Burden Of Childhood Tuberculosis Research Articles

1643. A scoping review of pediatric latent tuberculosis care cascades: Initial steps are lacking

BackgroundEach year an estimated 1 million children develop and ~200,000 die from tuberculosis (TB). The WHO has named identification and treatment of latent tuberculosis infection (LTBI) one of the cornerstones of efforts to eliminate TB by 2030. Identification and treatment of pediatric LTBI requires completion of a complex care cascade. While attention has been given to LTBI care cascades in adults, to date there has been no attempt to map literature on the pediatric LTBI care cascade.Facilitators and barriers to retention in steps of the pediatric LTBI care cascadeMethodsWe systematically searched PubMed, CINAHL, Cochrane and Embase databases for papers and abstracts describing screening, diagnosis, and treatment of pediatric LTBI. We categorized literature using seven step-offs in the pediatric LTBI care cascade, extrapolated from prior studies focused on adults: 1) intention to screen to initial test, 2) initial test to receipt of results, 3) receipt to referral for evaluation, 4) referral to completion of evaluation, 5) completion to treatment recommendation, 6) recommendation to treatment acceptance/initiation, and 7) initiation to treatment completion. Our aim was to assess factors that facilitated and inhibited completion of each cascade step, and to identify knowledge gaps in this literature.ResultsWe identified 137 studies that met inclusion criteria. Most studies described multiple step-offs in the care cascade, although the focus of most (120/137 studies) was on initiation and completion of LTBI therapy (the final step in the care cascade). Several effective strategies to improve medication adherence were described, including selective use of nursing visits, directly observed therapy, shorter treatment regimens, and peer counseling. Reports of facilitators and barriers for retention in upstream step-offs in the cascade were scarce, revealing a lack of published evidence for how to retain children from pre-screening to treatment initiation (Table). ConclusionWhile existing literature describes LTBI treatment initiation and completion in children, our analysis reveals a lack of data guiding retention of children from LTBI screening through treatment initiation. This review highlights the need to further understand early steps of the care cascade, in order to help alleviate the burden of TB in children.DisclosuresJessica Haberer, MD, MS, Merck (Consultant)

Improving case detection of tuberculosis in hospitalised Kenyan children\u2014employing the behaviour change wheel to aid intervention design and implementation

BackgroundThe true burden of tuberculosis in children remains unknown, but approximately 65% go undetected each year. Guidelines for tuberculosis clinical decision-making are in place in Kenya, and the National Tuberculosis programme conducts several trainings on them yearly. By 2018, there were 183 GeneXpert® machines in Kenyan public hospitals. Despite these efforts, diagnostic tests are underused and there is observed under detection of tuberculosis in children. We describe the process of designing a contextually appropriate, theory-informed intervention to improve case detection of TB in children and implementation guided by the Behaviour Change Wheel.MethodsWe used an iterative process, going back and forth from quantitative and qualitative empiric data to reviewing literature, and applying the Behaviour Change Wheel guide. The key questions reflected on included (i) what is the problem we are trying to solve; (ii) what behaviours are we trying to change and in what way; (iii) what will it take to bring about desired change; (iv) what types of interventions are likely to bring about desired change; (v) what should be the specific intervention content and how should this be implemented?ResultsThe following behaviour change intervention functions were identified as follows: (i) training: imparting practical skills; (ii) modelling: providing an example for people to aspire/imitate; (iii) persuasion: using communication to induce positive or negative feelings or stimulate action; (iv) environmental restructuring: changing the physical or social context; and (v) education: increasing knowledge or understanding. The process resulted in a multi-faceted intervention package composed of redesigning of child tuberculosis training; careful selection of champions; use of audit and feedback linked to group problem solving; and workflow restructuring with role specification.ConclusionThe intervention components were selected for their effectiveness (from literature), affordability, acceptability, and practicability and designed so that TB programme officers and hospital managers can be supported to implement them with relative ease, alongside their daily duties. This work contributes to the field of implementation science by utilising clear definitions and descriptions of underlying mechanisms of interventions that will guide others to do likewise in their settings for similar problems.

Burden of Tuberculosis in South African Children During Treatment for Underlying Malignancies: A Single-center Experience in Johannesburg.

