TST-positive Children Research Articles

Potential effect of household contact management on childhood tuberculosis: a mathematical modelling study.

SummaryBackgroundTuberculosis is recognised as a major cause of morbidity and mortality in children, with most cases in children going undiagnosed and resulting in poor outcomes. Household contact management, which aims to identify children with active tuberculosis and to provide preventive therapy for those with HIV or those younger than 5 years, has long been recommended but has very poor coverage globally. New guidelines include widespread provision of preventive therapy to children with a positive tuberculin skin test (TST) who are older than 5 years.MethodsIn this mathematical modelling study, we provide the first global and national estimates of the impact of moving from zero to full coverage of household contact management (with and without preventive therapy for TST-positive children older than 5 years). We assembled data on tuberculosis notifications, household structure, household contact co-prevalence of tuberculosis disease and infection, the efficacy of preventive therapy, and the natural history of childhood tuberculosis. We used a model to estimate households visited, children screened, and treatment courses given for active and latent tuberculosis. We calculated the numbers of tuberculosis cases, deaths, and life-years lost because of tuberculosis for each intervention scenario and country.FindingsWe estimated that full implementation of household contact management would prevent 159 500 (75% uncertainty interval [UI] 147 000–170 900) cases of tuberculosis and 108 400 (75% UI 98 800–116 700) deaths in children younger than 15 years (representing the loss of 7 305 000 [75% UI 6 663 000–7 874 000] life-years). We estimated that preventing one child death from tuberculosis would require visiting 48 households, screening 77 children, giving 48 preventive therapy courses, and giving two tuberculosis treatments versus no household contact management.InterpretationHousehold contact management could substantially reduce childhood disease and death caused by tuberculosis globally. Funding and research to optimise its implementation should be prioritised.FundingUK Medical Research Council, US National Institutes of Health, Fulbright Commission, Janssen Global Public Health.

Evaluation of Treatment Indications, Tuberculin Skin Test, and Bacillus Calmette-Guerin Vaccination Scars in the Cases of Latent Tuberculosis Infection Treatment

The aim of our study was to evaluate the latent tuberculosis infection (LTBI) treatment application and to investigate if there is change between tuberculin skin test (TST) results according to bacillus Calmette-Guerin (BCG) scar numbers after LTBI treatment with isoniazid (INH). Data were collected from the LTBI treatment files from the dispensary of 2006. The results were statistically evaluated. Latent tuberculosis infection was administered to 253 cases in 2006. The male/female case rate was 51/49. The age of most patients was under 15 years out of 14 cases. The mean age was 8.92±6.87 years (range, 0-84 years). One case had liver function test abnormality and INH was stopped in the first month of treatment. The completion rate of LTBI treatment was 95%. BCG vaccination rate was 93%. Active tuberculosis did not develop during the LTBI treatment in our study. Of all the cases, 221 scar numbers and TST were full. Of all cases 221 the scar numbers and TST value were full.TST of the 221 cases according to BCG vaccine scar numbers and indications were compared pre- and post-treatment with INH. Indications for LTBI treatment in these cases were close contact with smear-positive active pulmonary tuberculosis cases (n=77, 35%), TST-positive children aged <15 years (n=138, 62%), and the other (n=6, 3%) immunosuppressed patient cases. After treatment with INH, TST values decreased in the TST-positive children aged <15 years with one and 2 scars, with a statistically significant this result were found statistically significant (p<0.05). The age of patients in most cases with LTBI treatment was under 15 years. The treatment completion rate and BCG vaccination rate were high. One case had liver function test abnormality. Active tuberculosis did not develop during the LTBI treatment. In the group with TST-positive children aged <15 years with one and 2 BCG vaccine scars, the decrease between pre- and post-treatment TST results showed a statistically significant difference.

