Human MCTS1-dependent translation of JAK2 is essential for IFN-γ immunity to mycobacteria.

Human inherited disorders of interferon-gamma (IFN-γ) immunity underlie severe mycobacterial diseases. We report X-linked recessive MCTS1 deficiency in men with mycobacterial disease from kindreds of different ancestries (from China, Finland, Iran, and Saudi Arabia). Complete deficiency of this translation re-initiation factor impairs the translation of a subset of proteins, including the kinase JAK2 in all cell types tested, including T lymphocytes and phagocytes. JAK2 expression is sufficiently low to impair cellular responses to interleukin-23 (IL-23) and partially IL-12, but not other JAK2-dependent cytokines. Defective responses to IL-23 preferentially impair the production of IFN-γ by innate-like adaptive mucosal-associated invariant T cells (MAIT) and γδ T lymphocytes upon mycobacterial challenge. Surprisingly, the lack of MCTS1-dependent translation re-initiation and ribosome recycling seems to be otherwise physiologically redundant in these patients. These findings suggest that X-linked recessive human MCTS1 deficiency underlies isolated mycobacterial disease by impairing JAK2 translation in innate-like adaptive T lymphocytes, thereby impairing the IL-23-dependent induction of IFN-γ.

Brain white matter hyperintensities in Kawasaki disease: A case-control study.

Background: Cerebrovascular involvement of Kawasaki disease (KD) is poorly studied. White matter hyperintensities (WMH) indicate cerebral small vessel disease and increase the risk for stroke. Purpose: To investigate whether childhood KD is associated with WMHs and other cerebrovascular findings later in adulthood. Materials and methods: In this case-control study, patients diagnosed with KD (cases) at our tertiary hospital between 1978 and 1995 were invited to brain magnetic resonance (MRI) between 2016 and 2017. Migraine patients (controls) with available brain MRI were matched with cases (ratio 4:1) by age (±2 years) and sex. Two blinded neuroradiologists evaluated independently cerebrovascular findings from the brain MRI scans. Modified Scheltens' visual rating scale was used to evaluate WMH burden and the total WMH volume was measured using manual segmentation. Results: Mean age [years, (SD)] at the time of brain MRI was 33.3 (3.8) and 32.8 (4.0) for cases (n = 40) and controls (n = 160), respectively (P = 0.53). Mean follow-up time for cases was 29.5 years (4.3). Total volume of WMHs (median) was 0.26 cm3 (IQR 0.34) for cases and 0.065 cm3 (IQR 0.075) for controls, P = 0.039. Cases had higher total WMH burden (P = 0.003), deep WMH burden (P = 0.003), and more periventricular WMHs (prevalence 7.5 vs. 0%, P = 0.008) than controls. Cases had greater risk of having total Scheltens' score ≥2 vs. < 2 (odds ratio, 6.88; 95% CI: 1.84-25.72, P = 0.0041) and ≥3 vs. < 3 (odds ratio, 22.71; 95% CI: 2.57-200.53, P = 0.0049). Diabetes type 1/type 2, hypertension, smoking status or hypercholesterolemia were not risk factors for WMH burden, p > 0.1. Myocarditis at the acute phase of KD increased the risk for periventricular WMHs (P < 0.05). Three cases (7.5%) and three controls (1.9%) had lacune of presumed vascular origin (P = 0.0096). Conclusion: History of KD could be associated with an increased WMH burden. More studies are needed to confirm our results.

Childhood nontuberculous mycobacterial lymphadenitis-observation alone is a good alternative to surgery.

OBJECTIVE: Cervicofacial lymphadenitis caused by nontuberculous mycobacteria (NTM) is commonly treated with surgery or antimicrobial therapy. The aim of this study was to analyze the utility of our new blood-based diagnostic method and the treatment protocol, surgery or observation alone, in NTM lymphadenitis in children. METHODS: All patients under 16 years of age with cervicofacial NTM lymphadenitis diagnosed and treated at Children's Hospital or at the Department of Otorhinolaryngology, Helsinki University Hospital (Helsinki, Finland) in 2007-2017 were retrospectively reviewed. RESULTS: Fifty-two patients, 33 (63%) of whom were girls, were included in the study. The median age at initial presentation of the NTM lymphadenitis was 2.9 years. The novel blood-test had been performed on 49 (94%) of the patients and in all of them it was indicative of NTM infection. A sample for mycobacterial culture was available from 34 patients, and Mycobacterium avium was the most common species detected. Most patients (n = 33, 63%) were treated conservatively with observation alone. Of these, nine patients (27%) did not develop a skin fistula, and the lymphadenitis resolved without drainage. CONCLUSIONS: The novel blood test is clinically feasible method for diagnosing childhood cervicofacial NTM lymphadenitis noninvasively. Observation alone is a good alternative to surgery, without the risk of complications.

Invasive Group A Streptococcal Infections in Children: A Nationwide Survey in Finland.

