Risk of SARS-CoV-2 Infection Among Households With Children in France, 2020-2022.

Importance: Understanding the contribution of children to SARS-CoV-2 circulation in households is critical for designing public health policies and mitigation strategies. Objective: To identify temporal changes in the risk of SARS-CoV-2 infection in people living with children. Design, Setting, and Participants: This case-control study included online questionnaire responses from French adults between October 2020 and October 2022. Eligible cases were adults with ongoing SARS-CoV-2 infection with an email address on record with the national health insurance system, which centralized all new diagnoses in France. Eligible controls were adults who had never tested positive for SARS-CoV-2 until February 2021, when eligibility was extended to all adults without ongoing SARS-CoV-2 infection. Exposure: Transmission of SARS-CoV-2 from a child (aged under 18 years) within the household in the descriptive analysis, as reported by the participating case. Sharing household with a child (of any age or broken down by school level) in the case-control analysis. Main Outcome and Measures: Ongoing SARS-CoV-2 infection diagnosed by reverse transcription-polymerase chain reaction or supervised rapid antigen test (ie, not self-tests). Results: A total of 682 952 cases were included for the descriptive analysis (68.8% female, median [IQR] age, 44 [34-55] years). Among those, 45 108 (6.6%) identified a household child as the source case; this proportion peaked at 10.4% during the Omicron BA.1 wave (December 20, 2021, to April 8, 2022). For the case-control analysis, we matched 175 688 cases (with a 4:1 ratio) for demographic characteristics with 43 922 controls. In multivariable logistic regression analysis, household exposure to children was associated with an increased risk of infection mainly at the end of summer 2021 (receding Delta wave) and during winter 2022 (Omicron BA.1 wave). In subgroup analysis by school level of the child, living with children under the age of 6 was associated with increased odds of infection throughout the study period, peaking at an odds ratio (OR) 1.8 (95% CI, 1.6-2.1) for children looked after by professional in-home caregivers, 1.7 (95% CI, 1.5-1.7) for children in day care facilities, and 1.6 (95% CI, 1.4-1.8) for children in preschool. The ORs associated with household exposure to children aged 6 to 14 years increased during the Delta (August 14, 2021, to December 19, 2021) and Omicron BA.1 waves, reaching 1.6 (95% CI, 1.5-1.7) for primary school children and 1.4 (95% CI, 1.3-1.5) for middle school children. Exposure to older children aged 15 to 17 years was associated with a moderate risk until April 2021, with an OR of 1.2 (95% CI, 1.2-1.3) during curfew in early 2021 (December 4, 2020, to April 8, 2021). Conclusions and Relevance: The presence of children, notably very young ones, was associated with an increased risk of SARS-CoV-2 infection in other household members, especially during the Delta and Omicron BA.1 waves. These results should help to guide policies targeting children and immunocompromised members of their household.

Molecular Detection of Orthohantavirus puumalaense in Plasma and Urine Samples from Hospitalized Patients Presenting with a Serologically Confirmed Acute Hantavirus Infection in France.

Molecular detection of Orthohantavirus puumalaense (PUUV) RNA during the course of the disease has been studied in blood of patients in Sweden and Slovenia. The use of urine has been poorly investigated. The aims of this work were to study PUUV RNA detection in plasma from a cohort of patients in France where a different PUUV lineage circulates and to assess the use of urine instead of plasma. Matched plasma and urine samples were collected daily from hospitalized patients presenting with fever, pain, and thrombocytopenia within the last 8 days and testing positive for IgM and IgG against PUUV in serum collected at inclusion and/or approximately 1 month after release. RNA was extracted from samples, and PUUV RNA was detected using real-time reverse transcription-PCR for plasma and urine samples. Sixty-seven patients presented a serologically confirmed acute hantavirus infection. At inclusion, PUUV RNA was detected in plasma from 55 of 62 patients (88.7%) sampled within the first week after disease onset, whereas it was detected in 15 of 60 (25.0%) of matched urine samples. It was then detected from 33 (71.7%) and 2 (4.4%) of 46 patients discharged from the hospital during the second week after disease onset, in plasma and urine, respectively. When PUUV RNA was detected in urine it was also detected in plasma, and not vice versa. Detection of PUUV RNA in plasma from hospitalized patients in France is similar to that observed in Sweden and Slovenia. Urine is not an appropriate sample for this detection.

