Role of FDG-PET/CT in children with fever of unknown origin.

PURPOSE: To determine the role of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/computed tomography (CT) in children with fever of unknown origin (FUO). METHODS: This retrospective single-center study included 110 children (0-18 years) with FUO who underwent FDG-PET/CT between 2010 and 2019. The diagnostic value of FDG-PET/CT for identifying cause of fever was calculated, treatment modifications after FDG-PET/CT were assessed, and logistic regression analyses were performed to identify clinical and biochemical factors associated with FDG-PET/CT outcome. RESULTS: In 53 out of 110 patients (48%), FDG-PET/CT identified a (true positive) cause of fever. Endocarditis (11%), systemic juvenile idiopathic arthritis (5%), and inflammatory bowel disorder (5%) were the most common causes of FUO. In 42 patients (38%), no cause of fever was found on FDG-PET/CT. In 58 out of 110 patients (53%), treatment modifications were made after FDG-PET/CT. FDG-PET/CT achieved a sensitivity of 85.5%, specificity of 79.2%, positive predictive value of 84.1%, and negative predictive value of 80.9%. On multivariate logistic regression, C-reactive protein was positively associated with finding a true positive focus of fever on FDG-PET/CT (OR = 1.01 (95% CI 1.00-1.02) per mg/L increase in CRP), while leukocyte count was negatively associated with finding a true positive focus of fever (OR = 0.91 (95% CI 0.85-0.97) per 109 leukocytes/L increase). CONCLUSION: FDG-PET/CT is a valuable diagnostic tool in the evaluation of children with FUO, since it may detect a true underlying cause in almost half (48%) of all cases where none was found otherwise. It allows full-body evaluation in patients without disease-specific symptoms on one examination. CRP and leukocyte count were significantly associated with FDG-PET/CT results, which may contribute to a priori assessment on the outcome of FDG-PET/CT. Future research could be aimed at evaluating more patient-specific factors to prospectively estimate the added value of FDG-PET/CT in children with FUO.

Primary immunodeficiencies in the Netherlands: national patient data demonstrate the increased risk of malignancy.

PURPOSE: To analyze the data of the national registry of all Dutch primary immune deficiency (PID) patients, according to the European Society for Immunodeficiencies (ESID) definitions. RESULTS: In the Netherlands, 745 patients had been registered between 2009 and 2012. An overall prevalence of 4.0 per 100,000 inhabitants was calculated. The most prevalent PID was 'predominantly antibody disorder (PAD)' (60.4%). In total, 118 transplantations were reported, mostly hematopoietic stem cell transplantations (HSCT). Almost 10% of the PID patients suffered from a malignancy, in particular 'lymphoma' and 'skin cancer'. Compared to the general Dutch population, the relative risk of developing any malignancy was 2.3-fold increased, with a >10-fold increase for some solid tumors (thymus, endocrine organs) and hematological disease (lymphoma, leukemia), varying per disease category. CONCLUSIONS: The incidence rate and characteristics of PID in the Netherlands are similar to those in other European countries. Compared to the general population, PID patients carry an increased risk to develop a malignancy.

The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement.

Anti-tumour necrosis factor (TNF) monoclonal antibodies or soluble TNF receptors have become an invaluable treatment against chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. Individuals who are treated with TNF antagonists are at an increased risk of reactivating latent infections, especially tuberculosis (TB). Following TNF antagonist therapy, the relative risk for TB is increased up to 25 times, depending on the clinical setting and the TNF antagonist used. Interferon-γ release assays or, as an alternative in individuals without a history of bacille Calmette-Guérin vaccination, tuberculin skin testing is recommended to screen all adult candidates for TNF antagonist treatment for the presence of latent infection with Mycobacterium tuberculosis. Moreover, paediatric practice suggests concomitant use of both the tuberculin skin test and an interferon-γ release assay, as there are insufficient data in children to recommend one test over the other. Consequently, targeted preventive chemotherapy is highly recommended for all individuals with persistent M. tuberculosis-specific immune responses undergoing TNF antagonist therapy as it significantly reduces the risk of progression to TB. This TBNET consensus statement summarises current knowledge and expert opinions and provides evidence-based recommendations to reduce the TB risk among candidates for TNF antagonist therapy.

