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Abstract Purpose The aim of the study was to identify settings associated with SARS-CoV-2 transmission throughout the COVID-19 pandemic in France. Methods Cases with recent SARS-CoV-2 infection were matched with controls (4:1 ratio) on age, sex, region, population size, and calendar week. Odds ratios for SARS-CoV-2 infection were estimated for nine periods in models adjusting for socio-demographic characteristics, health status, COVID-19 vaccine, and past infection. Results Between October 27, 2020 and October 2, 2022, 175,688 cases were matched with 43,922 controls. An increased risk of infection was documented throughout the study for open-space offices compared to offices without open space (OR range across the nine periods: 1.12 to 1.57) and long-distance trains (1.25 to 1.88), and during most of the study for convenience stores (OR range in the periods with increased risk: 1.15 to 1.44), take-away delivery (1.07 to 1.28), car-pooling with relatives (1.09 to 1.68), taxis (1.08 to 1.89), airplanes (1.20 to 1.78), concerts (1.31 to 2.09) and night-clubs (1.45 to 2.95). No increase in transmission was associated with short-distance shared transport, car-pooling booked over platforms, markets, supermarkets and malls, hairdressers, museums, movie theatres, outdoor sports, and swimming pools. The increased risk of infection in bars and restaurants was no longer present in restaurants after reopening in June 2021. It persisted in bars only among those aged under 40 years. Conclusion Closed settings in which people are less likely to wear masks were most affected by SARS-CoV-2 transmission and should be the focus of air quality improvement. ClinicalTrials.gov (03/09/2022) NCT04607941.

Across 133 confirmed mpox zoonotic index cases reported during 1970–2021 in Africa, cases occurred year-round near the equator, where climate is consistent. However, in tropical regions of the northern hemisphere under a dry/wet season cycle, cases occurred seasonally. Our findings further support the seasonality of mpox zoonotic transmission risk.

In this multicenter study conducted in France, we challenged the hypothesis of the transmission of pathogens other than Borrelia spp. in 22 patients developing erythema migrans following a tick bite. Using a combination of high-throughput microfluidic PCRs and agnostic metagenomics on skin biopsies and blood samples, no microorganisms other than Borrelia spp. was found.

Abstract Background Chronic hepatitis C virus (HCV) infection negatively impacts health-related quality of life (HRQL). We aimed to assess patient-reported outcomes (PROs) to evaluate the impact of treating chronic HCV with directly acting antivirals (DAAs) on HRQL. Methods PROs were assessed prospectively using the PROQOL-HCV questionnaire before (week 0), at the end (week 12), and after DAA treatment at week 24. HRQL was measured in six different dimensions: physical health, emotional health, future uncertainty, intimate relationships, social health, and cognitive functions. Results A total of 500 HCV patients receiving DAAs were enrolled; of them, 399 were included in the analysis (median age 57 years, 59% females). HRQL increased significantly between baseline, end of treatment, and week 24 for all dimensions (P

Abstract Background French Polynesia (FP) comprises 75 inhabited islands scattered across five archipelagos. Between July and October 2021, the SARS-CoV-2 Delta variant triggered a much stronger second epidemic wave in FP than the original Wuhan strain, which was dominant from August 2020 to March 2021. Although previous seroprevalence surveys made it possible to determine the proportion of the population infected by SARS-CoV-2 on the two most populated islands (Tahiti and Moorea) after the first (20.6% in Tahiti and 9.4% in Moorea) and second (57.7% in Tahiti) epidemic waves, no data are available for more remote islands. We used blood samples and personal data collected before, during, and after the second wave from inhabitants of several islands within the five archipelagos to assess the prevalence of SARS-CoV-2 infections and identify associated factors. Methods Blood samples and personal data were collected between April and December 2021 as part of the MATAEA study, a cross-sectional survey conducted on a random sample of the adult population representative of the five FP archipelagos and stratified by age and gender. IgG antibodies targeting the SARS-CoV-2 nucleocapsid (N) protein were detected using a recombinant antigen-based microsphere immunoassay. Factors associated with anti-SARS-CoV-2-N seropositivity were identified using logistic regression models. Results Of 1,120 participants, 503 (44.9%) tested positive for anti-SARS-CoV-2-N antibodies, corresponding to a weighted prevalence of 56.8% for the FP population aged 18–69 years. The seroprevalence increased from 21.9% to 62.1% before and during/after the Delta wave. Of these infections, only 28.4% had been diagnosed by health professionals. The odds of being seropositive were lower in males, participants recruited before the Delta wave, those who had never been married, those with a diagnosed respiratory allergy, smokers, and those vaccinated against COVID-19. Conclusions Our results confirm the high impact of the Delta wave in FP. By the end of 2021, 56.8% of the FP population aged 18–69 years had been infected by SARS-CoV-2; the majority of these infections went undetected. Individuals with respiratory allergies were found to be less susceptible to SARS-CoV-2 infection.

Abstract Background We aimed to study the source of infection for recently SARS-CoV-2-infected individuals from October 2020 to August 2022 in France. Methods Participants from the nationwide ComCor case–control study who reported recent SARS-CoV-2 infection were asked to document the source and circumstances of their infection through an online questionnaire. Multivariable logistic regression was used to identify the factors associated with not identifying any source of infection. Results Among 584,846 adults with a recent SARS-CoV-2 infection in France, 46.9% identified the source of infection and an additional 22.6% suspected an event during which they might have become infected. Known and suspected sources of infection were household members (30.8%), extended family (15.6%), work colleagues (15.0%), friends (11.0%), and possibly multiple/other sources (27.6%). When the source of infection was known, was not a household member, and involved a unique contact (n = 69,788), characteristics associated with transmission events were indoors settings (91.6%), prolonged (> 15 min) encounters (50.5%), symptomatic source case (64.9%), and neither the source of infection nor the participant wearing a mask (82.2%). Male gender, older age, lower education, living alone, using public transportation, attending places of public recreation (bars, restaurants, nightclubs), public gatherings, and cultural events, and practicing indoor sports were all independently associated with not knowing the source of infection. Conclusion Two-thirds of infections were attributed to interactions with close relatives, friends, or work colleagues. Extra-household indoor encounters without masks were commonly reported and represented avoidable circumstances of infection. Trial registration ClinicalTrials.gov registration number: NCT04607941.

