A multidisciplinary and structured investigation of three suspected clusters of transverse upper limb reduction defects in France.

INTRODUCTION: Between 2019-2021, facing public concern, a scientific expert committee (SEC) reanalysed suspected clusters of transverse upper limb reduction defects (TULRD) in three administrative areas in France, where initial investigations had not identified any risk exposure. We share here the national approach we developed for managing suspicious clusters of the same group of congenital anomalies occurring in several areas. METHODS: The SEC analysed the medical records of TURLD suspected cases and performed spatiotemporal analyses on confirmed cases. If the cluster was statistically significant and included at least three cases, the SEC reviewed exposures obtained from questionnaires, environmental databases, and a survey among farmers living near to cases' homes concerning their plant product use. RESULTS: After case re-ascertainment, no statistically significant cluster was observed in the first administrative areas. In the second area, a cluster of four children born in two nearby towns over two years was confirmed, but as with the initial investigations, no exposure to a known risk factor explaining the number of cases in excess was identified. In the third area, a cluster including just two cases born the same year in the same town was confirmed. DISCUSSION: Our experience highlights that in the event of suspicious clusters occurring in different areas of a country, a coordinated and standardised approach should be preferred.

Primary resistance of hepatitis B virus to nucleoside and nucleotide analogues.

Nucleoside and nucleotide analogues (NUCs) targeting hepatitis B virus are capable of selecting resistant viruses upon long-term administration as monotherapies. The prevalence of resistance-associated substitutions (RASs) and fitness-associated substitutions at baseline of NUC therapy and their impact on treatment responses remain unknown. A total of 232 treatment-naïve patients chronically infected with hepatitis B virus (HBV) consecutively referred for the first time to one of French reference centres were included. The nearly full-length HBV reverse transcriptase was sequenced by means of deep sequencing, and the sequences were analysed. RASs were detected in 25% of treatment-naïve patients, generally representing low proportions of the viral quasispecies. All amino acid positions known to be associated with HBV resistance to currently approved NUCs or with increased fitness of resistant variants were affected, except position 80. RASs at positions involved in lamivudine, telbivudine and adefovir resistance were the most frequently detected. All patients with RASs detectable by next-generation sequencing at baseline who were treatment-eligible and treated with currently recommended drugs achieved a virological response. The presence of pre-existing HBV RASs has no impact on the outcome of therapy if potent drugs with a high barrier to resistance are used.

Molecular epidemiology and mechanisms of resistance of azithromycin-resistant Neisseria gonorrhoeae isolated in France during 2013-14.

OBJECTIVES: The objective of this study was to determine the prevalence and mechanisms of azithromycin resistance of Neisseria gonorrhoeae French isolates from 2013 to 2014. METHODS: N. gonorrhoeae samples isolated in a network of laboratories were tested for susceptibility to azithromycin between April 2013 and March 2014. Fifty-four isolates that were non-susceptible to azithromycin and 18 susceptible isolates were characterized for molecular mechanisms of resistance by PCR/sequencing and genotyped using N. gonorrhoeae multiantigen sequence typing (NG-MAST). RESULTS: Among the 970 N. gonorrhoeae isolates, 54 (5.56%) were non-susceptible to azithromycin, 9 (1%) were resistant and 45 (4.6%) showed intermediate resistance. Azithromycin-non-susceptible isolates harboured a C2599T mutation in the rrl gene encoding the 23S rRNA alleles (5.5%), a C substitution in the mtrR promoter (5.5%), an A deletion in the mtrR promoter (53.7%) and mutations in the L4 ribosomal protein (14.8%) and in the MtrR repressor (25.9%). No isolates showed an L22 mutation or carried an erm, ere, mef(A)/(E) or mphA gene. Thirty different STs were highlighted using the NG-MAST technique. The predominant genogroups non-susceptible to azithromycin were G21 (31%), G1407 (20%) and G2400 (15%). Genogroup G2400 (15%) was revealed to be a novel cluster prevalent in the south of France and resistant to azithromycin, ciprofloxacin and tetracycline. CONCLUSIONS: Our study highlights that the prevalence of resistance of N. gonorrhoeae to azithromycin in France is low and essentially due to multiple genetic mutations. Its dissemination occurs through three major genogroups including a novel one in France (G2400).