Reduction of SARS-CoV-2 intra-household child-to-parent transmission associated with ventilation: results from a case-control study.

PURPOSE: Our objective was to describe circumstances of SARS-CoV-2 household transmission and to identify factors associated with a lower risk of transmission in a nationwide case-control study in France. METHODS: In a descriptive analysis, we analysed cases reporting transmission from someone in the household (source case). Index cases could invite a non-infected household member to participate as a related control. In such situations, we compared the exposures of the index case and related control to the source case by conditional logistic regression matched for household, restricted to households in which the source case was a child, and the index case and related control were the infected child's parents. RESULTS: From October 27, 2020 to May 16, 2022, we included 104 373 cases for the descriptive analysis with a documented infection from another household member. The source case was mostly the index case's child (46.9%) or partner (45.7%). In total, 1026 index cases invited a related control to participate in the study. In the case-control analysis, we included 611 parental pairs of cases and controls exposed to the same infected child. COVID-19 vaccination with 3 + doses versus no vaccination (OR 0.1, 95%CI: 0.04-0.4), isolation from the source case (OR 0.6, 95%CI: 0.4-0.97) and the ventilation of indoor areas (OR 0.6, 95%CI: 0.4-0.9) were associated with lower risk of infection. CONCLUSION: Household transmission was common during the SARS-CoV-2 pandemic in France. Mitigation strategies, including isolation and ventilation, decreased the risk of secondary transmission within the household. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT04607941.

SARS-CoV-2 self-test uptake and factors associated with self-testing during Omicron BA.1 and BA.2 waves in France, January to May 2022.

BackgroundFollowing the SARS-CoV-2 Omicron variant spread, the use of unsupervised antigenic rapid diagnostic tests (self-tests) increased.AimThis study aimed to measure self-test uptake and factors associated with self-testing.MethodsIn this cross-sectional study from 20 January to 2 May 2022, the case series from a case-control study on factors associated with SARS-CoV-2 infection were used to analyse self-testing habits in France. A multivariable quasi-Poisson regression was used to explore the variables associated with self-testing among symptomatic cases who were not contacts of another infected individual. The control series from the same study was used as a proxy for the self-test background rate in the non-infected population of France.ResultsDuring the study period, 179,165 cases who tested positive through supervised tests were recruited. Of these, 64.7% had performed a self-test in the 3 days preceding this supervised test, of which 79,038 (68.2%) were positive. The most frequently reported reason for self-testing was the presence of symptoms (64.6%). Among symptomatic cases who were not aware of being contacts of another case, self-testing was positively associated with being female, higher education, household size, being a teacher and negatively associated with older age, not French by birth, healthcare-related work and immunosuppression. Among the control series, 12% self-tested during the 8 days preceding questionnaire filling, with temporal heterogeneity.ConclusionThe analysis showed high self-test uptake in France with some inequalities which must be addressed through education and facilitated access (cost and availability) for making it a more efficient epidemic control tool.

SARS-CoV-2 incubation period across variants of concern, individual factors, and circumstances of infection in France: a case series analysis from the ComCor study.

