Impact of Zika Virus Emergence in French Guiana: A Large General Population Seroprevalence Survey.

BACKGROUND: Since the identification of Zika virus (ZIKV) in Brazil in May 2015, the virus has spread throughout the Americas. However, ZIKV burden in the general population in affected countries remains unknown. METHODS: We conducted a general population survey in the different communities of French Guiana through individual interviews and serologic survey during June-October 2017. All serum samples were tested for anti-ZIKV immunoglobulin G antibodies using a recombinant antigen-based SGERPAxMap microsphere immunoassay, and some of them were further evaluated through anti-ZIKV microneutralization tests. RESULTS: The overall seroprevalence was estimated at 23.3% (95% confidence interval [CI], 20.9%-25.9%) among 2697 participants, varying from 0% to 45.6% according to municipalities. ZIKV circulated in a large majority of French Guiana but not in the most isolated forest areas. The proportion of reported symptomatic Zika infection was estimated at 25.5% (95% CI, 20.3%-31.4%) in individuals who tested positive for ZIKV. CONCLUSIONS: This study described a large-scale representative ZIKV seroprevalence study in South America from the recent 2015-2016 Zika epidemic. Our findings reveal that the majority of the population remains susceptible to ZIKV, which could potentially allow future reintroductions of the virus

Spatial Distribution and Burden of Emerging Arboviruses in French Guiana.

Despite the health, social and economic impact of arboviruses in French Guiana, very little is known about the extent to which infection burden is shared between individuals. We conducted a large multiplexed serological survey among 2697 individuals from June to October 2017. All serum samples were tested for IgG antibodies against DENV, CHIKV, ZIKV and MAYV using a recombinant antigen-based microsphere immunoassay with a subset further evaluated through anti-ZIKV microneutralization tests. The overall DENV seroprevalence was estimated at 73.1% (70.6-75.4) in the whole territory with estimations by serotype at 68.9% for DENV-1, 38.8% for DENV-2, 42.3% for DENV-3, and 56.1% for DENV-4. The overall seroprevalence of CHIKV, ZIKV and MAYV antibodies was 20.3% (17.7-23.1), 23.3% (20.9-25.9) and 3.3% (2.7-4.1), respectively. We provide a consistent overview of the burden of emerging arboviruses in French Guiana, with useful findings for risk mapping, future prevention and control programs. The majority of the population remains susceptible to CHIKV and ZIKV, which could potentially facilitate the risk of further re-emergences. Our results underscore the need to strengthen MAYV surveillance in order to rapidly detect any substantial changes in MAYV circulation patterns

Vaccination coverage in the context of the emerging Yellow Fever threat in French Guiana

International audienceBackground: French Guiana, a French overseas department located in South America between Brazil and Surinam, is the only European territory geographically located in the Amazonian forest complex and is considered endemic for yellow fever (YF). In the context of the emergent threat of YF in Latin America, we conducted a large household cross-sectional survey from June to October 2017 to estimate vaccination coverage in the population and to determine associations with sociodemographic and geographical characteristics.Methodology/principal findings: In total, 1,415 households and 2,697 individuals were included from the 22 municipalities of French Guiana. YF vaccination coverage was estimated at 95.0% (95% CI: 93.4-96.2) in the entire territory but was spatially heterogeneous, with the lowest levels estimated in the western part of the territory along the Surinamese cross-border region, particularly in children under 16 years who were not enrolled in school, immigrant adults and disadvantaged populations with low socioeconomic indexes.Conclusions/significance: Despite the good vaccination coverage against YF in the general population of French Guiana resulting from the compulsory nature of YF vaccination for residents and travelers, there is an urgent need to improve vaccination coverage in vulnerable populations living in the northwestern part of the territory to limit the risk of transmission in the context of the emerging YF threat in South America. Despite the relative rarity of YF and the significant number of infectious and tropical diseases in French Guiana, clinicians should adopt a high index of suspicion for YF, particularly in vulnerable and at-risk populations

