Emerging souvenirs-clinical presentation of the returning traveller with imported arbovirus infections in Europe.

BACKGROUND: Arboviruses are an emerging group of viruses that are causing increasing health concerns globally, including in Europe. Clinical presentation usually consists of a nonspecific febrile illness that may be accompanied by rash, arthralgia and arthritis, with or without neurological or haemorrhagic syndromes. The range of differential diagnoses of other infectious and noninfectious aetiologies is broad, presenting a challenge for physicians. While knowledge of the geographical distribution of pathogens and the current epidemiological situation, incubation periods, exposure risk factors and vaccination history can help guide the diagnostic approach, the nonspecific and variable clinical presentation can delay final diagnosis. AIMS AND SOURCES: This narrative review aims to summarize the main clinical and laboratory-based findings of the three most common imported arboviruses in Europe. Evidence is extracted from published literature and clinical expertise of European arbovirus experts. CONTENT: We present three cases that highlight similarities and differences between some of the most common travel-related arboviruses imported to Europe. These include a patient with chikungunya virus infection presenting in Greece, a case of dengue fever in Turkey and a travel-related case of Zika virus infection in Romania. IMPLICATIONS: Early diagnosis of travel-imported cases is important to reduce the risk of localized outbreaks of tropical arboviruses such as dengue and chikungunya and the risk of local transmission from body fluids or vertical transmission. Given the global relevance of arboviruses and the continuous risk of (re)emerging arbovirus events, clinicians should be aware of the clinical syndromes of arbovirus fevers and the potential pitfalls in diagnosis.

Laboratory preparedness and response with a focus on arboviruses in Europe.

BACKGROUND: The global health burden of arboviruses is continuously rising, which results in increasing pressure on local and (inter)national laboratory infrastructures. Timely and accurate diagnosis of cases is one of the main pillars for public health and clinical responses to an arbovirus emergence. AIMS AND SOURCES: This narrative review aims to summarize recent advances and to identify needs in laboratory preparedness and response activities, with a focus on viruses transmitted by arthropods in Europe. The review is based on evidence extracted from PubMed searches, Public Health and clinical laboratory experiences from the authors and the authors' opinions substantiated by peer-reviewed scientific literature. CONTENT: We illustrate the importance of inter-epidemic laboratory preparedness activities to ensure adequate Public Health and clinical responses. We describe the status of arbovirus endemicity and emergence in Europe thereby highlighting the need for preparedness for these viruses. We discuss the components and pitfalls of an adequate laboratory preparedness and response and the broader context of the current landscape of international research, clinical and laboratory preparedness networks. The complexity of arbovirus laboratory preparedness and response is described. IMPLICATIONS: Outbreak preparedness plans need to look beyond national reference laboratories, to include first-line responding onsite hospital laboratories and plans for strengthening of such local capacity and capability as required depending on the nature of the outbreak. In particular, the diagnosis of arbovirus infections is complicated by the existence of geographic overlap of circulation of numerous arboviruses, the overlap in clinical manifestation between many arboviruses and other aetiologies and the existence of cross-reactivity between related arboviruses in serology testing. Inter-epidemic preparedness activities need strong national and international networks addressing these issues. However, the current mushrooming of European preparedness networks requires governance to bring the European preparedness and response to a next level.

Preparing clinicians for (re-)emerging arbovirus infectious diseases in Europe.

BACKGROUND: Arthropod-borne virus (Arbovirus) infections are considered an emerging threat for Europe, with an increase in cases in recent decades. The increase in global travel and trade has contributed to the introduction of vectors and viruses into new geographical areas. Tropical arboviruses such as dengue and chikungunya have re-emerged causing local, sporadic outbreaks ignited by travel-imported cases. The recent Zika virus outbreak in the Americas highlighted a need to strengthen preparedness for (re-)emerging arbovirus infections globally. AIMS: To strengthen preparedness for the early identification of (re-)emerging arbovirus outbreaks in Europe and highlight areas for research. SOURCES: An evidence review of published and grey literature together with consultations with European arbovirus experts. CONTENT: This paper presents an overview of endemic and travel-imported arboviruses of clinical significance in Europe. The overview includes syndromic presentation, risk factors for infection and risk of transmission as well as an update on treatments and vaccinations and surveillance notifications and reporting. The paper also presents predictive modelled risks of further geographical expansion of vectors and viruses. IMPLICATIONS: There are a range of arboviruses of clinical significance to Europe. There has been an increase in notifications of endemic and travel-imported arbovirus cases in recent years and an increased geographical range of vectors and viruses. The heterogeneity in surveillance reporting indicates a risk for the early identification of (re-)emerging outbreaks. The data presented show a need to strengthen preparedness for (re-)emerging arbovirus infections and a need for research into neglected arboviruses, risks of non-vector transmission and effective therapeutics and vaccinations.

Using the UK primary care Quality and Outcomes Framework to audit health care equity: preliminary data on diabetes management.

BACKGROUND: The incentivization of UK primary care through the Quality and Outcomes Framework (QOF) has released an unprecedented supply of data that in theory could aid health equity audit and reduce health inequalities. The current system allows for 'exception reporting' whereby patients can be excluded from calculation of payment for reasons such as failure to attend review. We speculated that such exclusions could be linked to socioeconomic deprivation. METHODS: We assessed 'exception reporting' rates for 15 diabetes indicators using 2004/05 QOF data for 49 general practitioner (GP) practices in Brighton and Hove and related it to a deprivation ranking for each practice. RESULTS: The standardized diabetes prevalence was 26% higher (P < 0.001) in the highest compared to the lowest quintile of deprivation. Correlations between 'exception reporting' and deprivation were seen for 10 of the 15 diabetes indicators (r = 0.20-0.41, P < 0.05). Practices with a more deprived patient population were more likely to report 'exceptions' for QOF indicators, although there was no such relationship with the achievement of QOF targets. CONCLUSIONS: Strategies to reduce health inequalities need to take into account that high levels of exception reporting, particularly in practices with deprived populations, may be disguising unmet need in those populations.

Cytokines and nitric oxide inhibit the enzyme activity of catalase but not its protein or mRNA expression in insulin-producing cells.

Pancreatic beta-cells have low activities of the antioxidant enzyme catalase. Nitric oxide interacts with the haem group of catalase inhibiting its activity. We have studied the activity of catalase in beta-cells under conditions mimicking prediabetes and in which nitric oxide is generated from cytokine treatment in vitro. We also studied whether there is regulation of catalase enzyme activity by nitric oxide at the protein or gene expression level. RINm5F insulin-producing cells, treated for 24 h with cytokines, showed increased medium nitrite production (17+/-2.2 vs 0.3+/-0.2 pmol/ micro g protein) and significantly decreased cellular catalase activity (42.4+/-4.5%) compared with control cells. A similar reduction was seen in catalase-overexpressing RIN-CAT cells and in rat or human pancreatic islets of Langerhans. Catalase activity was also suppressed by the long-acting nitric oxide donor diethylenetriamine/nitric oxide adduct (Deta-NO) and this inhibition was reversible. The inhibition of catalase activity by cytokines in RINm5F cells was significantly reversed by the addition of the nitric oxide synthase 2 (NOS2) inhibitors nitro monomethylarginine or N-(3-(aminomethyl)benzyl)acetamidine (1400W). Protein expression was found to be unchanged in cytokine- or Deta-NO-treated RINm5F cells, while mRNA expression was marginally increased. We have shown that inhibition of catalase activity by cytokines is nitric oxide dependent and propose that this inhibition may confer increased susceptibility to cytokine- or nitric oxide-induced cell killing.