Immunologic-based Diagnosis of Latent Tuberculosis Among Children Younger Than 5 Years of Age Exposed and Unexposed to Tuberculosis in Tanzania

Said, Khadija; Hella, Jerry; Ruzegea, Mwajabu; Solanki, Rajesh; Chiryamkubi, Magreth; Mhimbira, Francis; Ritz, Nicole; Schindler, Christian; Mandalakas, Anna M.; Manji, Karim; Tanner, Marcel; Utzinger, Jürg; Fenner, Lukas

doi:10.1097/inf.0000000000002131

Cited by 11 publications

(9 citation statements)

References 30 publications

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“…IGRA performance depends on intact cellular Th1 responses. Helminth infections, which primarily induce Th2 responses, may alter cytokine production and thereby increase the rate of indeterminate results (20, 150, 160, 161).…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Indeterminate Interferon-Gamma Release Assay for the Diagnosis of Tuberculosis in Children—A Systematic Review and Meta-Analysis

et al. 2019

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Background: Interferon-gamma release assays (IGRA) are well-established immunodiagnostic tests for tuberculosis (TB) in adults. In children these tests are associated with higher rates of false-negative and indeterminate results. Age is presumed to be one factor influencing cytokine release and therefore test performance. The aim of this study was to systematically review factors associated with indeterminate IGRA results in pediatric patients. Methods: Systematic literature review guided by the preferred reporting items for systematic reviews and meta-analyses (PRISMA) searching PubMed, EMBASE, and Web of Science. Studies reporting results of at least one commercially available IGRA (QuantiFERON-TB, T-SPOT.TB) in pediatric patient groups were included. Random effects meta-analysis was used to assess proportions of indeterminate IGRA results. Heterogeneity was assessed using the I 2 value. Risk differences were calculated for studies comparing QuantiFERON-TB and T-SPOT.TB in the same study. Meta-regression was used to further explore the influence of study level variables on heterogeneity. Results: Of 1,293 articles screened, 133 studies were included in the final analysis. These assessed QuantiFERON-TB only in 77.4% (103/133), QuantiFERON-TB and T-SPOT.TB in 15.8% (21/133), and T-SPOT.TB only in 6.8% (9/133) resulting in 155 datasets including 107,418 participants. Overall 4% of IGRA results were indeterminate, and T-SPOT.TB (0.03, 95% CI 0.02–0.05) and QuantiFERON-TB assays (0.05, 95% CI 0.04–0.06) showed similar proportions of indeterminate results; pooled risk difference was−0.01 (95% CI −0.03 to 0.00). Significant differences with lower proportions of indeterminate assays with T-SPOT.TB compared to QuantiFERON-TB were only seen in subgroup analyses of studies performed in Africa and in non-HIV-infected immunocompromised patients. Meta-regression confirmed lower proportions of indeterminate results for T-SPOT.TB compared to QuantiFERON-TB only among studies that reported results from non-HIV-infected immunocompromised patients ( p < 0.001). Conclusion: On average indeterminate IGRA results occur in 1 in 25 tests performed. Overall, there was no difference in the proportion of indeterminate results between both commercial assays. However, our findings suggest that in patients in Africa and/or patients with immunocompromising conditions other than HIV infection the T-SPOT.TB assay appears to produce fewer indeterminate results.

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Section: Discussionmentioning

confidence: 99%

Risk Factors for Indeterminate Interferon-Gamma Release Assay for the Diagnosis of Tuberculosis in Children—A Systematic Review and Meta-Analysis

et al. 2019

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“…Even though 66.6% children had a known adult contact with TB, in a high burden TB setting like India, exposure from non-household sources in the community are important. Contact tracing of children of sputum-smear positive adults and chemoprophylaxis with isoniazid preventive therapy (IPT) can be an important strategy to prevent active TB 23 .…”

Section: Discussionmentioning

confidence: 99%

Clinical profile and outcome of children with tuberculosis in a tertiary care hospital in Mumbai, India

