CCL1 and IL-2Ra differentiate Tuberculosis disease from latent infection Irrespective of HIV infection in low TB burden countries.

OBJECTIVES: To evaluate the performance of selected host immunological biomarkers in differentiating tuberculosis (TB) disease from latent TB infection (LTBI) in HIV uninfected and infected individuals enrolled in TB low-burden countries. DESIGN: Participants with TB disease (N = 85) and LTBI (N = 150) were recruited from prospective cohorts at hospitals in Norway and Denmark. Plasma concentrations of 54 host markers were assessed by Luminex multiplex immunoassays. Using receiver operator characteristic curves and general discriminant analysis, we determined the abilities of individual and combined biomarkers to discriminate between TB disease and LTBI including when patients were stratified according to HIV infection status. RESULTS: Regardless of the groups compared, CCL1 and IL-2Ra were the most accurate single biomarkers in differentiating TB disease from LTBI. Regardless of HIV status, a 4-marker signature (CCL1+RANTES+CRP+MIP-1α) derived from a training set (n = 155) differentiated TB disease from LTBI in the test set (n = 67) with a sensitivity of 56.0% (95% CI, 34.9-75.6) and a specificity of 85.7% (95% CI, 71.5-94.6). A 5-marker signature derived from the HIV uninfected group (CCL1+RANTES+MIP-1α+procalcitonin+IP-10) performed in HIV-infected individuals with a sensitivity of 75.0% and a specificity of 96.7% after leave-one-out cross validation. A 2-marker signature (CCL1+TNF-α) identified in HIV-infected persons performed in HIV-uninfected with a sensitivity and specificity of 66.7% and 100% respectively in the test set. CONCLUSIONS: Plasma CCL1 and IL-2Ra have potential as biomarkers for differentiating TB disease from LTBI in low TB burden settings unaffected by HIV infection. Combinations between these and other biomarkers in bio-signatures for global use warrant further exploration.

A man in his forties with increasing shortness of breath. / En mann i 40-årene med økende pustevansker.

BACKGROUND: Diffuse large B-cell lymphoma is an aggressive non-Hodgkin lymphoma. The patients are often critically ill with a variety of symptoms, but the disease is potentially curable. CASE PRESENTATION: A previously healthy man in his forties was admitted to the local hospital feeling unwell, with dyspnoea, cough, fever and weight loss. The clinical examination was normal. Lactate dehydrogenase and sedimentation rate were elevated. Blood smear and bone marrow biopsy were normal. In the weeks that followed, the patient became critically ill with respiratory failure, exhaustion and continuous fever. Computed tomography (CT) scan revealed diffuse lung infiltrates in addition to hepatosplenomegaly. High levels of ferritin, triglycerides and soluble interleukin-2 receptor were also found. Haemophagocytic lymphohistiocytosis was suspected, and the patient was admitted to the intensive care unit. Biopsies confirmed diffuse large B-cell lymphoma, and treatment was started immediately. INTERPRETATION: The clinical manifestations of lymphoma are diverse. In this case report the suspicion of haemophagocytic lymphohistiocytosis led to a thorough search for a malignant disease, primarily lymphoma. Patients with diffuse large B-cell lymphoma are often critically ill, deteriorating rapidly. Histological verification of the diagnosis and immediate start of treatment are essential for the outcome.

Non-tuberculous mycobacterial pulmonary infections. / Lungeinfeksjoner med ikke-tuberkuløse mykobakterier.

BAKGRUNN: Lungeinfeksjoner med ikke-tuberkuløse mykobakterier påvises jevnlig i klinisk praksis. Diagnostikk og behandling er utfordrende, og internasjonale retningslinjer bygger i stor grad på erfaring og kasuistikker. Temaet er kort og generelt omtalt i Tuberkuloseveilederen, utover det finnes ingen nasjonal behandlingsveileder om temaet. Denne artikkelen sammenfatter den nyeste kunnskapen om emnet, med hovedvekt på diagnostikk og behandling. KUNNSKAPSGRUNNLAG: Vi søkte i PubMed, Embase og Cochrane etter alle oversiktsartikler og systematiske oversiktsartikler i tidsrommet 2007-17 om ikke-tuberkuløse mykobakterier som årsak til lungesykdom. RESULTATER: Ved diagnostikk og behandling av lungeinfeksjoner med ikke-tuberkuløse mykobakterier må både kliniske, radiologiske og mikrobiologiske funn vurderes før man beslutter om det er behandlingsindikasjon. Identifikasjon av art og eventuell underart av påvist mykobakterie og resistensmønster er av stor betydning. Behandlingen består av en kombinasjon av flere medikamenter over lang tid som ofte har mange bivirkninger og interaksjoner. FORTOLKNING: Behandlingsresultatene for lungeinfeksjoner med ikke-tuberkuløse mykobakterier er varierende. Det er viktig å ta stilling til om nytten av behandlingen forventes å oppveie ulempene den kan medføre. For mange pasienter vil optimalisering av øvrig behandling for den underliggende lungesykdommen være viktigst. Pasientene må følges opp regelmessig med ekspektoratprøver og monitorering av bivirkninger.

Treatment completion for latent tuberculosis infection in Norway: a prospective cohort study.

BACKGROUND: Successful treatment of latent tuberculosis infection (LTBI) is essential to reduce tuberculosis (TB) incidence rates in low-burden countries. This study measures treatment completion and determinants of non-completion of LTBI treatment in Norway in 2016. METHODS: This prospective cohort study included all individuals notified with LTBI treatment to the Norwegian Surveillance System for Infectious Diseases (MSIS) in 2016. We obtained data from MSIS and from a standardized form that was sent to health care providers at the time of patient notification to MSIS. We determined completion rates. Pearson's chi squared test was used to study associations between pairs of categorical variables and separate crude and multivariable logistic regression models were used to identify factors associated with treatment completion and adverse drug effects. RESULTS: We obtained information on treatment completion from 719 of the 726 individuals notified for LTBI treatment in 2016. Overall, 91% completed treatment. Treatment completion was highest in the foreign-born group [foreign-born, n = 562 (92%) vs Norwegian-born, n = 115 (85%), p = 0.007]. Treatment completion did not differ significantly between prescribed regimens (p = 0.124). Adverse events were the most common reason for incomplete treatment. We found no significant differences in adverse events when comparing weekly rifapentine (3RPH) with three months daily isoniazid and rifampicin (3RH). However, there were significantly fewer adverse events with 3RPH compared to other regimens (p = 0.037). Age over 35 years was significantly associated with adverse events irrespective of regimen (p = 0.024), whereas immunosuppression was not significantly associated with adverse events after adjusting for other variables (p = 0.306). Treatment under direct observation had a significant effect on treatment completion for foreign-born (multivariate Wald p-value = 0.017), but not for Norwegian-born (multivariate Wald p-value = 0.408) individuals. CONCLUSIONS: We report a very high treatment completion rate, especially among individuals from countries with high TB incidence. The follow-up from tuberculosis-coordinators and the frequent use of directly observed treatment probably contributes to this. Few severe adverse events were reported, even with increased age and in individuals that are more susceptible. While these results are promising, issues of cost-effectiveness and targeting treatment to individuals at highest risk of TB are important components of public health impact.