Abstract 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.

BackgroundAsymptomatic and paucisymptomatic infections account for a substantial portion of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmissions. The value of intensified screening strategies, especially in emergency departments (EDs), in reaching asymptomatic and paucisymptomatic patients and helping to improve detection and reduce transmission has not been documented. The objective of this study was to evaluate in EDs whether an intensified SARS-CoV-2 screening strategy combining nurse-driven screening for asymptomatic/paucisymptomatic patients with routine practice (intervention) could contribute to higher detection of SARS-CoV-2 infections compared to routine practice alone, including screening for symptomatic or hospitalized patients (control).Methods and findingsWe conducted a cluster-randomized, two-period, crossover trial from February 2021 to May 2021 in 18 EDs in the Paris metropolitan area, France. All adults visiting the EDs were eligible. At the start of the first period, 18 EDs were randomized to the intervention or control strategy by balanced block randomization with stratification, with the alternative condition being applied in the second period. During the control period, routine screening for SARS-CoV-2 included screening for symptomatic or hospitalized patients. During the intervention period, in addition to routine screening practice, a questionnaire about risk exposure and symptoms and a SARS-CoV-2 screening test were offered by nurses to all remaining asymptomatic/paucisymptomatic patients. The primary outcome was the proportion of newly diagnosed SARS-CoV-2-positive patients among all adults visiting the 18 EDs. Primary analysis was by intention-to-treat. The primary outcome was analyzed using a generalized linear mixed model (Poisson distribution) with the center and center by period as random effects and the strategy (intervention versus control) and period (modeled as a weekly categorical variable) as fixed effects with additional adjustment for community incidence. During the intervention and control periods, 69,248 patients and 69,104 patients, respectively, were included for a total of 138,352 patients. Patients had a median age of 45.0 years [31.0, 63.0], and women represented 45.7% of the patients. During the intervention period, 6,332 asymptomatic/paucisymptomatic patients completed the questionnaire; 4,283 were screened for SARS-CoV-2 by nurses, leading to 224 new SARS-CoV-2 diagnoses. A total of 1,859 patients versus 2,084 patients were newly diagnosed during the intervention and control periods, respectively (adjusted analysis: 26.7/1,000 versus 26.2/1,000, adjusted relative risk: 1.02 (95% confidence interval (CI) [0.94, 1.11]; p = 0.634)). The main limitation of this study is that it was conducted in a rapidly evolving epidemiological context.ConclusionsThe results of this study showed that intensified screening for SARS-CoV-2 in EDs was unlikely to identify a higher proportion of newly diagnosed patients.Trial registrationTrial registration number: ClinicalTrials.gov NCT04756609.

BackgroundFrench Polynesia is a French overseas collectivity in the Southeast Pacific, comprising 75 inhabited islands across five archipelagoes. The human settlement of the region corresponds to the last massive migration of humans to empty territories, but its timeline is still debated. Despite their recent population history and geographical isolation, inhabitants of French Polynesia experience health issues similar to those of continental countries. Modern lifestyles and increased longevity have led to a rise in non-communicable diseases (NCDs) such as obesity, diabetes, hypertension, and cardiovascular diseases. Likewise, international trade and people mobility have caused the emergence of communicable diseases (CDs) including mosquito-borne and respiratory diseases. Additionally, chronic pathologies including acute rheumatic fever, liver diseases, and ciguatera, are highly prevalent in French Polynesia. However, data on such diseases are scarce and not representative of the geographic fragmentation of the population.ObjectivesThe present project aims to estimate the prevalence of several NCDs and CDs in the population of the five archipelagoes, and identify associated risk factors. Moreover, genetic analyses will contribute to determine the sequence and timings of the peopling history of French Polynesia, and identify causal links between past genetic adaptation to island environments, and present-day susceptibility to certain diseases.MethodsThis cross-sectional survey is based on the random selection of 2,100 adults aged 18–69 years and residing on 18 islands from the five archipelagoes. Each participant answered a questionnaire on a wide range of topics (including demographic characteristics, lifestyle habits and medical history), underwent physical measurements (height, weight, waist circumference, arterial pressure, and skin pigmentation), and provided biological samples (blood, saliva, and stool) for biological, genetic and microbiological analyses.ConclusionFor the first time in French Polynesia, the present project allows to collect a wide range of data to explore the existence of indicators and/or risk factors for multiple pathologies of public health concern. The results will help health authorities to adapt actions and preventive measures aimed at reducing the incidence of NCDs and CDs. Moreover, the new genomic data generated in this study, combined with anthropological data, will increase our understanding of the peopling history of French Polynesia.Clinical trial registrationhttps://clinicaltrials.gov/, identifier: NCT06133400.

There have been increasing reports of extensively drug-resistant (XDR) Shigella sonnei infections in recent years. In this laboratory surveillance study from France, the authors document the rise of XDR isolates from 2005 to 2021 and perform whole genome sequencing to investigate their genomic diversity and evolutionary history.

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

Many countries introduced COVID certificates that were required to access public venues. Here, the authors analyse data from France, Germany, and Italy, and estimate that these policies led to increased vaccine uptake of 6-13 percentage points with subsequent beneficial impacts on health and economic outcomes.

Abstract Background Vaccination is expected to change the epidemiology and management of SARS-CoV-2 epidemics. Methods We used an age-stratified compartmental model calibrated to French data to anticipate these changes and determine implications for the control of an autumn epidemic. We assumed vaccines reduce the risk of hospitalization, infection, and transmission if infected by 95%, 60%, and 50%, respectively. Results In our baseline scenario characterized by basic reproduction number R0=5 and a vaccine coverage of 70–80–90% among 12–17, 18–59, and ≥ 60 years old, important stress on healthcare is expected in the absence of measures. Unvaccinated adults ≥60 years old represent 3% of the population but 43% of hospitalizations. Given limited vaccine coverage, children aged 0–17 years old represent a third of infections and are responsible for almost half of transmissions. Unvaccinated individuals have a disproportionate contribution to transmission so that measures targeting them may help maximize epidemic control while minimizing costs for society compared to non-targeted approaches. Of all the interventions considered including repeated testing and non-pharmaceutical measures, vaccination of the unvaccinated is the most effective. Conclusions With the Delta variant, vaccinated individuals are well protected against hospitalization but remain at risk of infection and should therefore apply protective behaviors (e.g., mask-wearing). Targeting non-vaccinated individuals may maximize epidemic control while minimizing costs for society. Vaccinating children protects them from the deleterious effects of non-pharmaceutical measures. Control strategies should account for the changing SARS-CoV-2 epidemiology.