BACKGROUND: The incidence of invasive group A streptococcus (iGAS) infections varies in time and geographically for unknown reasons. We performed a nationwide survey to assess the population-based incidence rates and outcomes of children with iGAS infections. METHODS: We collected data on patients from hospital discharge registries and the electronic databases of microbiological laboratories in Finland for the period 1996-2010. We then recorded the emm types or serotypes of the strains. The study physician visited all university clinics and collected the clinical data using the same data entry sheet. RESULTS: We identified 151 children with iGAS infection. Varicella preceded iGAS infection in 20% of cases and fasciitis infection in 83% of cases. The annual incidence rate of iGAS infection was 0.93 per 100,000 in 1996-2000, 1.80 in 2001-2005 and 2.50 in 2006-2010. The proportion of emm 1.0 or T1M1 strains peaked in 1996-2000 and again in 2006-2010, to 44% and 37% of all typed isolates. The main clinical diagnoses of the patients were severe soft-tissue infection (46%), sepsis (28%), empyema (10%), osteoarticular infection (9%) and primary peritonitis (5%). Severe pain was the most typical symptom for soft-tissue infections. More than half of the patients underwent surgery and received clindamycin. The readmission rate was 7%, and the case fatality rate was 2%. CONCLUSIONS: The incidence rate of pediatric iGAS infections tripled during our study. The increase was not, however, the result of a change in the strain types causing iGAS. Varicella immunization would likely have prevented a significant number of the cases.

Elispot Igra With Purified Protein Derivative Stimulation For Diagnosing Nontuberculous Mycobacterial Cervical Lympadenitis.

Childhood cervical lymphadenitis caused by nontuberculous mycobacteria is a diagnostic challenge for the clinician. We present a new promising diagnostic method for childhood nontuberculous mycobacterial lymphadenitis. The modified T-SPOT.TB test with purified protein derivative as an additional antigen is noninvasive with estimated sensitivity and specificity of 1.00 and 0.81, respectively.

An outbreak of CTX-M-15 -producing Escherichia coli, Enterobacter cloacae, and Klebsiella in a children's hospital in Finland.

Four different extended-spectrum ß -lactamase (ESBL)-producing bacteria from a pediatric surgery ward were studied. The presence of TEM-, SHV-, and CTX-M-type ß -lactamases was analyzed and the relatedness of the isolates studied with a repetitive PCR system (DiversiLab) and pulsed-fi eld gel electrophoresis (PFGE). Molecular analysis showed that a clonal dissemination of CTX-M-15-producing Escherichia coli and Enterobacter cloacae had occurred.

[Lymphadenitis caused by nontuberculous mycobacteriae]. / Lasten atyyppiset mykobakteeri-infektiot lisääntyvät.

Lymphadenitis caused by nontuberculous mycobacteriae has been increasingly seen in Finland since the cessation of universal BCG vaccination in 2006. An otherwise healthy child develops a slowly growing unilateral mass in the cervicofacial region. Without treatment, the lymphadenitis suppurates and forms a draining sinus, which dries after some weeks or months, leaving a scar. Surgical excision is curative treatment but cannot always be performed because of risk to the facial nerve or need of extensive surgery. In these cases, observation without antimicrobial treatment is usually recommended. The parents need professional information and support.

Pregnancy outcome among HIV-infected women in the Helsinki metropolitan area.

BACKGROUND: Antiretroviral medication and good obstetric practice have greatly reduced the rate of vertical transmission of human immunodeficiency virus (HIV) infection. The incidence of HIV infection has remained low in Finland. Universal antenatal screening has been offered to all pregnant women since 1998. METHODS: We analyzed the outcomes of 52 pregnancies among 45 HIV-infected mothers delivering at our department during 1993-2003. A multidisciplinary team planned the management strategy individually and supported the mother's adherence to treatment. RESULTS: The incidence of HIV infection among women delivering in our hospital district increased from 0.6/10,000 (95% CI 0-1.6) to 4.8/10,000 (95% CI 1.4-8.2) between 1993 and 2002. HIV infection was diagnosed during pregnancy in 40% (18/45) of the mothers. Antiretroviral medication was used prior to pregnancy in 17 (33%) cases; in 34 (66%) cases of the pregnancies, medication was started during the pregnancy. A good virological response (i.e. HIV RNA load <1000/ml during the last trimester) to antiretroviral medication was achieved in 90% (36/40) of the patients; in 60% (24/40) of cases, the HIV RNA load was below the assay detection limit. One mother with advanced HIV infection succumbed to pneumonia shortly after delivery. Of the infants, 92% were born at term, and their mean (+/-SD) birth weight was 3350 +/- 395 g. The Caesarean section (CS) rate was 25% (13/52). All newborns were in good condition, and their mean umbilical pH was 7.23. All newborns received antiretroviral medication. One infant was infected with HIV, the mother was found HIV-positive postpartum. None of the infants born to mothers known to be HIV positive were infected. CONCLUSIONS: A combination of universal antenatal screening and multidisciplinary management allows individualized treatment and prevents vertical transmission of HIV infection.

Etiological diagnosis of childhood pneumonia by use of transthoracic needle aspiration and modern microbiological methods.

Childhood pneumonia is usually treated without determining its etiology. The causative organism can be isolated from specimens of blood, empyema fluid, or lung aspirate, but this is rarely done. The potential of transthoracic needle aspiration for identification of causative agents was tested with use of modern microbiological methods. Aspiration was performed for 34 children who had radiological signs compatible with community-acquired pneumonia and had alveolar consolidation. In addition to bacterial and viral cultures and viral antigen detection, nucleic acid detection for common respiratory pathogens was performed on aspirate specimens. Aspiration disclosed the etiology in 20 (59%) of 34 cases overall and in 18 (69%) of 26 patients from whom a representative specimen was obtained. Aspiration's advantages are high microbiological yield and a relatively low risk of a clinically significant adverse event. Aspiration should be used if identification of the causative agent outweighs the modest risk of the procedure.