Seroprevalence and incidence of Puumala orthohantavirus in its bank vole (Myodes glareolus) host population in northeastern France: Between-site and seasonal variability.

Given the difficulty of measuring pathogen transmission in wildlife, epidemiological studies frequently rely on cross-sectional seroprevalence. However, seropositivity indicates only exposure to a pathogen at an unknown time. By allowing to obtain repeated test results from individuals sampled multiple times over an extended period, longitudinal data help reduce this uncertainty. We used capture-mark-recapture data on bank vole (Myodes glareolus) individuals collected at four sites over ten years in northeastern France to investigate the impact of environmental variables on seroprevalence and incidence of Puumala orthohantavirus (PUUV). PUUV causes a chronic infection without apparent symptoms, that may however impair survival of its rodent host in the wild. Viral transmission between rodents may occur through direct contact or via the environment. Principal component analysis was used to deal with multicollinearity among environmental variables. Incidence and seroprevalence were investigated with either generalized estimating equations or Poisson regression models depending on the number of observations for each season. In spring, only the factor site was found to be significant for seroprevalence, while a principal component including meteorological conditions of the previous winter and the normalized difference vegetation index (NDVI) of both the previous winter and spring had a significant effect on incidence. In autumn, only the factor site was significant for incidence, while two principal components, including either the meteorological conditions of the autumn and previous spring or NDVI of the autumn significantly affected seroprevalence. We discuss these results in light of the particular demography of small mammals. We encourage other researchers to investigate the relationships between demographic parameters of wild host populations and the environment, by using both incidence and seroprevalence.

Identifying drivers of fox and cat faecal deposits in kitchen gardens in order to evaluate measures for reducing contamination of fresh fruit and vegetables.

Preventing foodborne pathogen contamination of raw fruit and vegetables in the field is critically important for public health. Specifically, it involves preventing faecal deposit by wildlife or domestic animals in fields of crops and kitchen gardens. The present study aims to identify the drivers of fox, dog and cat faecal deposits in kitchen gardens in order to mitigate the risk of contamination of raw produce with parasites shed in carnivore faeces. The focus was on Echinococcus multilocularis, ranked highest in the importance of foodborne parasites in Europe, but attention was also paid to other parasites of major concern - Toxoplasma gondii and Toxocara spp. During the winters of 2014 to 2016, faecal samples were collected from 192 kitchen gardens located in north-eastern France. From these samples, 77% contained scat of carnivores. Molecular analyses revealed that 59% of the 1016 faeces collected were from cats, 31% from foxes, and 10% from dogs. The ease of accessibility to kitchen gardens, the presence of food in the vicinity, and the composition of the surrounding vegetation were used to explain the distribution of fox and cat faeces. Generalized Linear Mixed Effects modelling showed that: i) fencing was not efficient in reducing cat faecal deposits, but drastically decreases those of foxes; ii) the abundance of Microtus sp. indicates a reason for the presence of both fox and cat faecal deposits, iii) the abundance of Arvicola terrestris, the proximity of fruit trees or farms and the predominance of forest and grassland around the village are all drivers of fox faecal deposits. These results point to the importance of fencing around kitchen gardens located in E. multilocularis endemic areas, particularly those surrounded by forest and grassland or close to fruit trees or farms.

First insights into Puumala orthohantavirus circulation in a rodent population in Alsace, France.

In-depth knowledge on the mechanisms that maintain infection by a zoonotic pathogen in an animal reservoir is the key to predicting and preventing transmission to humans. The Puumala orthohantavirus (PUUV), the most prevalent orthohantavirus in Western Europe, causes a mild form of haemorrhagic fever with renal syndrome (HFRS) in humans. In France, this endemic illness affects the north-eastern part of the country. We conducted a 4-year capture-mark-recapture study in a bank vole population, combined with molecular analyses, to explore the epidemiological situation of PUUV in Alsace, a French region where human cases have occurred, but for which no studies have been conducted on this reservoir host. PUUV-infected bank voles were detected in the 2 years that showed high bank vole density with a prevalence of 4%. The individual PUUV sequences identified in this study were similar from year to year and similar to other French sequences. On a very small spatial scale, the distribution of seropositive bank voles was very heterogeneous in time and space. The short distances travelled on average by bank voles resulted in spatial clusters of seropositive rodents, which spread only very gradually throughout the year.

