Bartonella and intraocular inflammation: a series of cases and review of literature

Chris Kalogeropoulos1, Ioannis Koumpoulis1, Andreas Mentis2, Chrisavgi Pappa1, Paraskevas Zafeiropoulos1, Miltiadis Aspiotis11Department of Ophthalmology, Medical School, University of Ioannina, Greece; 2Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens, GreecePurpose: To present various forms of uveitis and/or retinal vasculitis attributed to Bartonella infection and review the impact of this microorganism in patients with uveitis.Methods: Retrospective case series study. Review of clinical records of patients diagnosed with Bartonella henselae and Bartonella quintana intraocular inflammation from 2001 to 2010 in the Ocular Inflammation Department of the University Eye Clinic, Ioannina, Greece. Presentation of epidemiological and clinical data concerning Bartonella infection was provided by the international literature.Results: Eight patients with the diagnosis of Bartonella henselae and two patients with B. quintana intraocular inflammation were identified. Since four patients experienced bilateral involvement, the affected eyes totaled 14. The mean age was 36.6 years (range 12–62). Uveitic clinical entities that we found included intermediate uveitis in seven eyes (50%), vitritis in two eyes (14.2%), neuroretinitis in one eye (7.1%), focal retinochoroiditis in one eye (7.1%), branch retinal vein occlusion (BRVO) due to vasculitis in one eye (7.1%), disc edema with peripapillary serous retinal detachment in one eye (7.1%), and iridocyclitis in one eye (7.1%). Most of the patients (70%) did not experience systemic symptoms preceding the intraocular inflammation. Antimicrobial treatment was efficient in all cases with the exception of the case with neuroretinitis complicated by anterior ischemic optic neuropathy and tubulointerstitial nephritis.Conclusion: Intraocular involvement caused not only by B. henselae but also by B. quintana is being diagnosed with increasing frequency. A high index of suspicion is needed because the spectrum of Bartonella intraocular inflammation is very large. In our study the most common clinical entity was intermediate uveitis.Keywords: Bartonella, neuroretinitis, intermediate uveitis, retinal vascular occlusio

Paging on Complex Architectures

Advances in technology allow to build computer systems of ever increasing performances and capabilities. However, the effective use of such computational resources is often made difficult by the complexity of the system itself. Crucial to the performance of a computing device is the orchestration of the flow of data across the memory hierarchy. Specifically, given a fast but small memory (a cache) through which all the data that have to be processed must pass, it is necessary to establish a set of rules, then implemented by an algorithm, that define which data has to be evicted from such a memory to make room for new incoming data. The goal is that of minimizing the number of times that requested data is outside the cache (faults), since fetching data from farther levels of the memory hierarchy incurs high costs, in terms of time and also of energy. This thesis studies two generalizations of this problem, known as the paging problem. This problem is intrinsically online, as future data requests issued by a computer program are typically unknown. Motivated by the recent diffusion of multi-threaded and multi-core architectures, whereby several threads or processes can be executed simultaneously, and/or there are several processing units, and by the recent and rapidly growing interest in reducing power consumptions of computer systems, in the first part of the thesis we study a variation of paging which rewards the efficient usage of memory resources. In this problem the goal is that of minimizing a combination of both the number of faults and the cache occupancy of the process' data in fast memory. The main results of this part are two: the first is an impossibility result that indicates that, roughly speaking, online algorithms cannot compete in practice with algorithms that know in advance all the data requests issued by the process; the second is the design of an online algorithm that has almost the best performance among all the possible online algorithms. In the second part of the thesis we concentrate on the management of a cache shared among several concurrent processes. As outlined above, this has direct application in multi-threaded or multi-core architectures. In this problem the fast memory has to service a sequence of requests which is the interleaving of the requests issued by t different processes. Through its replacement decisions, the algorithm dynamically allocates the cache space among the processes, and this clearly impacts their progress. The main goal here is to minimize the time needed to complete the service of all the request sequences. We show tight lower and upper bounds on the performance of online algorithms for several variants of the problem