Children with cancer are immunocompromised with increased susceptibility to infections. We evaluated the burden of tuberculosis in children with cancer. Children with cancer were enrolled and screened for Mycobacterium tuberculosis infection using the tuberculin skin test and enzyme-linked immune absorbent spot (T-SPOT.TB; Oxford Immunotec Ltd, Oxford, United Kingdom). Children with physician-suspected tuberculosis were investigated for M. tuberculosis using microscopy and culture on sputum or gastric washings. We enrolled 169 children; 10.7% were living with HIV. The tuberculin skin test was positive in 2.9% of patients, who were treated for tuberculosis and excluded from further analysis. The enzyme-linked immune absorbent spot (T-SPOT.TB) was either negative or indeterminate in the first 100 children screened. The incidence of tuberculosis was 7.6 per 100 child-years; 35.3% were culture-confirmed. Tuberculosis was diagnosed at a mean of 5.5 months from cancer diagnosis. A greater proportion of children living with HIV (44.4%) developed tuberculosis than those without (17.2%; adjusted P = 0.042). Children treated for high-risk acute lymphoblastic leukemia, advanced stage non-Hodgkin lymphoma and acute myeloid leukemia (P = 0.009) and those with a higher exposure-period (per 100 child-years) to corticosteroids courses (350 vs. 29.4; P < 0.001) had a higher incidence of tuberculosis. Twenty-six of 34 children (76.5%) with tuberculosis died; multiple infections were identified at the time of death. Screening children for tuberculosis infection at cancer diagnosis was of limited value. The high rate of tuberculosis and poor outcomes emphasize the need for a high index of suspicion to diagnose tuberculosis and consideration for antituberculosis treatment, especially for those with identified risk factors.

Study of Clinico-Radiological Profile in Childhood Tuberculosis

Background: Tuberculosis still is one of the deadliest diseases in the world killing nearly 2 million people every year. In India, two deaths occur every three minutes from tuberculosis. The actual global disease burden of childhood tuberculosis is not known, as childhood Tuberculosis is notoriously difficult to diagnose because of the absence of a ‘gold standard’ as bacteriologic confirmation is rarely achieved. The present study was designed to study clinical profile of various forms of childhood TB. Objective of this study was to study clinic-epidemiological profile of various forms of childhood TB.Subject and Method:Retrospective analysis of clinical profile of 100 patients of childhood TB in the age group of 6 months to 12 years. A detailed clinical history, family history of contact with Koch’s disease, history of BCG vaccination of each child was recorded. A complete examination was carried out and findings regarding the general and systemic examination were recorded. Result:Age distribution in our study showed that 51% cases in the age of 5-12 years, 47% cases in the age group 1-5 years and 2 % cases falling in the age group 0-1 years, with male to female ratio of a 1.27:1. 95% of the patients belonged to the lower socio-economic class. The distribution of TB was- pulmonary tuberculosis(42%),TBME(30%),pleural effusion(12%),abdominal TB (12%), TB lymphadenitis(4%), Osteotuberculosis(2%), miliary TB(2%). 12% of the patients had mild to moderate malnutrition (PEM Grade I, II)and 57 % were severely malnourished. 72% of the patients were BCG vaccinated and history of Koch’s contact were present in 21% of all cases. The most frequently seen symptoms were fever (88%), cough (65%), weight loss in 50%, anorexia in 35% of cases and in physical examination cachexia was the most common (50%) followed by hepatomegaly (40%),lymphadenopathy(16%) and Splenomegaly (8%) of cases. Conclusion:childhood TB is commonly seen in children more than 1 year, lower socioeconomic class and in severely malnourished children.

