Endemic Cases Research Articles

Rickettsioses in Denmark: A retrospective survey of clinical features and travel history

Rickettsia spp. can be found across the globe and cause disease of varying clinical severity, ranging from life-threatening infections with widespread vasculitis to milder, more localized presentations. Vector and, to some degree, reservoir are hematophagous arthropods, with most species harboured by ticks. In Denmark, rickettsiae are known as a cause of imported travel-related infections, but are also found endemically in ticks across the country. Data are, however, lacking on the geographical origin and clinical features of diagnosed cases.In this study, we have examined the travel history and clinical features of two groups of patients; 1) hospital-patients diagnosed with rickettsioses in the years 2010–2015 and 2) patients from primary health care (PHC) centers in Denmark having demonstrated anti-rickettsia antibodies in the years 2012–2015. The patients were identified using the Danish National Patient Registry (DNPR) and through the serological database at the State Serum Institute, where the laboratory diagnosis of rickettsioses is currently centralized. Data were collected for 86 hospital patients and 26 PHC center patients by reviewing hospital medical records and performing telephone interviews with PHC centers.Of the hospital patients, 91% (78/86) had a history of international travel 14 days prior to symptom start, with most having imported their infection from southern Africa, South Africa in particular (65%), and presenting with a clinical picture most compatible with African tick-bite fever caused by R. africae. Only two patients presented with a CRP > 100 mg/L and no mortalities were reported. At the PHC centers, most patients presented with mild flu-like symptoms and had an unknown (50%) or no history (19%) of international travel, raising the possibility of endemic rickettsioses. In view of our findings, rickettsioses do not appear to constitute a major public health problem in Denmark, with most cases being imported infections and potential endemic cases presenting as mild infections.

Impact on social networks after announcement of a case of Hansen's disease in an immigrant in Chile

Hansen's disease (HD) is a curable disease of low transmissibility which doesn't need social segregation or public notice. The announcement of a HD case in an immigrant by a governmental medical employee allowed to evaluate its impact within social networks (SN) in Chile, a country without endemic cases. To measure the impact and tone of mentions within SN after the announcement of an imported case. Mention analysis from -21 to +21 days of the notice using commercial software. Mentions were assigned to a positive, neutral or negative tone and net feeling calculated according to established formula. The day of the announcement immigrant mentions concentrated on HD (45%) and tone was distributed almost equally between positive and negative mentions but net feeling analysis indicated predominance of negative values the first day and a dynamic oscillation thereafter. A net negative feeling was registered at least during 3 different dates. Announcement of a HD case hoarded immigrant mentions towards this disease with a significant fraction of negative comments within SN. Because, there is no public health justification to divulgate this disease, this negative impact generated by an official clerk, could has been avoided. Analysis of SN is a useful tool to explore an infectious disease impact on public opinion.

Stability Analysis Susceptible, Exposed, Infected, Recovered (SEIR) Model for Spread Model for Spread of Dengue Fever in Medan

Dengue fever is endemic disease which spread through vector, Aedes Aegypty. This disease is found more than 100 countries, such as, United State, Africa as well Asia, especially in country that have tropic climate. Mathematical modeling in this paper, discusses the speed of the spread of dengue fever. The model adopting divided over four classes, such as Susceptible (S), Exposed (E), Infected (I) and Recovered (R). SEIR model further analyzed to detect the re-breeding value based on the number reported case by dengue in Medan city. Analysis of the stability of the system in this study is asymptotically stable indicating a case of endemic and unstable that show cases the endemic cases. Simulation on the mathematical model of SEIR showed that require a very long time to produce infected humans will be free of dengue virus infection. This happens because of dengue virus infection that occurs continuously between human and vector populations.