Impact of Male Circumcision among heterosexual HIV cases: comparisons between three low HIV prevalence countries.

BACKGROUND: Studies performed in high-HIV prevalence countries showed a strong epidemiological association between male circumcision (MC) and the prevention of HIV transmission. We estimated the potential impact of MC on the general heterosexual population in low-HIV prevalence countries. METHODS: Cross-national comparisons, including data on newly diagnosed HIV cases among heterosexuals living in Israel (where almost all males undergo MC), to similar data from the Netherlands and France (where <10 % of males are circumcised) were performed. National data from HIV registers and Bureaus of Statistics for the period of 2004-2010, global rates, rates by sex, age, and year of HIV-diagnosis were compared. MC and potential biases were examined. RESULTS: Annual rates of new HIV diagnoses per 100,000 were significantly lower in Israel compared to the Netherlands and France (for men: 0.26-0.70, 1.91-2.28, and 2.69-3.47, respectively; for women: 0.10-0.34, 1.10-2.10 and 2.41-3.08, respectively). Similarly, HIV-rates were much lower in Israel when comparing by age groups. Although Gross National Income per capita in 2010 was lower in Israel compared to the Netherlands and France, access to HIV testing and treatment were not different between countries. Also, the number of sexual-partners and condom-use in the general population showed a high similarity between the countries. CONCLUSIONS: The lower rate of HIV among heterosexuals in Israel compared to the Netherlands and France might be explained by MC routinely practiced in Israel, since other parameters of influence on HIV transmission were rather similar between the countries. However, recommendation for systematic MC in low HIV prevalence countries requires further investigations.

Sexual behaviours of homosexual and bisexual men in France: a generational approach.

OBJECTIVE: In high-income countries, the social and epidemiological contexts surrounding homosexuality and AIDS have changed profoundly in recent decades. This work sought to examine key indicators of the long-term sexual trajectories of successive generations of men who have sex with men (MSM) in France. METHODS: We performed a longitudinal analysis of the French Gay Press surveys, which were self-administered socio-behavioural questionnaires, repeated from 1985 to 2011 in the gay press, and on the internet in 2004 and 2011. An age-cohort analysis using graphical representations and multivariate logistic regressions was conducted among participants aged 18-59 (N = 38 821). RESULTS: First sexual intercourse occurred more often with a male partner in younger generations than in older ones: 76.0% in MSM who turned 18 in 1956-1959, 75.6% in 1980-1983, 83.7% in 2008-2011, p(overall) = 0.0002). Every generation showed the same pattern of sexual trajectory between 1985 and 2011: globally, the frequency of masturbation increased from the 1985 survey to the early 1990s and then decreased from the late 1990s to the end of the study period. Inversely, the frequency of oral and anal sex decreased in the mid-1980s and increased from 1990 to 2011. The frequency of both oral sex and anal intercourse is currently quite high, regardless of generation (>95% and around 80%, respectively). Compared to their predecessors, recent generations of young MSM reported more frequent oral and anal sex, but fewer male partners in the previous 12 months. DISCUSSION: While the increased frequency of first intercourse with a man over successive generations since the 1970s may be related to reduced social pressure for heterosexuality, there is evidence that sexual norms among MSM are widespread, with practices spreading across age groups and generations. Although AIDS profoundly affected sexual practices in the 1980s, further AIDS-related events (discovery of HIV antiretroviral drugs and their use in prevention) do not appear to have accentuated ongoing trends in sexual practices.

Burden of HIV and hepatitis C co-infection: the changing epidemiology of hepatitis C in HIV-infected patients in France.