The Epidemiology of Tuberculosis in Children

AbstractThe epidemiology of tuberculosis, particularly in children, is highly intertwined with socio-political factors, such as poverty, access to healthcare, and migration. Growing evidence around the world shows that more children have tuberculosis (TB) than was previously thought, most of whom are undiagnosed and untreated, and that TB is a significant cause of morbidity and mortality in children in TB endemic areas. Since TB in young children results from recent transmission, the incidence of pediatric TB is a marker of epidemic control in a community and an indirect indicator of the effectiveness of TB control programs. It is estimated that pediatric TB represents between 4 and 21% of all TB cases, depending on the background prevalence in the country, and at least 10 to 20% of the total cases in areas with poor epidemic control. However, a precise estimate of the global burden of TB in children is difficult due to challenges in case ascertainment, diagnosis, and weak surveillance systems in many countries with a high burden of disease. Several recent estimates highlight these difficulties and provide a starting point to motivate further study. In addition, since drug-resistant TB in young children reflects transmission of resistant strains in the community and occurs with the same frequency as in treatment-naive adults, accurate monitoring of drug-susceptibility patterns in pediatric TB cases will inform optimal empiric treatment regimens in both adults and children, in the context of increasing rates of drug-resistant TB globally.

Global Burden of Childhood Tuberculosis.

In 2015, the World Health Organization (WHO) declared tuberculosis (TB) to be responsible for more deaths than any other single infectious disease. The burden of TB among children has frequently been dismissed as relatively low with resulting deaths contributing very little to global under-five all-cause mortality, although without rigorous estimates of these statistics the burden of childhood TB was, in reality, unknown. Recent work in the area has resulted in a WHO estimate of 1 million new cases of childhood TB in 2014 resulting in 136,000 deaths. Around 3% of these cases likely have multidrug-resistant TB and at least 40,000 are in HIV-infected children. TB is now thought to be a major or contributory cause of many deaths in children under five years old, despite not being recorded as such, and is likely in the top ten causes of global mortality in this age group. In particular, recent work has shown that TB is an underlying cause of a substantial proportion of pneumonia deaths in TB-endemic countries. Childhood TB should be given higher priority: we need to identify children at greatest risk of TB disease and death and make more use of tools such as active case-finding and preventive therapy. TB is a preventable and treatable disease from which no child should die.

Global burden of drug-resistant tuberculosis in children: A mathematical modelling study

Global burden of drug-resistant tuberculosis in children: A mathematical modelling study

Smear positivity in paediatric and adult tuberculosis: systematic review and meta-analysis

BackgroundTuberculosis (TB) diagnosis continues to rely on sputum smear microscopy in many settings. We conducted a meta-analysis to estimate the percentage of children and adults with tuberculosis that are sputum smear positive.MethodsWe searched PubMed, MEDLINE, Embase, and Global Health databases for studies that included both children and adults with all forms of active TB. The pooled percentages of children and adults with smear positive TB were estimated using the inverse variance heterogeneity model. This review was registered in the PROSPERO database under registration number CRD42015015331.ResultsWe identified 20 studies meeting our inclusion criteria that reported smear positivity for a total of 18,316 children and 162,574 adults from 14 countries. The pooled percentage of paediatric TB cases that were sputum smear positive was 6.8 % (95 % Confidence Interval (CI) 2.2–12.2 %), compared with 52.0 % (95 % CI 40.0–64.0 %) among adult cases. Eight studies reported data separately for children aged 0–4 and 5–14. The percentage of children aged 0–4 that were smear positive was 0.5 % (95 % CI 0.0–1.9 %), compared with 14.0 % (95 % CI 8.9–19.4 %) among children aged 5–14.ConclusionsChildren, especially those aged 0–4, are much less likely to be sputum smear positive than adults. National TB programs relying on sputum smear for diagnosis are at risk of under-diagnosing and underestimating the burden of TB in children.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-016-1617-9) contains supplementary material, which is available to authorized users.

Prevalence and health-care seeking behavior of chest symptomatic among children in Udupi, Karnataka

Background: Globally, the burden of tuberculosis is estimated to be highest in India. As per Revised National Tuberculosis Control Program (RNTCP) India 2011 Report, 44,357 smear-positive cases were diagnosed among all age groups in Karnataka State, and Udupi reported 8% of pediatric cases in all new cases. Tuberculosis often goes undiagnosed in children; the success of tuberculosis control depends on early diagnosis and appropriate treatment, which is the epidemiological basis of the global plan to stop tuberculosis. Considering these aspects, this study was undertaken.Objective: To find out the prevalence of chest symptomatic in children below 15 years and to study the health-care seeking behavior of caregivers. Materials and Methods: A community-based cross-sectional study was carried out in the rural areas of Udupi Taluk,Karnataka, India. A two-stage cluster sampling technique was adopted to conduct this study. The caregivers of children below 15 years of age were interviewed for the collection of data. Chest symptomatic was considered as the children having persistent fever with cough more than 2 weeks in the last 3 months.Result: Prevalence of chest symptomatic was 0.64%, and 93.5% of caregivers had consulted health-care facility for treatment of their children. A total of 98.7% of children were vaccinated with Bacillus Calmette–Guerin (BCG) vaccine, whereas 1.29% of children were not vaccinated with BCG vaccine.Conclusion: Community awareness and strengthening of RNTCP for early detection and treatment of chest symptoms among children may contribute in reducing the burden of childhood tuberculosis.

