Tuberculin skin testing and T-SPOT.TB in internationally adopted children.

BACKGROUND: Diagnosis of latent tuberculosis infection is a problem in children because of lack of a diagnostic standard and potential impact of previous Bacille Calmette-Guérin vaccination and exposure to environmental mycobacteria. Effectiveness and usefulness of interferon-gamma release assays in infants and younger children have yet to be clearly demonstrated. METHODS: Prospective cohort study including 109 children (4 months to 16 years) seen in an international adoption clinic at Nationwide Children's Hospital, Columbus, OH. Children were adopted from 14 countries, mostly (72.5%) from China, Russia and Ethiopia. Correspondence between tuberculin skin test (TST) and the T-SPOT.TB assay was evaluated. Factors associated with positive results on the TST and T-SPOT.TB were determined, and the impact of age on test performance was specifically addressed. RESULTS: TST was positive in 23.4% (25 of 107). T-SPOT.TB was positive in 4.6% (5 of 109). Overall agreement between TST and T-SPOT.TB was 71%, with prevalence-adjusted, bias-adjusted Kappa of 0.68. History of Mycobacterium tuberculosis exposure was associated with positive results on TST (odds ratio: 25.4, 95% confidence interval: 4.8-261.6, exact logistic regression) and T-SPOT.TB (odds ratio: 78.9, 95% confidence interval: 9.7-∞). All 5 children with positive T-SPOT.TB had TST induration ≥15 mm. No patient less than 1 year of age (n = 17) had positive TST or T-SPOT.TB. Positive TST was not associated with Bacille Calmette-Guérin vaccination or scar. CONCLUSIONS: TST was positive in a significant percentage of international adoptees. T-SPOT.TB was rarely positive and discordant results reflected negative T-SPOT.TB with positive TST. In this population latent tuberculosis infection may be over-estimated by TST. Regardless, in our context at the time of the study, treatment decisions were based upon TST results, not results of the T-SPOT.TB assay. Age was consistently associated with findings on TST and T-SPOT.TB with no positive result on either test for any child <1 year of age.

Completion of Latent Tuberculosis Therapy in Children: Impact of Country of Origin and Neighborhood Clinics.

BACKGROUND: Successful treatment of latent tuberculosis infection (LTBI) is an important objective in the United States' strategy for tuberculosis (TB) control. We review the impact of demographic variables and community treatment upon completion of medical therapy of LTBI in a large pediatric cohort. METHODS: We performed a retrospective analysis of prospectively collected data from children referred for evaluation and treatment of LTBI. Children were followed in the main hospital TB clinic or in 1 of 2 hospital-run neighborhood clinics. Those completing and not completing medical treatment were compared based on demographic and history variables, clinic location, and distance to clinic. Propensity score techniques were used to match children treated at the main hospital and neighborhood clinics on collected demographic and history variables. RESULTS: Of 1516 children evaluated, 1184 (78.1%) initiated medical therapy and returned for at least 1 visit. Of these, treatment was completed by 89.2% (166 of 186) of children in the neighborhood clinics versus 83.2% (830 of 998) of children in the main hospital TB clinic (P < .037). Neighborhood and main hospital clinic children did not differ in rates of completion when propensity score-matched groups were compared. Country of origin was the most important factor in determining both initiation and completion of therapy. CONCLUSIONS: Obstacles remain for successful initiation and treatment of children from identified geographic regions. Most of the dropout occurs early in treatment, and use of neighborhood clinics does not provide an obvious advantage when similar patient groups are compared. Emphasis upon initial education and early non-clinic follow-up may be useful in enhancing therapy completion.

Oral acyclovir suppression and neurodevelopment after neonatal herpes.

BACKGROUND: Poor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease. METHODS: We enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy. RESULTS: A total of 74 neonates were enrolled--45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P=0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P=0.09). CONCLUSIONS: Infants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.).

Evaluation of a modified interferon-gamma release assay for the diagnosis of latent tuberculosis infection in adult and paediatric populations that enables delayed processing.