BACKGROUND: The incubation period of SARS-CoV-2 has been estimated for the known variants of concern. However, differences in study designs and settings make comparing variants difficult. We aimed to estimate the incubation period for each variant of concern compared with the historical strain within a unique and large study to identify individual factors and circumstances associated with its duration. METHODS: In this case series analysis, we included participants (aged ≥18 years) of the ComCor case-control study in France who had a SARS-CoV-2 diagnosis between Oct 27, 2020, and Feb 4, 2022. Eligible participants were those who had the historical strain or a variant of concern during a single encounter with a known index case who was symptomatic and for whom the incubation period could be established, those who reported doing a reverse-transcription-PCR (RT-PCR) test, and those who were symptomatic by study completion. Sociodemographic and clinical characteristics, exposure information, circumstances of infection, and COVID-19 vaccination details were obtained via an online questionnaire, and variants were established through variant typing after RT-PCR testing or by matching the time that a positive test was reported with the predominance of a specific variant. We used multivariable linear regression to identify factors associated with the duration of the incubation period (defined as the number of days from contact with the index case to symptom onset). FINDINGS: 20 413 participants were eligible for inclusion in this study. Mean incubation period varied across variants: 4·96 days (95% CI 4·90-5·02) for alpha (B.1.1.7), 5·18 days (4·93-5·43) for beta (B.1.351) and gamma (P.1), 4·43 days (4·36-4·49) for delta (B.1.617.2), and 3·61 days (3·55-3·68) for omicron (B.1.1.529) compared with 4·61 days (4·56-4·66) for the historical strain. Participants with omicron had a shorter incubation period than participants with the historical strain (-0·9 days, 95% CI -1·0 to -0·7). The incubation period increased with age (participants aged ≥70 years had an incubation period 0·4 days [0·2 to 0·6] longer than participants aged 18-29 years), in female participants (by 0·1 days, 0·0 to 0·2), and in those who wore a mask during contact with the index case (by 0·2 days, 0·1 to 0·4), and was reduced in those for whom the index case was symptomatic (-0·1 days, -0·2 to -0·1). These data were robust to sensitivity analyses correcting for an over-reporting of incubation periods of 7 days. INTERPRETATION: SARS-CoV-2 incubation period is notably reduced in omicron cases compared with all other variants of concern, in young people, after transmission from a symptomatic index case, after transmission to a maskless secondary case, and (to a lesser extent) in men. These findings can inform future COVID-19 contact-tracing strategies and modelling. FUNDING: Institut Pasteur, the French National Agency for AIDS Research-Emerging Infectious Diseases, Fondation de France, the INCEPTION project, and the Integrative Biology of Emerging Infectious Diseases project.

National Monkeypox Surveillance, Central African Republic, 2001-2021.

We analyzed monkeypox disease surveillance in Central African Republic (CAR) during 2001-2021. Surveillance data show 95 suspected outbreaks, 40 of which were confirmed as monkeypox, comprising 99 confirmed and 61 suspected monkeypox cases. After 2018, CAR's annual rate of confirmed outbreaks increased, and 65% of outbreaks occurred in 2 forested regions bordering the Democratic Republic of the Congo. The median patient age for confirmed cases was 15.5 years. The overall case-fatality ratio was 7.5% (12/160) for confirmed and suspected cases, 9.6% (8/83) for children <16 years of age. Decreasing cross-protective immunity from smallpox vaccination and recent ecologic alterations likely contribute to increased monkeypox outbreaks in Central Africa. High fatality rates associated with monkeypox virus clade I also are a local and international concern. Ongoing investigations of zoonotic sources and environmental changes that increase human exposure could inform practices to prevent monkeypox expansion into local communities and beyond endemic areas.

SARS-CoV-2 exposures of healthcare workers from primary care, long-term care facilities and hospitals: a nationwide matched case-control study.

