Revaccination with Bacille Calmette-Guérin (BCG) is associated with an increased risk of abscess and lymphadenopathy

The reported frequency and types of adverse events following initial vaccination and revaccination with Bacille Calmette-Guérin (BCG) varies worldwide. Using active surveillance in a randomised controlled trial of BCG vaccination (the BRACE trial), we determined the incidence and risk factors for the development of BCG injection site abscess and regional lymphadenopathy. Injection site abscess occurred in 3% of 1387 BCG-vaccinated participants; the majority (34/41, 83%) resolved without treatment. The rate was higher in BCG-revaccinated participants (OR 3.6, 95% CI 1.7–7.5), in whom abscess onset was also earlier (median 16 vs. 27 days, p = 0.008). No participant with an abscess had a positive interferon-gamma release assay. Regional lymphadenopathy occurred in 48/1387 (3%) of BCG-vaccinated participants, with a higher rate in revaccinated participants (OR 2.1, 95% CI 1.1–3.9). BCG-associated lymphadenopathy, but not injection site abscess, was influenced by age and sex. A previous positive tuberculin skin test was not associated with local reactions. The increased risk of injection site abscess or lymphadenopathy following BCG revaccination is relevant to BCG vaccination policy in an era when BCG is increasingly being considered for novel applications.

Prediction Tool to Identify Children at Highest Risk of Tuberculosis Disease Progression Among Those Exposed at Home

Background There is a dearth of research to understand which children, among those who are exposed at home to tuberculosis (TB), are at the highest risk of TB disease, to tailor care. We sought to identify predictors of TB progression in children. Methods We conducted a prospective cohort study of children living with adults with pulmonary TB in Lima, Peru (2009–2012). We applied classification and regression tree analysis to examine potential predictors of incident TB disease during 12 months in 3 age groups (0–4, 5–9, and 10–14 years). We calculated the relative risk (RR) for top predictors in each age group. Results Among 4545 children 0–14 years old, 156 (3.4%) were diagnosed with TB within 1 year of household exposure to TB (3.4%, 2.3%, and 4.7% in children 0–4, 5–9, and 10–14 years old, respectively). The most important predictor of TB was having a positive tuberculin skin test (TST) result, with RRs of 6.6 (95% CI, 4.0–10.7), 6.6 (95% CI, 3.2–13.6), and 5.2 (95% CI, 3.0–9.0) in the age groups 0–4, 5–9, and 10–14 years, respectively. In young children with a positive TST, not using isoniazid preventive treatment further increased risk of disease (RR, 12.2 [95% CI, 3.8–39.2]). Conclusions We present a tool that identifies child household contacts at high risk of TB disease progression based on data collected during contact tracing. In addition to the use of TB preventive therapy for all children exposed at home to TB, those children at highest risk of progressing to TB disease may benefit from more frequent follow-up.

"MANTOUX TESTING IN UVEITIS PATIENTS AND TREATMENT OF PRESUMED INTRAOCULAR TUBERCULOSIS IN WESTERN UP"