Delineation of an endemic tick paralysis zone in southeastern Australia

Tick paralysis has a major impact on pet dog and cat populations in southeastern Australia. It results from envenomation by Ixodes holocyclus and Ixodes cornuatus ticks, the role of Ixodes cornuatus in the epidemiology of this disease in Australia being unclear. The aim of this study was to describe the geographical distribution of tick paralysis cases in southeastern Australia using data from a national disease surveillance system and to compare characteristics of “endemic” cases with those reported outside this endemic zone (“sporadic” cases). Data were collated and a proportional symbol map of all cases by postcode was created. A 15-case isopleth was developed based on descriptive spatial statistics (directional ellipses) and then kernel smoothing to distinguish endemic from sporadic cases. During the study period (January 2010–December 2015) 12,421 cases were reported, and 10,839 of these reported by clinics located in 434 postcodes were included in the study. Endemic cases were predominantly reported from postcodes in coastal southeastern Australia, from southern Queensland to eastern Victoria. Of those cases meeting selection criteria, within the endemic zone 10,767 cases were reported from 351 (88%) postcodes and outside this zone 72 cases were reported from 48 (12%) postcodes. Of these latter 48 postcodes, 18 were in Victoria (26 cases), 16 in New South Wales (28 cases), 7 in Tasmania (9 cases), 5 in South Australia (7 cases) and 2 in Queensland (2 cases). Seasonal distribution in reporting was found: 62% of endemic and 52% of sporadic cases were reported in spring. The number of both endemic and sporadic cases reported peaked in October and November, but importantly a secondary peak in reporting of sporadic cases in April was found. In non-endemic areas, summer was the lowest risk season whilst in endemic areas, autumn was the lowest risk season. Two clusters of sporadic cases were identified, one in South Australia (P=0.022) during the period 22 May to 2 June 2012 and another in New South Wales (P=0.059) during the period 9 October to 29 November 2012. Endemic and sporadic cases did not differ with respect to neuter status (P=0.188), sex (P=0.205), case outcome (P=0.367) or method of diagnosis (P=0.413). However, sporadic cases were 4.2-times more likely to be dogs than cats (P<0.001). The endemic tick paralysis zone described is consistent with previous anecdotal reports. Sporadic cases reported outside this zone might be due to a history of pet travel to endemic areas, small foci of I. holocyclus outside of the endemic zone, or in the case of southern areas, tick paralysis caused by I. cornuatus.

External Validation of Three Prediction Tools for Patients at Risk of a Complicated Course of Clostridium difficile Infection: Disappointing in an Outbreak Setting.

OBJECTIVE Estimating the risk of a complicated course of Clostridium difficile infection (CDI) might help doctors guide treatment. We aimed to validate 3 published prediction models: Hensgens (2014), Na (2015), and Welfare (2011). METHODS The validation cohort comprised 148 patients diagnosed with CDI between May 2013 and March 2014. During this period, 70 endemic cases of CDI occurred as well as 78 cases of CDI related to an outbreak of C. difficile ribotype 027. Model calibration and discrimination were assessed for the 3 prediction rules. RESULTS A complicated course (ie, death, colectomy, or ICU admission due to CDI) was observed in 31 patients (21%), and 23 patients (16%) died within 30 days of CDI diagnosis. The performance of all 3 prediction models was poor when applied to the total validation cohort with an estimated area under the curve (AUC) of 0.68 for the Hensgens model, 0.54 for the Na model, and 0.61 for the Welfare model. For those patients diagnosed with CDI due to non-outbreak strains, the prediction model developed by Hensgens performed the best, with an AUC of 0.78. CONCLUSION All 3 prediction models performed poorly when using our total cohort, which included CDI cases from an outbreak as well as endemic cases. The prediction model of Hensgens performed relatively well for patients diagnosed with CDI due to non-outbreak strains, and this model may be useful in endemic settings. Infect Control Hosp Epidemiol 2017;38:897-905.

Hepatitis E in Canadian blood donors.

Hepatitis E virus (HEV) is a virus of emerging importance to transfusion medicine as studies on blood donors and other populations demonstrate that the prevalence of endemic cases is higher than previously recognized and the risk to vulnerable transfusion recipients is not insignificant. We carried out an HEV prevalence study on 13,993 Canadian blood donors with polymerase chain reaction (PCR) testing on all donors and antibody testing on a subset of 4102 donors. HEV antibody-positive and age- and sex-matched antibody-negative donors were invited to participate in a scripted telephone interview about risk factors. There were no PCR-positive samples found (95% confidence interval [CI], 0%-0.026%). The seroprevalence of HEV in our tested population was 5.9% (95% CI, 5.16%-6.59%). HEV antibody positivity was associated with male sex and increasing age. In case-control analysis history of living outside Canada (odds ratio [OR], 2.9; 95% CI, 1.56-5.32) and contact with farm animals (OR, 1.5; 95% CI, 1.01-2.28) were associated with HEV seropositivity. This is the largest data set to date on HEV infection in Canada. Results suggest low lifetime exposure to HEV and that infectious donations are rare.