In this study, Tran Kiem et al. examine the contribution of different age groups to COVID-19 transmission. Using data from the French epidemic in summer 2020, they report that while individuals aged 80 years and older are more at risk, pandemic control in the absence of vaccines required measures targeted at all age groups.

Summary: Background: The protective immunity against omicron following a BNT162b2 Pfizer booster dose among elderly individuals (ie, those aged >65 years) is not well characterised. Methods: In a community-based, prospective, longitudinal cohort study taking place in France in which 75 residents from three nursing homes were enrolled, we selected 38 residents who had received a two-dose regimen of mRNA vaccine and a booster dose of Pfizer BNT162b2 vaccine. We excluded individuals that did not receive three vaccine doses or did not have available sera samples. We measured anti-S IgG antibodies and neutralisation capacity in sera taken 56 (28-68) and 55 (48-64) days (median (range)) after the 2nd and 3rd vaccine doses, respectively. Antibodies targeting the SARS-CoV-2 Spike protein were measured with the S-Flow assay as binding antibody units per milliliter (BAU/mL). Neutralising activities in sera were measured as effective dilution 50% (ED50) with the S-Fuse assay using authentic isolates of delta and omicron BA.1. Findings: Among the 38 elderly individuals recruited to the cohort study between November 23rd, 2020 and April 29th, 2021, with median age of 88 (range 72-101) years, 30 (78.95%) had been previously infected with SARS-CoV-2. After three vaccine doses, serum neutralising activity was lower against omicron BA.1 (median ED50 of 774.5, range 15.0-34660.0) than the delta variant (median ED50 of 4972.0, range 213.7-66340.0), and higher among previously infected (ie, convalescent; median ED50 against omicron: 1088.0, range 32.6-34660.0) compared with infection-naive residents (median ED50 against omicron: 188.4, range 15.0-8918.0). During the French omicron wave in December 2021-January 2022, 75% (6/8) of naive residents were infected, compared to 25% (7/30) of convalescent residents (P=0.0114). Anti-Spike antibody levels and neutralising activity against omicron BA.1 after a third BNT162b2 booster dose were lower in those with breakthrough BA.1 infection (n=13) compared with those without (n=25), with a median of 1429.9 (range 670.9-3818.3) BAU/mL vs 2528.3 (range 695.4-8832.0) BAU/mL (P=0.029) and a median ED50 of 281.1 (range 15.0-2136.0) vs 1376.0 (range 32.6-34660.0) (P=0.0013), respectively. Interpretation: This study shows that elderly individuals who received three vaccine doses elicit neutralising antibodies against the omicron BA.1 variant of SARS-CoV-2. Elderly individuals who had also been previously infected showed higher neutralising activity compared with naive individuals. Yet, breakthrough infections with omicron occurred. Individuals with breakthrough infections had significantly lower neutralising titers compared to individuals without breakthrough infection. Thus, a fourth dose of vaccine may be useful in the elderly population to increase the level of neutralising antibodies and compensate for waning immunity. Funding: Institut Pasteur, Fondation pour la Recherche Médicale (FRM), European Health Emergency Preparedness and Response Authority (HERA), Agence nationale de recherches sur le sida et les hépatites virales – Maladies Infectieuses Emergentes (ANRS-MIE), Agence nationale de la recherche (ANR), Assistance Publique des Hôpitaux de Paris (AP-HP) and Fondation de France.

Abstract Higher transmissibility of SARS-CoV-2 in cold and dry weather conditions has been hypothesized since the onset of the COVID-19 pandemic but the level of epidemiological evidence remains low. During the first wave of the pandemic, Spain, Italy, France, Portugal, Canada and USA presented an early spread, a heavy COVID-19 burden, and low initial public health response until lockdowns. In a context when testing was limited, we calculated the basic reproduction number (R0) in 63 regions from the growth in regional death counts. After adjusting for population density, early spread of the epidemic, and age structure, temperature and humidity were negatively associated with SARS-CoV-2 transmissibility. A reduction of mean absolute humidity by 1 g/m3 was associated with a 0.15-unit increase of R0. Below 10 °C, a temperature reduction of 1 °C was associated with a 0.16-unit increase of R0. Our results confirm a dependency of SARS-CoV-2 transmissibility to weather conditions in the absence of control measures during the first wave. The transition from summer to winter, corresponding to drop in temperature associated with an overall decrease in absolute humidity, likely contributed to the intensification of the second wave in north-west hemisphere countries. Non-pharmaceutical interventions must be adjusted to account for increased transmissibility in winter conditions.

Abstract Monkeypox is an emerging infectious disease, which has a clinical presentation similar to smallpox. In the two past decades, Central Africa has seen an increase in the frequency of cases, with many monkeypox virus (MPXV) isolates detected in the Democratic Republic of Congo (DRC) and the Central African Republic (CAR). To date, no complete MPXV viral genome has been published from the human cases identified in the CAR. The objective of this study was to sequence the full genome of 10 MPXV isolates collected during the CAR epidemics between 2001 and 2018 in order to determine their phylogenetic relationships among MPXV lineages previously described in Central Africa and West Africa. Our phylogenetic results indicate that the 10 CAR isolates belong to three lineages closely related to those found in DRC. The phylogenetic pattern shows that all of them emerged in the rainforest block of the Congo Basin. Since most human index cases in CAR occurred at the northern edge of western and eastern rainforests, transmissions from wild animals living in the rainforest is the most probable hypothesis. In addition, molecular dating estimates suggest that periods of intense political instability resulting in population movements within the country often associated also with increased poverty may have led to more frequent contact with host wild animals. The CAR socio-economic situation, armed conflicts and ecological disturbances will likely incite populations to interact more and more with wild animals and thus increase the risk of zoonotic spillover.

