Stratification by interferon-γ release assay level predicts risk of incident TB.

INTRODUCTION: Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting. METHODS: In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009-30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model. RESULTS: The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL). CONCLUSIONS: Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI.

No effect of treatment with intravenous ganciclovir on Epstein-Barr virus viremia demonstrated after pediatric liver transplantation.

EBV after pediatric LT is a risk factor for PTLD. We wanted to evaluate the effect of intravenous ganciclovir on EBV viremia and to identify risk factors for chronic EBV viremia. All pediatric patients who underwent LT in Norway from 2002 until 2015 were reviewed. Twenty-two of 38 patients with viremia were treated with intravenous ganciclovir for a median of 22 (21-38) days. Treated and untreated patients were not different with respect to EBV seroconversion prior to transplantation or age at transplantation, but treated patients had significantly earlier viremia after transplantation (P=.005). There was no difference in the proportion of patients with reduction in virus load in patients treated with ganciclovir compared to untreated patients at 8 weeks. After 1 year, five of 19 patients treated with ganciclovir and six of 14 untreated patients had reduced virus load compared to start of viremia (P=.27). In conclusion, treatment with intravenous ganciclovir did not change the proportion of patients with reduction in EBV load at 8 weeks and 1 year after viremia. Younger age at transplantation, short time from transplantation to viremia, and lack of EBV seroconversion prior to transplantation were significant predictors of chronic EBV viremia.

A Cross-Sectional Study of the Prevalence of Gastrointestinal Symptoms and Pathology in Patients With Common Variable Immunodeficiency.

OBJECTIVES: The objective of this study was to study the prevalence of gastrointestinal (GI) symptoms and histopathology in patients with common variable immunodeficiency (CVID) as well as linking the findings to GI infections and markers of systemic immune activation. METHODS: In this cross-sectional study, we addressed GI symptoms in 103 patients and GI histopathological findings in 53 patients who underwent upper and lower endoscopic examination. The most frequent histopathological findings were linked to GI symptoms, B-cell phenotype, and markers of systemic immune activation (soluble (s)CD14, sCD25, and sCD163). Microarray analysis compared "celiac-like disease" in CVID to celiac disease. Screening for selected bacterial and viral infections in fecal samples and gut mucosal biopsies was performed. RESULTS: The main findings of this study were as follows: most common GI symptoms were bloating (34%), pain (30%), and diarrhea (26%). The most frequent histopathological findings were increased intraepithelial lymphocytes in the descending part of the duodenum, i.e., "celiac-like disease" (46% of patients), decreased numbers of plasma cells in GI tract mucosa (62%), and lymphoid hyperplasia (38%), none of which were associated with GI symptoms. Reduced plasma cells in GI mucosa were associated with B-cell phenotypic characteristics of CVID, and increased serum levels of sCD14 (P=0.025), sCD25 (P=0.01), and sCD163 (P=0.04). Microarray analyses distinguished between CVID patients with "celiac-like disease" and celiac disease. Positive tests for bacterial and viral infections were scarce both in fecal samples and gut mucosal biopsies, including PCR test for norovirus in biopsy specimens (0 positive tests). CONCLUSIONS: In conclusion, GI pathology is common in CVID, but does not necessarily cause symptoms. However, reduced plasma cells in GI mucosa were linked to systemic immune activation, "celiac-like disease" in CVID and true celiac disease appear to be different disease entities, as assessed by gene expression, and infections (including norovirus) are rarely a cause of the CVID enteropathy.

Persistent Low Toxoplasma IgG Avidity Is Common in Pregnancy: Experience from Antenatal Testing in Norway.

The parasite Toxoplasma gondii might harm the fetus if a woman is infected during pregnancy. IgG seroconversion and significant increase in IgG antibody amount in pregnancy indicates maternal infection. Presence of toxoplasma immunoglobulin M (IgM), immunoglobulin G (IgG) and low IgG avidity in a single serum sample indicates possible maternal infection, but positive toxoplasma IgM and low IgG avidity may persist for months and even years. We aimed to evaluate avidity development during pregnancy in a retrospective study. Serial blood samples from 176 pregnant women admitted to Oslo University Hospital 1993-2013 for amniocentesis because of suspected toxoplasma infection were included. Data were obtained from journals and laboratory records. The avidity method used was based on Platelia Toxo IgG assay. Mean maternal age at first serology was 29.9 years (SD 5.2, range 18-42). In 37 (21%) women only the avidity increased from low to high in < 3 months. In 139 (79%) the IgG avidity remained below the high threshold ≥ 3 months and within this group 74 (42%) women had stable low IgG avidity during the observation period. Median gestational age at first test was 10.6 weeks (range 4.6-28.7). Fetal infection was detected in four children, but none among children whose mother had stable low IgG avidity. The first antenatal toxoplasma serology should ideally be collected in early pregnancy and if stable values of toxoplasma IgM and low IgG-avidity are detected in a second sample after three to four weeks, the need for amniocentesis can be questioned.