Detection of Salmonella human carriers in Colombian outbreak areas.

Salmonellosis, a zoonotic and foodborne disease, is a public health problem in developing countries. With the aim of identifying human carriers of Salmonella, a survey was performed in five regions of Colombia with reported salmonellosis outbreaks. The general population and cholecystectomy surgical patients were included in this study. Stool samples from 667 volunteers and gallbladder bile samples from 199 surgical patients were examined. Detection of Salmonella from cultured stool and bile samples was determined by polymerase chain reaction (PCR). Multiplex PCR and biochemical and serological tests were performed to identify the serovars of the isolates. Nine (1.35%) stool samples were positive for Salmonella: two S. Newport, two S. Anatum, one S. Sinstorf, and four Salmonella spp. A total of 11 gallbladder bile samples were positive: S. Enteritidis was isolated from 3 bile cultures (1.5%), and 8 samples (4%) were positive for Salmonella spp. Our results show the presence of Salmonella carriers in the inhabitants of regions with reported outbreaks and suggest that these carriers are potential sources of infection in endemic and epidemic cases. Carriers also suggest Salmonella zoonotic transmission, since broiler and beef cattle are hosts to the Salmonella serotypes isolated. It is important to establish the source of infection in regions where salmonellosis is endemic in order to control transmission.

Molecular Evaluation of High Fluoroquinolone Resistant Genes in Endemic Cases of Shigellosis, Northeast Part of Karnataka, India

ObjectivesShigellosis is an acute infection of the intestine caused by bacteria in the genus Shigella and also an important cause of diarrhea in developing countries. This study was carried out to find the extent and nature of the emerging resistance in north part of Karnataka, India, and surrounding region with huge population, and also focused on the molecular mechanism of development of resistance against different generations of fluoroquinolones and explored the diversity of restriction endonucleases; we also tried to establish the significance of reduced minimal inhibitory concentrations (MIC) values. MethodsA total of 32 multidrug-resistant Shigella species (isolated from infants’ stools) were subjected to MICs of fluoroquinolone-resistant isolates done by both broth dilution and E-test method. The genes implicated in resistance to fluoroquinolone generations ciprofloxacin, ofloxacin, and gatifloxacin (gyrA, gyrB, parC, and parE) were amplified using polymerase chain reaction (PCR) method and restriction digestion analysis of PCR product were performed using PvuI and HaeII enzymes. FindingsFluoroquinolone-resistant Shigella species (n = 32) comprising S dysenteriae, S flexneri, and S sonnei were selected for MIC; 90.6% (29/32), 93.75% (30/32), and 93.75% (30/32) of isolates were ciprofloxacin, ofloxacin, and gatifloxacin resistant and showed the MIC range from 4-128 μg/mL. The PCR amplification results were positive for all species and asserted the presence of gyrA, gyrB, parC, and pare and sizes of the amplified products. The restriction banding patterns of amplified resistant genes were employed to detect differences among the Shigella species. ConclusionsThe present study found that the genetic basis and its characterization of fluoroquinolone resistance in Shigella isolates was considered for the common resistant genes, namely, gyrA, gyrB, parC, and pare, and had mutations at position 83 of gyrA and at position 80 of parC of the quinolone-resistant determining regions and associated molecular mechanism. Our study beneficial in identification of the causative agents of the infections, careful control and cautions use of antibiotics must be promoted, particularly to monitor the emergence of isolates that are fully resistant to fluoroquinolones.