Abstract Background Prevalence of neonatal microcephaly in populations without Zika-epidemics is sparse. The study aimed to report baseline prevalence of congenital microcephaly and its relationship with prenatal factors in an area at risk of Zika outbreak. Methods This study included singletons born after 24 gestational weeks in 2017–2018 at four hospitals in Guangzhou, China. Microcephaly was defined as a head circumference at birth >3SD below the mean for sex and gestational age. Prevalence of microcephaly was estimated by binomial exact method. Multivariable logistic regression was used to examine the associations of microcephaly with prenatal factors. The population attributable fraction (PAF) for associated risk factors was calculated. Results Of 46,610 live births included, 154 (3.3, 95% CI 2.8–3.9 per 1000 live births) microcephalies were identified. Maternal hepatitis B virus carriers (HBV, OR 1.80, 95% CI 1.05–3.10) and primipara (OR 2.68, 95% CI 1.89–3.81) had higher risk of having a microcephalic baby. Higher prevalence of microcephaly was observed in women who had premature labor (OR 1.98, 95% CI 1.17–3.34) and had a baby with fetal growth restriction (OR 16.38, 95% CI 11.81–22.71). Four identified factors (HBV, primiparity, preterm labor, and fetal growth restriction) contributed to 66.4% of the risk of microcephaly. Conclusions The prevalence of microcephaly in Guangzhou was higher than expected. This study identified four prenatal risk factors that, together, contributed to two-thirds of the increased risk of microcephaly. This is the first reported association between maternal HBV carrier status and microcephaly.

Previous human cases or epidemics have suggested that Monkeypox virus (MPXV) can be transmitted through contact with animals of African rainforests. Although MPXV has been identified in many mammal species, most are likely secondary hosts, and the reservoir host has yet to be discovered. In this study, we provide the full list of African mammal genera (and species) in which MPXV was previously detected, and predict the geographic distributions of all species of these genera based on museum specimens and an ecological niche modelling (ENM) method. Then, we reconstruct the ecological niche of MPXV using georeferenced data on animal MPXV sequences and human index cases, and conduct overlap analyses with the ecological niches inferred for 99 mammal species, in order to identify the most probable animal reservoir. Our results show that the MPXV niche covers three African rainforests: the Congo Basin, and Upper and Lower Guinean forests. The four mammal species showing the best niche overlap with MPXV are all arboreal rodents, including three squirrels: Funisciurus anerythrus, Funisciurus pyrropus, Heliosciurus rufobrachium, and Graphiurus lorraineus. We conclude that the most probable MPXV reservoir is F. anerythrus based on two niche overlap metrics, the areas of higher probabilities of occurrence, and available data on MPXV detection.

Abstract Background In utero exposure to Zika virus (ZIKV) is known to be associated with birth defects. The impact of in utero ZIKV exposure on neurodevelopmental outcomes in early childhood remains unclear. The objective of this study was to determine the impact of in utero ZIKV exposure on neurodevelopment at 24 months of age among toddlers who were born normocephalic to women who were pregnant during the 2016 ZIKV outbreak in French territories in the Americas. Methods We conducted a population-based mother-child cohort study of women whose pregnancies overlapped with the 2016 ZIKV epidemic in Guadeloupe, Martinique, and French Guiana. Infants were included in this analysis if maternal ZIKV infection during pregnancy could be determined, the newborn had a gestational age ≥ 35 weeks, there were no abnormal transfontanelle cerebral ultrasound findings after delivery or no abnormal ultrasound findings on the last ultrasound performed during the third trimester of the mother’s pregnancy, there was an absence of microcephaly at birth, and the parent completed the 24-month neurodevelopment assessment of the infant at 24 months (± 1 month) of age. ZIKV exposure of the toddler was determined by evidence of maternal ZIKV infection during pregnancy. Neurodevelopment assessments included the Ages and Stages Questionnaire (ASQ) for five dimensions of general development—communication, gross motor, fine motor, problem solving, and personal-social skills; the Modified Checklist for Autism on Toddlers (M-CHAT) for behavior; and the French MacArthur Inventory Scales (IFDC) for French language acquisition. Results Between June 2018 and August 2019, 156 toddlers with and 79 toddlers without in utero ZIKV exposure completed neurodevelopment assessments. Twenty-four (15.4%) ZIKV-exposed toddlers and 20 (25.3%) ZIKV-unexposed toddlers had an ASQ result below the reference − 2SD cut-off (P = 0.10) for at least one of the five ASQ dimensions. Conclusion In one of the largest population-based cohorts of in utero ZIKV-exposed, normocephalic newborns to date, there were minimal differences apparent in neurodevelopment outcomes at 24 months of age compared to ZIKV-unexposed toddlers at 24 months of age. Trial registration ClinicalTrials.gov, NCT02810210 . Registered 20 June 2016.

Hepatitis E virus (HEV) infection is responsible for major endemic outbreaks in developing countries. Human immunodeficiency virus (HIV) and HEV are widespread in the Central African Republic. We report the first documented case of an HEV infection in a 36-month-old child already suffering from HIV and severe acute malnutrition (SAM). The HIV patient was hospitalized for SAM with persistent diarrhea and prolonged fever. The presence of IgG anti-HEV antibodies was noted. Sequencing of the amplified HEV RNA revealed the presence of genotype 3c. The alanine aminotransferase level was slightly above average. The patient died despite being treated by antiretroviral therapy accompanied by probabilistic antibiotic therapy and nutritional rehabilitation. HEV/HIV co-infection in a malnourished patient can accelerate a fatal outcome. In the presence of biological abnormalities in a severe acutely malnourished HIV-infected patient, HEV RNA detection should be added to the standard medical assessment in sub-Saharan African countries.

Summary: 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.

Summary: There is increasing evidence that elimination strategies have resulted in better outcomes for public health, the economy, and civil liberties than have mitigation strategies throughout the first year of the COVID-19 pandemic. With vaccines that offer high protection against severe forms of COVID-19, and increasing vaccination coverage, policy makers have had to reassess the trade-offs between different options. The desirability and feasibility of eliminating SARS-CoV-2 compared with other strategies should also be re-evaluated from the perspective of different fields, including epidemiology, public health, and economics. To end the pandemic as soon as possible—be it through elimination or reaching an acceptable endemic level—several key topics have emerged centring around coordination, both locally and internationally, and vaccine distribution. Without coordination it is difficult if not impossible to sustain elimination, which is particularly relevant in highly connected regions, such as Europe. Regarding vaccination, concerns remain with respect to equitable distribution, and the risk of the emergence of new variants of concern. Looking forward, it is crucial to overcome the dichotomy between elimination and mitigation, and to jointly define a long-term objective that can accommodate different political and societal realities.