BACKGROUND & AIMS: To better evaluate the HIV-HCV co-infection burden in the context of new effective HCV treatment. METHODS: We reviewed all the epidemiological data available on HCV-related disease in HIV-infected patients in France. Sources of data have been selected using the following criteria: (i) prospective cohorts or cross-sectional surveys; (ii) conducted at a national level; (iii) in the HIV-infected population; (iv) able to identify HCV co-infection and chronic active hepatitis C (HCV RNA positive); and (v) conducted during the period 2003-2012. RESULTS: The overall prevalence of HIV-HCV co-infection has decreased from 22-24% to 16-18%. This prevalence decreased from 93% to 87% among injecting drug users while it increased from 4% to 6% among men who have sex with men. The characteristics of patients have changed: decrease in the proportion of patients with chronic active hepatitis C (HCV RNA positive) from 77% to 63% and in the genotypes 2 and 3 HCV infection; increase in the proportion of HCV genotype 1 (from 45-50% to 58%) and genotype 4 (from 15% to 22%). The proportion of patients treated with highly active antiretroviral therapy increased from 76% to 95%, with higher rates of undetectable HIV viral load (47% in 2004 vs. 85% in 2012). CONCLUSION: The decreasing prevalence and the change in patients profile in HIV-HCV co-infection underline the importance of continuing efforts to educate physicians and patients. This should increase the benefit of viral risk reduction policies and increase the access of co-infected patients to HCV treatment.

Characteristics of patients recently infected with HIV-1 non-B subtypes in France: a nested study within the mandatory notification system for new HIV diagnoses.

The presence of HIV-1 non-B subtypes in Western Europe is commonly attributed to migration of individuals from non-European countries, but the possible role of domestic infections with non-B subtypes is not well investigated. The French mandatory anonymous reporting system for HIV is linked to a virological surveillance using assays for recent infection (<6 months) and serotyping. During the first semester of years 2007 to 2010, any sample corresponding to a non-B recent infection was analyzed by sequencing a 415-bp env region, followed by phylogenetic analysis and search for transmission clusters. Two hundred thirty-three recent HIV-1 infections with non-B variants were identified. They involved 5 subtypes and 7 circulating recombinant forms (CRFs). Ninety-two cases (39.5%) were due to heterosexual transmissions, of which 39 occurred in patients born in France. Eighty-five cases (36.5%) were identified in men having sex with men (MSM). Forty-three recent non-B infections (18.5%) segregated into 14 clusters, MSM being involved in 11 of them. Clustered transmission events included 2 to 7 cases per cluster. The largest cluster involved MSM infected by a CRF02_AG variant. In conclusion, we found that the spread of non-B subtypes in France occurs in individuals of French origin and that MSM are particularly involved in this dynamic.

Late diagnosis and entry to care after diagnosis of human immunodeficiency virus infection: a country comparison.

BACKGROUND: Testing for HIV infection and entry to care are the first steps in the continuum of care that benefit individual health and may reduce onward transmission of HIV. We determined the percentage of people with HIV who were diagnosed late and the percentage linked into care overall and by demographic and risk characteristics by country. METHODS: Data were analyzed from national HIV surveillance systems. Six countries, where available, provided data on two late diagnosis indicators (AIDS diagnosis within 3 months of HIV diagnosis, and AIDS diagnosis within 12 months before HIV diagnosis) and linkage to care (≥ 1 CD4 or viral load test result within 3 months of HIV diagnosis) for people diagnosed with HIV in 2009 or 2010 (most recent year data were available). PRINCIPAL FINDINGS: The percentage of people presenting with late stage disease at HIV diagnosis varied by country, overall with a range from 28.7% (United States) to 8.8% (Canada), and by transmission categories. The percentage of people diagnosed with AIDS who had their initial HIV diagnosis within 12 months before AIDS diagnosis varied little among countries, except the percentages were somewhat lower in Spain and the United States. Overall, the majority of people diagnosed with HIV were linked to HIV care within 3 months of diagnosis (more than 70%), but varied by age and transmission category. CONCLUSIONS: Differences in patterns of late presentation at HIV diagnosis among countries may reflect differences in screening practices by providers, public health agencies, and people with HIV. The percentage of people who received assessments of immune status and viral load within 3 months of diagnosis was generally high.

First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission, France, May 2013.

In May 2013, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection was diagnosed in an adult male in France with severe respiratory illness, who had travelled to the United Arab Emirates before symptom onset. Contact tracing identified a secondary case in a patient hospitalised in the same hospital room. No other cases of MERS-CoV infection were identified among the index case's 123 contacts, nor among 39 contacts of the secondary case, during the 10-day follow-up period.

