Osteomyelitis Caused by Bacillus Calmette-Guérin Vaccination in a Healthy Toddler.

Bacillus Calmette-Guérin (BCG) osteomyelitis in immunocompetent children is a rare complication of BCG immunization which presents with nonspecific findings and often leads to delayed diagnosis. We report a 1-year and 10-month-old male infant with complaining of knee pain and limping for 5 months. He received surgical debridement due to suspicion of malignancy but BCG osteomyelitis of the distal femur was diagnosed with the culture of the specimens which revealed to have Mycobacterium bovis-BCG strain. He was successfully treated with antituberculous therapy lasting for 1 year.

A fatal case of tuberculous meningitis in a child with juvenile idiopathic arthritis: a diagnostic challenge.

The prognosis of tuberculous meningitis, a rare form of extrapulmonary tuberculosis, depends on the stage of treatment initiation. We report a fatal case of tuberculous meningitis. The patient had received successive tumor necrosis factor (TNF) antagonists and abatacept to treat juvenile idiopathic arthritis, with negative results for polymerase chain reaction and acid-fast bacilli on smear, had normal cerebrospinal fluid (CSF) adenosine deaminase and glucose levels. Six weeks post-admission, the CSF culture demonstrated Mycobacterium tuberculosis. The altered immunological responses caused by anti-TNF treatment made the diagnosis challenging. Clinicians should bear this in mind and, if suspected, treatment should be initiated immediately.

Frequency of Mycobacterium bovis and mycobacteria in primary immunodeficiencies.

AIM: Susceptibility to mycobacterial diseases is observed in some primary immunodeficiency diseases. In this study, we aimed to evaluate mycobacterial infections in primary immunodeficiency diseases. MATERIAL AND METHODS: Patients under follow-up by Ege University Pediatric Immunology Department for severe combined and combined immunodeficiencies, interleukin 12/ interferon gamma receptor deficiency, nuclear factor kappa-beta essential modulator deficiency and chronic granulomatosis disease were evaluated retrospectively in terms of the frequency and characteristics of mycobacterial infections using a questionnaire form for demographic properties, clinical features and laboratory tests. RESULTS: A diagnosis of mycobacterial infection was made clinically in a total of 25 patients including five (11.3%) of 45 patients who had severe combined immune deficiency, 12 (52.3%) of 21 patients who had chronic granulomatous disease, four patients (100%) who had interferon gamma receptor 2 partical deficiency, two patients (100%) who had interleukin 12 receptor beta 1 deficiency and one patient (100%) who had nuclear factor kapa-beta essential modulator deficiency. Mycobacterium strain could be typed in 14 (33%) of these 25 patients including Mycobacterium bovis, Mycobacterium chelonea, Mycobacterium elephantis, Mycobacterium fortuitum, and Mycobacterium tuberculosis. All patients were treated with anti-tuberculosis therapy. Thirty-six percent of these 25 patients underwent hematopoietic stem cell transplantation. Eight patients (five before, three after transplantation) died. CONCLUSIONS: Non-tuberculosis mycobacteria including mainly Mycobacterium bovis were observed with a higher rate compared to Mycobacterium tuberculosis in primary immunodeficiencies, especially in those affecting the interleukin 12/interferon gamma pathway. Early diagnosis of primary immunodeficiencies with neonatal screening program and preventing administration of the Bacille Calmette-Guerin vaccine in these patients is important.

A fatal case of tuberculous meningitis in a child with juvenile idiopathic arthritis: a diagnostic challenge

Abstract The prognosis of tuberculous meningitis, a rare form of extrapulmonary tuberculosis, depends on the stage of treatment initiation. We report a fatal case of tuberculous meningitis. The patient had received successive tumor necrosis factor (TNF) antagonists and abatacept to treat juvenile idiopathic arthritis, with negative results for polymerase chain reaction and acid-fast bacilli on smear, had normal cerebrospinal fluid (CSF) adenosine deaminase and glucose levels. Six weeks post-admission, the CSF culture demonstrated Mycobacterium tuberculosis. The altered immunological responses caused by anti-TNF treatment made the diagnosis challenging. Clinicians should bear this in mind and, if suspected, treatment should be initiated immediately.