Primary toxoplasmosis with critical illness and multi-organ failure in an immunocompetent young man.

An immunocompetent young man became critically ill with multi-organ failure due to primary toxoplasmosis. Although treated successfully, he relapsed after 1 y with bilateral toxoplasmic chorioretinitis. Severe disseminated toxoplasmosis rarely occurs in immunocompetent patients and may reflect an increased risk of relapse. Secondary prophylaxis must be considered.

Infectious immune status in an obstetric population of Pakistani immigrants in Norway.

AIM: To investigate cytomegalovirus, rubella, varicella, toxoplasma, and hepatitis B immune status and factors associated with susceptibility for infections among Pakistani pregnant women in Norway. METHODS: A total of 206 pregnant Pakistani women living in Norway participated in the evaluation. Blood samples were collected during pregnancy and tested for IgG antibodies against cytomegalovirus, rubella virus, varicella-zoster virus, Toxoplasma gondii, and hepatitis B (HB) virus. RESULTS: All women had IgG antibodies against cytomegalovirus. Positivity for rubella IgG was 92%, 93% had varicella IgG antibodies, while 17% had toxoplasma IgG. Eleven per cent were anti-HBc positive, one of whom was HBsAg positive, which means that blood and cervix secretions are infectious with risk of virus transmission to the baby at the time of birth. Six women were only anti-HBc positive, they may have low-level HB infection, and risk of transmission cannot be excluded. Age younger than 25 years, having less than two children, and having lived less than 5 years in Norway were factors significantly associated with varicella-seronegative status, and thus susceptible for primary infection. CONCLUSIONS: To decrease the incidence of neonatal and maternal morbidity related to rubella, varicella, toxoplasma, and hepatitis B in our Pakistani immigrant population, we should intensify our rubella antenatal screening programme and focus upon rubella vaccination postpartum. We should offer varicella-seronegative women immunisation, advise toxoplasma-seronegative women to avoid visit to their home country during pregnancy, and give hepatitis B vaccine to all newborns regardless of maternal HBsAg status.

Sexually transmitted infections among Pakistani pregnant women and their husbands in Norway.

AIM: To assess frequency and determine the factors associated with Chlamydia trachomatis, herpes simplex virus type 2, and hepatitis B seropositivity among Pakistani pregnant women and their husbands in Norway. METHODS: All together 112 couples of Pakistani origin living in Norway participated in our study. Blood samples were tested for immunoglobulin G (IgG) antibodies against C. trachomatis, herpes simplex virus type 2, and hepatitis B. RESULTS: Pakistani women had significantly lower age, education level, and years of residence in Norway compared to their male partners. Among the men, 12% had positive chlamydial IgG antibodies in contrast to 1% of the women. These couples were discordant, meaning that the 13 wives of positive men were not infected with C. trachomatis, and the husband of one positive woman was not infected either. Four percent of women and 2% of men were positive for herpes simplex type 2. Only one couple was concordantly positive for herpes simplex type 2, the remaining four couples were discordant. Twelve percent of women and 21% of men were, or had been, infected with hepatitis B. CONCLUSION: Sexually transmitted infections did not seem to be prevalent in Pakistani immigrant couples in Norway. However, it was striking that most couples were discordant. Pakistani immigrants should be offered hepatitis B vaccine.

Sudden infant death syndrome (SIDS)--standardised investigations and classification: recommendations.

Sudden infant death syndrome (SIDS) still accounts for considerable numbers of unexpected infant deaths in many countries. While numerous theories have been advanced to explain these events, it is increasingly clear that this group of infant deaths results from the complex interaction of a variety of heritable and idiosyncratic endogenous factors interacting with exogenous factors. This has been elegantly summarised in the "three hit" or "triple risk" model. Contradictions and lack of consistencies in the literature have arisen from diverse autopsy approaches, variable applications of diagnostic criteria and inconsistent use of definitions. An approach to sudden infant death is outlined with discussion of appropriate tissue sampling, ancillary investigations and the use of controls in research projects. Standardisation of infant death investigations with the application of uniform definitions and protocols will ensure optimal investigation of individual cases and enable international comparisons of trends.

Serum adiponectin concentration prior to clinical onset of preeclampsia.

OBJECTIVE: This study assesses whether the adipokine adiponectin is a useful marker in pregnant women who subsequently develop preeclampsia (PE). METHODS: A retrospective case-control study was conducted to measure the total serum levels of adiponectin, measured by radioimmunoassay kit, in serum samples stored in serological biobanks. RESULTS: Total serum adiponectin concentrations between the groups were not significantly different (p = 0.22). There were no obvious clinical signs of the preeclamptic inflammatory process at the time when samples were drawn. CONCLUSION: Using this design, total adiponectin appeared not be a useful pre-clinical marker of PE.