Transmission dynamics of Q fever in French Guiana: A population-based cross-sectional study

International audienceBackground: Q fever is a zoonosis caused by Coxiella burnetii which is among the major agents of community-acquired pneumonia in French Guiana. Despite its relatively high incidence, its epidemiology in French Guiana remains unclear, and all previous studies have considered transmission from livestock unlikely, suggesting that a wild reservoir is responsible for transmission.Methods: A country-wide seroprevalence survey of 2697 participants from French Guiana was conducted. Serum samples were tested for phase II IgG antibodies by ELISA and indirect immunofluorescence assays (IFAs). Factors associated with Q fever were investigated, and a serocatalytic model was used to reconstruct the annual force of infection.Findings: The overall weighted seroprevalence was estimated at 9.6% (95% confidence interval (CI): 8.2%–11.0%). The model revealed constant, low-level circulation across French Guiana, particularly affecting middle-aged males (odds ratio (OR): 3.0, 95% credible interval (CrI): 1.7–5.8) and individuals living close to sheep farms (OR: 4, 95% CrI: 1.5–12). The overall annual number of cases was estimated at 579 (95% CrI: 492–670). In the region around Cayenne, the main urban municipality, the high seroprevalence was explained by an outbreak that may have occurred between 1996 and 2003 and that infected 10% (95% CrI: 6.9%–14%) of the population and males and females alike.Interpretation: This study reveals for the first time Q fever dynamics of transmission and the role of domestic livestock in transmission in French Guiana and highlights the urgent need to reinforce Q fever surveillance in livestocks of the entire Guianese territory

Characteristics Associated with Olfactory and Taste Disorders in COVID-19

International audienceIntroduction: Olfactory and taste disorders (OTDs) have been reported in COVID-19 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the mechanisms of which remain unclear. We conducted a detailed analysis of OTDs as part of 2 seroepidemiological investigations of COVID-19 outbreaks. Methods: Two retrospective cohort studies were conducted in a high school and primary schools of Northern France following a COVID-19 epidemic in February-March 2020. Students, their relatives, and school staff were included. Anti-SARS-CoV-2 antibodies were identified using a flow-cytometry-based assay detecting anti-S IgG. Results: Among 2,004 participants (median [IQR] age: 31 [11–43] years), 303 (15.2%) tested positive for SARS-CoV-2 antibodies. OTDs were present in 91 (30.0%) and 92 (30.3%) of them, respectively, and had 85.1 and 78.0% positive predictive values for SARS-CoV-2 infection, respectively. In seropositive participants, OTDs were independently associated with an age above 18 years, female gender, fatigue, and headache. Conclusion: This study confirms the higher frequency of OTDs in females than males and adults than children. Their high predictive value for the diagnosis of COVID-19 suggests that they should be systematically searched for in patients with respiratory symptoms, fever, or headache. The association of OTDs with headache, not previously reported, suggests that they share a common mechanism, which deserves further investigation

Assessing the burden of arboviral diseases using a multiplexed serological survey in French Guiana

