Invasive Pneumococcal Disease Among Immunocompromised Persons: Implications for Vaccination Programs.

BACKGROUND: In 2012/2013, a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) was recommended for immunocompromised adults in the United States and Canada. To assess the potential benefits of this recommendation, we assessed the serotype-specific burden of invasive pneumococcal disease (IPD) among immunocompromised individuals. METHODS: From 1995 to 2012, population-based surveillance for IPD was conducted in Metropolitan Toronto and Peel Region, Canada. Disease incidence and case fatality were measured in immunocompromised populations over time, and the contribution of different serotypes determined. RESULTS: Overall, 2115/7604 (28%) episodes of IPD occurred in immunocompromised persons. IPD incidence was 12-fold higher (95% confidence interval [CI], 8.7-15) in immunocompromised compared to immunocompetent persons; the case fatality rate was elevated in both younger (odds ratio [OR] 1.8) and older (OR 1.3) adults. Use of immunosuppressive medications was associated with a 2.1-2.7 fold increase in the risk of IPD. Five years after PPV23 program implementation, IPD incidence had declined significantly in immunocompromised adults (IRR 0.57, 95% CI, .40-.82). Ten years after pediatric PCV7 authorization, IPD due to PCV7 serotypes had decreased by 90% (95% CI, 77%-96%) in immunocompromised persons of all ages. In 2011/2012, 37% of isolates causing IPD in immunocompromised persons were PCV13 serotypes and 27% were PPV23/not PCV13 serotypes. CONCLUSIONS: Immunocompromised individuals comprised 28% of IPD. Both PPV23 and herd immunity from pediatric PCV7 were associated with reductions in IPD in immunocompromised populations. PCV13 vaccination of immunocompromised adults may substantially reduce the residual burden until herd immunity from pediatric PCV13 is fully established.

Epidemiology and clinical management of tuberculosis in children in Canada.

Although often regarded as a foreign disease, latent tuberculosis or tuberculosis disease will be encountered in many clinical situations by the Canadian child health practitioner. There are key differences between tuberculosis in children and adults. In the present article, the changing epidemiology of tuberculosis in children in Canada and around the world, the pathogenesis of infection, diagnostic tests, and clinical management of childhood latent tuberculosis and tuberculosis disease are reviewed.

Même si la tuberculose latente et la tuberculose sont souvent considérées comme des maladies étrangères, le dispensateur canadien de soins des enfants les observera souvent dans bien des situations cliniques. Il y a des différences clés entre la tuberculose chez l'enfant et chez l'adulte. Dans le présent article, les auteurs analysent l'évolution de l'épidémiologie de la tuberculose chez les enfants du Canada et de l'étranger, la pathogenèse de l'infection, les tests diagnostiques et la prise en charge de la tuberculose latente et de la tuberculose pendant l'enfance.

Quantiferon Gold-in-tube assay for TB screening in HIV infected children: influence of quantitative values.

BACKGROUND: HIV infected children are at increased risk of TB disease and require annual TB screening. Data on use of IGRA for TB screening in them are limited. We retrospectively evaluated the usefulness of Quantiferon Gold-in-tube test (QFT), an IGRA in screening for LTBI in relatively healthy, immunologically stable HIV infected children. METHODS: HIV infected children with no prior history of TB were screened for latent TB as part of routine care. They underwent risk of TB assessment, TST and QFT. QFT was repeated twice or three times depending on the quantitative values. Independent test validation was also performed. RESULTS: Eighty one children had 109 QFT tests. All had adequate mitogen responses. The initial QFT was positive in 15 (18.5%) children; quantitative IGRA responses were 0.35-1.0 IU/mL in 9 (60%), 1.0-10 IU/mL in5 (33.3%) and >10 IU/mL in 1 (6.7%). None that tested positive had documented TB exposure or TB disease. Baseline characteristics in the QFT positive and negative groups were similar. Repeat testing within 17 weeks demonstrated reversion to negative in 79% of cases. Repeat blinded independent testing of all QFT positive results and a random selection of initial negative tests demonstrated concordance in 96% of cases. Seven children (QFT > 1.0 IU/mL or positive TST) were offered INH preventive therapy. In no case has TB disease developed in 2 years of close follow-up. CONCLUSIONS: QFT is a valid method for LTBI screening relatively healthy, immunologically stable HIV infected children. However, reversion to negative on repeat testing and lack of correlation with TST results and risk of TB exposure makes interpretation difficult.