OBJECTIVES: This study assessed the roles of various exposures and personal protective equipment (PPE) use on healthcare workers' (HCWs) risk of COVID-19 working in primary care, long-term-care facilities or hospitals. METHODS: We conducted a matched case-control (1:1) study (10 April through 9 July 2021). Cases (HCWs with confirmed COVID-19) and controls (HCWs without any COVID-19-positive test or symptoms) were invited by E-mail to complete an online questionnaire on their exposures and PPE use over the 10-day period preceding inclusion. Risk factors were analysed using multivariable conditional logistic regression. RESULTS: A total of 2076 cases and 2076 matched controls were included. The analysis retained exposure to an infected person outside work (adjusted OR 19.9 (95% CI, 12.4-31.9)), an infected colleague (OR 2.26 (95% CI, 1.53-3.33)) or COVID-19 patients (OR 2.37 (95% CI, 1.66-3.40)), as independent predictors of COVID-19 in HCWs, while partial (OR 0.30 (95% CI, 0.22-0.40)) or complete (OR 0.19 (95% CI, 0.14-0.27)) immunisation was protective. Eye protection (OR 0.57 (95% CI, 0.37-0.87)) and wearing a gown (OR 0.58 (95% CI, 0.34-0.97)) for COVID-19 patient care were protective, while wearing an apron slightly increased the risk of infection (OR 1.47 (95% CI, 1.00-2.18)). Protection of N95 respirators and surgical face masks did not differ. Compared to medical professions, being a nurse (OR 3.79 (95% CI, 2.50-5.76)) or a nurse's aide (OR 9.08 (95% CI, 5.30-15.5)) was associated with COVID-19. Results were consistent across all healthcare settings. DISCUSSION: HCWs were more likely to get COVID-19 in their personal sphere than during occupational activities. Our results suggest that eye protection for HCWs during patient care should be actively promoted.

Impact of SARS-CoV-2 Delta variant on incubation, transmission settings and vaccine effectiveness: Results from a nationwide case-control study in France.

BACKGROUND: We aimed to assess the settings and activities associated with SARS-CoV-2 infection in the context of B.1.617.2 (Delta) variant circulation in France, as well as the protection against symptomatic Delta infection. METHODS: In this nationwide case-control study, cases were SARS-CoV-2 infected adults recruited between 23 May and 13 August 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire and multivariable logistic regression analysis was used to determine the association between acute SARS-CoV-2 infection and recent activity-related exposures, past history of SARS-CoV-2 infection, and COVID-19 vaccination. FINDINGS: We did not find any differences in the settings and activities associated with Delta versus non-Delta infections and grouped them for subsequent analyses. In multivariable analysis involving 12634 cases (8644 Delta and 3990 non-Delta) and 5560 controls, we found individuals under 40 years and attending bars (aOR:1.9; 95%CI:1.6-2.2) or parties (aOR:3.4; 95%CI:2.8-4.2) to be at increased risk of infection. In those aged 40 years and older, having children attend daycare (aOR:1.9; 95%CI:1.1-3.3), kindergarten (aOR:1.6; 95%CI:1.2-2.1), primary school (aOR:1.4; 95%CI:1.2-1.6) or middle school (aOR:1.3; 95%CI:1.2-1.6) were associated with increased risk of infection. We found strong protection against symptomatic Delta infection for those with prior infection whether it was recent (2-6 months) (95%; 95%CI:90-97) or associated with one dose (85%; 95%CI:78-90) or two doses of mRNA vaccine (96%; 95%CI:87-99). For those without past infection, protection was lower with two doses of mRNA vaccine (67%; 95%CI:63-71). INTERPRETATION: In line with other observational studies, we find reduced vaccine effectiveness against symptomatic Delta infections. The settings and activities at increased risk of infection indicate where efforts to reinforce individual and public health measures need to be concentrated.

Factors Associated with Stunted Growth in Children Under Five Years in Antananarivo, Madagascar and Bangui, Central African Republic.

OBJECTIVES: With a fourth of all under-five children affected, stunting remains one of the biggest health challenges worldwide. Even though the main underlying factors are known, the exact pathways to stunting varying in affected regions, and interventions thus need to be tailored to the local contexts. This study aimed assessing and comparing factors associated with stunting in two understudied sub-Saharan urban contexts with some of the highest stunting prevalence globally: Bangui, Central African Republic (~ 36%) and Antananarivo, Madagascar (42%). METHODS: We performed a case-control study on 175 + 194 stunted and 237 + 230 non-stunted control children aged 2-5 years and matched for age, gender and district of residency. Factors associated with stunting were identified using a standardized, paper questionnaire delivered by trained interviewers. Statistical analysis was done using logistic regression modelling. RESULTS: In both sites, formal maternal education lowered the risk of being stunted and restricted access to soap, suffering of anaemia and low birth weight were associated with higher risk of stunting. Short maternal stature, household head different from parents, diarrhoea and coughing were associated with an increased risk and continuing breastfeeding was associated with a lower risk of stunting in Antananarivo. Previous severe undernutrition and dermatitis/ fungal skin infections were associated with higher and changes in diet during pregnancy with lower risk of stunting in Bangui. CONCLUSIONS: Our results suggest maternal education, antenatal care, iron supplementation and simple WASH interventions such as using soap and infection control as general and breastfeeding (Antananarivo) or better nutrition (Bangui) as area-specified interventions.