Hepatitis B knowledge, perceptions and practices in the French general population: the room for improvement.

BACKGROUND: Little is known about the knowledge, perceptions and prevention practices of the French general population with respect to Hepatitis B virus (HBV) infection. This article describes this population's knowledge of HBV, their perceptions of the disease, and associated screening and vaccination practices. It compares these indicators with those observed in the same population for HIV, an infection with a chronic course and transmission modes resembling those of HBV. METHODS: A module on hepatitis B was added into the HIV KABP (Knowledge, Attitudes, Beliefs and Practices) survey which was carried out telephonically in 2010 among a random sample of 9,014 individuals aged between 18-69 and living in metropolitan France. RESULTS: Compared with HIV, the general population was less aware that needle exchange during intravenous drug use and sexual relationships are HBV transmission modes (HBV: 89.9% and 69.7%; HIV: 99.1% and 99.4%). The fear of both illnesses was similar at 20.3%. The individual perceived risk of infection was higher for HBV than for HIV with, respectively, 60.8% and 40.3% of respondents believing they had an equal or greater risk of being infected than the average person. However, the percentage of those reporting HBV screening during their lifetime (27.4%) was half that for HIV screening (61.4%). In multivariate analysis, HBV screening was reported more often by individuals born in areas with high HBV endemicity (OR = 2.1 [95% CI: 1.5-2.9]) than by those born in low HBV endemicity areas, and more often by those who reported they had taken drugs intravenously during their lifetime (OR = 2.2 [95% CI: 1.2-4.2]) than those who did not report such behavior. Almost one in two respondents (47%) reported HBV vaccination. The intermediate or high endemicity groups did not report vaccination more often than those born in low endemicity areas nor did those reporting intravenously drug use compared with those who did not. CONCLUSIONS: This study highlights very contrasting levels of knowledge, perceptions and practices regarding HBV and HIV in the French general population. Our results demonstrate the need to improve the general and high-risk populations' knowledge of HBV, in particular concerning sexual transmission, in order to improve screening and vaccination practices.

Understanding providers' offering and patients' acceptance of HIV screening in emergency departments: a multilevel analysis. ANRS 95008, Paris, France.

OBJECTIVE: We assessed the EDs' characteristics associated with the offer and acceptance rates of a nontargeted HIV rapid-test screening in 29 Emergency Departments (EDs) in the metropolitan Paris region (11.7 million inhabitants), where half of France's new HIV cases are diagnosed annually. METHODS: EDs nurses offered testing to all patients 18-64-year-old, able to provide consent, either with or without supplemental staff (hybrid staff model or indigenous staff model). The EDS' characteristics collected included structural characteristics (location, type, size), daily workload (patients' number and severity, length of stay in hours), staff's participation (training, support to the intervention, leadership), type of week day (weekends vs weekdays) and time (in days). Associations between these variables and the staff model, the offer and acceptance rates were studied using multilevel modeling. RESULTS: Indigenous staff model was more frequent in EDs with a lower daily patient flow and a higher staff support score to the intervention. In indigenous-model EDs, the offer rate was associated with the patient flow (OR = 0.838, 95% CI = 0.773-0.908), was lower during weekends (OR = 0.623, 95% CI = 0.581-0.667) and decreased over time (OR = 0.978, 95% CI = 0.975-0.981). Similar results were found in hybrid-model EDs. Acceptance was poorly associated with EDs characteristics in indigenous-model EDs while in hybrid-model EDs it was lower during weekends (OR = 0.713, 95% CI = 0.623-0.816) and increased after the first positive test (OR = 1.526, 95% CI = 1.142-2.038). The EDs' characteristics explained respectively 38.5% and 15% of the total variance in the offer rate across indigenous model-EDs and hybrid model-EDs vs 12% and 1% for the acceptance rate. CONCLUSION: Our findings suggest the need for taking into account EDs' characteristics while considering the implementation of an ED-based HIV screening program. Strategies allowing the optimization of human resources' utilization such as HIV targeted screening in the EDs might be privileged.