Tuberculosis is re-emergingasaglobalhealthproblem.Itisaslowlyprogressive,chronic,granulomatous infectioncausedby M.tuberculosiswhichusuallyaffectslungs,butcanalsoaffectotherorganslikeCVS,GI,CNS,SKINandEYES. Choroidal tubercles and tuberculomas are reported to be the most common intraocular manifestations of TB and the most commonintraocularclinicalpresentationappearstobeposterioruveitis. ThediagnosisofocularTBisconsideredinsettingsof1.IsolationofM.tuberculosisfromocularfluidsortissuespecimen.Byamicrobiologicalorhistopathologicalstudy,PCR. 2.AspresumedoculardiseasesuggestiveofTBwithprovensystemicactivedisease. 3.Presumedoculardiseasewithoutevidenceofactivesystemicdisease. DiagnosticCriteriaForPresumedIntraocularTbUveitiswere. 1.Ocular findings consistent with possible intraocular TB with no other cause of uveitis suggested by history of symptoms,or ancillarytestings. 2.StronglypositiveMANTOUX OR TUBERCULINSKINTESTING(>10mmareaofinduration/necrosis) 3.Responsetoantituberculartherapywithabsenceofrecurrences. The aims of our study were to evaluate prevalence of Mantoux positive in newly referred uveitis patients in whom systemic evaluationwasperformedandtoassesstheoutcomeoftreatmentforpresumedintraoculartuberculosisinselectedpatients. MATERIALANDMETHOD The studywas conductedin theRetinaClinic atUpgradeddepartmentof Ophthalmology,LLRM medicalcollege,Meerut,India.Itwasaprospective,noncomparative,interventionalcaseseries. PatientsofocularinflammationreferredtoRetinaClinicwhounderwentsystemicevaluationwereincludedinthestudy A total of patients who satisfy the inclusion criteria , underwent systemic evaluation which include blood tests, chest radiograph,and tuberculin skin testing (0.05 _g purified protein derivative in 0.1 ml,equivalent to 2.5 tuberculin units) Both erythema and induration was measured at 48 hours,and the result were judged to be positive if induration was more than 10 mm Antituberculosis therapyi.eisoniazid300mg/day,rifampin600mg/day,ethambutol 15mg/kg/day,andpyrazinamide25–30 mg /kg/ day for the first 2 months ,thereafter rifampin and isoniazid were used for another 4–7 months was initiated for patients who had clinical findings consistent with possible intraocular tuberculosis,a positive tuberculin skin test result Responsetotherapywasassessedintermsofincreaseordecreaseorresolution OBSERVATIONAND RESULT Ofthe total 32patients 9patients havepositive tubercular contact history and30patientswere mantouxpositive.(94%),ofwhich78%havetheirindurationsizeof>15mmand8patientshavepositivex-rayfindings.(25%) Out of these 32 patients, 25 received antituberculous therapy for 9 months. In addition all of these patients also received systemicprednisone(1mg/kg/day)untilaclinicaleffectwasseenandthenaslowreductionofdosewasdone. 7patientsweredroppedoutfromthestudy. Out of these 25 patients which were started on treatment, 24 patients (96%) showed improvement in their clinical status, 19 patients (76%) showed improvement in their visual acuity after treatment and 35.6 % patients attained visual acuity of 6/9 or better. CONCLUSION Treatment with antitubercular therapy combined with systemic corticosteroids induces resolution of inflammation with no recurrences. So, mantoux testing should remain an integral part of the systemic work-up for uveitis patients.

Evaluation of latent tuberculosis infection in liver transplant recipients

Background and Objectives: Tuberculosis is one of the main reasons for mortality in liver transplant recipients. Since Iran is considered as a tuberculosis-endemic country, the present study aims to evaluate the outcome of latent tuberculosis infection in transplant recipients after liver transplantation. Materials and Methods: The present analytical cross-sectional study was performed on transplanted patients in Imam Khomeini Complex Hospital in Tehran Iran from 2006 to 2016. All patients with positive tuberculin skin test were enrolled. Variables including demographic information, therapeutic and outcome data were gathered and analyzed. Results: Among 675 transplant recipients, 100 patients had positive tuberculin skin test (14.8%). Sixty seven percent of recipients were men and the mean age was 72.67 ± 1.3 years. All patients' received Isoniazid prophylaxis before transplantation. The mean duration of anti- tuberculosis prophylaxis before and after transplant were 2.7 ± 1.9 and 3.6 ± 5.5 months, respectively. Tuberculosis has not been occurred in none of these patients after a mean follow up time of 45.21 ± 3 months. During the study period, four subjects infected by Mycobacterium tuberculosis, while their skin test was negative before transplant. Conclusion: According to our study, tuberculin skin test is a reliable and sensitive test for diagnosis of latent tuberculosis in liver transplant candidates. Isoniazid prophylaxis is well tolerated in patients with end stage liver diseases and liver transplant recipients.

Unnoticed Adverse Effect of Isoniazid during Childhood Tuberculosis Preventive Treatment: Hyperuricemia

Objective Isoniazid for 6 to 9 months is the most widely used form of tuberculosis (TB) preventive treatment. We aimed to assess the adverse effects of isoniazid by using the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and uric acid (SUA) in children and adolescents receiving long-term isoniazid for latent TB infection. Methods The study included children ≤18 years of age who underwent TB preventive treatment with isoniazid (IPT) between 2015 and 2019 at a university hospital. Serum transaminase, SUA, urea, and creatinine levels of patients were measured before the initiation of IPT, 15th day, and once a month during treatment. Patients with ALT, AST, or SUA results above cut-off levels during treatment were evaluated. The final values in follow-up were included in the data analysis. Results A total of 141 children who underwent IPT were included. In total, 70 children had family members with confirmed TB disease, and 71 children had a positive tuberculin skin test. SUA increased above cut-off values in 16 children (11.3%), and half of them had uric acid levels over 7 mg/dL. The median duration of the development of hyperuricemia was 4.0 months. ALT or AST increased above cut-off values in 23 children (16.3%). ALT was above cut-off values in seven patients, AST was high in 20 patients. The median duration to the development of AST and/or ALT levels above cut-off was 4.0 months. Two patients had hepatotoxic transaminase levels. Three patients had both elevated transaminases and SUA levels. Conclusion Isoniazid may also cause hyperuricemia besides elevation in transaminases in children.