Analysis of ZP1 gene reveals differences in zona pellucida composition in carnivores.

The zona pellucida (ZP) is an extracellular envelope that surrounds mammalian oocytes. This coat participates in the interaction between gametes, induction of the acrosome reaction, block of polyspermy and protection of the oviductal embryo. Previous studies suggested that carnivore ZP was formed by three glycoproteins (ZP2, ZP3 and ZP4), with ZP1 being a pseudogene. However, a recent study in the cat found that all four proteins were expressed. In the present study, in silico and molecular analyses were performed in several carnivores to clarify the ZP composition in this order of mammals. The in silico analysis demonstrated the presence of the ZP1 gene in five carnivores: cheetah, panda, polar bear, tiger and walrus, whereas in the Antarctic fur seal and the Weddell seal there was evidence of pseudogenisation. Molecular analysis showed the presence of four ZP transcripts in ferret ovaries (ZP1, ZP2, ZP3 and ZP4) and three in fox ovaries (ZP2, ZP3 and ZP4). Analysis of the fox ZP1 gene showed the presence of a stop codon. The results strongly suggest that all four ZP genes are expressed in most carnivores, whereas ZP1 pseudogenisation seems to have independently affected three families (Canidae, Otariidae and Phocidae) of the carnivore tree.

Hospitalization of HIV positive patients: Significant demand affecting all hospital sectors.

BACKGROUND: In a context of the evolution of severe morbidities in patients living with HIV (PLWH), the aim of this study was to describe reasons for hospitalization and the mode of care for the patients requiring hospitalization. METHODS: All admissions (≥24h) of PLWH to 10 hospitals in the south of Paris (COREVIH Ile-de-France Sud) between 1/1/2011 and 12/31/2011 were identified. The hospital database and the file of patients followed in the HIV referral department of each hospital were matched. Detailed clinical and biological data were collected, by returning to the individual medical records, for a random sample (65% of hospitalized patients). RESULTS: A total of 3013 hospitalizations (1489 patients) were recorded in 2011. The estimated rate of hospitalized patients was about 8% among the 10105 PLWH routinely managed in COREVIH Ile-de-France Sud in 2011. The majority (58.5%) of these hospitalizations occurred in a unit other than the HIV referral unit. Non-AIDS-defining infections were the main reason for admission (16.4%), followed by HIV-related diseases (15.6%), hepatic/gastrointestinal diseases (12.0%), and cardiovascular diseases (10.3%). The median length of stay was 5 days overall (IQR: 2-11), it was longer among patients admitted to a referral HIV care unit than to another ward. HIV infection had been diagnosed >10 years previously in 61.4% of these hospitalized patients. They often had associated comorbidities (coinfection HCV/HVB 40.5%, smoking 45.8%; hypertension 33.4%, dyslipidemia 28.8%, diabetes 14.8%). Subjects over 60 years old accounted for 15% of hospitalized patients, most of them were virologically controlled under HIV treatment, and cardiovascular diseases were their leading reason for admission. CONCLUSION: Needs for hospitalization among PLWH remain important, with a wide variety in causes of admission, involving all hospital departments. It is essential to prevent comorbidities to reduce these hospitalizations, and to maintain a link between the management of PLWH, that becomes rightly, increasing ambulatory, and recourse to specialized inpatient services.

Spatial and Temporal Epidemiology of Nephropathia Epidemica Incidence and Hantavirus Seroprevalence in Rodent Hosts: Identification of the Main Environmental Factors in Europe.