We aimed to describe adverse pregnancy outcomes among women who had symptomatic, RT-PCR-confirmed ZIKV infection and early childhood outcomes among their infants. We enrolled pregnant women with symptomatic, RT-PCR-confirmed ZIKV infection in a prospective cohort study, and their infants in a prospective pediatric cohort study. We defined adverse pregnancy and early childhood outcomes based on selected neurologic, ophthalmologic, auditory, musculoskeletal, and anthropometric abnormalities. We used RT-PCR and serologic tests to determine the ZIKV infection status of the child. Between 10 March and 24 November 2016, we enrolled 546 pregnant women with RT-PCR-confirmed ZIKV infection. The overall risk of adverse pregnancy and early childhood outcomes possibly related to in utero ZIKV exposure was 15.7% (95% CI: 12.8–19.0), distributed as follows: 3.6% (95% CI: 2.3–5.6) severe sequelae or fatality; 2.7% (95% CI: 1.6–4.5) major abnormalities; 9.4% (95% CI:7.1–12.2) mild abnormalities. The risk of severe sequelae or fatality was higher when ZIKV infection occurred during the first trimester (7.0%), compared to the second (2.7%) or third trimester (1.4%) (p = 0.02). Among the infants for whom ZIKV infection status could be determined, the vertical transmission rate was 3.0% (5/167) (95% CI: 1.1–7.2). Among pregnant women with symptomatic, RT-PCR-confirmed ZIKV infection, severe or major pregnancy or early childhood outcomes were present in 6.3% of fetuses and infants. Severe outcomes occurred more frequently in fetuses and infants whose mothers had been infected in the first trimester.

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”).

Background: Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting risk of reinfection and durability of vaccine protection. Methods: This is a prospective, monocentric, longitudinal, cohort clinical study. Healthcare workers (HCW) from Strasbourg University Hospital were enrolled between April 6th and May 7th, 2020 and followed up to 422 days. Serial serum samples were tested for antibodies against the Receptor Binding Domain (RBD) of the spike protein and nucleocapsid protein (N) to characterize the kinetics of SARS-CoV-2 antibodies and the incidence of reinfection. Live-neutralization assays were performed for a subset of samples before and after vaccination to analyze sensitivity to SARS-CoV-2 variants. Findings: A total of 4290 samples from 393 convalescent COVID-19 and 916 COVID-19 negative individuals were analyzed. In convalescent individuals, SARS-CoV-2 antibodies followed a triphasic kinetic model with half-lives at month (M) 11–13 of 283 days (95% CI 231–349) for anti-N and 725 days (95% CI 623–921) for anti-RBD IgG, which stabilized at a median of 1.54 log BAU/mL (95% CI 1.42–1.67). The incidence of SARS-CoV-2 infections was 12.22 and 0.40 per 100 person-years in COVID-19-negative and COVID-19-positive HCW, respectively, indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7%. Live-virus neutralization assay revealed that after one year, variants D614G and B.1.1.7, but less so B.1.351, were sensitive to anti-RBD antibodies at 1.4 log BAU/mL, while IgG ≥ 2.0 log BAU/mL strongly neutralized all three variants. These latter anti-RBD IgG titers were reached by all vaccinated HCW regardless of pre-vaccination IgG levels and type of vaccine. Interpretation: Our study demonstrates a long-term persistence of anti-RBD antibodies that may reduce risk of reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against variants. Fun1ding: None.

Summary: 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”).

Background: Children are underrepresented in the COVID-19 pandemic and often experience milder disease than adolescents and adults. Reduced severity is possibly due to recent and more frequent seasonal human coronaviruses (HCoV) infections. We assessed the seroprevalence of SARS-CoV-2 and seasonal HCoV specific antibodies in a large cohort in north-eastern France. Methods: In this cross-sectional seroprevalence study, serum samples were collected from children and adults requiring hospital admission for non-COVID-19 between February and August 2020. Antibody responses to SARS-CoV-2 and seasonal HCoV (229E, HKU1, NL63, OC43) were assessed using a bead-based multiplex assay, Luciferase-Linked ImmunoSorbent Assay, and a pseudotype neutralisation assay. Findings: In 2,408 individuals, seroprevalence of SARS-CoV-2-specific antibodies was 7-8% with three different immunoassays. Antibody levels to seasonal HCoV increased substantially up to the age of 10. Antibody responses in SARS-CoV-2 seropositive individuals were lowest in adults 18-30 years. In SARS-CoV-2 seronegative individuals, we observed cross-reactivity between antibodies to the four HCoV and SARS-CoV-2 Spike. In contrast to other antibodies to SARS-CoV-2, specific antibodies to sub-unit 2 of Spike (S2) in seronegative samples were highest in children. Upon infection with SARS-CoV-2, antibody levels to Spike of betacoronavirus OC43 increased across the whole age spectrum. No SARS-CoV-2 seropositive individuals with low levels of antibodies to seasonal HCoV were observed. Interpretation: Our findings underline significant cross-reactivity between antibodies to SARS-CoV-2 and seasonal HCoV, but provide no significant evidence for cross-protective immunity to SARS-CoV-2 infection due to a recent seasonal HCoV infection. In particular, across all age groups we did not observe SARS-CoV-2 infected individuals with low levels of antibodies to seasonal HCoV. Funding: This work was supported by the « URGENCE COVID-19 » fundraising campaign of Institut Pasteur, by the French Government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (Grant No. ANR-10-LABX-62-IBEID), and by the REACTing (Research & Action Emerging Infectious Diseases), and by the RECOVER project funded by the European Union's Horizon 2020 research and innovation programme under grant agreement No. 101003589, and by a grant from LabEx IBEID (ANR-10-LABX-62-IBEID).