Impact of original, B.1.1.7, and B.1.351/P.1 SARS-CoV-2 lineages on vaccine effectiveness of two doses of COVID-19 mRNA vaccines: Results from a nationwide case-control study in France.

BACKGROUND: We aimed to assess the effectiveness of two doses of mRNA COVID-19 vaccines against COVID-19 with the original virus and other lineages circulating in France. METHODS: In this nationwide case-control study, cases were SARS-CoV-2 infected adults with onset of symptoms between 14 February and 3 May 2021. Controls were non-infected adults from a national representative panel matched to cases by age, sex, region, population density and calendar week. Participants completed an online questionnaire on recent activity-related exposures and vaccination history. Information about the infecting virus was based on a screening RT-PCR for either B.1.1.7 or B.1.351/P.1 variants. FINDINGS: Included in our analysis were 7 288 adults infected with the original SARS-CoV-2 virus, 31 313 with the B.1.1.7 lineage, 2 550 with B.1.351/P1 lineages, and 3 644 controls. In multivariable analysis, the vaccine effectiveness (95% confidence interval) seven days after the second dose of mRNA vaccine was estimated at 88% (81-92), 86% (81-90) and 77% (63-86) against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. Recent (2 to 6 months) history of virologically confirmed SARS-CoV-2 infection was found to be 83% (76-88), 88% (85-91) and 83% (71-90) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively; and more distant (> 6 months) infections were 76% (54-87), 84% (75-90), and 74% (41-89) protective against COVID-19 with the original virus, the B.1.1.7 lineage, and the B.1.351/P.1 lineages, respectively. INTERPRETATION: In real-life settings, two doses of mRNA vaccines proved to be effective against COVID-19 with the original virus, B.1.1.7 lineage and B.1.351/P.1 lineages. FUNDING: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance "Tous unis contre le virus").

Cost-effectiveness of adding a birth dose of hepatitis B vaccine in the Dafra district of the Hauts-Bassins Region in Burkina Faso (NéoVac Study).

BACKGROUND: The World Health Organization (WHO) recommends a first hepatitis B vaccine dose within 24 h of birth (HepB-BD) to prevent mother-to-child transmission. Evidence for this strategy's economic value in Africa is limited. We assessed the costs and cost-effectiveness of adding HepB-BD to the current three-dose pentavalent schedule (HepB3) in the Dafra district of the Hauts-Bassins Region in Burkina Faso. METHODS: Using a decision tree combined with a Markov model, we estimated the expected number of life-years (LY) and disability-adjusted life-years (DALYs) saved, incremental costs, and incremental cost-effectiveness ratios (ICER) of HepB-BD + HepB3 versus HepB3 alone in Dafra's 2017 birth cohort (n = 11,462). Institutional delivery rates, vaccine coverage, and vaccination costs from a health system perspective were estimated from field-collected data. We estimated the effectiveness of HepB-BD, age-specific transition probabilities, and horizontal transmission risks using data from previous African studies. Costs and health outcomes were discounted at an annual rate of 3%. We conducted one-way and probabilistic sensitivity analyses to assess uncertainty. RESULTS: In the base-case analysis without discounting, HepB-BD + HepB3 yielded a net cost saving of US$18,979 and saved 163 DALYs compared with HepB3 alone. With discounting, HepB-BD + HepB3 compared with HepB3 resulted in an incremental cost of US$554 and 31 DALYs averted, translating into an ICER of US$18/DALY averted. In one-way sensitivity analyses, HepB-BD + HepB3 remained cost-effective (at the cost-effectiveness threshold of US$671 i.e. the Burkina Faso per-capita gross domestic product) for all parameter changes. However, results were very sensitive to variations in HepB-BD unit cost per vaccinated neonate and perinatal transmission risk in mothers carrying the hepatitis B e antigen. The probabilities of HepB-BD + HepB3 being cost-effective were 71.7% and 86.7%, at the cost-effectiveness thresholds of US$335 and US$671, respectively. CONCLUSION: Introducing HepB-BD in Burkina Faso is likely to be cost-effective.