Pereira

2019

Sri Lanka J Child Health

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Introduction: As children are usually infected by an adult with pulmonary tuberculosis (TB), childhood TB reflects transmission of Mycobacterium tuberculosis within a community Objective: To study clinical profile and outcome of children with TB from 0 to 12 years of age in a tertiary care hospital in Mumbai, India. Method: A prospective observational descriptive study of 30 children with TB was conducted over 18 months at a tertiary general hospital in Mumbai and followed up till recovery. Results: Out of the 30 children with TB, 3 (10%) were below the age of 1 year, 8 (26.6%) were aged 1-5 years and 19 (63.3%) were above 5 years of age. Male to female ratio was 1:1.3. Extrapulmonary TB was more common (63.3%) than pulmonary TB (36.6%). Twenty (66.6%) children had a history of previous adult contact with TB, 29 (96.6%) were vaccinated with BCG and 10 (33.3%) were malnourished. Common clinical features were cough (53.3%), fever (46.6%), weight loss (46.6%) and lymphadenopathy (33.3%). Anaemia and raised ESR were seen in 46.6% and 73.3% respectively. All 30 children were non-reactive for the HIV antibody test. Tuberculin sensitivity test was positive in 16 out of 30 children (53.3%). Drug-resistant TB was seen in 2 (6.6%) children. All 30 cases (100%) recovered completely with their primary regimen. Conclusions: In this study, extra-pulmonary TB was found in 63.3% of children. TST positivity (>10mm) was found in only 53.3% of children with TB. Complete resolution of symptoms was seen in _________________________________________ 1

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“…Eight studies included in this review reported on paediatric patients living with HIV. [28][29][30][31][32][33][34][35] Of these, HIV seroprevalence was high (23.5%) in one study, which reported on children and adolescents starting TPT in Brazil. 30 In the remainder, HIV seroprevalence was relatively low (0.8%-4.5%).…”

Section: Resultsmentioning

confidence: 99%

A scoping review of paediatric latent tuberculosis infection care cascades: initial steps are lacking

2021

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Background and objectivesIdentifying and treating children with latent tuberculosis infection (TB infection) is critical to prevent progression to TB disease and to eliminate TB globally. Diagnosis and treatment of TB infection requires completion of a sequence of steps, collectively termed the TB infection care cascade. There has been no systematic attempt to comprehensively summarise literature on the paediatric TB infection care cascade.MethodsWe performed a scoping review of the paediatric TB infection care cascade. We systematically searched PubMed, Cumulative Index to Nursing and Allied Health Literature, Cochrane and Embase databases. We reviewed articles and meeting abstracts that included children and adolescents ≤21 years old who were screened for or diagnosed with TB infection, and which described completion of at least one step of the cascade. We synthesised studies to identify facilitators and barriers to retention, interventions to mitigate attrition and knowledge gaps.ResultsWe identified 146 studies examining steps in the paediatric TB infection care cascade; 31 included children living in low-income and middle-income countries. Most literature described the final cascade step (treatment initiation to completion). Studies identified an array of patient and caregiver-related factors associated with completion of cascade steps. Few health systems factors were evaluated as potential predictors of completion, and few interventions to improve retention were specifically tested.ConclusionsWe identified strengths and gaps in the literature describing the paediatric TB infection care cascade. Future research should examine cascade steps upstream of treatment initiation and focus on identification and testing of at-risk paediatric patients. Additionally, future studies should focus on modifiable health systems factors associated with attrition and may benefit from use of behavioural theory and implementation science methods to improve retention.

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Immunologic-based Diagnosis of Latent Tuberculosis Among Children Younger Than 5 Years of Age Exposed and Unexposed to Tuberculosis in Tanzania

Cited by 11 publications

References 30 publications

Risk Factors for Indeterminate Interferon-Gamma Release Assay for the Diagnosis of Tuberculosis in Children—A Systematic Review and Meta-Analysis

Risk Factors for Indeterminate Interferon-Gamma Release Assay for the Diagnosis of Tuberculosis in Children—A Systematic Review and Meta-Analysis

Clinical profile and outcome of children with tuberculosis in a tertiary care hospital in Mumbai, India

A scoping review of paediatric latent tuberculosis infection care cascades: initial steps are lacking

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