Burkitt Lymphoma Genome Sequencing Project (BLGSP): Introduction

Introduction: Burkitt Lymphoma (BL) is an aggressive B-cell lymphoma with a translocation involving MYC and immunoglobulin(Ig) loci. It is most common in children, but also affects adults, and occurs in sporadic, endemic and HIV-associated forms. The Epstein-Barr virus (EBV)-associated endemic subtype is the most common pediatric cancer in equatorial Africa, but also occurs in other parts of the world, for example in the rain forest of Brazil. Intensive chemotherapy is effective, but the associated toxicity requires supportive care that is not readily available in resource-poor regions. Previously published molecular characterization of small numbers of tumors indicated that the mutation profiles of endemic and sporadic cases are similar, but not identical. One goal of the BLGSP is to conduct comprehensive molecular characterization of BL by sequencing DNA and RNA from a large BL cohort - including endemic, sporadic, pediatric and adult cases - in order to define the genetic and phenotypic features that drive these cancers. These data will be analyzed with an intent toward developing new therapeutic strategies that can be deployed worldwide.Methods: The goal is to collect 160 BL cases, of which 50% will be endemic, 38% sporadic (pediatric and adult) and 12% from HIV+ patients. For the discovery phase, each tumor requires case-matching normal DNA as well as treatment, outcome and other clinical information. The optimal source of tumor DNA and RNA is from frozen tissue with at least 50% tumor nuclei, but FFPE immobilization is also accepted. Accrual locations include Africa, Brazil, Europe and the US. The BLGSP has developed extensive standard operating procedures for tissue collection, pathology review and tissue processing to reduce the variation associated with these parameters in the interpretation of the results (see https://ocg.cancer.gov/programs/cgci/projects/burkitt-lymphoma). The project also established procedures that allow sharing of all clinical and sample information through the National Cancer Institute Genomic Data Commons (https://gdc.cancer.gov). Molecular characterization includes whole genome sequencing of tumor and normal DNA (80X and 40X coverage, respectively), RNA-sequencing (RNA-seq) and micro-RNA sequencing. These data will enable the BLGSP to identify chromosomal rearrangements, chromosomal copy number alternations, somatic mutations (single nucleotide, insertions, deletions), viral insertions, expression signatures, viral expressions and miRNA regulation of transcripts.Results: To date we have accrued 80 cases of BL of which 75% passed diagnostic pathology review. There was an additional 25% attrition at the tissue processing stage, either due to low quality nucleic acids or low percent tumor nuclei. We have completed sequencing for 45 cases, all but one of which have a MYC translocation involving one of the 3 Ig loci; one case has a MYC rearrangement by FISH analysis that is being characterized further. We have identified recurrent mutations in ID3, DDX3X, ARID1A, FOXO1, TP53, SMARCA4 and other genes. Most mutations are supported by the RNA-seq data, which is also useful in defining the pattern of EBV genome transcription. Preliminary unsupervised hierarchical clustering and principal component analysis of gene expression data defined sample clusters that do not correspond to mutation status or EBV infection, warranting further investigation. Some genes accumulated somatic mutations in a BL subtype-specific fashion.Discussion: BLGSP is an ongoing international collaborative project that will provide a comprehensive molecular portrait of BL subtypes when completed, with the potential to suggest new molecular targets for therapy that can eventually lead to effective treatments that are less toxic than the current regimens. DisclosuresCasper:Janssen: Consultancy, Research Funding; Roche: Consultancy, Other: Travel, Accommodation, Expenses; TempTime: Consultancy, Other: Travel, Accommodation, Expenses; Up to Date: Patents & Royalties; GSK: Other: Travel, Accommodation, Expenses. Abramson:Kite Pharma: Consultancy; Abbvie: Consultancy; Seattle Genetics: Consultancy; Gilead: Consultancy. Noy:Pharmacyclics, LLC, an AbbVie Company: Other: travel, accommodations, expenses, Research Funding.

Mapping Risk of Malaria Transmission in Mainland Portugal Using a Mathematical Modelling Approach.

Malaria is currently one of the world´s major health problems. About a half-million deaths are recorded every year. In Portugal, malaria cases were significantly high until the end of the 1950s but the disease was considered eliminated in 1973. In the past few years, endemic malaria cases have been recorded in some European countries. With the increasing human mobility from countries with endemic malaria to Portugal, there is concern about the resurgence of this disease in the country. Here, we model and map the risk of malaria transmission for mainland Portugal, considering 3 different scenarios of existing imported infections. This risk assessment resulted from entomological studies on An. atroparvus, the only known mosquito capable of transmitting malaria in the study area. We used the malariogenic potential (determined by receptivity, infectivity and vulnerability) applied over geospatial data sets to estimate spatial variation in malaria risk. The results suggest that the risk exists, and the hotspots are concentrated in the northeast region of the country and in the upper and lower Alentejo regions.