HCV Defective Genomes Promote Persistent Infection by Modulating the Viral Life Cycle

Defective interfering (DI) RNAs have been detected in several human viruses. HCV in-frame deletions mutants (IFDMs), missing mainly the envelope proteins, have been found in patient sera and liver tissues. IFDMs replicate independently and can be trans-packaged into infectious virions in the presence of full length viral genome. So far, their biological role is unclear. In this study, we have isolated and cloned IFDMs from sera samples and liver tissues of patients infected with HCV genotypes 1b, 2a, and 3a. IFDMs were present in up to 26% of samples tested. Using the in vitro HCV cell culture system, co-expression of the wild type (wt) HCV replicon with HCV IFDMs RNA resulted in increased HCV replication. Additionally, co-transfection of the HCV full length genome RNA and a defective mutant missing the envelope region led to increased viral release, collectively suggesting an important biological role for IFDMs in the virus life cycle. Recently, exosomes, masters of intercellular communication, have been implicated in the transport of HCV viral genomes. We report for the first time that exosomal RNA isolated from HCV sera samples contains HCV defective genomes. We also demonstrate that inhibition of exosomal biogenesis and release influences HCV viral replication. Overall, we provide evidence that the presence of HCV IFDMs affects both viral replication and release. IFDMs exploit exosomes as means of transport, a way to evade the immune system, to spread more efficiently and possibly maintain persistent infection

Disease Burden Attributed to Drug use in the Nordic Countries: a Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2019

The Nordic countries share similarities in many social and welfare domains, but drug policies have varied over time and between countries. We wanted to compare differences in mortality and disease burden attributed to drug use over time. Using results from the Global Burden of Disease (GBD) study, we extracted age-standardized estimates of deaths, DALYs, YLLs and YLDs per 100 000 population for Denmark, Finland, Iceland, Norway, and Sweden during the years 1990 to 2019. Among males, DALY rates in 2019 were highest in Finland and lowest in Iceland. Among females, DALY rates in 2019 were highest in Iceland and lowest in Sweden. Sweden have had the highest increase in burden since 1990, from 252 DALYs to 694 among males, and from 111 to 193 among females. Norway had a peak with highest level of all countries in 2001–2004 and thereafter a strong decline. Denmark have had the most constant burden over time, 566–600 DALYs among males from 1990 to 2010 and 210–240 DALYs among females. Strict drug policies in Nordic countries have not prevented an increase in some countries, so policies need to be reviewed.publishedVersio

High genetic diversity of measles virus, World Health Organization European region, 2005-2006

During 2005-2006, nine measles virus (MV) genotypes were identified throughout the World Health Organization European Region. All major epidemics were associated with genotypes D4, D6, and B3. Other genotypes (B2, D5, D8, D9, G2, and H1) were only found in limited numbers of cases after importation from other continents. The genetic diversity of endemic D6 strains was low; genotypes C2 and D7, circulating in Europe until recent years, were no longer identified. The transmission chains of several indigenous MV strains may thus have been interrupted by enhanced vaccination. However, multiple importations from Africa and Asia and virus introduction into highly mobile and unvaccinated communities caused a massive spread of D4 and B3 strains throughout much of the region. Thus, despite the reduction of endemic MV circulation, importation of MV from other continents caused prolonged circulation and large outbreaks after their introduction into unvaccinated and highly mobile communities

Retrospective Analysis of Six Years of Acute Flaccid Paralysis Surveillance and Polio Vaccine Coverage Reported by Italy, Serbia, Bosnia and Herzegovina, Montenegro, Bulgaria, Kosovo, Albania, North Macedonia, Malta, and Greece