Impact of Introducing Hepatitis B Birth Dose Vaccines into the Infant Immunization Program in Burkina Faso: Study Protocol for a Stepped Wedge Cluster Randomized Trial (NéoVac Study).

To achieve global hepatitis elimination by 2030, it is critical to prevent the mother-to-child transmission (MTCT) of hepatitis B virus (HBV). Since 2009, the WHO has recommended administering hepatitis B vaccine to all neonates within 24 h of birth to prevent MTCT. However, many countries in sub-Saharan Africa only provide hepatitis B immunization at the age of 6, 10, and 14 weeks or 8, 12, and 16 weeks using a combined vaccine. To accelerate the introduction of the hepatitis B birth dose vaccine (HepB-BD) into sub-Saharan Africa, it is critical to establish to what extent the addition of HepB-BD can further reduce HBV transmission in areas where three-dose infant vaccination has been implemented. We therefore designed a study to evaluate the impact, acceptability, and cost-effectiveness of incorporating the HepB-BD into the routine immunization program in a real-life field condition in Burkina Faso, where the hepatitis B vaccination is currently scheduled at 8-12-16 weeks. Through a multidisciplinary approach combining epidemiology, anthropology, and health economics, the Neonatal Vaccination against Hepatitis B in Africa (NéoVac) study conducts a pragmatic stepped wedge cluster randomized controlled trial in rural areas of the Hauts-Bassins Region. The study was registered in ClinicalTrials.gov (identifier: NCT04029454). A health center is designated as a cluster, and the introduction of HepB-BD will be rolled out sequentially in 24 centers. Following an initial period in which no health center administers HepB-BD, one center will be randomly allocated to incorporate HepB-BD. Then, at a regular interval, another center will be randomized to cross from the control to the intervention period, until all 24 centers integrate HepB-BD. Pregnant women attending antenatal care will be systematically invited to participate. Infants born during the control period will follow the conventional immunization schedule (8-12-16 weeks), while those born in the interventional period will receive HepB-BD in addition to the routine vaccines (0-8-12-16 weeks). The primary outcome, the proportion of hepatitis B surface antigen (HBsAg) positivity in infants aged at 9 months, will be compared between children born before and after HepB-BD introduction. The study will generate data that may assist governments and stakeholders in sub-Saharan Africa to make evidence-based decisions about whether to add HepB-BD into the national immunization programs.

Exposures associated with SARS-CoV-2 infection in France: A nationwide online case-control study.