ObjectiveTo assess the level of circulation of DENV, CHIKV, ZIKV, MAYV in French Guiana.IntroductionArboviral infections have become a significant public health problem with the emergence and re-emergence of arboviral diseases worldwide in recent decades [1-6]. Given the increasing number of cases, geographic spread, but also health, social and economic impact of arboviral outbreaks, estimating their true burden represents a crucial issue but remains a difficult task [7-10].In French Guiana, the epidemiology of arboviral diseases has been marked by the occurrence several major dengue fever (DENV) outbreaks over the past few decades, recent emergences of Chikungunya (CHKV) and Zika virus (ZIKV) and the circulation of Mayaro virus (MAYV) [11-14].MethodsTo assess antibody seroprevalence against DENV, CHIKV, ZIKV, MAYV a random 2-stage household cross-sectional survey was conducted among the general population. We enrolled 2,697 individuals aged 1-87 years from June 1 to 12 October 2017. We performed detection of DENV, CHIKV, ZIKV, MAYV IgG antibodies on collected blood samples using a microsphere immunoassay (MIA). Socio-economic data, environmental variables and exposure to mosquitoes, perceptions of the illness and risk of contracting arboviral infections were collected using a standardized questionnaire administrated to all individuals included in the survey. Cross-reactivity between same families of viruses was taking into account using seroneutralisation and modeling approaches.ResultsOverall seroprevalence rates for antibodes against DENV were 69.5% [66.4%-72.5%] and differed significantly according to age and geographical area. Seroprevalence rates of CHIKV, ZIKV and MAYV antibodies were respectively 19.3% [16.5%-22.5%], 23.1% [19.5%-27.2%] and 9.6% [8.1%-11.3%] and did not differed significantly according to gender or age.The distribution of seroprevalence rates for CHIKV, ZIKV antibodies differed from extrapolations obtained from routine surveillance systems and brings valuable information to assess the epidemic risk of future outbreaks. MAYV has been circulating in the southern part of FG, at levels that appear to be substantially higher than those estimated from epidemiological and virological surveillance.ConclusionsSerological surveys provide the most direct measurement for defining the immunity landscape for infectious diseases, but the methodology remains difficult to implement particularly in the context of high cross-reactivity between flaviviruses or alphaviruses [15]. The development of reliable, rapid and affordable diagnosis tools and the use of innovative modeling approaches represent a significant issue concerning the ability of seroprevalence surveys to differentiate infections when multiple viruses co-circulate.References1. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013;496: 504–507. pmid:235632662. Stanaway JD, Shepard DS, Undurraga EA, Halasa YA, Coffeng LE, Brady OJ, et al. The global burden of dengue: an analysis from the Global Burden of Disease Study 2013. Lancet Infect Dis. 2016;16: 712–723. pmid:268746193. Brathwaite Dick O, San Martín JL, Montoya RH, del Diego J, Zambrano B, Dayan GH. The history of dengue outbreaks in the Americas. Am J Trop Med Hyg. 2012;87: 584–593. pmid:230428464. Petersen LR, Jamieson DJ, Powers AM, Honein MA. Zika Virus. N Engl J Med. 2016;374: 1552–1563. pmid:270285615. Staples JE, Breiman RF, Powers AM. Chikungunya fever: an epidemiological review of a re-emerging infectious disease. Clin Infect Dis Off Publ Infect Dis Soc Am. 2009;49: 942–948. pmid:196636046. Duffy MR, Chen T-H, Hancock WT, Powers AM, Kool JL, Lanciotti RS, et al. Zika Virus Outbreak on Yap Island, Federated States of Micronesia. N Engl J Med. 2009;360: 2536–2543. pmid:195160347. Donoso Mantke O, Lemmer K, Biel SS, Groen J, Schmitz H, Durand JP, et al. Quality control assessment for the serological diagnosis of dengue virus infections. J Clin Virol. 2004;29: 105–112. pmid:147470298. Noden BH, Musuuo M, Aku-Akai L, van der Colf B, Chipare I, Wilkinson R. Risk assessment of flavivirus transmission in Namibia. Acta Trop. 2014;137: 123–129. pmid:248657929. Martins AC, Pereira TM, Oliart-Guzmán H, Delfino BM, Mantovani SAS, et al. Seroprevalence and Seroconversion of Dengue and Implications for Clinical Diagnosis in Amazonian Children, Seroprevalence and Seroconversion of Dengue and Implications for Clinical Diagnosis in Amazonian Children. Interdiscip Perspect Infect Dis Interdiscip Perspect Infect Dis. 2014;2014: e703875. pmid:2554855810. Conlan JV, Vongxay K, Khamlome B, Jarman RG, Gibbons RV, Fenwick SG, et al. Patterns of Flavivirus Seroprevalence in the Human Population of Northern Laos. Am J Trop Med Hyg. 2015;93: 1010–1013. pmid:2630492511. Flamand C, Quenel P, Ardillon V, Carvalho L, Bringay S, Teisseire M. The epidemiologic surveillance of dengue-fever in French Guiana: when achievements trigger higher goals. Stud Health Technol Inform. 2011;169: 629–633. pmid:2189382412. Adde A, Roucou P, Mangeas M, Ardillon V, Desenclos J-C, Rousset D, et al. Predicting Dengue Fever Outbreaks in French Guiana Using Climate Indicators. PLOS Negl Trop Dis. 2016;10: e0004681. pmid:2712831213. Fritzell C, Raude J, Adde A, Dusfour I, Quenel P, Flamand C. Knowledge, Attitude and Practices of Vector-Borne Disease Prevention during the Emergence of a New Arbovirus: Implications for the Control of Chikungunya Virus in French Guiana. PLOS Negl Trop Dis. 2016;10: e0005081. pmid:2780227514. Flamand C, Fritzell C, Matheus S, Dueymes M, Carles G, Favre A, et al. The proportion of asymptomatic infections and spectrum of disease among pregnant women infected by Zika virus: systematic monitoring in French Guiana, 2016. Eurosurveillance. 2017;22.15. Fritzell C, Rousset D, Adde A, Kazanji M, Van Kerkhove MD, Flamand C (2018) Current challenges and implications for dengue, chikungunya and Zika seroprevalence studies worldwide: A scoping review. PLoS Negl Trop Dis 12(7): e0006533