Missed opportunities for HIV testing in newly-HIV-diagnosed patients, a cross sectional study.

BACKGROUND: In France, 1/3 HIV-infected patients is diagnosed at an advanced stage of the disease. We describe missed opportunities for earlier HIV testing in newly-HIV-diagnosed patients. METHODS: Cross sectional study. Adults living in France for ≥1 year, diagnosed with HIV-infection ≤6 months earlier, were included from 06/2009 to 10/2010. We collected information on patient characteristics at diagnosis, history of HIV testing, contacts with healthcare settings, and occurrence of HIV-related events 3 years prior to HIV diagnosis. During these 3 years, we assessed whether or not HIV testing had been proposed by the healthcare provider upon first contact in patients notifying that they were MSM or had HIV-related conditions. RESULTS: 1,008 newly HIV-diagnosed patients (mean age: 39 years; male: 79%; MSM: 53%; diagnosed with an AIDS-defining event: 16%). During the 3-year period prior to HIV diagnosis, 99% of participants had frequented a healthcare setting and 89% had seen a general practitioner at least once a year. During a contact with a healthcare setting, 91/191 MSM (48%) with no HIV-related conditions, said being MSM; 50 of these (55%) did not have any HIV test proposal. Only 21% (41/191) of overall MSM who visited a healthcare provider received a test proposal. Likewise, 299/364 patients (82%) who sought care for s had a missed opportunity for HIV testing. CONCLUSIONS: Under current screening policies, missed opportunities for HIV testing remain unacceptably high. This argues in favor of improving risk assessment, and HIV-related conditions recognition in all healthcare facilities.

An 18-year follow-up of HIV knowledge, risk perception, and practices in young adults.

OBJECTIVE: To evaluate trends over the last 18 years in HIV-related knowledge, risk perceptions, and sexual behaviors in young adults. METHODS: Data were obtained from six KABP (knowledge, attitudes, beliefs, and practices) surveys (1992, 1994, 1998, 2001, 2004, and 2010) from representative samples of the French population. Surveys were similar in terms of data collection and target populations: 2362 men and 2774 women aged 18-29 were interviewed by telephone. RESULTS: Young people were very familiar with the true routes of HIV transmission throughout the full period. However, in 2010, approximately 30% erroneously believed that mosquito bites could transmit HIV versus only 12% in 1994. They were less convinced about the efficacy of condoms in protecting against HIV: approximately 50% in 2010 versus 70-80% in 1992-1994. The proportion of respondents very afraid of AIDS significantly decreased from a maximum of 44% in 1994 to approximately 20% in 2010. Condom use at first intercourse was widespread after 1995 and sex without condoms in the previous year was far less frequently reported in 2010 than in 1992. Nevertheless, the proportion of individuals reporting condom use at their most recent intercourse in 2010 was the lowest reported since 1994, with an increase in young men reporting no contraception use from 9.2% in 2004 to 18.8% in 2010. CONCLUSION: Young people appear to misunderstand certain sexually transmitted infection/HIV transmission mechanisms. Other indicators for 2010 reflected a low level of HIV risk perception, distrust in condom efficacy, and a decrease in adopting prevention practices, which highlights the need to adapt preventive strategies.

[Current epidemiology of bacterial STIs in France]. / Épidémiologie actuelle des infections sexuellement transmissibles bactériennes en France.

Sexually transmitted infections (STIs) remains a major problem of public health in France. Voluntary networks of physicians (RésIST) and laboratories (Rénago, Rénachla, lymphogranuloma venereum: LGV network) produce indicators showing the evolution of the main bacterial STIs. In 2010, the main findings were the following. The number of gonococcal infections has increased throughout the decade 2000 to 2010. The decrease in susceptibility of gonococcal strains to first-line antibiotics (extended-spectrum cephalosporins) needs to keep great attention. The number of screening and diagnosis of chlamydial urogenital infections also continues to rise in both sexes, particularly due to increased screening among young people. The relatively stable number of cases of early syphilis and of rectal LGV needs to be confirmed over the coming years. Both of these STIs affect overwhelmingly homo/bisexual men. There is still a high level of HIV co-infection with LGV and syphilis, and to a lesser extent with gonorrhea. We observe that condom use is still inadequate, especially during oral sex.