In Europe, the increasing number of nephropathia epidemica (NE) infections in humans, caused by Puumala virus carried by bank voles (Myodes glareolus), has triggered studies of environmental factors driving these infections. NE infections have been shown to occur in specific geographical areas characterized by environmental factors that influence the distribution and dynamics of host populations and virus persistence in the soil. Here, we review the influence of environmental conditions (including climate factors, food availability and habitat conditions) with respect to incidence in humans and seroprevalence in rodents, considering both direct and indirect transmission pathways. For each type of environmental factor, results and discrepancies between studies are presented and examined in the light of biological hypotheses. Overall, food availability and temperature appear to be the main drivers of host seroprevalence and NE incidence, but data quality and statistical approaches varied greatly among studies. We highlight the issues that now need to be addressed and suggest improvements for study design in regard to the current knowledge on hantavirus epidemiology.

Echinococcus granulosus infection in dogs in Sidi Kacem Province (North-West Morocco).

This study was undertaken in the Province of Sidi Kacem in northwest Morocco between April 2010 and March 2011. The main objective of the study was to determine the prevalence of Echinococcus granulosus (Eg) infection in owned dogs. This province was selected as a case study because of the social conditions, geographic and climatic diversity making it a model representative of many parts of Morocco. The survey was carried out in 23 rural communes and in the 5 municipalities (urban districts) of the Province and sampling was undertaken in randomly selected households. A total of 273 owned dogs comprising 232 from the 23 rural communes (rural dogs) and 41 from the 5 municipalities (urban dogs) were tested. Arecoline hydrobromide purgation was selected as the diagnostic method of choice to enable visualisation of expelled worms by dog owners, thereby imparting messages on the transmission mode of Eg to humans and farm animals. Of the 273 dogs tested, purgation was effective in a total of 224 dogs (82.1%). The overall estimated prevalence of Eg infection was 35.3% (79/224, 95% CI 22.3-47.0%). Dogs inhabiting rural communes were at greater risk of infection (38.0%, 95% CI 31.1-45.3%) than dogs roaming in municipalities or urban areas (18.8%, 95% CI 7.2-36.4%) and the prevalence of infection was higher in those inhabiting rural communes with slaughterhouses (62.7%, 95% CI 48.1-75.9%) than in communes without (29.1%, 95% CI 21.7-37.2%). This first assessment of Eg infection in Sidi Kacem Province indicates a key role of rural slaughterhouses in parasite transmission to dogs.

Expression pattern of the CXCL12/CXCR4-CXCR7 trio in Kaposi sarcoma skin lesions.

BACKGROUND: Recent studies have independently implicated the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, in the pathophysiology of Kaposi sarcoma (KS). OBJECTIVES: We investigated whether the CXCL12/CXCR4-CXCR7 protein trio could constitute KS biomarkers. METHODS: Endothelial and spindle cells positive for CXCL12/CXCR4-CXCR7, human herpesvirus-8 latency-associated nuclear antigen (LANA), Ki67 antigen (proliferation) and vascular endothelial growth factor (VEGF) were quantitated in skin lesions from patients with AIDS-associated KS, patients with classic KS and patients with angiomas, using immunohistochemistry and quantitative image analysis (16, 21 and 20 skin lesions, respectively). Plasma CXCL12 concentrations were measured by enzyme-linked immunosorbent assay from 20 patients with AIDS-KS, 12 HIV-infected patients without KS and 13 healthy donors' samples. RESULTS: Cells positive for CXCL12, CXCR4, CXCR7, LANA, Ki67 and VEGF were significantly enriched in patients with AIDS-associated KS and classic KS vs. angiomas (P < 0·001), and in nodular vs. macular/papular KS lesions (P < 0·05). CXCL12, CXCR4 and CXCR7 detection correlated with LANA, Ki67 and VEGF detection (r > 0·4; P < 0·05). However, plasma CXCL12 concentrations did not differ between patients with AIDS-associated KS, HIV-infected patients without KS, and healthy donors. CONCLUSIONS: The CXCL12/CXCR4-CXCR7 trio is upregulated in KS and correlates with KS pathophysiological markers and the severity of skin lesions. Histological assessment of the CXCL12 axis could serve as a valuable biomarker for KS diagnosis and progression.

Non-AIDS-related malignancies: expert consensus review and practical applications from the multidisciplinary CANCERVIH Working Group.

