Secular trends in incidence of acute gastroenteritis in general practice, France, 1991 to 2015.

We analysed 25 years of general practitioner (GP) visits for acute gastroenteritis (AG) surveillance in France, by the GP Sentinelles network. We searched for time trends of acute gastroenteritis incidence during winter periods. Data from emergency departments and drug reimbursement were additional data sources. A time-series analysis was performed using a generalised additive model for all data sources for the winter period. Virological data were incorporated and compared with the three data sources. The cumulative incidence of GP visits for winter AG exhibited an increasing trend from 1991 until 2008, when it reached 6,466 per 100,000 inhabitants. It decreased thereafter to 3,918 per 100,000 inhabitants in 2015. This decreasing trend was observed for all age groups and confirmed by the generalised additive model. For emergency department visits a decreasing trend was observed from 2004. Drug reimbursement data analyses demonstrated a decreasing trend from when data began in 2009. The incidence reported by GPs and emergency departments was lower following the emergence of norovirus GII.4 2012 (p < 0.0001). Winter AG incidences seem to follow long-term rising and decreasing trends that are important to monitor through continuous surveillance to evaluate the impact of prevention strategies, such as future immunisation against acute viral gastroenteritis.

Practical considerations for sensitivity analysis after multiple imputation applied to epidemiological studies with incomplete data.

BACKGROUND: Multiple Imputation as usually implemented assumes that data are Missing At Random (MAR), meaning that the underlying missing data mechanism, given the observed data, is independent of the unobserved data. To explore the sensitivity of the inferences to departures from the MAR assumption, we applied the method proposed by Carpenter et al. (2007).This approach aims to approximate inferences under a Missing Not At random (MNAR) mechanism by reweighting estimates obtained after multiple imputation where the weights depend on the assumed degree of departure from the MAR assumption. METHODS: The method is illustrated with epidemiological data from a surveillance system of hepatitis C virus (HCV) infection in France during the 2001-2007 period. The subpopulation studied included 4343 HCV infected patients who reported drug use. Risk factors for severe liver disease were assessed. After performing complete-case and multiple imputation analyses, we applied the sensitivity analysis to 3 risk factors of severe liver disease: past excessive alcohol consumption, HIV co-infection and infection with HCV genotype 3. RESULTS: In these data, the association between severe liver disease and HIV was underestimated, if given the observed data the chance of observing HIV status is high when this is positive. Inference for two other risk factors were robust to plausible local departures from the MAR assumption. CONCLUSIONS: We have demonstrated the practical utility of, and advocate, a pragmatic widely applicable approach to exploring plausible departures from the MAR assumption post multiple imputation. We have developed guidelines for applying this approach to epidemiological studies.

A three-source capture-recapture estimate of the number of new HIV diagnoses in children in France from 2003-2006 with multiple imputation of a variable of heterogeneous catchability.

BACKGROUND: Nearly all HIV infections in children worldwide are acquired through mother-to-child transmission (MTCT) during pregnancy, labour, delivery or breastfeeding. The objective of our study was to estimate the number and rate of new HIV diagnoses in children less than 13 years of age in mainland France from 2003-2006. METHODS: We performed a capture-recapture analysis based on three sources of information: the mandatory HIV case reporting (DOVIH), the French Perinatal Cohort (ANRS-EPF) and a laboratory-based surveillance of HIV (LaboVIH). The missing values of a variable of heterogeneous catchability were estimated through multiple imputation. Log-linear modelling provided estimates of the number of new HIV infections in children, taking into account dependencies between sources and variables of heterogeneous catchability. RESULTS: The three sources observed 216 new HIV diagnoses after record-linkage. The number of new HIV diagnoses in children was estimated at 387 (95%CI [271-503]) from 2003-2006, among whom 60% were born abroad. The estimated rate of new HIV diagnoses in children in mainland France was 9.1 per million in 2006 and was 38 times higher in children born abroad than in those born in France. The estimated completeness of the three sources combined was 55.8% (95% CI [42.9 - 79.7]) and varied according to the source; the completeness of DOVIH (28.4%) and ANRS-EPF (26.1%) were lower than that of LaboVIH (33.3%). CONCLUSION: Our study provided, for the first time, an estimated annual rate of new HIV diagnoses in children under 13 years old in mainland France. A more systematic HIV screening of pregnant women that is repeated during pregnancy among women likely to engage in risky behaviour is needed to optimise the prevention of MTCT. HIV screening for children who migrate from countries with high HIV prevalence to France could be recommended to facilitate early diagnosis and treatment.