Background: The roll-out of COVID-19 vaccines is a multi-faceted challenge whose performance depends on pace of vaccination, vaccine characteristics and heterogeneities in individual risks. Methods: We developed a mathematical model accounting for the risk of severe disease by age and comorbidity, and transmission dynamics. We compared vaccine prioritisation strategies in the early roll-out stage and quantified the extent to which measures could be relaxed as a function of the vaccine coverage achieved in France. Findings: Prioritizing at-risk individuals reduces morbi-mortality the most if vaccines only reduce severity, but is of less importance if vaccines also substantially reduce infectivity or susceptibility. Age is the most important factor to consider for prioritization; additionally accounting for comorbidities increases the performance of the campaign in a context of scarce resources. Vaccinating 90% of ≥65 y.o. and 70% of 18–64 y.o. before autumn 2021 with a vaccine that reduces severity by 90% and susceptibility by 80%, we find that control measures reducing transmission rates by 15–27% should be maintained to remain below 1000 daily hospital admissions in France with a highly transmissible variant (basic reproduction number R0 = 4). Assuming 90% of ≥65 y.o. are vaccinated, full relaxation of control measures might be achieved with a vaccine coverage of 89–100% in 18–64 y.o or 60–69% of 0–64 y.o. Interpretation: Age and comorbidity-based vaccine prioritization strategies could reduce the burden of the disease. Very high vaccination coverage may be required to completely relax control measures. Vaccination of children, if possible, could lower coverage targets necessary to achieve this objective. Funding: We acknowledge financial support from Haute Autorite de Sante, the Investissement d'Avenir program, the Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases program (grant ANR-10-LABX-62-IBEID), Sante Publique France, the INCEPTION project (PIA/ANR-16-CONV-0005), AXA, Groupama and the European Union's Horizon 2020 research and innovation program under grants 101003589 (RECOVER) and 874735 (VEO).

Background: In 2016-2017, 68 women in Southern Vietnam had RT-PCR confirmed Zika virus (ZIKV) infection during pregnancy. We report here the outcomes of the pregnancies and the virological analyses related to this outbreak. Methods: We collected clinical and epidemiological information from the women who were enrolled in the study. Medical records related to the pregnancy in 2016–2017 were retrieved for those who were not able to be enrolled in the study. Children born to women with ZIKV infection during pregnancy were also enrolled. Serum samples were evaluated for presence of ZIKV antibodies. Phylogenetic analyses were performed on Zika virus genomes sequenced from the 2016–2017 serum samples. Findings: Of the 68 pregnancies, 58 were livebirths and 10 were medically terminated. Four of the medical records from cases of fetal demise were able to be retrieved, of which one was consistent with congenital ZIKV infection. Of the 58 women with a livebirth, 21 participated in the follow-up investigation. All but two women had serologic evidence of ZIKV infection. Of the 21 children included in the study (mean age: 30.3 months), 3 had microcephaly at birth. No other clinical abnormalities were reported and no differences in neurodevelopment were observed compared to a control group. Phylogenetic analysis revealed a clade within the ZIKV Asian lineage and branch at the root of samples from the 2013–2014 French Polynesian outbreak. The prM S139N mutation was not observed. Interpretation: We have been able to demonstrate a clade within the ZIKV Asian lineage implicated in adverse pregnancy outcomes in Southern Vietnam. Funding: INCEPTION project (PIA/ANR-16-CONV-0005) and a grant received from BNP Paribas Simplidon.

Summary: Many SARS-CoV-2-infected individuals remain asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mildly symptomatic, and 21 hospitalized patients with COVID-19. We measure anti-spike immunoglobulin G (IgG), IgA, and IgM levels with the S-Flow assay and map IgG-targeted epitopes with a Luminex assay. We also evaluate neutralization, complement deposition, and antibody-dependent cellular cytotoxicity (ADCC) using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC, and trigger complement deposition. Antibody levels and functions are lower in asymptomatic individuals than they are in symptomatic cases. Antibody functions are correlated, regardless of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells.

Objectives We aimed to review SARS-CoV-2 seroprevalence studies conducted in Europe to understand how they may be used to inform ongoing control strategies for COVID-19.Design Scoping review of peer-reviewed publications and manuscripts on preprint servers from January 2020 to 15 September 2020.Primary measure Seroprevalence estimate (and lower and upper CIs). For studies conducted across a country or territory, we used the seroprevalence estimate and the upper and lower CIs and compared them to the total number of reported infections to calculate the ratio of reported to expected infections.Results We identified 23 population-based seroprevalence studies conducted in Europe. Among 12 general population studies, seroprevalence ranged from 0.42% among residual clinical samples in Greece to 13.6% in an area of high transmission in Gangelt, Germany. Of the eight studies in blood donors, seroprevalence ranged from 0.91% in North-Western Germany to 23.3% in a high-transmission area in Lombardy region, Italy. In three studies which recruited individuals through employment, seroprevalence ranged from 0.5% among factory workers in Frankfurt, Germany, to 10.2% among university employees in Milan, Italy. In comparison to nationally reported cases, the extent of infection, as derived from these seroprevalence estimates, is manyfold higher and largely heterogeneous.Conclusion Exposure to the virus in Europe has not reached a level of infection that would prevent further circulation of the virus. Effective vaccine candidates are urgently required to deliver the level of immunity in the population.

BackgroundIn the French Territories in the Americas (FTA), the risk of birth defects possibly associated with Zika virus (ZIKV) infection was 7.0% (95%CI: 5.0 to 9.5) among foetuses/infants of 546 women with symptomatic RT-PCR confirmed ZIKV infection during pregnancy. Many of these defects were isolated measurement-based microcephaly (i.e. without any detected brain or clinical abnormalities) or mild neurological conditions. We wanted to estimate the proportion of such minor findings among live births of women who were pregnant in the same region during the outbreak period but who were not infected with ZIKV.MethodsIn Guadeloupe, pregnant women were recruited at the time of delivery and tested for ZIKV infection. The outcomes of live born infants of ZIKV non-infected women were compared to those of ZIKV-exposed live born infants in Guadeloupe, extracted from the FTA prospective cohort.ResultsOf 490 live born infants without exposure to ZIKV, 42 infants (8.6%, 95%CI: 6.2-11.4) had mild abnormalities that have been described as 'potentially linked to ZIKV infection'; all but one of these was isolated measurement-based microcephaly. Among the 241 live born infants with ZIKV exposure, the proportion of such abnormalities, using the same definition, was similar (6.6%, 95%CI: 3.8-10.6).ConclusionsIsolated anthropometric abnormalities and mild neurological conditions were as prevalent among infants with and without in-utero ZIKV exposure. If such abnormalities had not been considered as 'potentially linked to ZIKV' in the original prospective cohort in Guadeloupe, the overall estimate of the risk of birth defects considered due to the virus would have been significantly lower, at approximately 1.6% (95% CI: 0.4-4.1).Trial registrationClinicalTrials.gov (NCT02916732).