Malignancies represent a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. The introduction of combined antiretroviral therapy has modified the spectrum of malignancies in HIV infection with a decreased incidence of acquired immunodeficiency syndrome (AIDS) malignancies such as Kaposi's sarcoma and non-Hodgkin's lymphoma due to partial immune recovery and an increase in non-AIDS-defining malignancies due to prolonged survival. Management of HIV-infected patients with cancer requires a multidisciplinary approach, involving both oncologists and HIV physicians to optimally manage both diseases and drug interactions between anticancer and anti-HIV drugs. The French CANCERVIH group presents here a review and an experience of managing non-AIDS malignancies in HIV-infected individuals.

Slaughterhouse survey of cystic echinococcosis in cattle and sheep from the Republic of Moldova.

The Echinococcus granulosus tapeworm is responsible for cystic echinococcosis (CE), a zoonotic disease with worldwide distribution. The life cycle of the parasite is mainly domestic and takes place between dogs and livestock species. A slaughterhouse survey was conducted in 2012 in the Republic of Moldova in order to estimate the prevalence of CE. A total of 1525 cattle, 5580 sheep and 12,700 pigs were surveyed. No CE infection was observed in pigs, while prevalence was estimated at 59.3% in cattle and 61.9% in sheep. Infection was significantly higher in animals raised in private households than in those from collective farms. The frequency of infection increased with age in both species. In cattle and in sheep, infection of both the liver and lungs was the most common, while infection in the lungs only was much less frequent. Farm type appears to be an important factor in CE infection in Moldova, due to the extensive farming and the home-slaughtering undertaken in the majority private sector, despite a high prevalence of CE also recorded in the public sector. The low fertility of cysts in cattle (1.1%) compared to sheep (47.6%) confirmed the maintenance of E. granulosus sensu stricto in a dog-sheep life cycle which excludes cattle. Further studies are needed to obtain a complete overview of the parasite's epidemiology in its intermediate and definitive hosts, in order to implement control and preventive measures, with specific attention given to farms in the private sector.

Integrated health messaging for multiple neglected zoonoses: Approaches, challenges and opportunities in Morocco.

Integrating the control of multiple neglected zoonoses at the community-level holds great potential, but critical data is missing to inform the design and implementation of different interventions. In this paper we present an evaluation of an integrated health messaging intervention, using powerpoint presentations, for five bacterial (brucellosis and bovine tuberculosis) and dog-associated (rabies, cystic echinococcosis and leishmaniasis) zoonotic diseases in Sidi Kacem Province, northwest Morocco. Conducted by veterinary and epidemiology students between 2013 and 2014, this followed a process-based approach that encouraged sequential adaptation of images, key messages, and delivery strategies using auto-evaluation and end-user feedback. We describe the challenges and opportunities of this approach, reflecting on who was targeted, how education was conducted, and what tools and approaches were used. Our results showed that: (1) replacing words with local pictures and using "hands-on" activities improved receptivity; (2) information "overload" easily occurred when disease transmission pathways did not overlap; (3) access and receptivity at schools was greater than at the community-level; and (4) piggy-backing on high-priority diseases like rabies offered an important avenue to increase knowledge of other zoonoses. We conclude by discussing the merits of incorporating our validated education approach into the school curriculum in order to influence long-term behaviour change.

Efficacy of anakinra for various types of crystal-induced arthritis in complex hospitalized patients: a case series and review of the literature.

BACKGROUND: There are few data on anakinra use after failure of conventional medications for crystal-induced peripheral arthritis and/or crowned dens syndrome among complex hospitalized patients. METHODS: We retrospectively analyzed the outcome of six patients affected with subacute crystal-induced arthritis who had received anakinra in second or third line therapy, including three patients with crowned dens syndrome and three others with gouty arthritis. Patients' comorbidities, reasons for anakinra use and associated drugs, and outcomes were recorded. RESULTS: All patients presented with elevated inflammatory syndrome, systemic symptoms with poly/oligoarthritis. Except for absolute contraindications, all patients were previously treated with full or decreased dose of NSAID, colchicine, and/or glucocorticoids, with unsatisfactory response. All three gouty patients exhibited complete responses in all acute involvements under anakinra within 3 to 5 days, including one of them who needed the reintroduction of colchicine treatment that was previously unsuccessful. Crowned dens syndrome patients, including two with pseudogout and one with subacute hydroxyapatite deposition disease, needed 9 to 11 days to achieve complete response. Tolerance to anakinra was good. CONCLUSION: In case series of complex hospitalized patients, anakinra showed good activity in crowned dens syndrome and associated crystal-induced peripheral arthritis, with longer treatment duration than in gouty arthritis.