Clinical Predictors of Culture-confirmed Pulmonary Tuberculosis in Children in a High Tuberculosis and HIV Prevalence Area

The burden of childhood tuberculosis (TB) remains significant especially in areas of high HIV prevalence. Clinical diagnosis predominates, despite advances in molecular and microbiological diagnostics. The aim of this study is to identify clinical features associated with culture-confirmed pulmonary TB (PTB) in children. Children admitted to hospital were enrolled in a study of novel diagnostics for PTB in South Africa. Standardized clinical, radiological and microbiological data were collected. Definite TB was defined by culture of Mycobacterium tuberculosis from a respiratory specimen. Adjusted odds ratios for definite TB were calculated using a multivariate logistic regression model. Adjusted odds ratio (AOR) for definite TB increased with a history of fever for more than 1 week [AOR: 8.54, 95% confidence interval (CI): 2.37-30.74], with a chest radiograph (CXR) suggestive of PTB (AOR: 10.0, 95% CI: 3.22-31.2) and with a positive tuberculin skin test (TST; AOR: 64.4, 95% CI: 14.3-290.5). The likelihood ratio of having definite TB if 2 of these factors (CXR and TST) were present compared with having none of them was 17.7. Cough, household contact with TB, HIV status and wheezing were not significantly associated with definite TB. Prolonged fever, CXR suggestive of TB or a positive TST were predictive of definite TB and should be considered in composite scoring systems for TB diagnosis in high HIV prevalence settings. Other commonly associated symptoms were not associated with definite TB.

Newer Diagnostic Tests for Pulmonary Tuberculosis in Children.

It has been well recognized that the diagnosis of pulmonary tuberculosis in children is often compromised by non-specific symptoms, paucibacillary nature of the disease, and the difficulty in collecting the specimen. Consequently, most tuberculosis cases in children are not confirmed, due to which the estimation of the global burden of tuberculosis in children may be inaccurate. There has also been a common misperception that diagnosis of tuberculosis and collecting respiratory specimen in children is always difficult. Because of this, microbiological confirmation of tuberculosis in young children is not routinely attempted in most endemic areas. With the emergence of HIV-related tuberculosis disease and drug-resistant tuberculosis, the availability of accurate, rapid and child friendly diagnostic tools to identify Mycobacterium tuberculosis in respiratory specimen are urgently required in endemic settings. There have been a large number of studies evaluating new diagnostic tests for tuberculosis in the past decade, but few have been evaluated in children. This review will address the developments in respiratory specimen collection and laboratory diagnostic tests of tuberculosis, with a focus on those that have been evaluated in children.

Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study.

Confirmation of a diagnosis of tuberculosis in children (aged <15 years) is challenging; under-reporting can result even when children do present to health services. Direct incidence estimates are unavailable, and WHO estimates build on paediatric notifications, with adjustment for incomplete surveillance by the same factor as adult notifications. We aimed to estimate the incidence of infection and disease in children, the prevalence of infection, and household exposure in the 22 countries with a high burden of the disease. Within a mechanistic mathematical model, we combined estimates of adult tuberculosis prevalence in 2010, with aspects of the natural history of paediatric tuberculosis. In a household model, we estimated household exposure and infection. We accounted for the effects of age, BCG vaccination, and HIV infection. Additionally, we tested sensitivity to key structural assumptions by repeating all analyses without variation in BCG efficacy by latitude. The median number of children estimated to be sharing a household with an individual with infectious tuberculosis in 2010 was 15,319,701 (IQR 13,766,297-17,061,821). In 2010, the median number of Mycobacterium tuberculosis infections in children was 7,591,759 (5,800,053-9,969,780), and 650,977 children (424,871-983,118) developed disease. Cumulative exposure meant that the median number of children with latent infection in 2010 was 53,234,854 (41,111,669-68,959,804). The model suggests that 35% (23-54) of paediatric cases of tuberculosis in the 15 countries reporting notifications by age in 2010 were detected. India is predicted to account for 27% (22-33) of the total burden of paediatric tuberculosis in the 22 countries. The predicted proportion of tuberculosis burden in children for each country correlated with incidence, varying between 4% and 21%. Our model has shown that the incidence of paediatric tuberculosis is higher than the number of notifications, particularly in young children. Estimates of current household exposure and cumulative infection suggest an enormous opportunity for preventive treatment. UNITAID and the US Agency for International Development.