Prevalence of Latent Tuberculosis Among Children Living in Households with Smear Positive Pulmonary Tuberculosis Patients

This multicentre cross sectional analytical study was conducted in 2012 in Chittagong, Bangladesh, to evaluate the prevalence of latent tuberculosis infection (LTBI) among children living in households with smear positive pulmonary tuberculosis patient. Two groups of subjects were selected. Sixty five children of 3-12 years living with selected smear positive TB patient and children of same age living with healthy parents were included. For this purpose, sputum positive adult TB patients were selected. Mantoux test (TST) was done in 130 children. To exclude active TB disease in TST positive children, CXR P/A view was taken. Sociodemographic information were also included. The study found that the prevalence of LTBI among children who have household TB contacts was 41.5%, and Children who did not have household TB contact had the prevalence of LTBI of 9.2%. Parents’ educational status showed that 74.1% of MT positive children had illiterate father and 63% children had illiterate mother. Ninety two percent of MT positive children were from lower and lower middle class family and only 7.2% were from upper class family. It was found that, mean family members were much higher (4.39±0.77) in MT positive cases comparing with MT negative cases (3.7±0.85). 88.9% of MT positive children were living in the same bed and 55.6% were living in different beds in the same house. The present study found that the prevalence of LTBI among children with household contacts of TB patient was higher than non-contact children Parent’s illiteracy, lower socio-economic, large family, sharing of same indoor environment further increased the prevalence of LTBI among the contacts.

FACTORS AFFECTING TB TRANSMISSION FROM ADULT TO CHILDREN WITHIN HOUSEHOLDS IN THE GAMBIA

BackgroundChildhood tuberculosis (TB) has significant impact on public health worldwide and it is believed that most children acquire TB from an adult smear-positive index case within their household. To further...

Identifying children with tuberculosis among household contacts in The Gambia.

Greater Banjul Area of the Gambia. To identify co-prevalent tuberculosis (TB) among child contacts of adults with smear-positive TB. Child contacts aged <15 years in the immediate household and compound were prospectively enrolled and evaluated for TB disease using screening questionnaires and the tuberculin skin test (TST). Symptomatic and/or TST-positive (10 mm) contacts were further investigated. Of 4042 child contacts who underwent symptom screening and TST, 3339 (82.6%) were diagnosed as TB-exposed but not infected, 639 (15.8%) were latently infected and 64 (1.6%) had co-prevalent TB. Of the 64 TB cases, 50 (78.1%) were from within the immediate household of the index case, and 14 (21.9%) from within the same compound. Of the 27 asymptomatic but TST-positive children diagnosed with TB, 7 were microbiologically confirmed. The median age of the TB cases was 4.4 years (interquartile range 1.9-6.9); 53.1% were aged <5 years. Of the 4042 child contacts, 206 (5%) slept in the same bed as the index case; 28.1% of all TB cases occurred in this group. Symptom screening alone would have detected only 57.8% of the co-prevalent cases. In our community setting, if contact tracing is restricted to symptom screening and immediate households only, nearly half of all co-prevalent TB disease in child contacts would be missed.

Interferon‐gamma release assays can effectively screen migrants for the tuberculosis infection, but urgent, active cases need clinical recognition

Increasing numbers of migrants to Sweden are screened for tuberculosis (TB), and a rational approach to screening is required. We evaluated positive tuberculin skin tests (TSTs) and interferon-gamma release assays (IGRAs) on paediatric migrants in relation to the TB incidence in the corresponding foreign-born populations in Stockholm. This study examined the characteristics of migrants under the age of 18 who were referred to a paediatric TB clinic at Karolinska University Hospital from 2008 to 2014 by primary care centres in Stockholm County. We saw 943 TST-positive children with a median age of 14 years at the TB clinic and performed IGRAs on 557. IGRA positivity ranged from 64% in migrants from Somalia to 20% in those from the former Soviet Union and eastern Europe, with an estimated population level prevalence of 18.8% and 4.2%, respectively. These were significantly correlated to TB incidence in foreign-born Stockholm children. We diagnosed active TB in 20 screened migrants, and advanced, symptomatic TB was diagnosed in 10 recently arrived migrants without screening. IGRAs showed higher specificity than TST in identifying tuberculosis. TB screening should focus on migrants from high-incidence countries, but this may be inadequate to detect advanced TB cases.