Strengthening Tuberculosis Services for Children and Adolescents in Low Endemic Settings.

In low tuberculosis-burden countries, children and adolescents with the highest incidence of tuberculosis (TB) infection or disease are usually those who have immigrated from high-burden countries. It is, therefore, essential that low-burden countries provide healthcare services to immigrant and refugee families, to assure that their children can receive proper testing, evaluation, and treatment for TB. Active case-finding through contact tracing is a critical element of TB prevention in children and in finding TB disease at an early, easily treated stage. Passive case-finding by evaluating an ill child is often delayed, as other, more common infections and conditions are suspected initially. While high-quality laboratory services to detect Mycobacterium tuberculosis are generally available, they are often underutilized in the diagnosis of childhood TB, further delaying diagnosis in some cases. Performing research on TB disease is difficult because of the low number of cases that are spread over many locales, but critical research on the evaluation and treatment of TB infection has been an important legacy of low-burden countries. The continued education of medical providers and the involvement of educational, professional, and non-governmental organizations is a key element of maintaining awareness of the presence of TB. This article provides the perspective from North America and Western Europe but is relevant to many low-endemic settings. TB in children and adolescents will persist in low-burden countries as long as it persists throughout the rest of the world, and these wealthy countries must increase their financial commitment to end TB everywhere.

Tuberculosis: evidence review for newly arriving immigrants and refugees.

BACKGROUND: The foreign-born population bears a disproportionate health burden from tuberculosis, with a rate of active tuberculosis 20 times that of the non-Aboriginal Canadian-born population, and could therefore benefit from tuberculosis screening programs. We reviewed evidence to determine the burden of tuberculosis in immigrant populations, to assess the effectiveness of screening and treatment programs for latent tuberculosis infection, and to identify potential interventions to improve effectiveness. METHODS: We performed a systematic search for evidence of the burden of tuberculosis in immigrant populations and the benefits and harms, applicability, clinical considerations, and implementation issues of screening and treatment programs for latent tuberculosis infection in the general and immigrant populations. The quality of this evidence was assessed and ranked using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: Chemoprophylaxis with isoniazid is highly efficacious in decreasing the development of active tuberculosis in people with latent tuberculosis infection who adhere to treatment. Monitoring for hepatotoxicity is required at all ages, but close monitoring is required in those 50 years of age and older. Adherence to screening and treatment for latent tuberculosis infection is poor, but it can be increased if care is delivered in a culturally sensitive manner. INTERPRETATION: Immigrant populations have high rates of active tuberculosis that could be decreased by screening for and treating latent tuberculosis infection. Several patient, provider and infrastructure barriers, poor diagnostic tests, and the long treatment course, however, limit effectiveness of current programs. Novel approaches that educate and engage patients, their communities and primary care practitioners might improve the effectiveness of these programs.

Distinguishing Features of Adolescents With Undiagnosed Infectious Tuberculosis Attending a Pediatric Emergency Department.

More than 10 days of fever or 13 days of cough differentiated adolescent patients presenting to a pediatric emergency department with infectious tuberculosis (TB) from most patients with pneumonia. Upper lobe involvement was significantly more common in patients with TB. Symptom- and radiograph-based algorithms could minimize TB exposure and aid diagnosis.

Choosing Wisely: Computed Tomography in the Diagnosis of Adolescents With Intrathoracic Tuberculosis.

In a retrospective study of adolescents with intrathoracic tuberculosis (TB), 26 out of the 81 (32%) patients had undergone chest computed tomography (CT). Chest CT was considered unnecessary in 7 (27%), necessary in 7 (27%), and possibly/probably helpful in 12 (46%). Promptly obtaining specimens for sputum smear microscopy, molecular testing, as well as culture for Mycobacterium tuberculosis could avoid several unnecessary CTs.

Impact of the COVID-19 pandemic on the provision of routine childhood immunizations in Ontario, Canada.