The monocyte-to-lymphocyte: defining a normal range, sex-specific differences in the tuberculosis disease spectrum and diagnostic indices.

Background. The monocyte–to–lymphocyte (ML) ratio has been advocated as a biomarker in tuberculosis. Our objective was to evaluate its clinical role in diagnosis, prognosis and treatment outcome. Methods. Complete blood counts from an unselected population aged 16 to 65 years defined normal values of the ratio and associations with other indices. Blood counts, inflammatory markers and clinical parameters were measured in patients with and those screened for tuberculosis. We examined the ratio for its associations with these variables and for diagnosis, screening, prediction of poor prognosis and response to treatment. Results. In the unselected population, ML ratios were higher in males than females and correlated with neutrophil counts (Spearmans ρ=0.48, P<0.00001, n=14,573). In 356 patients notified with tuberculosis, ratios were higher in males (high monocyte counts), especially in smear–positive pulmonary tuberculosis (S+PTB), lung cavitation and raised inflammatory markers. The sensitivities for confirmed tuberculosis were 42% (males) and 32% (females), with specificities of 70% and 71% respectively. Using sex–specific cut–offs in 629 adults screened for tuberculosis and with a positive tuberculin skin test or interferon–gamma release assay, diagnostic sensitivities for active tuberculosis were better in males (25%; all and contacts of a S+PTB index, respectively) than females (14–17%) with specificities of 89–96%. Positive likelihood ratios were better with upper limits alone but were still poor (6.64 when screening for tuberculosis, with an area under the curve of 0.688). Ratios did not predict death or response to treatment. Ratios were especially higher in males than female ratios in the 16–45 years age group. Conclusions. Severe tuberculosis and male sex associated with high ML ratios. The ratio performed poorly as a clinical aid.

Air-travel related TB incident follow up – effectiveness and outcomes: a systematic review

BackgroundThe World Health Organization (WHO) recommends following up passengers following possible exposure to a case of infectious tuberculosis (TB) during air travel. This is known to be time consuming and difficult, and increasingly so with higher numbers of flights and passengers to and from countries with high TB endemicity each year.ObjectivesThis paper systematically reviews the literature on contact tracing investigations following a plane exposure to active pulmonary TB. Evidence for in-flight transmission was assessed by reviewing the positive results of contacts without prior risk factors for latent TB.Data sources & EligibilityA search of Medline, EMBASE, BIOSIS, Cochrane Library and Database of Systematic Reviews was carried out, with no restrictions on study design, index case characteristics, duration of flight or publication date.ResultsTwenty-two papers were included, with a total of 469 index cases and 15 889 contacts. Only 26.4% of all contacts identified completed screening following exposure. The yield of either a single positive tuberculin skin test (TST) or a TST conversion attributable to in-flight transmission is between 0.19% (95%CI 0.13–0.27) and 0.74% (95%CI 0.61–0.88) of all contacts identified (0.00%, 95%CI 0.00–0.00 and 0.13%, 95%CI 0.00–0.61 in random effects meta-analysis).LimitationsThe main limitation is heterogeneity of reporting.Conclusions and implications of key findingsThe evidence behind the criteria for initiating investigations is weak and it has been widely demonstrated that active screening of contacts is labour intensive and unlikely to be effective. Based on our findings, formal comprehensive contact tracing may be of limited utility following a plane exposure.

Diagnostic code agreement for electronic health records and claims data for tuberculosis

OBJECTIVE: To measure the frequency of diseases related to latent tuberculosis infection (LTBI) and tuberculosis (TB), we assessed the agreement between diagnosis codes for TB or LTBI in electronic health records (EHRs) and insurance claims for the same person.METHODS: In a US population-based, retrospective cohort study, we matched TB-related Systematized Nomenclature of Medicine–Clinical Terms (SNOMED CT) EHR codes and International Statistical Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) claims codes. Furthermore, LTBI was identified using a published ICD-based algorithm and all LTBI- and TB-related SNOMED CT codes.RESULTS: Of people with the 10 most frequent TB-related claim codes, 50% did not have an exact-matched EHR code. Positive tuberculin skin test was the most frequent unmatched EHR code and people with the 10 most frequent TB EHR codes, 40% did not have an exact-matched claim code. The most frequent unmatched claim code was TB screening encounter. EHR codes for LTBI matched to claims codes for TB testing; pulmonary TB; and nonspecific, positive or adverse tuberculin reaction.CONCLUSION: TB-related EHR codes and claims diagnostic codes often disagree, and people with claims codes for LTBI have unexpected EHR codes, indicating the need to reconcile these coding systems.