Markers for Ongoing or Previous Hepatitis E Virus Infection Are as Common in Wild Ungulates as in Humans in Sweden.

Hepatitis E virus (HEV) is a human pathogen with zoonotic spread, infecting both domestic and wild animals. About 17% of the Swedish population is immune to HEV, but few cases are reported annually, indicating that most infections are subclinical. However, clinical hepatitis E may also be overlooked. For identified cases, the source of infection is mostly unknown. In order to identify whether HEV may be spread from wild game, the prevalence of markers for past and/or ongoing infection was investigated in sera and stool samples collected from 260 hunted Swedish wild ungulates. HEV markers were found in 43 (17%) of the animals. The most commonly infected animal was moose (Alces alces) with 19 out of 69 animals (28%) showing HEV markers, followed by wild boar (Sus scrofa) with 21 out of 139 animals (15%), roe deer (Capreolus capreolus) with 2 out of 30 animals, red deer (Cervus elaphus) with 1 out of 15 animals, and fallow deer (Dama dama) 0 out of 7 animals. Partial open reading frame 1 (ORF1) of the viral genomes from the animals were sequenced and compared with those from 14 endemic human cases. Phylogenetic analysis revealed that three humans were infected with HEV strains similar to those from wild boar. These results indicate that wild animals may be a source of transmission to humans and could be an unrecognized public health concern.

Electrophysiological pattern of Neuropapathy in Guillain-Barre Syndrome

Guillain Barre Syndrome is an acute immune mediated polyneuropathy. We conducted a prospective study in Neurology Department, Mayo Hospital, Lahore to evaluate different electrophysiological patterns in Guillain Barre Syndrome. A total of 25 cases were registered over the period of one year and nerve conduction and electromyography was done on each patient. The break down of different patterns of neuropathy was 36% demylinated, 12% axonal and 52% of mixed variety having both demylinating and axonal components. From our study we conclude that pattern of neuropathy in GBS is nearly same as reported in most European and local studies except Chinese endemic cases where axonal form is more frequent.

Comparison of Exposure to Risk Factors for Giardiasis Among Endemic and Travel Cases

In public health reporting, a distinction is made between Canadian-acquired and international travel-related cases, but there is no differentiation between domestic travel-related and endemic cases. The objective of this presentation is to explore how demographic and exposure factors related to giardiasis vary between travel and endemic cases, for residents of the Region of Waterloo (Ontario). We found that exposure to risk factors for giardiasis varies among domestic-travel, international-travel, and endemic cases. Consequently, a distinction should be made between these case types in developing prevention strategies.

A Review of Methods for Detecting Tick-Borne Encephalitis Virus Infection in Tick, Animal, and Human Specimens.

Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted arbovirus causing human disease in Europe and Asia. Over the past decades, the incidence of TBEV infection has significantly increased, with over 13,000 annual hospital referrals in endemic countries and cases emerging in previously unaffected regions. Specific detection of TBEV is required to diagnose suspected human cases or during surveillance of tick vectors and/or susceptible animal species. Widely used techniques for diagnosis comprise serological methods to detect viral antigens or antibodies and nucleic acid tests to detect viral RNA in target specimens. Moreover, virus isolation using susceptible cell lines or vertebrates, electron microscopy, or immunohistochemistry can also be employed on specific occasions. The purpose of this review is to compile and outline various approaches and techniques for detecting TBEV infection in ticks, wild animals, and humans. Specific sections for specimen collection and storage, nucleic acid testing, and serological assays cover various aspects of dynamics, performance characteristics, and utility in the diagnostic workup of suspected cases. Impact of immunoglobulin M testing and quantification, immunoglobulin G avidity, and real-time and quantitative polymerase chain reaction methods were overviewed with assay comparisons. Recent advances in serological assays to mitigate the impact of cross-reactions were further discussed along with the detailed interpretation of laboratory test results in human infections.

Kaposi sarcoma incidence in Mozambique: national and regional estimates.