Changes in the influence of lymphoma- and HIV-specific factors on outcomes in AIDS-related non-Hodgkin lymphoma.

BACKGROUND: We undertook the present analysis to examine the shifting influence of prognostic factors in HIV-positive patients diagnosed with aggressive non-Hodgkin lymphoma (NHL) over the last two decades. PATIENTS AND METHODS: We carried out a pooled analysis from an existing database of patients with AIDS-related lymphoma. Individual patient data had been obtained prior from prospective phase II or III clinical trials carried out between 1990 until 2010 in North America and Europe that studied chemo(immuno)therapy in HIV-positive patients diagnosed with AIDS-related lymphomas. Studies had been identified by a systematic review. We analyzed patient-level data for 1546 patients with AIDS-related lymphomas using logistic regression and Cox proportional hazard models to identify the association of patient-, lymphoma-, and HIV-specific variables with the outcomes complete response (CR), progression-free survival, and overall survival (OS) in different eras: pre-cART (1989-1995), early cART (1996-2000), recent cART (2001-2004), and contemporary cART era (2005-2010). RESULTS: Outcomes for patients with AIDS-related diffuse large B-cell lymphoma and Burkitt lymphoma improved significantly over time, irrespective of baseline CD4 count or age-adjusted International Prognostic Index (IPI) risk category. Two-year OS was best in the contemporary era: 67% and 75% compared with 24% and 37% in the pre-cART era (P < 0.001). While the age-adjusted IPI was a significant predictor of outcome in all time periods, the influence of other factors waxed and waned. Individual HIV-related factors such as low CD4 counts (<50/mm(3)) and prior history of AIDS were no longer associated with poor outcomes in the contemporary era. CONCLUSIONS: Our results demonstrate a significant improvement of CR rate and survival for all patients with AIDS-related lymphomas. Effective HIV-directed therapies reduce the impact of HIV-related prognostic factors on outcomes and allow curative antilymphoma therapy for the majority of patients with aggressive NHL.

Using the genetics of Echinococcus multilocularis to trace the history of expansion from an endemic area.

Alveolar echinococcosis, caused by the cestode Echinococcus multilocularis, is the most serious parasitic disease for humans in Europe, with a sylvatic life cycle generally between small rodents and red foxes. General expansion of the range of E. multilocularis has been observed across Europe over the last 15years. In France, a westward spread of the known endemic areas of the parasite was described recently. For genotyping, the microsatellite EmsB was used to trace expansion in five French areas. A total of 22 EmsB profiles were identified, with five similar to those previously described in other parts of Europe. An imbalance of genetic diversity was observed between the five areas which also revealed their interconnection with the presence of common profiles, notably the two main profiles both present in all regions except one in the North. These two findings are similar to those described at the European level, highlighting transmission of the parasite by a mainland-island system. A spatio-temporal scenario of the expansion of E. multilocularis can be proposed with spread from the French historical focus in eastern France to the Lorraine, the Champagne-Ardenne and finally the North, while simultaneously another expansion has occurred from the historical focus into the West. The colonization by the parasite into the West and North areas from the historical focus was probably due to the migration of foxes several decades ago. Recent detection of the parasite in new endemic "départements" may be due to more active research rather than a recent spread of the parasite. Regarding the numerous data obtained by the different EmsB analyses, principally across Europe, centralization of all the profiles described in a public databank appears necessary in order to obtain a precise understanding of transmission of the parasite from one country to another.

Fox baiting against Echinococcus multilocularis: contrasted achievements among two medium size cities.

In Europe, most cities are currently colonized by red foxes (Vulpes vulpes), which are considered to be the main definitive host of the zoonotic cestode Echinococcus multilocularis. The risk of transmission to humans is of particular concern where high fox populations overlap with high human populations. The distribution of baits containing praziquantel has successfully reduced the infection pressure in rural areas and in small plots within large cities. The purpose of this study was to assess its efficiency in two medium size cities (less than 100,000 inhabitants) in areas of high human alveolar echinococcosis incidence. From August 2006 to March 2009, 14 baiting campaigns of praziquantel treatment were run in Annemasse and Pontarlier (Eastern France), each of which encompassed 33 km(2), with a density of 40 baits/km(2). The bait consumption appeared to be lower in strictly urban context compared to suburban areas (78.9% vs. 93.4%) and lower in Annemasse than in Pontarlier (82.2% vs. 89.5%). During our study, the prevalence of E. multilocularis, as assessed by EM-ELISA on fox faeces collected in the field in Annemasse, was lower within the treated area than in the rural control area. A "before/during" treatment comparison revealed a significant decrease of spring prevalence from 13.3% to 2.2%. No significant change in prevalence was detected in Pontarlier (stable prevalence: 9.1%) where the contamination of the treated area followed the temporal trend observed in the control area. There, a greater resilience of the parasite's life cycle, probably due to a strong pressure of recontamination from outside the treated area, may have counteracted the prophylaxis treatment. These contrasted outcomes suggest that the frequency of fox anthelmintic treatment should be adapted to the local situation.

Prevalence survey and first molecular characterization of Echinococcus granulosus in France.

Human cystic echinococcosis (hydatid disease) caused by the Echinococcus granulosus tapeworm continues to be a substantial cause of morbidity and mortality in many parts of the world. France is still considered as endemic area, but the current infestation by E. granulosus of intermediate hosts in France remains currently unknown due to the absence of official data reporting for the last 20 years. A 1-year prevalence survey was conducted in the 24 slaughterhouses of ten departments of the South of France. We demonstrate that the E. granulosus parasite is still currently present at low prevalence at slaughterhouses in the study area (4 cases for 100,000 sheep and 3 cases for 100,000 cattle). In addition, we assess the presence of genotype G1 in infected animals and identify for the first time in France genotypes G2 and G3 of E. granulosus sensu stricto.

(18)F-FDG PET/CT in tuberculosis: an early non-invasive marker of therapeutic response.

OBJECTIVE: To evaluate the potential of (18)F-fluoro-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for early therapeutic intervention in patients with probable or confirmed tuberculosis (TB). METHODS: Twenty-one consecutive human immunodeficiency virus negative patients were prospectively included. All patients underwent (18)F-FDG PET/CT before and after 1 month of anti-tuberculosis treatment. The maximum standardised uptake value (SUV(max)) of the most (18)F-FDG avid lesions was recorded. RESULTS: The median age of patients was 36 years (range 18-84); 33.3% were male, 80.9% were born in endemic countries, and 23.8% had a past history of TB. TB was confirmed on culture in 8, on histology in 9 and on the basis of clinical symptoms in 4 patients. (18)F-FDG PET/CT detected active pulmonary TB (n = 1), extra-pulmonary (n = 10) or both (n = 10). The second (18)F-FDG PET/CT showed reduced radiotracer uptake intensity in 19 of 21 patients, with a median percentage decrease of SUV(max) of 31% (range 2-84). Two patients showed no improvement. TB was ruled out in one patient during follow-up; the final diagnosis was a non-Hodgkin's lymphoma. The other patient was smear-positive for 3 months. CONCLUSION: (18)F-FDG PET/CT allows an easy evaluation of early therapeutic response in patients with TB, particularly extra-pulmonary TB.

Blood Epstein-Barr virus DNA load and risk of progression to AIDS-related systemic B lymphoma.

BACKGROUND: AIDS-related lymphoma (ARL) remains the main cause of AIDS-related deaths in the combined antiretroviral therapy (cART) era. Although most ARLs are associated with the Epstein-Barr virus (EBV), whether patients with high EBV burden are more at risk of developing ARL is unknown. This study investigated the relationship between high blood EBV DNA loads and subsequent progression to ARL. METHODS: We identified 43 cases of ARL diagnosed between 1988 and 2007 within two cohorts (ANRS SEROCO/HEMOCO and PRIMO) and for which stored serum and peripheral blood mononuclear cell (PBMC) samples were available within 3 years before ARL diagnosis. For each case, two controls matched for the cohort and CD4 cell count in the year of ARL diagnosis were selected. EBV DNA was measured in PBMCs and serum samples with a commercial kit. RESULTS: High levels of EBV DNA in PBMCs collected a median of 10 months before diagnosis were associated with an increased risk of developing systemic B lymphoma (adjusted odds ratio 2.47; 95% confidence interval 1.15; 5.32 for each 1 log copies/10(6) PBMC increase in EBV load) but not with primary brain lymphoma. CONCLUSION: In this study, HIV-infected patients with undetectable EBV DNA in PBMCs did not develop ARL in the following 3 years, while high levels of EBV DNA in PBMCs predicted subsequent progression to systemic B lymphoma. Clinicians should be aware of the increased risk of developing systemic B lymphoma in HIV-infected patients with a high blood EBV DNA load.

The model Lysozyme-PSSNa system for electrostatic complexation: Similarities and differences with complex coacervation.

We review, based on structural information, the mechanisms involved when putting in contact two nano-objects of opposite electrical charge, in the case of one negatively charged polyion, and a compact charged one. The central case is mixtures of PSS, a strong flexible polyanion (the salt of a strong acid, and with high linear charge density), and Lysozyme, a globular protein with a global positive charge. A wide accurate and consistent set of information in different situations is available on the structure at local scales (5-1000Å), due to the possibility of matching, the reproducibility of the system, its well-defined electrostatics features, and the well-defined structures obtained. We have related these structures to the observations at macroscopic scale of the phase behavior, and to the expected mechanisms of coacervation. On the one hand, PSS/Lysozyme mixtures show accurately many of what is expected in PEL/protein complexation, and phase separation, as reviewed by de Kruif: under certain conditions some well-defined complexes are formed before any phase separation, they are close to neutral; even in excess of one species, complexes are only modestly charged (surface charges in PEL excess). Neutral cores are attracting each other, to form larger objects responsible for large turbidity. They should lead the system to phase separation; this is observed in the more dilute samples, while in more concentrated ones the lack of separation in turbid samples is explained by locking effects between fractal aggregates. On the other hand, although some of the features just listed are the same required for coacervation, this phase transition is not really obtained. The phase separation has all the macroscopic aspects of a fluid (undifferentiated liquid/gas phase) - solid transition, not of a fluid-fluid (liquid-liquid) one, which would correspond to real coacervation). The origin of this can be found in the interaction potential between primary complexes formed (globules), which agrees qualitatively with a potential shape of the type repulsive long range attractive very short range. Finally we have considered two other systems with accurate structural information, to see whether other situations can be found. For Pectin, the same situation as PSS can be found, as well as other states, without solid precipitation, but possibly with incomplete coacervation, corresponding to differences in the globular structure. It is understandable that these systems show smoother interaction potential between the complexes (globules) likely to produce liquid-liquid transition. Finally, we briefly recall new results on Hyaluronan/Lysozyme, which present clear signs of coacervation in two liquid phases, and at the same time the existence of non-globular complexes, of specific geometry (thin rods) before any phase separation. These mixtures fulfill many of the requirements for complex coacervation, while other theories should also be checked like the one of Shklovskii et al.

OASIS: an assessment tool of epidemiological surveillance systems in animal health and food safety.

The purpose of this study was to develop a standardized tool for the assessment of surveillance systems on zoonoses and animal diseases. We reviewed three existing methods and combined them to develop a semi-quantitative assessment tool associating their strengths and providing a standardized way to display multilevel results. We developed a set of 78 assessment criteria divided into ten sections, representing the functional parts of a surveillance system. Each criterion was given a score according to the prescription of a scoring guide. Three graphical assessment outputs were generated using a specific combination of the scores. Output 1 is a general overview through a series of pie charts synthesizing the scores of each section. Output 2 is a histogram representing the quality of eight critical control points. Output 3 is a radar chart representing the level reached by ten system attributes. This tool was applied on five surveillance networks.