Global HIV epidemiology: specific patterns of the epidemic in the North and South.

Thirty years after the identification of the first cases of AIDS, it was estimated that 34 million of people were living with HIV worldwide in 2011. The incidence is declining but remains high, with 2.5 million of new HIV infections per year. Africa is the region of the world most heavily affected, accounting for three-quarters of the global burden of HIV infection and the same proportion for new infections. The incidence declines in most parts of the world while heterosexual transmission remains the dominant mode of HIV acquisition followed by homosexual transmission. Intravenous drug use continues to drive the epidemic in Eastern Europe and parts of Asia. Condom use remains the cornerstone of prevention of sexual transmission. Male medical circumcision has now been proven an effective public health intervention to prevent sexual transmission. Antiretroviral treatment may reduce sexual transmission at population level while improving the conditions of life and survival of those harbouring the virus. Harm-reduction together with blood safety prevent blood transmission. The prevention of mother-to-child transmission is now moving its global objective to elimination by the end of 2015. At least 20 years will be necessary for achieving HIV control at the worldwide level with currently available interventions.

HIV prevalence and sexual risk behaviors associated with awareness of HIV status among men who have sex with men in Paris, France.

A cross-sectional survey, using self-sampled finger-prick blood on blotting paper and anonymous behavioral self-administrated questionnaires was conducted in Paris in 2009 among MSM attending gay venues. Paired biological results and questionnaires were available for 886 participants. HIV seroprevalence was 17.7 % (95 % CI: 15.3-20.4). Four groups were identified according to their knowledge of their HIV biological status. Among the 157 found to be seropositive, 31 (19.7 %) were unaware of their status and reported high levels of sexual risk behaviors and frequent HIV testing in the previous 12 months. Among the 729 MSM diagnosed HIV-negative, 183 were no longer sure whether they were still HIV-negative, or had never been tested despite the fact that they engaged in at-risk sexual behaviors. This study provides the first estimate of HIV seroprevalence among MSM in Paris and underlines the specific need for combined prevention of HIV infection in this MSM population.

Biomarker-based HIV incidence in a community sample of men who have sex with men in Paris, France.

BACKGROUND: Population-based estimates of HIV incidence in France have revealed that men who have sex with men (MSM) are the most affected population and contribute to nearly half of new infections each year. We sought to estimate HIV incidence among sexually active MSM in Paris gay community social venues. METHODOLOGY/ PRINCIPAL FINDINGS: A cross-sectional survey was conducted in 2009 in a sample of commercial venues such as bars, saunas and backrooms. We collected a behavioural questionnaire and blood sample. Specimens were tested for HIV infection and positive specimens then tested for recent infection by the enzyme immunoassay for recent HIV-1 infection (EIA-RI). We assessed the presence of antiretroviral therapy among infected individuals to rule out treated patients in the algorithm that determined recent infection. Biomarker-based cross-sectional incidence estimates were calculated. We enrolled 886 MSM participants among which 157 (18%) tested HIV positive. In positive individuals who knew they were infected, 75% of EIA-RI positive results were due to ART. Of 157 HIV positive specimens, 15 were deemed to be recently infected. The overall HIV incidence was estimated at 3.8% person-years (py) [95%CI: 1.5-6.2]. Although differences were not significant, incidence was estimated to be 3.5% py [0.1-6.1] in men having had a negative HIV test in previous year and 4.8% py [0.1-10.6] in men having had their last HIV test more than one year before the survey, or never tested. Incidence was estimated at 4.1% py [0-8.3] in men under 35 years and 2.5% py [0-5.4] in older men. CONCLUSIONS/ SIGNIFICANCE: This is the first community-based survey to estimate HIV incidence among MSM in France. It includes ART detection and reveals a high level of HIV transmission in sexually active individuals, despite a high uptake of HIV testing. These data call for effective prevention programs targeting MSM engaged in high-risk behaviours.