Kaposi sarcoma is expressed in four clinical variants, all associated with human herpes virus type 8 infection, namely, classic, endemic, immunosuppression-related and AIDS-related. The latter currently accounts for most of the burden of Kaposi sarcoma in sub-Saharan Africa, reflecting the frequency of HIV infection and its management. We aimed to estimate the incidence of Kaposi sarcoma in Mozambique and in its provinces. We estimated the number of incident cases of Kaposi sarcoma by adding up the expected number of endemic and AIDS-related cases. The former were estimated from the rates observed in Kyandondo, Uganda (1960-1971). The latter were computed from the number of AIDS-related deaths in each region, assuming that the ratio between the AIDS-related Kaposi sarcoma incident cases and the number of AIDS-related deaths observed in the city of Beira applies to all regions. A total of 3862 Kaposi sarcoma cases were estimated to have occurred in Mozambique in 2007, mostly AIDS-related, in the age group 25-49 years, and in provinces from South/Centre. The age-standardized incidence rates were 36.1/100 000 in men and 11.5/100 000 in women, with a more than three-fold variation across provinces. We estimated a high incidence of Kaposi sarcoma in Mozambique, along with large regional differences. These results can be used to improve disease management and to sustain political decisions on health policies.

Genomic Epidemiology of Hypervirulent Serogroup W, ST-11 Neisseria meningitidis

Neisseria meningitidis is a leading bacterial cause of sepsis and meningitis globally with dynamic strain distribution over time. Beginning with an epidemic among Hajj pilgrims in 2000, serogroup W (W) sequence type (ST) 11 emerged as a leading cause of epidemic meningitis in the African ‘meningitis belt’ and endemic cases in South America, Europe, Middle East and China. Previous genotyping studies were unable to reliably discriminate sporadic W ST-11 strains in circulation since 1970 from the Hajj outbreak strain (Hajj clone). It is also unclear what proportion of more recent W ST-11 disease clusters are caused by direct descendants of the Hajj clone. Whole genome sequences of 270 meningococcal strains isolated from patients with invasive meningococcal disease globally from 1970 to 2013 were compared using whole genome phylogenetic and major antigen-encoding gene sequence analyses. We found that all W ST-11 strains were descendants of an ancestral strain that had undergone unique capsular switching events. The Hajj clone and its descendants were distinct from other W ST-11 strains in that they shared a common antigen gene profile and had undergone recombination involving virulence genes encoding factor H binding protein, nitric oxide reductase, and nitrite reductase. These data demonstrate that recent acquisition of a distinct antigen-encoding gene profile and variations in meningococcal virulence genes was associated with the emergence of the Hajj clone. Importantly, W ST-11 strains unrelated to the Hajj outbreak contribute a significant proportion of W ST-11 cases globally. This study helps illuminate genomic factors associated with meningococcal strain emergence and evolution.

Measles elimination in the World Health Organization European Region in light of recent outbreaks: Spotlight on the Balkans