[Acute flaccid myelitis after a respiratory tract infection; first Dutch case related to enterovirus type D68 infection]. / Acute slappe verlamming na een luchtweginfectie.

BACKGROUND: Acute flaccid myelitis (AFM) is a relatively rare disorder affecting the anterior horn of the spinal cord and brain stem. It is characterised by rapid progressive weakness of the limbs and respiratory muscles, often combined with cranial nerve dysfunction. This used to be seen in infections with the polio virus, but in recent years, AFM has been mainly associated with enterovirus D68 infection. CASE DESCRIPTION: A boy of nearly 4 years-old developed rapidly progressive weakness and respiratory failure after an upper airway infection. Initially, Guillain-Barré syndrome was suspected, but after further investigations enterovirus D68 was detected in the nasopharyngeal aspirate and the diagnosis of AFM was made. CONCLUSION: Progressive weakness after a respiratory tract infection should raise the suspicion of enterovirus-associated AFM. This syndrome can be distinguished from Guillain-Barré syndrome by its more rapid progression, asymmetrical weakness and greater involvement of the upper limbs. The diagnosis can be confirmed by typical findings on MRI and electromyography of the spinal cord and brain stem, combined with the detection of enterovirus D68 in nasopharyngeal specimens.

Rapid detection of a norovirus pseudo-outbreak by using real-time sequence based information.

BACKGROUND: Sequence based information is increasingly used to study the epidemiology of viruses, not only to provide insight in viral evolution, but also to understand transmission patterns during outbreaks. However, sequence analysis is not yet routinely performed by diagnostic laboratories, limiting its use in clinical practice. OBJECTIVES: To describe the added value of sequence based information available within 3 days after the detection of norovirus in fecal samples of patients and personnel during a suspected outbreak on a hospital ward. Results were used to guide the implementation of appropriate infection control measures, in particular closure of the ward. STUDY DESIGN: Observational study. RESULTS: Norovirus infection was detected in seven patients and two health care workers on an oncology ward of the children's hospital. Six of seven patients had a hospital acquired infection defined as a first day of illness more than two days after admission. After notification of the first two patients, supplementary infection control measures were taken to prevent further spread. Despite these measures, three additional patients with norovirus infection were identified. Characterization of the noroviruses of 5 out of 7 patients was available within 7 days after the notification of the first patient. Four different genotypes were detected, providing evidence for multiple introductions of different norovirus strains with only a few secondary cases rather than ongoing nosocomial transmission. Therefore, we maintained the already implemented infection control interventions without closure of the ward. CONCLUSIONS: Sequence based information available in real-time is helpful for understanding norovirus transmission in the hospital and facilitates appropriate infection control measures during an outbreak.

The significance of rhinovirus detection in hospitalized children: clinical, epidemiological and virological features.

Recent developments in molecular diagnostic tools have led to the easy and rapid detection of a large number of rhinovirus (HRV) strains. However, the lack of clinical and epidemiological data hampers the interpretation of these diagnostic findings. From October 2009 to January 2011, we conducted a prospective study in hospitalized children from whom samples were taken for the detection of respiratory viruses. Clinical, epidemiological and microbiological data from 644 patients with 904 disease episodes were collected. When HRV tested positive, strains were further characterized by sequencing the VP4/VP2 region of the HRV genome. HRV was the single respiratory virus detected in 254 disease episodes (28%). Overall, 99 different serotypes were detected (47% HRV-A, 12% HRV-B, 39% HRV-C). Patients with HRV had more underlying pulmonary illness compared with patients with no virus (p 0.01), or patients with another respiratory virus besides HRV (p 0.007). Furthermore, cough, shortness of breath and a need for oxygen were significantly more present in patients with HRV infection. Particularly, patients with HRV-B required extra oxygen. No respiratory symptom, except for oxygen need, was predictive of the presence of HRV. In 22% of HRV-positive disease episodes, HRV infection was hospital acquired. Phylogenetic analysis revealed several clusters of HRV; in more than 25% of these clusters epidemiological information was suggestive of transmission within specific wards. In conclusion, the detection of HRV may help in explaining respiratory illness, particular in patients with pulmonary co-morbidities. Identifying HRV provides opportunities for timely implementation of infection control measures to prevent intra-hospital transmission.