BACKGROUND: The COVID-19 pandemic has a worldwide impact on all health services, including childhood immunizations. In Canada, there is limited data to quantify and characterize this issue. METHODS: We conducted a descriptive, cross-sectional study by distributing online surveys to physicians across Ontario. The survey included three sections: provider characteristics, impact of COVID-19 on professional practice, and impact of COVID-19 on routine childhood immunization services. Multivariable logistic regression identified factors associated with modification of immunization services. RESULTS: A total of 475 respondents answered the survey from May 27th to July 3rd 2020, including 189 family physicians and 286 pediatricians. The median proportion of in-person visits reported by physicians before the pandemic was 99% and dropped to 18% during the first wave of the pandemic in Ontario. In total, 175 (44.6%) of the 392 respondents who usually provide vaccination to children acknowledged a negative impact caused by the pandemic on their immunization services, ranging from temporary closure of their practice (n = 18; 4.6%) to postponement of vaccines in certain age groups (n = 103; 26.3%). Pediatricians were more likely to experience a negative impact on their immunization services compared to family physicians (adjusted odds ratio [aOR] = 2.64, 95% CI: 1.48-4.68), as well as early career physicians compared to their more senior colleagues (aOR = 2.69, 95% CI: 1.30-5.56), whereas physicians from suburban settings were less impacted than physicians from urban settings (aOR = 0.62, 95% CI: 0.39-0.99). Some of the proposed solutions to decreased immunization services included assistance in accessing personal protective equipment, dedicated centers or practices for vaccination, universal centralized electronic immunization records and education campaigns for parents. CONCLUSIONS: COVID-19 has caused substantial modifications to pediatric immunization services across Ontario. Strategies to mitigate barriers to immunizations during the pandemic need to be implemented in order to avoid immunity gaps that could lead to an eventual increase in vaccine preventable diseases.

Epidemiology, clinical features and outcomes of incident tuberculosis in children in Canada in 2013-2016: results of a national surveillance study.

PURPOSE: Childhood tuberculosis disease is difficult to diagnose and manage and is an under-recognised cause of morbidity and mortality. Reported data from Canada do not focus on childhood tuberculosis or capture key epidemiologic, clinical and microbiologic details. The purpose of this study was to assess demographics, presentation and clinical features of childhood tuberculosis in Canada. METHODS: We conducted prospective surveillance from 2013 to 2016 of over 2700 paediatricians plus vertical tuberculosis programmes for incident tuberculosis disease in children younger than 15 years in Canada using the Canadian Paediatric Surveillance Program (CPSP). RESULTS: In total, 200 cases are included in this study. Tuberculosis was intrathoracic in 183 patients of whom 86% had exclusively intrathoracic involvement. Central nervous system tuberculosis occurred in 16 cases (8%). Fifty-one per cent of cases were hospitalised and 11 (5.5%) admitted to an intensive care unit. Adverse drug reactions were reported in 9% of cases. The source case, most often a first-degree relative, was known in 73% of cases. Fifty-eight per cent of reported cases were Canadian-born Indigenous children. Estimated study rates of reported cases (per 100 000 children per year) were 1.2 overall, 8.6 for all Indigenous children and 54.3 for Inuit children. CONCLUSION: Childhood tuberculosis may cause significant morbidity and resource utilisation. Key geographies and groups have very high incidence rates. Elimination of childhood tuberculosis in Canada will require well-resourced community-based efforts that focus on these highest risk groups.

A population-based study of tuberculosis in children and adolescents in Ontario.

BACKGROUND: There are few population-based data on presentation and treatment of tuberculosis (TB) in children and adolescents in Ontario. METHODS: We analyzed data from 121 patients less than 17 years of age with TB disease reported to the Province of Ontario between 1999 and 2002. Physician provider data were obtained from the College of Physicians and Surgeons of Ontario. RESULTS: Of the 121 patients, 84 (69.4%) patients were foreign born. The median time of residence in Canada before diagnosis was 2.7 years (range, 7 days-16 years). Diagnosis was made by symptoms in 78 (64.5%), by contact investigation in 25 (20.7%), and by immigration screening in 5 (4.1%) patients. Pulmonary TB occurred in 94 (77.7%) patients. When cases detected by contact tracing and screening were excluded, isolated extrapulmonary TB was present in 4 (23.5%), 6 (35.0%), and 19 (37.0%) of young children (0-4 years), older children (5-12 years), and adolescents (13-17 years), respectively. Eleven patients (9.1%) had drug-resistant strains. Eighty (66.1%) patients received directly observed therapy (DOT). Prescribed treatment was completed in 105 (86.8%) patients with a trend toward higher completion rates in those receiving DOT (P = 0.07). Of 57 physician providers, 50 (87.7%) had treated less than 1 pediatric TB patient/year during the study period. CONCLUSIONS: Extrapulmonary disease accounted for a high proportion of TB in older children and adolescents who presented with symptoms. One-third of patients did not receive DOT and most were cared for by physicians with limited experience in managing TB. Further studies are needed to determine whether these factors influence outcome in pediatric TB.