BACKGROUND: We aimed to assess the role of different setting and activities in acquiring SARS-CoV-2 infection. METHODS: In this nationwide case-control study, cases were SARS-CoV-2 infected adults recruited between 27 October and 30 November 2020. Controls were individuals from the Ipsos market research database matched to cases by age, sex, region, population density and time period. Participants completed an online questionnaire on recent activity-related exposures. FINDINGS: Among 3426 cases and 1713 controls, in multivariable analysis, we found an increased risk of infection associated with any additional person living in the household (adjusted-OR: 1•16; 95%CI: 1•11-1•21); having children attending day-care (aOR: 1•31; 95%CI: 1•02-1•62), kindergarten (aOR: 1•27; 95%CI: 1•09-1•45), middle school (aOR: 1•30; 95%CI: 1•15-1•47), or high school (aOR: 1•18; 95%CI: 1•05-1•34); with attending professional (aOR: 1•15; 95%CI: 1•04-1•26) or private gatherings (aOR: 1•57; 95%CI: 1•45-1•71); and with having frequented bars and restaurants (aOR: 1•95; 95%CI: 1•76-2•15), or having practiced indoor sports activities (aOR: 1•36; 95%CI: 1•15-1•62). We found no increase in risk associated with frequenting shops, cultural or religious gatherings, or with transportation, except for carpooling (aOR: 1•47; 95%CI: 1•28-1•69). Teleworking was associated with decreased risk of infection (aOR: 0•65; 95%CI: 0•56-0•75). INTERPRETATION: Places and activities during which infection prevention and control measures may be difficult to fully enforce were those with increased risk of infection. Children attending day-care, kindergarten, middle and high schools, but not primary schools, were potential sources of infection for the household. FUNDING: Institut Pasteur, Research & Action Emerging Infectious Diseases (REACTing), Fondation de France (Alliance" Tous unis contre le virus").

Systematic Booster after Rabies Pre-Exposure Prophylaxis to Alleviate Rabies Antibody Monitoring in Individuals at Risk of Occupational Exposure.

Pre-exposure rabies prophylaxis (PrEP) is recommended for people at frequent or increased risk of professional exposure to lyssavirus (including rabies virus). PrEP provides protection against unrecognized exposure. After the primary vaccination, one's immune response against rabies may decline over time. We aimed to evaluate the immune response to rabies in individuals immunized for occupational reasons before and after a booster dose of the rabies vaccine. With this aim, we retrospectively documented factors associated with an inadequate response in individuals vaccinated for occupational purposes. Our findings analyzed data from 498 vaccinated individuals and found that 17.2% of participants had an inadequate antibody titration documented after their primary vaccination without the booster, while inadequate response after an additional booster of the vaccine was evidenced in 0.5% of tested participants. This study showed that a single booster dose of vaccine after PrEP conferred a high and long-term immune response in nearly all individuals except for rare, low responders. A systematic rabies booster after primary vaccination may result in alleviating the monitoring strategy of post-PrEP antibody titers among exposed professionals.

Comparative Immunovirological and Clinical Responses to Antiretroviral Therapy Between HIV-1 Group O and HIV-1 Group M Infected Patients.

BACKGROUND: Little is known about impact of genetic divergence of human immunodeficiency virus type 1 group O (HIV-1/O) relative to HIV-1 group M (HIV-1/M) on therapeutic outcomes. We aimed to determine if responses to standardized combination antiretroviral therapy (cART) were similar between groups despite strain divergence. METHODS: We performed an open nonrandomized study comparing the immunological, virological, and clinical responses to cART based on 2 nucleoside reverse transcriptase inhibitors plus 1 ritonavir-boosted protease inhibitor, in naive and paired HIV-1/O vs HIV-1/M infected (+) patients (ratio 1:2), matched on several criteria. The primary endpoint was the proportion of patients with undetectable plasma viral load (pVL, threshold 60 copies/mL) at week (W) 48. Secondary endpoints were the proportion of patients with undetectable pVL at W24 and W96 and CD4 evolution between baseline and W24, W48, and W96. RESULTS: Forty-seven HIV-1/O+ and 94 HIV-1/M+ patients were included. Mean pVL at baseline was significantly lower by 1 log for HIV-1/O+ vs HIV-1/M+ patients. At W48, no significant difference was observed between populations with undetectable pVL and differences at W24 and W96 were not significant. A difference in CD4 gain was observed in favor of HIV-1/M at W48 and W96, but this was not significant when adjusted on both matched criteria and pVL at baseline. CONCLUSIONS: Our data demonstrate similar immunovirological and clinical response between HIV-1/O+ and HIV-1/M+ patients. They also reveal significantly lower baseline replication for HIV-1/O variants, suggesting specific virological properties and physiopathology that now need to be addressed. CLINICAL TRIALS REGISTRATION: NCT00658346.

Prosthetic Valve Candida spp. Endocarditis: New Insights Into Long-term Prognosis-The ESCAPE Study.