Influenza in the immediate post-pandemic era: a comparison with seasonal and pandemic influenza in hospitalized patients.

BACKGROUND: Comparative data on severity and treatment of seasonal, pandemic and post-pandemic influenza virus infections are scarce. OBJECTIVES: To systematically analyze characteristics of hospitalized patients with influenza in the post-pandemic period compared to seasonal and pandemic influenza. STUDY DESIGN: Clinical and virological data of patients hospitalized in a tertiary referral hospital with post-pandemic influenza (2010-2011) were compared with those during seasonal influenza epidemics (2007-2009) and the influenza A(H1N1)pdm09 pandemic (2009-2010). RESULTS: 82 patients were admitted during the post-pandemic period, compared to 85 during the pandemic and 60 during seasonal influenza epidemics. No differences were observed in the occurrence of complicated illness and the need for intensive care. However, radiographic pneumonia was significantly more often diagnosed in patients with influenza A(H1N1)pdm09 compared to patients with seasonal influenza A (25% versus 71% in pandemic, p=0.004, and 55% in post-pandemic, p=0.047). Oseltamivir was more frequently prescribed in post-pandemic and pandemic patients compared to previous influenza seasons (48.9% resp. 76.5% versus 6.5%, p<0.0001). During the post-pandemic period, patients with influenza B were significantly less often treated with oseltamivir compared to patients with influenza A (27.0% versus 48.9%, p=0.043), although the course of illness in patients with influenza B was comparable with influenza A. No upsurge of oseltamivir resistance was observed. CONCLUSIONS: In our center, severity of illness was comparable for all influenza seasons, although more radiographic pneumonia was diagnosed in patients with influenza A(H1N1)pdm09. Despite the increased use of oseltamivir, no increase in oseltamivir resistance was detected.

Decline in total serum IgE after treatment for tuberculosis.

BACKGROUND: Infection with Mycobacterium tuberculosis induces a type-1 immune response, whereas intestinal parasites elicit a type-2 response. Given that type-1 and type-2 responses inhibit each other, we investigated if M tuberculosis downregulates serum IgE, a marker of a type-2 response. METHODS: A prospective study was done in the Western Cape Province of South Africa, where tuberculosis and intestinal-parasite infection are common. Total serum IgE was determined for 37 controls and for 33 adolescent patients at presentation with tuberculosis and after successful completion of treatment. IgE specific for ascaris and allergens were measured in a subset of these individuals. Mantoux skin tests were done on 35 controls and on 31 patients at diagnosis. FINDINGS: Total IgE concentrations were high in controls (mean 313 kU/L) and in patients before treatment (mean 457 kU/L, p=0.085) and declined in all patients following successful treatment (mean 175 kU/L, p<0.0001). Posttreatment IgE concentrations did not differ from concentrations in controls. Ascaris-specific IgE was lower in controls (mean 1.73 kU/L) than in patients before treatment (4.62 kU/L, p=0.023) and was 2.39 kU/L in patients after treatment (p=0.0625). Tuberculin induration correlated inversely with IgE in patients but not in controls. INTERPRETATION: Infection with M tuberculosis as such is not incompatible with a prominent IgE response. IgE concentrations decreased after successful treatment of tuberculosis, showing that IgE concentrations in human beings can be downregulated under these circumstances, presumably due to enhancement of a type-1 response.