases) are among this age group, but the number could be even higher because many children are simply undiagnosed.' Childhood TB is emerging from the shadows. This quote comes from the recently launched international roadmap towards zero TB deaths in children. We provide a brief update of new developments and remaining challenges related to childhood TB, with particular emphasis on the new roadmap.

A prospective evaluation of the symptom-based screening approach to the management of children who are contacts of tuberculosis cases.

BACKGROUND: Child tuberculosis contact screening and management can enhance case finding and prevent tuberculosis disease. It is universally recommended but rarely implemented in tuberculosis-endemic settings. The World Health Organization (WHO)-recommended symptom-based screening approach could improve implementation but has not been prospectively evaluated. METHODS: We conducted a cohort study of children who were close contacts of pulmonary tuberculosis patients in Indonesia from August 2010 to December 2012. We performed clinical assessment, tuberculin skin test, and chest radiography in all eligible children irrespective of symptoms at baseline. Mycobacterial culture and Xpert MTB/RIF assay were performed on sputum from children with persistent symptoms of suspected tuberculosis. Children were managed according to WHO guidelines and were prospectively followed for 12 months. RESULTS: A total of 269 child contacts of 140 index cases were evaluated. At baseline, 21 (8%) children had tuberculosis diagnosed clinically; an additional 102 (38%) had evidence of infection without disease. Of children with any tuberculosis-related symptoms at baseline, 21% had tuberculosis diagnosed compared with none of the asymptomatic children (P < .001). After 12 months of follow-up, none of the 99 eligible young child contacts (<5 years) who received isoniazid preventive therapy (IPT) had developed disease compared with 4 of 149 (2.6%) asymptomatic older children who did not receive IPT. CONCLUSIONS: Symptom-based screening is an effective and simple approach to child tuberculosis contact management that can be implemented at the primary healthcare level.

Clinical Case Definitions for Classification of Intrathoracic Tuberculosis in Children: An Update.

Consensus case definitions for childhood tuberculosis have been proposed by an international expert panel, aiming to standardize the reporting of cases in research focusing on the diagnosis of intrathoracic tuberculosis in children. These definitions are intended for tuberculosis diagnostic evaluation studies of symptomatic children with clinical suspicion of intrathoracic tuberculosis, and were not intended to predefine inclusion criteria into such studies. Feedback from researchers suggested that further clarification was required and that these case definitions could be further improved. Particular concerns were the perceived complexity and overlap of some case definitions, as well as the potential exclusion of children with acute onset of symptoms or less severe disease. The updated case definitions proposed here incorporate a number of key changes that aim to reduce complexity and improve research performance, while maintaining the original focus on symptomatic children suspected of having intrathoracic tuberculosis. The changes proposed should enhance harmonized classification for intrathoracic tuberculosis disease in children across studies, resulting in greater comparability and the much-needed ability to pool study results.

Risk of infection and disease with Mycobacterium tuberculosis among children identified through prospective community-based contact screening in Indonesia.

OBJECTIVE: To identify characteristics of the child contact, index case or environment that are associated with infection or tuberculosis in child contacts in an urban community in Indonesia. METHOD: Children who were close contacts of an index case with pulmonary tuberculosis were screened for infection and disease in Yogyakarta, Indonesia from August 2010 to December 2012. Data of the index case and child were collected prospectively, and all child contacts had clinical assessment, tuberculin skin test (TST) and chest X-ray performed. Those with clinically suspected tuberculosis also had sputum examined by Xpert MTB/RIF and culture. Child contacts were managed according to national guidelines, followed for 12 months and had a final classification of either tuberculosis 'disease', latent tuberculous infection (LTBI) or 'exposed only'. RESULTS: About 269 children of 141 index cases were investigated. Final classification was tuberculosis in 25 (9%) and LTBI in 121 (45%). The risk of infection was significantly greater if the source case was female (AOR 1.7; 95% CI: 1.0-2.8), had sputum smear-positive tuberculosis (AOR 3.0; 95% CI 1.5-6.0) or slept in the same room (AOR 1.7, 95% CI 1.0-2.9). A positive TST was independently associated with a diagnosis of tuberculosis (AOR 7.3; 95% CI 2.4-22). CONCLUSION: This study highlights the high risk and the risk factors associated with tuberculosis and LTBI among child contacts in Indonesia.

The epidemiology of tuberculosis in children in Australia, 2003-2012.

OBJECTIVE: To describe the burden of and trends in paediatric tuberculosis (TB) in Australia between 2003 and 2012. DESIGN: A retrospective analysis of TB data from the National Notifiable Diseases Surveillance System (NNDSS) on TB in children (under 15 years of age) during the 10-year period, 2003-2012. RESULTS: TB notifications in Australia during the study period included 538 children (range, 37-66 cases per year), representing 4.6% of the total TB case load during the period (range, 3.8%-5.8% each year). Place of birth was recorded for 524 patients (97.4%); of these, 230 (43.9%) were born in Australia, 294 (56.1%) overseas. The average annual notification rate was 1.31 (95% CI, 1.20-1.43) cases per 100 000 child population. The rate was higher for overseas-born than for Australian-born children (9.57 [95% CI, 8.51-10.73] v 0.61 [95% CI, 0.53-0.69] cases per 100 000 children. The overall rate was highest among those aged 0-4 years. The annual notification rate was three times higher for Indigenous children than for non-Indigenous Australian-born children. Of 427 patients (79.4% of total) for whom the method of case detection was recorded, 37.0% were detected by contact screening, 8.7% by post-arrival immigration screening, and 54.3% by passive case detection. Pulmonary TB was the most common diagnostic classification (64.7% of patients). The most common risk factors were close contact with a TB case and recent residence in a country with a high incidence of TB. Treatment outcomes were satisfactory; 89.4% of children had completed treatment or were cured. CONCLUSIONS: The burden of paediatric TB in Australia is low but has not changed over the past decade. The highest rates are among children born overseas, emphasising the important role of immigration screening as Australia aspires to eliminate TB.

Morbidity and mortality in hospitalised neonates in central Vietnam.

AIM: This study explored neonatal morbidity and mortality in hospitalised patients in central Vietnam and risk factors associated with mortality. METHODS: We conducted a prospective cohort study of all newborn infants (<28 days) hospitalised in a neonatal unit over a 1-year period and followed until discharge. The main outcome measures were case fatality rate and the rate of different clinical diagnoses. RESULTS: There were 2555 admissions during the study period. The leading primary causes of admissions were infections (41%), haematological problems such as jaundice (23%) and prematurity and its complications (18%). The overall case fatality rate was 8.6%, and it was 59% among very low-birthweight (<1500 g) neonates. Mortality was inversely associated with birthweight and gestational age. Of the 220 deaths, 57% occurred within the first 7 days of life. Although the causes of death were often multifactorial, the leading primary causes were infections (32%), prematurity and its complications (25%), birth defects (24%) and birth asphyxia (6%). Risk factors associated with death were being outborn, early gestational age, small for gestational age, confirmed sepsis and birth defects. CONCLUSION: Mortality rates were high among hospitalised neonates in central Vietnam, and this paper suggests interventions that might improve outcomes.