Alternative dosing guidelines to improve outcomes in childhood tuberculosis : a mathematical modelling study

Background Malnourished and young children are particularly susceptible to severe forms of tuberculosis and poor treatment response. WHO dosing guidelines for drugs for tuberculosis treatment are based only on weight, which might lead to systematic underdosing and poor outcomes in these children. We aimed to assess and quantify the population effect of WHO guidelines for drug-susceptible tuberculosis in children in the 20 countries with the highest disease burden. Methods We used an integrated model that linked country-specific demographic data at the individual level from the 20 countries with the highest disease burden to pharmacokinetic, outcome, and epidemiological models. We estimated tuberculosis treatment outcomes in children younger than 5 years following WHO guidelines (children are dosed by weight bands corresponding to the number of fixed-dose combination tablets [75 mg rifampicin, 50 mg isoniazid, 150 mg pyrazinamide]) and two alternative dosing strategies: one based on a proposed algorithm that uses age, weight, and available formulations, in which underweight children would receive the same drug doses as would normal weight children of the same age; and another based on an individualised algorithm without dose limitations, in which derived doses results in target exposure attainment for the typical child. Findings We estimated that 57 234 (43%) of 133 302 children younger than 5 years who were treated for tuberculosis in 2017 were underdosed with WHO dosing and only 47% of children would reach the rifampicin exposure target. Underdosing and subtherapeutic exposures were more common among malnourished children than among age-matched healthy children. The proposed dosing approach improved estimated rifampicin target exposure attainment to 62% and equalised outcomes by nutritional status. An estimated third of unfavourable treatment outcomes might be resolved with this dosing strategy, saving the lives of a minimum of 2423 children in these countries annually. With individualised dosing approaches, almost all children could achieve adequate exposure for cure. Interpretation This work shows that a simple change in dosing procedure to include age and nutritional status, requiring no additional measurements or new drug formulations, is one approach to improve tuberculosis treatment outcomes in children, especially malnourished children who are at high risk of mortality

TB preventive therapy preferences among children and adolescents

BACKGROUND : TB preventive therapy (TPT) is critical for ending TB, yet implementation remains poor. With new global guidelines expanding TPT eligibility and regimens, we aimed to understand TPT preferences among children, adolescents and caregivers. METHODS : We undertook a discrete choice experiment among 131 children, 170 adolescents and 173 caregivers, and conducted 17 in-depth interviews in 25 clinics in Cape Town, South Africa. The design included attributes for location, waiting time, treatment duration, dosing frequency, formulation/size, side effects, packaging and taste. Mixed-effects logistic regression models were used for analysis. RESULTS : Among children and caregivers, the number and size of pills, taste and side effects were important drivers of preferences. Among adolescents and caregivers, clinic waiting times and side effects were significant drivers of preferences. Adolescents expressed concerns about being stigmatised, and preferred services from local clinics to services delivered in the community. Dosing frequency and treatment duration were only significant drivers of choice among adolescents, and only if linked to fewer clinic visits. CONCLUSIONS : Introducing shorter TPT regimens in isolation without consideration of preferences and health services may not have the desired effect on uptake and completion. Developing TPT delivery models and formulations that align with preferences must be prioritised.The Bill & Melinda Gates Foundation (Seattle, WA, USA) through their support of the South African National TB Think Tank; the Fogarty International Center of the National Institutes of Health (Bethesda, MD, USA); and the European Union.https://theunion.org/our-work/journals/ijtldam2024Family MedicineSDG-03:Good heatlh and well-bein

Interferon-gamma release assays for childhood tuberculosis: What does the future hold?

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Scoring systems for the diagnosis of childhood tuberculosis: Are we making progress?

[No abstract available]Editoria

Induced sputum microbiology in confirming pulmonary tuberculosis in children

[No abstract available]Editoria

Can we accurately diagnose tuberculosis infection in children?

[No abstract available]Lette

Criteria used for the diagnosis of childhood tuberculosis at primary health care level in a high-burden, urban setting

BACKGROUND: Children contribute a significant proportion of the total tuberculosis (TB) case load in high-burden settings and present a major diagnostic challenge. OBJECTIVE: To document the criteria used at primary health care level to diagnose childhood TB in a high-burden, urban setting. METHODS: This retrospective descriptive study was conducted at two primary health care clinics in Cape Town, South Africa. Information on all children (<15 years of age) entered into the TB register from January 2002 through December 2003 was retrieved for analysis. RESULTS: During the study period, 1277 cases of TB were entered into the TB register, of which 268 (21.0%) were children. Information on 256 (95.5%) children was available for analysis. The majority (206, 80.5%) had intrathoracic TB, of whom 107 (51.5%) had uncomplicated lymph node disease, 79 (38.3%) complicated lymph node disease, 8 (3.9%) a pleural effusion and 12 (5.8%) adult-type cavitating disease. According to modified WHO criteria, the diagnosis of TB was confirmed in 27 (10.5%), probable in 193 (75.4%) and suspect in 36 (14.1%). DISCUSSION: The diagnostic criteria used at primary health care level demonstrated good agreement with current guidelines, but depended heavily on chest radiograph interpretation. © 2005 The Union.Articl

HIV and childhood tuberculosis: The way forward

Tuberculosis has been a major cause of morbidity and mortality in under-resourced communities. By causing progressive immunodeficiency, the human immunodeficiency virus (HIV) increases susceptibility to tuberculosis in an already vulnerable community. Similarities in clinical presentation and radiological appearance contribute to diagnostic difficulties, as even in the absence of HIV childhood tuberculosis is not easy to diagnose. The majority of studies thus far have been descriptive and often cross-sectional, but have defined the extent of this complex interaction. There is now a need to undertake prospective diagnostic, therapeutic and prevention studies. An emerging concern is how to integrate antiretroviral with anti-tuberculosis treatment and to explore whether lessons learned in tuberculosis can support antiretroviral therapy. Interactions between therapies for both conditions also need careful study.Conference Pape

The burden of childhood tuberculosis and the accuracy of community-based surveillance data

BACKGROUND: Inadequate surveillance and diagnostic difficulties compromise the quality of epidemiological data on childhood tuberculosis (TB). OBJECTIVE: To document the incidence of childhood TB and to evaluate the accuracy of community-based surveillance data in a high-burden setting. METHODS: This prospective observational study was conducted from February 2003 to October 2004 at five primary health care clinics in Cape Town, South Africa. Comprehensive surveillance was done to ensure that all children <13 years of age treated for TB were included. RESULTS: During the study period, 443 children (<13 years of age) received anti-tuberculosis treatment, of whom 389 (87.8%) were recorded in the TB treatment register. The TB incidence calculated from the TB treatment register was 441/100 000/year amongst children and 845/100 000/year amongst adults. Fifty-four children treated for TB were not recorded in the TB treatment register, including 21/28 (75%) children with severe disease. DISCUSSION: Children <13 years of age contributed 13.7% of the total TB burden, but experienced more than half (52.2%) the TB incidence recorded in adults. Community-based surveillance data excluded the majority of children with severe disease. The accuracy of surveillance data is an important consideration when describing the epidemiology of childhood TB or measuring the success of public health interventions. © 2006 The Union.Articl