Here we analyzed six years of acute flaccid paralysis (AFP) surveillance, from 2015 to 2020, of 10 countries linked to the WHO Regional Reference Laboratory, at the Istituto Superiore di Sanità, Italy. The analysis also comprises the polio vaccine coverage available (2015–2019) and enterovirus (EV) identification and typing data. Centralized Information System for Infectious Diseases and Laboratory Data Management System databases were used to obtain data on AFP indicators and laboratory performance and countries’ vaccine coverage from 2015 to 2019. EV isolation, identification, and typing were performed by each country according to WHO protocols. Overall, a general AFP underreporting was observed. Non-Polio Enterovirus (NPEV) typing showed a high heterogeneity: over the years, several genotypes of coxsackievirus and echovirus have been identified. The polio vaccine coverage, for the data available, differs among countries. This evaluation allows for the collection, for the first time, of data from the countries of the Balkan area regarding AFP surveillance and polio vaccine coverage. The need, for some countries, to enhance the surveillance systems and to promote the polio vaccine uptake, in order to maintain the polio-free status, is evident

Multilocus Microsatellite Typing (MLMT) of Strains from Turkey and Cyprus Reveals a Novel Monophyletic L. donovani Sensu Lato Group

In eastern Mediterranean, leishmaniasis represents a major public health problem with considerable impact on morbidity and potential to spread. Cutaneous leishmaniasis (CL) caused by L. major or L. tropica accounts for most cases in this region although visceral leishmaniasis (VL) caused by L. infantum is also common. New foci of human CL caused by L. donovani complex strains were recently described in Cyprus and Turkey. Herein we analyzed Turkish strains from human CL foci in Çukurova region (north of Cyprus) and a human VL case in Kuşadasi. These were compared to Cypriot strains that were previously typed by Multilocus Enzyme Electrophoresis (MLEE) as L. donovani MON-37. Nevertheless, they were found genetically distinct from MON-37 strains of other regions and therefore their origin remained enigmatic. A population study was performed by Multilocus Microsatellite Typing (MLMT) and the profile of the Turkish strains was compared to previously analyzed L. donovani complex strains. Our results revealed close genetic relationship between Turkish and Cypriot strains, which form a genetically distinct L. infantum monophyletic group, suggesting that Cypriot strains may originate from Turkey. Our analysis indicates that the epidemiology of leishmaniasis in this region is more complicated than originally thought

The potential risks and impact of the start of the 2015–2016 influenza season in the WHO European Region: a rapid risk assessment

Background: Countries in the World Health Organization (WHO) European Region are reporting more severe influenza activity in the 2015–2016 season compared to previous seasons. Objectives: To conduct a rapid risk assessment to provide interim information on the severity of the current influenza season. Methods: Using the WHO manual for rapid risk assessment of acute public health events and surveillance data available from Flu News Europe, an assessment of the current influenza season from 28 September 2015 (week 40/2015) up to 31 January 2016 (week 04/2016) was made compared with the four previous seasons. Results: The current influenza season started around week 51/2015 with higher influenza activity reported in Eastern Europe compared to Western Europe. There is a strong predominance of influenza A(H1N1)pdm09 compared to previous seasons, but the virus is antigenically similar to the strain included in the seasonal influenza vaccine. Compared to the 2014/2015 season, there was a rapid increase in the number of severe cases in Eastern European countries with the majority of such cases occurring among adults aged < 65 years. Conclusions: The current influenza season is characterized by an early start in Eastern European countries, with indications of a more severe season. Currently circulating influenza A(H1N1)pdm09 viruses are antigenically similar to those included in the seasonal influenza vaccine, and the vaccine is expected to be effective. Authorities should provide information to the public and health providers about the current influenza season, recommendations for the treatment of severe disease and effective public health measures to prevent influenza transmission

The burden of injury in Central, Eastern, and Western European sub-region : a systematic analysis from the Global Burden of Disease 2019 Study

Background Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. Methods We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. Results In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. Conclusions Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries.Peer reviewe

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation