Epidemiology of Lyme borreliosis through two surveillance systems: the national Sentinelles GP network and the national hospital discharge database, France, 2005 to 2016.

BACKGROUND: Lyme borreliosis (LB) is the most frequent vector-borne disease in France. Since 2009, surveillance of LB is conducted by a sentinel network of general practitioners (GPs). This system, in conjunction with the national hospitalisation database was used to estimate the incidence and describe the characteristics of LB in France. AIM: To describe the estimated incidence and trends in GP consultations and hospital admissions for LB in France and identify risk groups and high-incidence regions. RESULTS: From 2011 to 2016, the mean yearly incidence rate of LB cases was 53 per 100,000 inhabitants (95% CI: 41-65) ranging from 41 in 2011 to 84 per 100 000 in 2016. A mean of 799 cases per year were hospitalised with LB associated diagnoses 2005-16. The hospitalisation incidence rate (HIR) ranged from 1.1 cases per 100,000 inhabitants in 2005 to 1.5 in 2011 with no statistically significant trend. We observed seasonality with a peak during the summer, important inter-regional variations and a bimodal age distribution in LB incidence and HIR with higher incidence between 5 and 9 year olds and those aged 60 years. Erythema migrans affected 633/667 (95%) of the patients at primary care level. Among hospitalised cases, the most common manifestation was neuroborreliosis 4,906/9,594 (51%). CONCLUSION: Public health strategies should focus on high-incidence age groups and regions during the months with the highest incidences and should emphasise prevention measures such as regular tick checks after exposure and prompt removal to avoid infection.

Travel-associated and autochthonous Zika virus infection in mainland France, 1 January to 15 July 2016.

During summer 2016, all the conditions for local mosquito-borne transmission of Zika virus (ZIKV) are met in mainland France: a competent vector, Aedes albopictus, a large number of travellers returning from ZIKV-affected areas, and an immunologically naive population. From 1 January to 15 July 2016, 625 persons with evidence of recent ZIKV infection were reported in mainland France. We describe the surveillance system in place and control measures implemented to reduce the risk of infection.

[Headache: classification and diagnosis]. / Hoofdpijn: classificatie en diagnose.

There are many types of headache and, moreover, many people have different types of headache at the same time. Adequate treatment is possible only on the basis of the correct diagnosis. Technically and in terms of content the current diagnostics process for headache is based on the 'International Classification of Headache Disorders' (ICHD-3-beta) that was produced under the auspices of the International Headache Society. This classification is based on a distinction between primary and secondary headaches. The most common primary headache types are the tension type headache, migraine and the cluster headache. Application of uniform diagnostic concepts is essential to come to the most appropriate treatment of the various types of headache.

Incidence and hospitalisation rates of Lyme borreliosis, France, 2004 to 2012.

Lyme borreliosis (LB) has become a major concern recently, as trends in several epidemiological studies indicate that there has been an increase in this disease in Europe and America over the last decade. This work provides estimates of LB incidence and hospitalisation rates in France. LB data was obtained from the Sentinelles general practitioner surveillance network (2009­2012) and from the Programme de Médicalisation des Systèmes d'Information (PMSI) data processing centre for hospital discharges (2004­09). The yearly LB incidence rate averaged 42 per 100,000 inhabitants (95% confidence interval (CI): 37­48), ranging from 0 to 184 per 100,000 depending on the region. The annual hospitalisation rate due to LB averaged 1.55 per 100,000 inhabitants (95% CI: 1.42­1.70). Both rates peaked during the summer and fall and had a bimodal age distribution (5­10 years and 50­70 years). Healthcare providers should continue to invest attention to prompt recognition and early therapy for LB, whereas public health strategies should keep promoting use of repellent, daily checks for ticks and their prompt removal.

[Genetic diversity of a rare hepatitis A virus genotype]. / Diversité génétique d'un génotype rare du virus de l'hépatite A.

PURPOSE OF THE STUDY: Very few is known on genotype II hepatitis A virus (HAV) since it is rarely isolated. From 2002 to 2007, the French observatory of HAV identified six sub-genotype IIA strains of which one from a patient having travelled to West Africa. To investigate the possible African origin of sub-genotype IIA, we determined its prevalence among French travellers in 2008 and characterised its genetic variability. PATIENTS AND METHODS: The 2008 mandatory notification records were screened for travel to Africa. Viral genotype was determined on the nucleotide sequencing of the VP1/2A junction region. The P1 region coding for capsid proteins was used to compare the genetic diversity of IIA isolates to those of other genotypes. RESULTS: In 2008, five out of 54 patients returning from West Africa were infected by IIA strains and an additional "autochthonous" case was identified. Two more African cases were identified in 2009. A total of 14 IIA isolates (eight African and six "autochthonous") were analysed. Nucleotide and amino-acid variability of IIA sequences was lower than that of the other genotypes. Phylogenetic analysis revealed the clustering of two "autochthonous" cases with African isolates whereas the other ones belonged to a different lineage. CONCLUSION: Most IIA strains isolated in France are imported by travellers returning from West Africa. However, the unexplained contamination mode of some "autochthonous" cases suggests another geographical origin to discover or a French reservoir to explore.

Large-scale screening and subsequent effects of migraine treatment on the work floor in the Netherlands.

In a large retail business group the ID Migraine Screening Test was sent to employees with three or more absences from work in the past year (n = 2893). Employees with positive results were invited for a neurological consultation and migraine patients were randomly assigned to: first attack 'treated as usual' and the second attack treated with 40 mg eletriptan, or reversed order. Of the 2893 employees, 799 responded (28%), 260 were positively screened for migraine (33%), 84 patients were diagnosed by a neurologist and 41 of the 75 included patients completed the protocol. Eletriptan induced pain-free response in 33.3% of the patients at 4 h compared with 0% after 'non-specific' treatment (P = 0.03). Eletriptan also significantly improved quality of life, but differences in absence from work and productivity loss could not be detected. In conclusion, in-company screening can be beneficial for undertreated employees, but implementation obstacles can reduce the effectiveness of screening.

Cluster of cases of hepatitis A with a travel history to Egypt, September-November 2008, France.

Since September 2008, 26 cases of hepatitis A with a history of travel to Egypt have been reported in France. Investigations indicate that a common source of contamination linked to Nile river cruises is the most likely explanation of the increase in the number of cases reported in France as well as in several other European Union countries.

An oyster-associated hepatitis A outbreak in France in 2007.

Following the notification of nine hepatitis A cases clustered in the Cotes d Armor district in northwestern France, epidemiological, environmental and microbiological investigations were set up in order to identify the source and vehicle of contamination and implement control measures. In total, 111 cases were identified in the outbreak, all of whom lived or had stayed as tourists in the Cotes d Armor district. Of the cases, 87% had eaten raw shellfish, and 81% specifically oysters. Traceback investigations carried out on raw shellfish consumed by the cases showed that the raw shellfish originated from a single shellfish farm. The shellfish were probably contaminated either in the submersible tanks or in a depuration land-based tank where they were stored. The source of contamination was not identified but shellfish could have been tainted by sewage overflows or by wastewater releases from a polluted storm sewer close to the shellfish farm or from on-site sanitation facilities. To prevent future hepatitis A outbreaks due to shellfish consumption from this area, hazards specific to each farm should be analysed. Timely information on sewage overflows should also be part of communities efforts regarding sewage collection and treatment.

A food-borne outbreak of hepatitis A virus (HAV) infection in a secondary school in Upper Normandy, France, in November 2006.

In November 2006, six symptomatic cases of hepatitis A in pupils of a secondary school in Upper Normandy, France, were reported to the district health service. This paper describes the outbreak investigation undertaken with the aim to identify the vehicle and source of infection, implement control measures and estimate the size of the outbreak. A primary case at the secondary school was defined as a pupil or a member of the staff with IgM anti-HAV detected in the serum and with onset of symptoms between 12 and 21 November 2006; a secondary case was defined as a contact to a primary case and who developed symptoms and had IgM anti-HAV two to seven weeks later. We performed a case control study of primary cases, controls being pupils visiting the same school (cases/controls 1:4) and inspected the canteen facilities. All 13 canteen employees were examined for anti-HAV IgM antibodies. A phylogenetic analysis of HAV of cases was performed. We identified 10 primary and 5 secondary cases. Among primary cases 90% reported eating liver pate at the canteen compared to 62% among controls (OR 5.5, 95% CI 0.62-256.9). One liver pate sample contained markers of faecal contamination. HAV genotypes were of one identical type. All 13 canteen employees were negative for IgM anti-HAV while four had anti-HAV total antibodies. We found deficiencies regarding food preparing procedures and insufficient hand washing facilities. The vehicle of the outbreak was believed to be the liver pate but the source of HAV could not be identified. Insufficient facilities in the canteen hindered staff from maintaining a high hygiene standard and were subsequently improved.

Outbreak of Salmonella enterica serotype Manhattan infection associated with meat products, France, 2005.

Between August 2005 and March 2006 in France, 69 cases of Salmonella enterica serotype Manhattan (Salmonella Manhattan) were reported, 51 (74%) of them from southeastern France. At the time of the alert (November 2005), 13 cases and 33 controls were interviewed. Cases were more likely than controls to have eaten pork sausages (OR=5.9, confidence interval CI [1.3; 26.9]) and beef (OR=9.3, CI [1.3; 68.6]). At the same time, 19 strains of Salmonella Manhattan isolated from meat products in southeastern France, reported to the French food safety agency (Afssa, Agence francaise de securite sanitaire des aliments) in September and November 2005, had an indistinguishable PFGE profile to the 7 human isolates of Salmonella Manhattan from the outbreak in southeastern France. Trace-back investigations revealed that pork samples came from one wholesaler whose pork products had tested positive for S. Manhattan during routine food testing in August 2005. This wholesaler supplied retail outlets in southeastern France. Additionally, a slaughterhouse supplying the wholesaler was inspected and widespread contamination with Salmonella spp. and S. Manhattan was found. Cooperation between the national agencies in charge of human health (Institut de veille sanitaire, InVS) and food safety (Afssa) allowed us to determine the most probable source of contamination and to take appropriate control measures.

Outbreak of Salmonella enterica serotype Manhattan infection associated with meat products, France, 2005.

Between August 2005 and March 2006 in France, 69 cases of Salmonella enterica serotype Manhattan (Salmonella Manhattan) were reported, 51 (74%) of them from southeastern France. At the time of the alert (November 2005), 13 cases and 33 controls were interviewed. Cases were more likely than controls to have eaten pork sausages (OR=5.9, confidence interval CI [1.3; 26.9]) and beef (OR=9.3, CI [1.3; 68.6]). At the same time, 19 strains of Salmonella Manhattan isolated from meat products in southeastern France, reported to the French food safety agency (Afssa, Agence française de sécurité sanitaire des aliments) in September and November 2005, had an indistinguishable PFGE profile to the 7 human isolates of Salmonella Manhattan from the outbreak in southeastern France. Trace-back investigations revealed that pork samples came from one wholesaler whose pork products had tested positive for S. Manhattan during routine food testing in August 2005. This wholesaler supplied retail outlets in southeastern France. Additionally, a slaughterhouse supplying the wholesaler was inspected and widespread contamination with Salmonella spp. and S. Manhattan was found. Cooperation between the national agencies in charge of human health (Institut de veille sanitaire, InVS) and food safety (Afssa) allowed us to determine the most probable source of contamination and to take appropriate control measures.

Mode of action of clonidine upon islet function: dissociated effects upon the time course and magnitude of insulin release.

Clonidine (0.08 to 80.0 ng/ml) caused a dose-related inhibition of glucose-stimulated insulin release, but failed to affect glucose oxidation, glucose-stimulated 45Ca net uptake, and adenylate cyclase activity in isolated rat islets. Phentolamine antagonized the effect of clonidine upon insulin release. Despite profound inhibition of insulin secretion, the drug failed to affect the time course for the changes evoked by glucose in either 45Ca fractional outflow rate from perfused islets or insulin release from the isolated perfused pancreas. The latter changes were multiphasic, revealing an initial secretory peak, a period of low secretory activity, and a second secretory elevation before establishing a period characterized by a steadily and slowly increasing insulin output. In the clonidine-treated islets, the secretory rate was not significantly different from the basal value during the period after the initial secretory response. Thus, despite continuous stimulation with glucose, insulin release appears as a discontinuous phenomenon, even when little insulin is secreted during the initial phase of stimulation.

Trends in HIV infection among sexually transmitted disease patients in Paris.

OBJECTIVE: To assess trends in HIV infection among sexually transmitted disease (STD) patients. DESIGN: Repeated unlinked anonymous survey, 1991-1993. SETTING: STD clinics in Paris, France. SUBJECTS: Patients (n = 4354) with a new suspected STD. METHODS: HIV antibody testing, using blood from syphilis samples. RESULTS: HIV prevalences were stable over time in all transmission groups. One-third of homo-/bisexual men were HIV-positive. Prevalence was 2.5 times higher among heterosexual patients from Africa or the Caribbean than among those from other countries. Among patients under 25 years of age prevalence significantly decreased from 4.3% in 1991 to 0.8% in 1993 (P = 0.01). Among homo-/bisexual men, despite a 50% reduction in the incidence of STD, the absolute number of those newly HIV-infected remained stable; median age increased from 28 years in 1991 to 32 years in 1993 (P = 0.02). Among heterosexuals, trends in HIV incidence were difficult to assess: recently infected patients were more likely to be identified in 1993 than in 1991, since the proportion of patients who reported a recent HIV-negative test increased over time. CONCLUSION: Prevalence studies contribute to define specific subgroups which should be targeted for prevention (HIV-positive or older homosexuals, heterosexuals from Africa and the Caribbean). Despite a decrease in both overall STD incidence and HIV prevalence among patients aged under 25 years, overall HIV incidence has not decreased, at least among homo-/bisexual men in whom recent HIV infections occurred at a high rate overall, and increased in those aged 35 years or more. Sentinel site-based HIV seroprevalence studies are best interpreted in the light of results obtained from different populations and through routine surveillance of STD.

HIV-1 diversity in France, 1996-1998. The AC 11 laboratory network.

OBJECTIVE: To study the distribution of HIV-1 subtypes in France and to describe the characteristics of patients infected with non-B subtypes. METHODS: All adults who tested HIV-1 positive on Western blot for the first time in one of the participating laboratories between September 1996 and March 1998 were eligible, whether or not they had been diagnosed previously elsewhere. Data on age, sex, country of birth, HIV-transmission group, dates of the last negative and first positive HIV test and clinical stage were collected. Serotyping was performed with a peptide subtype-specific enzyme immunoassay on each plasma sample and genotyping with heteroduplex mobility assay on each non-B serotype-infected patient. Patients characteristics were compared in B and non-B subtypes. RESULTS: Of the 2168 HIV-positive patients included by 32 laboratories, subtype,results were available for 2042. Among those, 73.4% were men, 12.2% born in sub-Saharan Africa, 41.5% infected through heterosexual contact and 67.6% in CDC stage A. Among the 2042 patients, 1 725 (84.5%) were infected with B subtype. Among the 317 non-B subtypes, subtype A was predominant (66.9%); all other subtypes (C, D, E, F, G, H, O) were present. Factors independently associated with a non-B subtype were to be included in the Paris area [adjusted odds ratio (aOR), 1.6; 95% confidence interval (CI), 1.1-2.3], to be born in sub-Saharan Africa (aOR, 26.0; 95% CI, 17.5-37.8) and to be infected through heterosexual contact (aOR, 4.2; 95% CI, 2.8-6.4). CONCLUSIONS: In France, although B subtype is still predominant, all non-B subtypes are now present. The diversity of HIV strains may affect diagnostic tests and clinical practice, especially viral load measurements. Moreover, the decreased susceptibility of non-B subtypes to antiretroviral drugs emphasizes the importance of surveillance of HIV diversity.

Determinants of delayed diagnosis of HIV infection in France, 1993-1995.

OBJECTIVE: To describe the circumstances of the first HIV-positive test and to study the determinants of a delayed diagnosis of HIV infection. METHODS: In a retrospective study among adult AIDS patients diagnosed between July 1993 and May 1995 in two French districts, data on socioeconomic characteristics, circumstances of first HIV-positive test and attitudes and behaviours regarding medical care were collected in a confidential interview and analysed for potential association with a late test, defined as a first HIV-positive test within 6 months of AIDS diagnosis. RESULTS: Of the 359 AIDS patients studied, 69 (19.2%) had a late test. Late testers were more likely than other patients to have had an HIV-positive test because of clinical symptoms (89.7 versus 38.9%, P < 0.001) and not to perceive themselves as being at risk of infection with HIV (53.6 versus 39.3%, P < 0.05). The proportion of late testers was 34.6% among heterosexually infected patients, 12.7% among homo-/ bisexual men and 9.6% among injecting drug users. Factors independently associated with a late test were male gender [adjusted odds ratio (aOR), 5.6; 95% confidence interval (CI), 1.7-18.9] and absence of earned income (aOR, 5.2; 95% CI, 1.4-19) among heterosexually infected patients; high education (aOR, 3.1; 95% CI, 1.0-9.6) and having consulted a person practising alternative medicine (aOR, 3.4; 95% CI, 1.2-10) in homo-/bisexual men. CONCLUSIONS: Despite incentives to be tested for HIV, many individuals in France are still tested too late, even if they are in known high-risk groups. Efforts to test HIV-infected people as early as possible should be made by increasing the perception of HIV risk and decreasing the level of missed opportunities for testing. Current case management approaches make this recommendation critically important from both public health and an individual perspective.

Pregnancy and contraception in a French cohort of HIV-infected women. SEROCO Study Group.