Evaluation of the Impact of Interferon-Gamma Release Assays on the Management of Childhood Tuberculosis

Interferon-gamma release assays are increasingly being used in low-incidence settings, but there is little information on whether test results influence clinical decisions in children. In June 2009, the Montreal Children's Hospital began implementing the QuantiFERON-TB Gold In-Tube (QFT) as a follow-up test to the tuberculin skin test (TST). Pediatric respirologists were asked to document how the QFT result changed their initial clinical management based on the TST. During a 2-year period, 399 children with TST and QFT results were recruited prospectively. The median age was 13 years. In the cohort, 83% were foreign-born and 82% were Bacille Calmette-Guérin vaccinated. The QFT was negative in 5 of 11 (45.5%) children diagnosed with active tuberculosis (TB). Among 55 TST+/QFT- children evaluated as TB contacts, the negative QFT changed the treatment decision in only 3 (5.5%), and isoniazid was prescribed to the remainder. In 201 TST+/QFT- children from targeted school and immigrant screening programs, a negative QFT result was used to withhold isoniazid in 145 (72.1%) children. These children were followed for 1 year, during which no TB cases occurred. In a multivariable analysis, history of TB contact and TST induration ≥20 mm were associated with fewer changes in clinical decisions. Our cohort study showed that pediatric respirologists used negative QFT results to withhold isoniazid in most low-risk children who were referred for a positive TST found through targeted screening programs. In contrast, in almost all TST-positive children who were evaluated as TB contacts, negative QFT results did not change clinical management.

Rapid diagnosis of Mycobacterium tuberculosis infection in children using interferon-gamma release assays (IGRAs)

Diagnosis of tuberculosis (TB) in children by the tuberculin skin test (TST) poses a diagnostic challenge for physicians due to its low specificity and cross-reactivity with nontuberculous mycobacteria and bacille Calmette-Guerin (BCG). Although interferon-gamma release assays (IGRAs) have been shown as novel TST alternatives for diagnosis of latent TB infection (LTBI) in adults, their effectiveness is less clear in children. The present study examined QuantiFERON-TB Gold (QFT-G) responses and IFN-gamma production capacity of TST-positive children, younger children ≤5 years. A total of 517 children of whom 434 were TST positive ranging in age from 1 month to 18 years were evaluated by the QFT-G. Of the 517 children, 434 (84%) were TST positive, 25 (5.8%) of whom were found to be QFT-G positive and 25 (5.4%) with an indeterminate response. Of the 517 children, 355 (68.7%) were previously BCG immunized and 310/355 (87.3%) were TST positive including 18/27 (66.7%) QFT-positive children. Adequate IFN-gamma production by purified TB peptides or mitogen was observed in 92.8% of children, 29.6% of whom were <5 years. This study shows that the QFT-G assay is useful for diagnosis of LTBI. The finding of 5.8% positive QFT-G in 434 TST-positive children underscores the superior specificity of the QFT-G than the TST and its greater cost effectiveness in preventing unnecessary and potentially toxic treatment in children. The study suggests that the majority of positive TST in children represent false-positive reactions and supports the use of IGRAs for diagnosis of LTBI in children, including those <5 years of age.

The Tuberculin Skin Test Is Unreliable in School Children BCG-vaccinated in Infancy and at Low Risk of Tuberculosis Infection

The tuberculin skin test (TST) is often used to screen for latent tuberculosis infection (LTBI) in school children, many of whom were bacille Calmette-Guérin (BCG)-vaccinated in infancy. The reliability of the TST in such children is unknown. TSTs performed in low-risk BCG-vaccinated and -nonvaccinated grade 1 and grade 6 First Nations (North American Indian) school children in the province of Alberta, Canada, were evaluated retrospectively. To further assess the specificity of the TST, BCG-vaccinated children with a positive TST (≥10 mm of induration) and no treatment of LTBI were administered a QuantiFERON-TB Gold In-Tube test (QFT-GIT, Cellestis International). A total of 3996 children, 2063 (51.6%) BCG-vaccinated and 1933 (48.4%) BCG-nonvaccinated, were screened for LTBI. Vaccinated children were more likely than nonvaccinated children to be TST positive (5.7% vs. 0.2%, P < 0.001). Vaccinated children with a positive TST were more likely to have a recent past TST as compared with those with a negative TST (6.8% versus 2.8%, P = 0.01). Among 65 BCG-vaccinated TST-positive children who underwent a QFT-GIT, only 5 (7.7%; 95% CI: 2.5%, 17.0%) were QFT-GIT positive. A TST of ≥15 mm was more likely to be associated with a positive QFT-GIT than a TST of 10 to 14 mm, 16.0% (95% CI: 4.5%, 36.1%) versus 2.5% (95% CI: 0.1%, 13.2%), P = 0.047. The TST is unreliable in school children, BCG-vaccinated in infancy, and who are at low risk of infection. The QFT-GIT is a useful confirmatory test for LTBI in BCG-vaccinated TST-positive school children.