Hepatitis C virus genotype 3 and the risk of severe liver disease in a large population of drug users in France.

Although risk factors for cirrhosis in chronic hepatitis C virus (HCV) infection have been identified, the role of HCV-genotype 3 remains controversial, and limited data are available in drug users. The aim of the study was to assess risk factors for severe liver disease (cirrhosis/hepatocellular carcinoma) in HCV-infected drug users between 2001 and 2007 in France. Patients who reported drug use and who had been referred for HCV infection to hepatology centers from a national surveillance system were identified. The severity of liver disease was assessed clinically and histologically (Metavir score). Factors associated with severe liver disease were analyzed after estimating missing values by multiple imputation (MI). Of the 4,065 drug users naive to anti-HCV treatment who were referred to the 26 participating centers, 8.0% had severe liver disease, 25.7% were infected with HCV-genotype 3. Factors associated independently with an increased risk of severe liver disease were HCV-genotype 3 (adjusted odds ratio, multiple imputation (aOR(MI)) = 1.6, [95% confidence interval, 95% CI: 1.2-2.1]), HIV infection (aOR(MI) = 1.8, [1.2-2.8]), male sex (aOR(MI) = 2.0, [1.4-2.8]), age over 40 years (aOR(MI) = 2.1, [1.6-2.9]), history of excessive alcohol consumption (aOR(MI) = 2.8, [2.1-3.7]), and duration of infection ≥18 years (aOR(MI) = 2.9, [2.0-4.3]). This analysis shows that HCV-genotype 3 is associated with severe liver disease in drug users, independently of age, sex, duration of infection, alcohol consumption, and co-infection with HIV. These results are in favor of earlier treatment for drug users infected with HCV- genotype 3 and confirm the need for concomitant care for excessive alcohol consumption.

Modest public health impact of nontargeted human immunodeficiency virus screening in 29 emergency departments.

BACKGROUND: To lower the number of undiagnosed infections and to improve early detection, international health agencies have promoted nontargeted human immunodeficiency virus (HIV) screening in health care settings, including emergency departments (EDs). This strategy remains controversial and has yet to be tested on a large scale. We assessed the public health impact of nontargeted HIV-rapid test (RT) screening among ED patients in the metropolitan area of Paris (11.7 million inhabitants), where half of France's new HIV cases are diagnosed annually. METHODS: During a randomly assigned 6-week period for each of the 29 participating EDs, 18- to 64-year-old patients who were able to provide consent for HIV testing were offered a fingerstick whole-blood HIV RT. Main outcome measures were the number of patients tested for HIV and their characteristics vs those of the general metropolitan Paris population and the proportion of newly diagnosed HIV-positive patients among those tested and their characteristics vs those from the national HIV case surveillance. RESULTS: Among 138,691 visits, there were 78,411 eligible patients, 20,962 of whom (27.0%) were offered HIV RT; 13,229 (63.1%) accepted testing and 12,754 (16.3%) were tested. The ED patients' characteristics reflected the general population distribution. Eighteen patients received new HIV diagnoses (0.14%; 95% confidence interval, 0.08%-0.22%). Like national HIV case surveillance patients, they belonged to a high-risk group (n = 17), were previously tested (n = 12), and were either symptomatic or had a CD4 lymphocyte count lower than 350/µL, suggesting late-stage infections (n = 8); 12 patients were linked to care. CONCLUSIONS: Nontargeted HIV testing in EDs was feasible but identified only a few new HIV diagnoses, often at late stages, and, unexpectedly, most patients belonged to a high-risk group. Our findings do not support the implementation of nontargeted screening of the general population in EDs.