No: 1446 Presentation at ESCV 2015: Oral 42 Subclass specific antibody responses to HCMV in transplant recipients and their association with constant heavy IgG chain polymorphism and virus replication S. Benedikt ∗, L. Weseslindtner, I. Gorzer, K. Pollak, E. Puchhammer-Stockl Department of Virology, Medical University Vienna, Austria Background: Human cytomegalovirus (HCMV) causes severe infections in transplant recipients. The significance of the HCMVspecific antibody (AB) response in limiting HCMV replication is so far not entirely clear. In the present study we therefore analysed the HCMV-specific subclass AB profile in lung transplant recipients (LTRs) and its association with HCMV-DNAemia. In addition, we have analyzed its association with the patients allotypes GM3 and GM17, which are expressed at the CH1 region of the constant y1 heavy chain, and differ by single genetic variations, mainly by the single nucleotide polymorphism (SNP) rs1071803 (359 a/g nucleotide variation). Methods: We determined HCMV-specific total IgG, IgG1 and IgG3 AB levels by ELISA and HCMV-DNAemia by quantitative PCR during the post-transplant follow-up in 57 LTRs, and in 44 of these the GM 359a/g variant (GM3/17) was determined by genotyping. Results: In seropositive LTRs HCMV ABs increased with HCMV viremia (p=0.0005), and this was significantly associated with development of low level DNAemia ( 1000 copies/ml: p=0.0516). Only IgG3 but no IgG1 increase was observed with viremia (IgG3: p=0.0004). IgG1 levels were significantly lower in patients with the 359g/g (GM3/3) than in those with the 359a/g (GM3/17) variant (p<0.0001). The IgG3 increase with viremia was significant especially in patients carrying the IgG1 low level 359g/g variant (p<0.0002). Conclusions: The present data suggest that the HCMV specific AB response significantly contributes to limit HCMV replication after transplantation and provide evidence that the patients GM 3/17 variant is significantly associated with their HCMV IgG subclass profile. http://dx.doi.org/10.1016/j.jcv.2015.07.052 Abstract No: 1477 Presentation at ESCV 2015: Oral 43 Measles elimination in the World Health Organization European Region in light of recent outbreaks: Spotlight on the Balkans J.M. Hubschen1,∗, I. Salimovic-Besic2,1, A. Dedeic-Ljubovic2,1, S. Rakic Adrovic3,1, A. Sausy1, C.P. Muller1 1 Department of Immunology, Luxembourg Institute of Health/Laboratoire National de Sante, Esch-Sur-Alzette, France 2 University Clinical Centre – Sarajevo, Department for Clinical Microbiology, Sarajevo, BiH, Bosnia and Herzegovina 3 Institute of Virology, Vaccine and Sera “Torlak”, Belgrade, Serbia Background: The World Health Organization European Region (WHO-EURO) has adopted the goal to eliminate measles by 2015, but in light of current case numbers and epidemics it is clear that this target will not bemet. Elimination is defined on a country level as the absence of endemic cases for at least 12months. To interrupt endemic transmission, a very high vaccination coverage overall in the country but also in the different regions and cohorts is required. TheWHOEURO region is very heterogeneous and has a multiplicity of challenges and problems. In 2014, more than 16,000 measles cases were registered in WHO-EURO and outbreaks were reported from many different countries including Bosnia and Herzegovina and Serbia. Methods: The currently ongoing outbreaks in Bosnia and Herzegovina and in Serbia are investigated combining clinical, epidemiological and laboratory data. The mainly affected cohorts are identified and special emphasis is placed on differences in outbreak causes and patterns and virus exportations from the Balkans to other countries within and outside of WHO-EURO. Results: The results of the outbreak investigations are used as a basis to discuss current challenges and threats to the WHOEURO measles elimination goal such as migrant populations, anti-vaccination groups, vaccination gaps resulting from political instability or inadequate planning, insufficient routine immunization coverage, lack of political and financial commitment, etc. Conclusion: To achievemeasles elimination in theWHOEURO region, each country has to address its specific problems and challenges, identify and immunize susceptible population groups, react quickly and efficiently in outbreak situations, and renew and reenforce its commitment to attain the elimination goal. http://dx.doi.org/10.1016/j.jcv.2015.07.053

The presence of Epstein-Barr virus significantly impacts the transcriptional profile in immunodeficiency-associated Burkitt lymphoma.

Burkitt lymphoma (BL) is an aggressive neoplasm derived from mature, antigen-experienced B-lymphocytes. Three clinical/epidemiological variants have been recognized, named sporadic, endemic and immunodeficiency-associated BL (ID-BL). Although they are listed within a unique entity in the current WHO Classification, recent evidence indicated genetic and transcriptional differences among the three sub-groups. Further, the presence of latently persisting Epstein-Barr virus (EBV) has been associated with specific features in endemic and sporadic cases. In this study, we explored for the first time whether EBV infection could be related with a specific molecular profile in immunodeficiency-associated cases. We studied 30 BL cases, including nine occurring in HIV-positive patients (5 EBV-positive and 4 EBV-negative) by gene and microRNA (miRNA) expression profiling. We found that ID-BL presented with different profiles based on EBV presence. Specifically, 252 genes were differentially expressed, some of them being involved in intracellular signaling and apoptosis regulation. Furthermore, 28 miRNAs including both EBV-encoded (N = 18) and cellular (N = 10) ones were differentially regulated. Of note, genes previously demonstrated to be targeted by such miRNA were consistently found among differentially expressed genes, indicating the relevant contribution of miRNA to the molecular profile of the examined cases. Grippingly, 17 out of the 252 differentially expressed genes turned out to be potentially targeted by both cellular and EBV-encoded miRNA, suggesting a complex interaction and not excluding a potential synergism. In conclusion, we documented transcriptional differences based on the presence of EBV in ID-BL, and suggested a complex interaction between cellular and viral molecules in the determination of the global molecular profile of the tumor.