[Evaluation of QuantiFERON®-TB Gold in Tube Test and Tuberculin Skin Test in the diagnosis of Mycobacterium tuberculosis infection]. / Mycobacterium tuberculosis enfeksiyonu tanisinda QuantiFERON®-TB Gold in Tube Testi ve Tüberkülin Deri Testinin degerlendirilmesi.

The aims of this study were to evaluate the sensitivity of QuantiFERON®-TB Gold in Tube (QFT) test and its agreement with the tuberculin skin test (TST), to investigate possible factors associated with indeterminate QFT test results and to explore the relationship between latent tuberculosis infection (LTBE) prevalence and the rate of tuberculosis (TB) cases in our region. 1455 cases with QFT test performed in Ege University Faculty of Medicine Hospital between 2013 and 2015 were included in the study and simultaneously TST results of 268 of 1455 cases were reached. TST results were evaluated according to both ≥ 10 mm and ≥ 15 mm cut-off values. The QFT results of the cases were compared according to their gender, age groups and clinical characteristics with chi-square test. Stratified analyses were also conducted according to age groups. Multivariate logistic regression was used to analyse factors associated with QFT positivity and indeterminate QFT results. Cohen's kappa was used to test the agreement between QFT and TDT, overall and stratified according to age groups. Among 1455 cases, 396 (27.2%) were QFT positive and 120 (8.2%) had an indeterminate QFT result. When the indeterminate results were excluded, QFT positivity was found as 29.7%. The highest indeterminate results were determined among 0-4 year-old and ≥ 65 year-old groups as 17.6% and 12.1%, respectively and lowest among the 55-64 age group as 4%. The comparison of the cases without any cellular immunity defect and the patients with hematologic malignancies or immune deficiency and patients under immunosuppressive treatment had two and 2.44 times more indeterminate QFT results, respectively. Among 268 cases with TST results reached, QFT positivity was 30.6%; 38.1% for TST ≥ 10 mm and 25.7% for TST ≥ 15. After the exclusion of indeterminate results, the agreement between QFT and TST ≥ 10 mm was 71.3% for positive cases and 75.5% for negative cases. The highest agreement between QFT and TST ≥ 10 mm was in the age group 35-64 and lowest in the age group ≥ 65. Among 43 culture-positive cases, 32 had QFT positive, six negative and five indeterminate results. When indeterminate results were excluded, the sensitivity of thetest was 84.2% (32/38) among culture-positive active TB cases. TST results were available for 17 of the culture-positive cases, among them QFT sensitivity was 76.5% (13/17), TST sensitivity 70.6% (12/17) and the sensitivity of both tests was 88.2% (15/17). The ratio of QFT positivity has increased as the age increased. Interestingly, QFT positivity was higher among females than males in the 15-34 age group and higher among males in the 35-64 age group. The rates of QFT positivity were lower among immunocompromised patients. When QFT and TST positivities were compared with the rate of TB cases among age groups, QFT positivity was observed as parallel to the rate of TB cases. In conclusion, although the sensitivity of QFT was higher than TST, it was found that it could not be considered as a gold standard in LTBE diagnosis. As active TB cases originate from the LTBE pool, QFT test results might be considered a better indicator of active TB development risk.

Assessment of tuberculosis infection during treatment with biologic agents in a BCG-vaccinated pediatric population.

Biologic therapies, such as tumor necrosis factor-alpha (TNF-α) blockers, are commonly used to treat rheumatological diseases in childhood. Screening patients for tuberculosis (TB) is highly recommended before starting therapy with TNF-α blockers. Despite appropriate screening, TB still remains a problem in patients receiving anti-TNF therapy in countries where TB is not endemic. TB in anti-TNF-treated patients is often diagnosed late due to altered presentation, and this delay results in high morbidity and mortality with a high proportion of extrapulmonary and disseminated disease. The aim of this study is to show the course of TB disease in children who are on biologic therapy, in an era where many of the children are BCG-vaccinated and TB is intermediately endemic. We recruited 71 patients with several types of inflammatory diseases. Six of them had a positive test result during TB screening and began taking isoniazid (INH) prophylactically. During the 3 years of follow-up, none of these patients developed TB disease. Biologic agents can be safely used in a BCG-vaccinated pediatric population, as long as patients are closely monitored to ensure that any cases of TB will be detected early.