Epidemiology and disease burden of tuberculosis in children: a global perspective.

Our understanding of the tuberculosis (TB) epidemic in children is incomplete due to challenges in diagnosis and reporting. Children have also been largely excluded from research and advocacy. However, the tide appears to be turning and interest in pediatric TB is increasing. In this article, we explore the epidemiology of childhood TB by first reviewing the natural history of TB in children and the factors that impact on each of the stages from exposure to disease. We then discuss how these factors affect what we see at a country and regional level. Finally, we assess the burden of childhood TB globally.

Xpert MTB/RIF: The newly endorsed TB diagnostic

Early diagnosis of drug-resistant tuberculosis is desirable to treat patient's regimens and to prevent the transmission of resistant strains. Real-time PCR assays have been developed to detect drug resistance rapidly, but none of them have been widely applied due to their complexity, high cost, or requirement for advanced instruments. GeneXpert is now approved by WHO for use in low income settings and can be used to screen pulmonary as well as extra pulmonary specimens for resistance to Rifampicin with as low as 2 h of Turnaround Time (TAT). Tuberculosis (TB) in children is rarely confirmed due to the lack of effective diagnostic tools; approximately 10–15% of pediatric TB is smear-positive due to paucibacillary samples and the difficulty of obtaining high-quality specimens from children. TB is one of the top ten killers of children worldwide. Every day, up to 200 children lose their lives to TB and every year, up to 74,000 needlessly die. It is estimated that over half a million cases of TB occur in children every year, although researchers believe this figure is much higher as childhood TB is under reported. The true burden of TB in children is unknown due to inadequate surveillance and reporting of childhood TB cases.

Tuberculosis diagnostics for children in high-burden countries: what is available and what is needed

Background: The diagnosis of childhood tuberculosis (TB) is complex and most of the new diagnostics for TB are for adults.Aims: To review the performance of TB diagnostics and their suitability to its characteristics in young children.Methods: Expert opinion and review of the literature.Main findings: The lack of a sufficient number of research studies on TB diagnostics for children hinders the preparation of systematic literature reviews. Information on test performance in children is often extrapolated from studies in adults and there is a dearth of evidence of test performance in children. Approaches to shorten the time required for diagnosis (by using a variety of specimens) are needed and there is preliminary evidence that such schemes are feasible. Diagnostics based on smear microscopy such as LED-FM, serological tests and IGRAS are unlikely to improve the diagnosis of active TB in children. Liquid and the MODS culture methods are more sensitive than solid culture, and new methods to detect mycobacterium nucleic acid or its components such as TrDNA fragments, LAMP assays and Xpert MTB/RIF have good potential to increase the number of cases confirmed. These tests should be evaluated in specimens which are easily accessible in children such as fine-needle aspiration biopsy, urine, blood and stools.Interpretation: The evaluation of new diagnostic tests for TB in children is overdue. The lack of suitable diagnostic tests hinders the proper management of children, the assessment of the real burden of childhood TB, evaluation of the efficacy of new treatments and vaccines and, ultimately, the development of effective control interventions.