OBJECTIVE: To describe the impact of HIV diagnosis on contraception, incidence of pregnancy and live-births among HIV-infected women in France. DESIGN: Follow-up of women included in a French cohort of HIV-infected adults (SEROCO). METHODS: In 17 hospital-based units and one private practitioners' network in the Paris area and south-east region of France, 412 HIV-infected women (volunteers) were enrolled from 1988 to 1993, shortly after HIV diagnosis (median, 3 months), and followed for a median of 3 years. The main outcome measures were incidence and outcome of pregnancy, proportions of women sexually active and methods of contraception. RESULTS: The incidence of pregnancy decreased significantly from 20.4 per 100 person-years in the year preceding HIV diagnosis to 7.9 per 100 person-years after HIV diagnosis (P < 0.001), whereas the proportion of pregnancies voluntarily interrupted doubled (63 versus 29%). The proportion of women who were sexually inactive increased from 5% before HIV diagnosis to 20% thereafter. During followup, 80% of sexually active women were using contraceptive methods. CONCLUSIONS: The study supports an association between the discovery of HIV infection and a decrease in the proportion of women who are sexually active, a decrease in the incidence of pregnancy in general and live-births in particular, and an increase in the proportion of pregnancies voluntarily interrupted. Nevertheless, 24% of the women became pregnant and around 20% of sexually active women were not using any contraception. The high rate of voluntary abortion may indicate that many of these pregnancies were unplanned and could have been prevented.

Five cases of somatostatinoma: clinical heterogeneity and diagnostic usefulness of basal and tolbutamide-induced hypersomatostatinemia.

Five cases of somatostatinoma are reported, four being primarily located in the pancreas and one in the duodenum. The diagnosis was based upon the histological and immunochemical characteristics of tumoral and metastatic tissue. A marked clinical heterogeneity was noted: one patient presented with gallstones, steatorrhea, and diabetes, two patients suffered from severe hypoglycemic attacks, and two cases were admitted for obstructive jaundice. This varying symptomatology was related to differences in the circulating levels of biologically active somatostatin and to a variable cellular composition of the tumor. In all cases, a basal and/or tolbutamide-induced hypersomatostatinemia was measured. It is concluded that the clinical and hormonal features of the earlier defined somatostatinoma syndrome are no requisite for the diagnosis of somatostatinoma; the analysis of plasma somatostatin immunoreactivity might lead to a higher detection rate of this endocrine tumor.

Ionophore-mediated cation translocation in artificial systems. II. - X537A-mediated calcium and sodium translocation.

The ionophore X537A translocates both calcium and sodium from an aqueous into an organic solution. At non saturating cationic concentrations, each atom of calcium seems to react with two molecules of ionophore, whereas each atom of sodium apparently reacts with only one molecule of X537A. The phenomena of sodium and calcium translocation, respectively, are competitive and are both inhibited when the pH of the aqueous phase is decreased.

Ionophore-mediated cation translocation in artificial systems. I. A23187-mediated calcium translocation.

The inophore A23187 stimulates the translocation of calcium from an aqueous Hepes buffer into an organic immiscible phase. At saturating calcium concentrations, 2 molecules of ionophore seem to complex each atom of calcium. Consistent with such a stoichiometric behaviour, the apparent ratio of calcium-ionophore association to dissociation rate constants increases as the concentration of ionophore is raised. As a result, at low calcium concentrations, the amount of translocated calcium increases as a power function of A23187 concentration. When allowance is made for such a phenomenon, the relation between calcium translocation and concentration is characterized by usual substrate-receptor binding kinetics.

Synergistic effects of hypoglycaemic sulphonylureas and antibiotic ionophores upon calcium translocation.

1 Hypoglycaemic sulphonylureas, such as tolbutamide and gliclazide, provoke the translocation of calcium from an aqueous medium into or across a hydrophobic region. The combined effect of sulphonylureas and antibiotic ionophores upon such a process was investigated. 2 The magnitude of the sulphonylurea-induced translocation of calcium was more marked in the presence than in the absence of A23187. Gliclazide and tolbutamide also enhanced, although less markedly, X537A-mediated calcium translocation. The effect of the sulphonylureas was even less marked in the presence of both ionophores, which acted synergistically in causing calcium translocation. 3 A non-hypoglycaemic sulphonylurea and diazoxide failed to affect ionophore-mediated calcium translocation. Gliclazide failed to enhance X537A-mediated sodium translocation. 4 It is proposed that the primary site of action of hypoglycaemic sulphonylureas upon calcium-dependent physiological processes may correspond to a drug-induced facilitation of calcium transport across the plasma membrane, as mediated by native ionophores.