Undiagnosed HIV prevalence based on nontargeted screening in emergency departments.

To estimate the 2009-2010 undiagnosed HIV prevalence in the Paris metropolitan region, where half of France's new HIV cases are diagnosed annually, we used a direct method based on a large sample of emergency department patients unaware of their HIV status. The overall expected prevalence was 0.09% (95% confidence interval 0.04-0.13). Undiagnosed infections were exclusively found in high-risk groups. This prevalence is below the 0.1% threshold suggested by regulatory authorities for implementing universal screening.

Population-based HIV-1 incidence in France, 2003-08: a modelling analysis.

BACKGROUND: Routine national incidence testing with enzyme immunoassay for recent HIV-1 infections (EIA-RI) has been done in France since January, 2003. From the reported number of HIV infections diagnosed as recent, and accounting for testing patterns and under-reporting, we aimed to estimate the incidence of HIV infection in France in 2003-08. METHODS: We analysed reports from the French National Institute for Public Health Surveillance for patients who were newly diagnosed with HIV between January, 2003, and December, 2008. Missing data were imputed with multiple imputation. Patients were classified with non-recent or recent infection on the basis of an EIA-RI test, which was calibrated with serial measurements from HIV seroconverters from the French ANRS-PRIMO cohort. We used an adapted stratified extrapolation approach to calculate the number of new HIV infections in men who have sex with men (MSM), injecting drug users (IDUs), and heterosexual men and women by nationality. Population sizes were obtained from the national census and national behavioural studies. FINDINGS: After accounting for under-reporting, there were 6480 (95% CI 6190-6780) new diagnoses of HIV infection in France in 2008. We estimate that there were 6940 (6200-7690) new HIV infections in 2008, suggesting an HIV incidence of 17 per 100 000 person-years. In 2008, there were 3550 (3040-4050) new infections in heterosexuals (incidence of 9 per 100 000 person-years), 3320 (2830-3810) in MSM (incidence of 1006 per 100 000 person-years), and 70 (0-190) in IDUs (incidence of 86 per 100 000 person-years). Overall HIV incidence decreased between 2003 and 2008 (p<0·0001), but remained comparatively high and stable in MSM. INTERPRETATION: In France, HIV transmission disproportionately affects certain risk groups and seems to be out of control in the MSM population. Incidence should be tracked to monitor transmission dynamics in the various population risk groups and to help to target and assess prevention strategies. FUNDING: French National Institute for Public Health Surveillance (InVS) and French National Agency for Research on AIDS and Viral Hepatitis (ANRS).

Risk factors for acquiring sporadic Campylobacter infection in France: results from a national case-control study.

BACKGROUND: To better document the risk factors for sporadic Campylobacter infection in France, we conducted a national case-control study from September 2002 to June 2004. METHODS: Cases with confirmed Campylobacter infection were sampled through the national surveillance laboratory network. Cases and controls who were matched for age, as well as attending physicians, were interviewed about foods consumed, food preparation practices, travel history, contact with cases and animals during the 8 days before the onset of infection, and any antibiotic use occurring during the 30 days before onset. Matched odds ratios [ORs] were calculated using conditional logistic regression and multiple imputation methods. RESULTS: A total of 285 pairs of cases and matched controls were enrolled. "Ate undercooked beef" (OR, 2.86; 95% confidence interval [CI], 1.65-4.95), "ate at restaurant" (OR, 2.20; 95% CI, 1.23-3.93), and "poor utensils hygiene in the kitchen" (OR, 2.12; 95% CI, 1.33-3.37) were the main independent risk factors for infection. Cases infected with a ciprofloxacin-resistant Campylobacter jejuni strain were more likely than controls to have used antibiotics in the month before onset. CONCLUSION: Good hygiene practices in the kitchen remain a strong recommendation to avoid cross-contamination. However, studies are needed to explore the mechanism of contamination throughout the food chain. The use of antibiotics in humans may favor the development of a resistant infection.