Background: Prosthetic valve endocarditis caused by Candida spp. (PVE-C) is rare and devastating, with international guidelines based on expert recommendations supporting the combination of surgery and subsequent azole treatment. Methods: We retrospectively analyzed PVE-C cases collected in Spain and France between 2001 and 2015, with a focus on management and outcome. Results: Forty-six cases were followed up for a median of 9 months. Twenty-two patients (48%) had a history of endocarditis, 30 cases (65%) were nosocomial or healthcare related, and 9 (20%) patients were intravenous drug users. "Induction" therapy consisted mainly of liposomal amphotericin B (L-amB)-based (n = 21) or echinocandin-based therapy (n = 13). Overall, 19 patients (41%) were operated on. Patients <66 years old and without cardiac failure were more likely to undergo cardiac surgery (adjusted odds ratios [aORs], 6.80 [95% confidence interval [CI], 1.59-29.13] and 10.92 [1.15-104.06], respectively). Surgery was not associated with better survival rates at 6 months. Patients who received L-amB alone had a better 6-month survival rate than those who received an echinocandin alone (aOR, 13.52; 95% CI, 1.03-838.10). "Maintenance" fluconazole therapy, prescribed in 21 patients for a median duration of 13 months (range, 2-84 months), led to minor adverse effects. Conclusion: L-amB induction treatment improves survival in patients with PVE-C. Medical treatment followed by long-term maintenance fluconazole may be the best treatment option for frail patients.

Simian Immunodeficiency Virus seroreactivity in inhabitants from rural Cameroon frequently in contact with non-human primates.

Central African tropical forests are home to several species of non-human primates (NHPs), infected by Simian Immunodeficiency Virus (SIV). It is well-known that HIV-1 epidemic is due to cross-transmission and adaptation of SIV to humans. The main goal of this work was to investigate if a NHP bite is a risk factor for SIV acquisition. A cross-sectional study was performed in rural Cameroon on 246 bitten individuals (mostly by adult NHPs), matched, according to sex, age, and ethnicity (Bantus and Pygmies), with an equal number of not-bitten subjects. Following a serological assay for a wide range of SIVs, we observed a high level of indeterminate seroreactivity (25.8%) in the total population, whereas 68.9% were sero-negative and 5.3% HIV-1 positive. Bites do not appear to be a risk factor for SIV seroreactivity, in contrast to Simian Foamy Virus and Simian T-Lymphotropic Virus type 1 in the same studied population.

How to estimate exposure when studying the temperature-mortality relationship? A case study of the Paris area.

Time series studies assessing the effect of temperature on mortality generally use temperatures measured by a single weather station. In the Paris region, there is a substantial measurement network, and a variety of exposure indicators created from multiple stations can be tested. The aim of this study is to test the influence of exposure indicators on the temperature-mortality relationship in the Paris region. The relationship between temperature and non-accidental mortality was assessed based on a time series analysis using Poisson regression and a generalised additive model. Twenty-five stations in Paris and its three neighbouring departments were used to create four exposure indicators. These indicators were (1) the temperature recorded by one reference station, (2) a simple average of the temperatures of all stations, (3) an average weighted on the departmental population and (4) a classification of the stations based on land use and an average weighted on the population in each class. The relative risks and the Akaike criteria were similar for all the exposure indicators. The estimated temperature-mortality relationship therefore did not appear to be significantly affected by the indicator used, regardless of study zone (departments or region) or age group. The increase in temperatures from the 90(th) to the 99(th) percentile of the temperature distribution led to a significant increase in mortality over 75 years (RR = 1.10 [95% CI, 1.07; 1.14]). Conversely, the decrease in temperature between the 10(th) and 1(st) percentile had a significant effect on the mortality under 75 years (RR = 1.04 [95% CI, 1.01; 1.06]). In the Paris area, there is no added value in taking multiple climatic stations into account when estimating exposure in time series studies. Methods to better represent the subtle temperature variations in densely populated areas in epidemiological studies are needed.