The objective of the study was to evaluate the specificity of a modified interferon-gamma release assay (IGRA) procedure that allows storage of blood samples for up to 32 h before processing. A total of 116 subjects were enrolled in the study. Two blood samples were collected from each volunteer; 1 specimen was processed within 8 h and analyzed using the T-SPOT®.TB test and the second specimen was stored overnight and processed 23-32 h later after addition of the T-Cell Xtend™ reagent and then analyzed using the T-SPOT.TB test. A total of 108 paired T-SPOT.TB and T-SPOT.TB plus T-Cell Xtend tests were analyzed on specimens from 97 adults and 11 children. The median age of the subjects was 28 y with 68.5% female and 78.7% white. The overall agreement between the 2 tests was 98.2% (106/108). The specificity of the T-SPOT.TB test was 99.1% (107/108) and for T-SPOT.TB plus T-Cell Xtend was 97.2%. The 2 tests were comparable in results. Increasing storage time of the collected blood specimen prior to processing provides flexibility for clinicians and laboratories. Additional studies in larger and diverse patient populations including immunocompromised and paediatric patients, and patients with active TB disease or latent tuberculosis infection are needed.

Lessons learned from two school tuberculosis investigations.

We describe the results from tuberculosis (TB) contact investigations of two high-school students. Following the development of active TB in two foreign-born students, contact investigations were performed to detect contacts with active TB disease or latent TB infection (LTBI). The two students developed pulmonary TB within 2 years of immigrating to the United States. Among household contacts, no case of active TB was identified; however, LTBI was identified in 7 of 20 persons screened (35%). Of the 104 high-risk school contacts identified, no cases of active TB disease were found, but 7 (9.3%) were diagnosed with LTBI. An additional 683 low-risk contacts were screened and 9 (1.5%) were positive. Schools and Public Health departments needs to be prepared for outbreak investigations and should screen only persons with a high risk of exposure to the index case with active TB in an attempt to identify secondary infections. Those persons with a low risk of exposure should not be screened.

Percutaneous ultrasound-guided intraorbital foreign body removal.

Percutaneous ultrasound-guided intraorbital foreign body removal was successfully performed for removal of an intraorbital wooden foreign body. A 13-month-old boy presented with left periorbital cellulitis, which developed 3 days after a fall from an all-terrain vehicle. Orbital CT showed preseptal and postseptal orbital cellulitis, and an 11 x 2 mm linear foreign body in the medial compartment of the left eye. Surgical exploration of the left eye was performed, with no foreign body identified. Following surgery, diagnostic sonography demonstrated a linear foreign body adjacent to the medial rectus muscle, with sonographic characteristics compatible with wood. The percutaneous procedure was performed with intravenous deep sedation. With sonographic guidance, a Hartmann forceps was advanced in the medial soft tissues of the orbit, and the foreign body was removed intact. Ophthalmologic follow-up over 6 months revealed no evidence of visual loss, nerve injury, or impairment of extraocular muscle function.

Completion of therapy for latent tuberculosis in children of different nationalities.

We performed a retrospective review of prospectively stored data on 545 children from 54 different birth countries with latent tuberculosis cared for in a pediatric tuberculosis clinic between August 1, 2005 and July 31, 2006. For analysis, patients were grouped into 6 geographic regions. The overall rate of completion of therapy was 54.4%. There were no significant differences among regions in the rate of completion of therapy by age, duration in the United States, or exposure to active tuberculosis. However, no children from Eastern Europe completed therapy compared with 67.9% from Central and South America. Of those children who did not complete therapy, parental refusal to start medication accounted for 54% and 80% of Eastern European and Asian children compared with <10% of children from Sub-Saharan Africa, Central and South America, and the United States.

Tuberculosis in children: an update.

TB is a common and serious global infection that is spread exclusively from person to person. The initial infection in most healthy people leads to LTBI 95% of the time, but untreated individuals have a 5% to 10% lifetime risk for reactivating their infection to develop highly infectious cavitary pulmonary TB or extrapulmonary disease. Following primary infection progressive disease is more likely to develop in children younger than 5 years old or those who are immunocompromised, particularly those with HIV infection. The diagnosis of TB in most of the world depends on the presence of a clinical illness typical for TB in concert with radiographic changes, the presence of AFB in sputum, or a positive TST. Newer methods of in vitro stimulation of T lymphocytes from TB-infected people to produce interferon may be more accurate than a TST but have yet to be well studied in children. Treatment of children with LTBI is generally 9 months of daily isoniazid unless the child has been in contact with an adult with known isoniazid-resistant TB. For active TB, children generally are treated for 6 months with an initial 2 months of isoniazid, rifampin, and pyrazinamide. Where exposure to an isoniazid-resistant strain is likely, ethambutol is added. After 2 months, pyrazinamide is discontinued unless the patient has been confirmed to have been infected with a resistant strain of M. tuberculosis. BCG, rarely used in the United States, is still considered important to prevent meningitis and miliary disease in very young children in areas of the world with a high prevalence of TB.