The child’s immune system and pediatric tuberculosis

That children are more likely develop a severe form of TB is reflective of the differences in the maturational stages of their immune systems, but a paucity of data is available about how this system matures and what the relationship of these developmental immune deficiencies are with infection. Maturational deficiencies in the adaptive and innate immune systems in infants and young children may result in immature macrophage and DC function; Th1-type responses to pathogens; and a propensity to develop Th2-type CD4 T-cells in response to immunogens. In vitro responses of two groups of TST positive children at risk for TB were examined by comparing Enzyme-Linked ImmunoSorbent Assay (ELISA)-based IGRAs with clinical and TST findings. Age-related changes in the immune capacity for specific and mitogen-induced IFN-γ production was also examined in these two groups. In the original guidelines for the use of QFT-G, the US Centers for Disease Control and Prevention recommended that additional studies were needed, especially in children under five years of age, both to establish the validity of the assay as a diagnostic tool in the younger age group and to compare the accuracy of the test with the TST for diagnosing active and latent TB. Of TST positive US children, 10 of the 196 (5%) were found to be QFT-G positive; nine had an indeterminate response; of the 130 children from the Philippines who had been immunized with BCG, 115 were TST positive, and seven were also QFT-G positive. In BCG immunized children, all were TST positive and BCG-immunized and because of a presumptive diagnosis of TB, all had received anti-TB therapy; of the 30 children, 14 (47%) were found to be QFT-G-IT positive and one had an indeterminate response. For the study of variations in age-related immune capacity, the capacity of IFN-γ production was measured in various age groups of children in response to specific TB peptides (ESAT-6, CFP-10 and TB7.7) as well as to mitogen in amounts used in the QFT-G and the QFT-G-IT assay kits that had been provided. Both studies suggest that ELISA QFT-G and QFT-G-IT assays are useful for diagnosing TB in children and that adequate IFN-γ production was observed in all children in both groups following lymphocyte stimulation by either purified TB peptides or mitogen including those less than 5 years of age.

School based screening for tuberculosis infection in Norway: comparison of positive tuberculin skin test with interferon-gamma release assay

BackgroundIn Norway, screening for tuberculosis infection by tuberculin skin test (TST) has been offered for several decades to all children in 9th grade of school, prior to BCG-vaccination. The incidence of tuberculosis in Norway is low and infection with M. tuberculosis is considered rare. QuantiFERON®TB Gold (QFT) is a new and specific blood test for tuberculosis infection. So far, there have been few reports of QFT used in screening of predominantly unexposed, healthy, TST-positive children, including first and second generation immigrants. In order to evaluate the current TST screening and BCG-vaccination programme we aimed to (1) measure the prevalence of QFT positivity among TST positive children identified in the school based screening, and (2) measure the association between demographic and clinical risk factors for tuberculosis infection and QFT positivity.MethodsThis cross-sectional multi-centre study was conducted during the school year 2005–6 and the TST positive children were recruited from seven public hospitals covering rural and urban areas in Norway. Participation included a QFT test and a questionnaire regarding demographic and clinical risk factors for latent infection. All positive QFT results were confirmed by re-analysis of the same plasma sample. If the confirmatory test was negative the result was reported as non-conclusive and the participant was offered a new test.ResultsAmong 511 TST positive children only 9% (44) had a confirmed positive QFT result. QFT positivity was associated with larger TST induration, origin outside Western countries and known exposure to tuberculosis. Most children (79%) had TST reactions in the range of 6–14 mm; 5% of these were QFT positive. Discrepant results between the tests were common even for TST reactions above 15 mm, as only 22 % had a positive QFT.ConclusionThe results support the assumption that factors other than tuberculosis infection are widely contributing to positive TST results in this group and indicate the improved specificity of QFT for latent tuberculosis. Our study suggests a very low prevalence of latent tuberculosis infection among 9th grade school children in Norway. The result will inform the discussion in Norway of the usefulness of the current TST screening and BCG-policy.