High prevalence of the EBER variant EB-8m in endemic nasopharyngeal carcinomas.

Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) are the most highly expressed transcripts in all EBV-associated tumors and are involved in both lymphoid and epithelioid carcinogenesis. Our previous study on Chinese isolates from non-endemic area of nasopharyngeal carcinoma (NPC) identified new EBER variants (EB-8m and EB-10m) which were less common but relatively more frequent in NPC cases than healthy donors. In the present study, we determined the EBER variants in NPC cases and healthy donors from endemic and non-endemic areas of NPC within China and compared the EBER variants, in relation to the genotypes at BamHI F region (prototype F and f variant), between population groups and between two areas. According to the phylogenetic tree, four EBER variants (EB-6m, EB-8m, EB-10m and B95-8) were identified. EB-6m was dominant in all population groups except for endemic NPC group, in which EB-8m was dominant. EB-8m was more common in endemic NPC cases (82.0%, 41/50) than non-endemic NPC cases (33.7%, 32/95) (p<0.0001), and it was also more frequent in healthy donors from endemic area (32.4%, 24/74) than healthy donors from non-endemic area (1.1%, 1/92) (p<0.0001). More importantly, the EB-8m was more prevalent in NPC cases than healthy donors in both areas (p<0.0001). The f variant, which has been suggested to associate with endemic NPC, demonstrated preferential linkage with EB-8m in endemic isolates, however, the EB-8m variant seemed to be more specific to NPC isolates than f variant. These results reveal high prevalence of EBER EB-8m variant in endemic NPC cases, suggesting an association between NPC development and EBV isolates carrying EB-8m variant. Our finding identified a small healthy population group that shares the same viral strain which predominates in NPC cases. It could be interesting to carry extensive cohort studies following these individuals to evaluate the risk to develop NPC.

Epidemiological changes in leishmaniasis in Spain according to hospitalization-based records, 1997-2011: raising awareness towards leishmaniasis in non-HIV patients.

In Spain, Leishmania infantum is endemic, human visceral and cutaneous leishmaniasis cases occurring both in the Peninsula, as well as in the Balearic Islands. We aimed to describe the clinical characteristics of leishmaniasis patients and the changes in the disease evolution after the introduction of antiretroviral therapy in 1997. In this descriptive study, we used Spanish Centralized Hospital Discharge Database for the hospitalized leishmaniasis cases between 1997 and 2011. We included in the analysis only the records having leishmaniasis as the first registered diagnosis and calculated the hospitalization rates. Disease trend was described taking into account the HIV status. Adjusted odds-ratio was used to estimate the association between clinical and socio-demographic factors and HIV co-infection. Of the total 8010 Leishmaniasis hospitalizations records, 3442 had leishmaniasis as first diagnosis; 2545/3442 (75.6%) were males and 2240/3442 (65.1%) aged between 14-65 years. Regarding disease forms, 2844/3442 (82.6%) of hospitalizations were due to visceral leishmaniasis (VL), while 118/3442 (3.4%) hospitalizations were cutaneous leishmaniasis (CL). Overall, 1737/2844 of VL (61.1%) were HIV negatives. An overall increasing trend was observed for the records with leishmaniasis as first diagnosis (p=0.113). Non-HIV leishmaniasis increased during this time period (p=0.021) while leishmaniasis-HIV co-infection hospitalization revealed a slight descending trend (p=0.717). Leishmaniasis-HIV co-infection was significantly associated with male sex (aOR=1.6; 95% CI: 1.25-2.04), 16-64 years age group (aOR=17.4; 95%CI: 2.1-143.3), visceral leishmaniasis aOR=6.1 (95%CI: 3.27-11.28) and solid neoplasms 4.5 (95% CI: 1.65-12.04). The absence of HIV co-infection was associated with lymph/hematopoietic neoplasms (aOR=0.3; 95%CI:0.14-0.57), other immunodeficiency (aOR=0.04; 95% CI:0.01-0.32) and transplant (aOR=0.01; 95%CI:0.00-0.07). Our findings suggest a significant increase of hospitalization in the absence of HIV co-infection, with a predomination of VL. We consider that clinicians in Spain should be aware of leishmaniasis not only in the HIV population but also in non HIV patients, especially for those having immunosuppression as an associate condition.