BackgroundHospitals are suspected of playing a key role in HCV epidemic dynamics in Egypt. This work aimed at assessing HCV prevalence and associated risk factors in patients and health-care workers (HCWs) of Ain Shams University (ASU) hospitals in Cairo.MethodsWe included 500 patients admitted to the internal medicine or surgery hospital from February to July, 2017, as well as 50 HCWs working in these same hospitals. Participants were screened for anti-HCV antibodies and HCV RNA. A questionnaire was administered to collect data on demographic characteristics and medical/surgical history. For HCWs, questions on occupational exposures and infection control practices were also included.ResultsThe overall prevalence of anti-HCV antibodies was 19.80% (95% CI: 16.54-23.52) among participating patients, and 8.00% (95% CI: 0.48-15.52) among participating HCWs. In HCWs, the only risk factors significantly associated with anti-HCV antibodies were age and profession, with higher prevalence in older HCWs and those working as cleaners or porters. In patients, in a multivariate logistic regression, age over 50 (aOR: 3.4 [1.9-5.8]), living outside Cairo (aOR: 2.1 [1.2-3.4]), admission for liver or gastro-intestinal complaints (aOR: 4.2 [1.8-9.9]), and history of receiving parenteral anti-schistosomiasis treatment (aOR: 2.7 [1.2-5.9]) were found associated with anti-HCV antibodies.ConclusionsWhile HCV prevalence among patients has decreased since the last survey performed within ASU hospitals in 2008, it is still significantly higher than in the general population. These results may help better control further HCV spread within healthcare settings in Egypt by identifying at-risk patient profiles upon admission.

Yersinia pestis, the bacterial causative agent of plague, remains an important threat to human health. Plague is a rodent-borne disease that has historically shown an outstanding ability to colonize and persist across different species, habitats, and environments while provoking sporadic cases, outbreaks, and deadly global epidemics among humans. Between September and November 2017, an outbreak of urban pneumonic plague was declared in Madagascar, which refocused the attention of the scientific community on this ancient human scourge. Given recent trends and plague's resilience to control in the wild, its high fatality rate in humans without early treatment, and its capacity to disrupt social and healthcare systems, human plague should be considered as a neglected threat. A workshop was held in Paris in July 2018 to review current knowledge about plague and to identify the scientific research priorities to eradicate plague as a human threat. It was concluded that an urgent commitment is needed to develop and fund a strong research agenda aiming to fill the current knowledge gaps structured around 4 main axes: (i) an improved understanding of the ecological interactions among the reservoir, vector, pathogen, and environment; (ii) human and societal responses; (iii) improved diagnostic tools and case management; and (iv) vaccine development. These axes should be cross-cutting, translational, and focused on delivering context-specific strategies. Results of this research should feed a global control and prevention strategy within a "One Health" approach.

We investigated the cause of seasonal outbreaks of pediatric acute encephalitis-like syndrome associated with litchi harvests (May–July) in northern Vietnam since 2008. Nineteen cerebrospinal fluid samples were positive for human enterovirus B, and 8 blood samples were positive for hypoglycemic toxins present in litchi fruits. Patients who were positive for hypoglycemic toxins had shorter median times between disease onset and admission, more reports of seizures, more reports of hypoglycemia (glucose level

Abstract While until recently the small and isolated Zika outbreaks in Eastern Asia and Pacific islands had been overlooked, the large-scale outbreak that started in Brazil in 2015 and the increase of microcephaly cases in the same place and time made media headlines. Considered as harmless until recently, Zika has given rise to an important global crisis that poses not only health challenges but also environmental, economical, social, and ethical challenges for states and people around the world. The main objective of this paper is to review the recent Zika outbreak by covering a broad range of disciplines and their interactions. This paper synthetises experts’ interviews and reactions conducted during a Massive Open Online Course (MOOC) entitled “In the footsteps of Zika…approaching the unknown.” It reviews knowledge and uncertainties around epidemiology, geographical dispersion of the virus and its vectors through globalization and climate change, and also its modes of transmission, diagnosis, symptoms, and treatment of the disease. The resulting societal and ethical issues in pregnancy and women of reproductive age were also addressed as well as the global outbreak alert and response network in international organizations and social media. This paper attempted to combine each piece of the jigsaw puzzle of the Zika phenomenon to complete the best realistic picture, while keeping in mind the balance between the interdisciplinary nature and international context of Zika and its unique characteristics.

Monkeypox is a rare viral zoonotic disease; primary infections are reported from remote forest areas of Central and West Africa. We report an investigation of a monkeypox outbreak in Lobaye, southwest Central African Republic, in October 2018.

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.

BACKGROUND:Human T-Lymphotropic Virus type 1 (HTLV-1) is a human oncoretrovirus that infects at least 5 to 10 million people worldwide and is associated with severe diseases. Africa appears as the largest HTLV-1 endemic area. However, the risk factors for the acquisition of HTLV-1 remain poorly understood in Central Africa. METHODS:We conducted an epidemiological survey between 2013 and 2017, in rural areas of 6 provinces of Gabon, in a rainforest environment. Epidemiological data were obtained and blood samples were collected after informed consent. Plasma were screened for HTLV-1 antibodies by ELISA and the positive samples were then tested by Western blot (WB). Genomic DNA derived from buffy-coat was subjected to two semi-nested PCRs amplifying either HTLV-1 env gene or LTR region fragments. RESULTS:We recruited 2,060 individuals over 15 years old, including 1,205 men and 855 women (mean age: 49 years). Of these, 299 were found to be ELISA HTLV-1/2 seropositive. According to WB criteria, 136 were HTLV-1 (6.6%), 25 HTLV-1/2 (1.2%) and 9 HTLV seroreactive (0.4%). PCR results showed that 146 individuals were positive for at least one PCR: 104 for the env gene and 131 for the LTR region. Based on both serological and molecular results, 179 individuals were considered infected with HTLV-1, leading to an overall prevalence of 8.7%. The distribution of HTLV-1 infection was heterogeneous across the country. Based on multivariable analyses, female gender, increasing age, ethnicity (Pygmy) and multiple hospitalizations (more than 5 times) were found to be independent risk factors for HTLV-1 infection. Furthermore, a non-human primate bite appeared to be marginally associated with a higher risk of HTLV-1 infection. CONCLUSION:Based on state-of-the-art serological and molecular methods, we have demonstrated that rural adult populations in Gabon are highly endemic for HTLV-1. Our results regarding risk factors should lead to public health actions aiming to reduce HTLV-1 transmission.