[Rifampicin-resistant Mycobacterium bovis BCG strain isolated from an infant with NEMO mutation]. / NEMO mutasyonlu bir bebekten izole edilen rifampisine dirençli Mycobacterium bovis BCG susu.

It is well known that disseminated Mycobacterium bovis BCG infection is developed after BCG vaccination in infants with congenital cellular immune deficiencies such as mutations in genes along the interleukin (IL)-12/interferon (IFN)-γ pathway and mutations in nuclear factor-kB essential modulator (NEMO). In this report, a rifampicin-resistant M.bovis BCG strain isolated from an infant with NEMO defect was presented. An 8-month-old male infant with NEMO defect admitted to the pediatric outpatient clinic of our hospital with fever, generalized lymphadenopathy and hepatosplenomegaly. Microscopic examination of the smears prepared from lymph node and liver biopsy specimens revealed abundant amount (3+) of acid-fast bacilli (AFB). Rifampicin-susceptible Mycobacterium tuberculosis complex (MTC) was detected by real-time PCR (GeneXpert MTB/RIF; Cepheid, USA) in the samples. The growth of mycobacteria was determined on the 20th day of culture performed in MGIT960 system (Becton Dickinson, USA). The isolate was identified as M.bovis BCG by GenoType MTBC kit (Hain Lifescience, Germany) and defined as M.bovis BCG [SIT 482 (BOV_1)] by spoligotyping. In the primary anti-tuberculosis drug susceptibility test performed by MGIT960 system, the isolate was found susceptible to rifampicin (RIF), isoniazid (INH), streptomycin (STM) and ethambutol (EMB). Then anti-tuberculosis treatment was started to the patient. However, the patient at the age of 2 years, re-admitted to the hospital with the complaint of hepatosplenomegaly. Smear of spontaneously draining abscess material obtained from subcutaneous nodules revealed intensive AFB positivity (3+) once again. In the present instance RIF-resistant MTC was detected with GeneXpert system in the specimen. The growth of mycobacteria was determined on the 13th day of culture and isolate was identified as M.bovis BCG. The present isolate was found susceptible to INH, STM and EMB but resistant to RIF. A mutation in the rpoB gene (codon 531, S531L) associated with RIF resistance was detected by using the partial sequencing of the rpoB gene. Patient died due to disseminated bovis BCG infection and multiple organ failure. To our knowledge, there are only six RIF-resistant M.bovis BCG strains isolated from patients in the literature. However, this is the first RIF-resistant M.bovis BCG strain isolated from a NEMO-deficient patient.

Mycobacterium celeriflavum sp. nov., a rapidly growing scotochromogenic bacterium isolated from clinical specimens.

Six strains of a rapidly growing scotochromogenic mycobacterium were isolated from pulmonary specimens of independent patients. Biochemical and cultural tests were not suitable for their identification. The mycolic acid pattern analysed by HPLC was different from that of any other mycobacterium. Genotypic characterization, targeting seven housekeeping genes, revealed the presence of microheterogeneity in all of them. Different species were more closely related to the test strains in various regions: the type strain of Mycobacterium moriokaense showed 99.0 % 16S rRNA gene sequence similarity, and 91.5-96.5 % similarity for the remaining six regions. The whole genome sequences of the proposed type strain and that of M. moriokaense presented an average nucleotide identity (ANI) of 82.9 %. Phylogenetic analysis produced poorly robust trees in most genes with the exception of rpoB and sodA where Mycobacterium flavescens and Mycobacterium novocastrense were the closest species. This phylogenetic relatedness was confirmed by the tree inferred from five concatenated genes, which was very robust. The polyphasic characterization of the test strains, supported by the ANI value, demonstrates that they belong to a previously unreported species, for which the name Mycobacterium celeriflavum sp. nov. is proposed. The type strain is AFPC-000207(T) ( = DSM 46765(T) = JCM 18439(T)).