Promising directions in the diagnosis of childhood tuberculosis

Estimates of the burden of childhood tuberculosis have been hampered by the lack of a reliable diagnostic test. Clinical scoring systems, radiological findings and tuberculin skin testing (the traditional methods used for diagnosis) are unreliable, particularly in the era of HIV. Microbiologic confirmation using induced sputum is feasible and has become increasingly important to define the burden of disease and to enable appropriate treatment. The availability of a rapid molecular diagnostic test (Xpert® MTB/RIF; Cepheid) is an important advance that can improve case detection in children and enable rapid detection of mycobacterial drug resistance. Xpert testing of two induced sputum specimens detected approximately 75% of children with culture-confirmed disease. Urine lipoarabinomannan has shown promise as a rapid diagnostic in a subgroup of HIV-infected severely immunocompromised adults, but there have been no data in children so far. Further research is needed to develop a rapid point-of-care, reliable and affordable diagnostic test for childhood tuberculosis that can be widely used.

High caseload of childhood tuberculosis in hospitals on Java Island, Indonesia: a cross sectional study.

BackgroundChildhood tuberculosis (TB) has been neglected in the fight against TB. Despite implementation of Directly Observed Treatment Shortcourse (DOTS) program in public and private hospitals in Indonesia since 2000, the burden of childhood TB in hospitals was largely unknown. The goals of this study were to document the caseload and types of childhood TB in the 0-4 and 5-14 year age groups diagnosed in DOTS hospitals on Java Island, Indonesia.MethodsCross-sectional study of TB cases recorded in inpatient and outpatient registers of 32 hospitals. Cases were analyzed by hospital characteristics, age groups, and types of TB. The number of cases reported in the outpatient unit was compared with that recorded in the TB register.ResultsOf 5,877 TB cases in the inpatient unit and 15,694 in the outpatient unit, 11% (648) and 27% (4,173) respectively were children. Most of the childhood TB cases were under five years old (56% and 53% in the inpatient and outpatient clinics respectively). The proportion of smear positive TB was twice as high in the inpatient compared to the outpatient units (15.6% vs 8.1%). Extra-pulmonary TB accounted for 15% and 6% of TB cases in inpatient and outpatient clinics respectively. Among children recorded in hospitals only 1.6% were reported to the National TB Program.ConclusionIn response to the high caseload and gross under-reporting of childhood TB cases, the National TB Program should give higher priority for childhood TB case management in designated DOTS hospitals. In addition, an international guidance on childhood TB recording and reporting and improved diagnostics and standardized classification is required

Human Immunodeficiency Virus and Tuberculosis Coinfection in Children

The burden of childhood tuberculosis (TB) is influenced by the human immunodeficiency virus (HIV) epidemic and this dangerous synergy affects various aspects of both diseases; from pathogenesis and the epidemiologic profile to clinical presentation, diagnosis, treatment, and prevention. HIV-infected infants and children are at increased risk of developing severe forms of TB. The TB diagnosis is complicated by diminished sensitivity and specificity of clinical features and diagnostic tools like the tuberculin skin test and chest x-ray. Although alternative ways of pulmonary sampling and the development of interferon-γ assays have shown to lead to some improvement of TB diagnosis in HIV-infected children, new diagnostic tools are urgently needed. Coadministration of anti-TB treatment and antiretroviral drugs induces severe complications, and this highlights the need to define optimal treatment regimens. Practical implementation of these regimens in TB control programs should be combined with isoniazid preventive therapy in TB-exposed HIV-infected children. The risk of severe complications after Bacille Calmette-Guérin vaccination of HIV-infected children emphasizes the need for new nonviable vaccines. This article reviews the current status of pediatric HIV-TB coinfection with specific emphasis on the diagnosis and treatment.

Childhood tuberculosis guidelines of the Southern African Society for Paediatric Infectious Diseases

The World Health Organization has led the way in terms of guiding global policy in the management of children with suspected and/or confrmed tuberculosis (TB), through the publication in 2006 of its ‘Guidance for national tuberculosis programmes on the management of tuberculosis in children’. National policy documents in settings with a high TB burden may not comply with these latest management strategies. This document, formulated on behalf of the Southern African Society for Paediatric Infectious Diseases, sets out to inform healthcare workers in southern Africa about the latest policies with regard the management of children with suspected TB in the region, in order to streamline case management according to current evidence and practice. As such, its main objectives are to raise awareness about the burden of childhood TB in the region, to intensify case fnding and to conform management according to common, contemporary practice which will hopefully beneft childhood TB outcomes.