To inform epidemic response strategies for the African meningitis belt after a meningococcal serogroup A conjugate vaccine was introduced in 2010, we compared the effectiveness and efficiency of meningitis surveillance and vaccine response strategies at district and health area levels using various thresholds of weekly incidence rates. We analyzed reports of suspected cases from 3 regions in Niger during 2002–2012 (154,392 health area weeks), simulating elimination of serogroup A meningitis by excluding health area years with identification of such cases. Effectiveness was highest for health area surveillance and district vaccination (58–366 cases; thresholds 7–20 cases/100,000 doses), whereas efficiency was optimized with health area vaccination (5.6–7.7 cases/100,000 doses). District-level intervention prevented

To determine when risk for Buruli ulcer is highest, we examined seasonal patterns in a highly disease-endemic area of Cameroon during 2002–2012. Cases peaked in March, suggesting that risk is highest during the high rainy season. During and after this season, populations should increase protective behaviors, and case detection efforts should be intensified.

Numerous genetic polymorphisms have been identified as associated with disease or treatment outcome, but the routine implementation of genotyping into actionable medical care remains limited. Point-of-care (PoC) technologies enable rapid and real-time treatment decisions, with great potential for extending molecular diagnostic approaches to settings with limited medical infrastructure (e.g., CLIA certified diagnostic laboratories). With respect to resource-limited settings, there is a need for simple devices to implement biomarker guided treatment strategies. One relevant example is chronic hepatitis C infection, for which several treatment options are now approved. Single nucleotide polymorphisms (SNPs) in the IL-28B / IFNL3 locus have been well described to predict both spontaneous clearance and response to interferon based therapies. We utilized the Genedrive® platform to develop an assay for the SNP rs12979860 variants (CC, CT and TT). The assay utilizes a hybrid thermal engine, permitting rapid heating and cooling, enabling an amplification based assay with genetic variants reported using endpoint differential melting cure analysis in less than 60 minutes. We validated this assay using non-invasive buccal swab sampling in a prospective study of 246 chronic HCV patients, achieving 100% sensitivity and 100% specificity (95% exact CI: 98.8-100%)) in 50 minutes as compared to conventional lab based PCR testing. Our results provide proof of concept that precision medicine is feasible in resource-limited settings, offering the first CE-IVD (in vitro diagnostics) validated PoC SNP test. We propose that IL-28B genotyping may be useful for directing patients towards lower cost therapies, and rationing use of costly direct antivirals for use in those individuals showing genetic risk.

During January 2007–July 2012, a total of 3,220 suspected yellow fever cases were reported in the Central African Republic; 55 were confirmed and 11 case-patients died. Mean delay between onset of jaundice and case confirmation was 16.6 days. Delay between disease onset and blood collection could be reduced by increasing awareness of the population.

To compare dynamics of localized meningitis epidemics (LE) by meningococcal (Nm) serogroup, we analyzed a surveillance database of suspected and laboratory-confirmed Nm cases from 373 health areas (HA) of three regions in Niger during 2002-2012 and one region concerned by NmC epidemics during 2015. We defined LE as HA weekly incidence rates of ≥20 suspected cases per 100,000 during ≥2 weeks and assigned the predominant serogroup based on polymerase chain reaction testing of cerebrospinal fluid. Among the 175 LE, median peak weekly incidence rate in LE due to NmA, W, X and C were 54, 39, 109 and 46 per 100,000, respectively. These differences impacted ability of the epidemic to be detected at the district level. While this analysis is limited by the small number of LE due to NmX (N = 4) and NmW (N = 5), further research should explore whether strategies for prevention and response to meningitis epidemics need to be adapted according to predominant meningococcal serogroups.

Since the end of the 1990s, unexplained outbreaks of acute encephalitis in children coinciding with litchi harvesting (May–July) have been documented in the Bac Giang Province in northern Vietnam. A retrospective ecologic analysis of data for 2004–2009 involving environmental, agronomic, and climatic factors was conducted to investigate the suspected association between the outbreaks and litchi harvesting. The clinical, biological, and immunologic characteristics of the patients suggested a viral etiology. The ecologic study revealed an independent association between litchi plantation surface proportion and acute encephalitis incidence: Incidence rate ratios were 1.52 (95% CI 0.90–2.57), 2.94 (95% CI 1.88–4.60), and 2.76 (95% CI 1.76–4.32) for second, third, and fourth quartiles, respectively, compared with the lowest quartile. This ecologic study confirmed the suspected association between incidence of acute encephalitis and litchi plantations and should be followed by other studies to identify the causative agent for this syndrome.

Little is known about severe imported Plasmodium falciparum malaria in industrialized countries where the disease is not endemic because most studies have been case reports or have included

Few immigrant travelers have Plasmodium falciparum infections >2 months after leaving malaria-endemic areas. We conducted a case–control study to identify factors associated with prolonged P. falciparum infection in immigrant travelers. Results suggest that P. falciparum infection should be systematically suspected, even months after travel, especially in pregnant women and first-arrival immigrants.

Recent studies have suggested that bats are the natural reservoir of a range of coronaviruses (CoVs), and that rhinolophid bats harbor viruses closely related to the severe acute respiratory syndrome (SARS) CoV, which caused an outbreak of respiratory illness in humans during 2002–2003. We examined the evolutionary relationships between bat CoVs and their hosts by using sequence data of the virus RNA-dependent RNA polymerase gene and the bat cytochrome b gene. Phylogenetic analyses showed multiple incongruent associations between the phylogenies of rhinolophid bats and their CoVs, which suggested that host shifts have occurred in the recent evolutionary history of this group. These shifts may be due to either virus biologic traits or host behavioral traits. This finding has implications for the emergence of SARS and for the potential future emergence of SARS-CoVs or related viruses.