Estimated protection against COVID-19 based on predicted neutralisation titres from multiple antibody measurements in a longitudinal cohort, France, April 2020 to November 2021

International audienceBackgroundThe risk of SARS-CoV-2 (re-)infection remains present given waning of vaccine-induced and infection-acquired immunity, and ongoing circulation of new variants.AimTo develop a method that predicts virus neutralisation and disease protection based on variant-specific antibody measurements to SARS-CoV-2 antigens.MethodsTo correlate antibody and neutralisation titres, we collected 304 serum samples from individuals with either vaccine-induced or infection-acquired SARS-CoV-2 immunity. Using the association between antibody and neutralisation titres, we developed a prediction model for SARS-CoV-2-specific neutralisation titres. From predicted neutralising titres, we inferred protection estimates to symptomatic and severe COVID-19 using previously described relationships between neutralisation titres and protection estimates. We estimated population immunity in a French longitudinal cohort of 905 individuals followed from April 2020 to November 2021.ResultsWe demonstrated a strong correlation between anti-SARS-CoV-2 antibodies measured using a low cost high-throughput assay and antibody response capacity to neutralise live virus. Participants with a single vaccination or immunity caused by infection were especially vulnerable to symptomatic or severe COVID-19. While the median reduced risk of COVID-19 from Delta variant infection in participants with three vaccinations was 96% (IQR: 94–98), median reduced risk among participants with infection-acquired immunity was only 42% (IQR: 22–66).ConclusionOur results are consistent with data from vaccine effectiveness studies, indicating the robustness of our approach. Our multiplex serological assay can be readily adapted to study new variants and provides a framework for development of an assay that would include protection estimates

SARS-CoV-2 infection in primary schools in northern France: A retrospective cohort study in an area of high transmission

Posté sur MedRxiv le 29 juin 2020Background: The extent of SARS-CoV-2 transmission among pupils in primary schools and their families is unknown.Methods: Between 28-30 April 2020, a retrospective cohort study was conducted among pupils, their parents and relatives, and staff of primary schools exposed to SARS-CoV-2 in February and March 2020 in a city north of Paris, France. Participants completed a questionnaire that covered sociodemographic information and history of recent symptoms. A blood sample was tested for the presence of anti-SARS-CoV-2 antibodies using a flow-cytometry-based assay.Results: The infection attack rate (IAR) was 45/510 (8.8%), 3/42 (7.1%), 1/28 (3.6%), 76/641 (11.9%) and 14/119 (11.8%) among primary school pupils, teachers, non-teaching staff, parents, and relatives, respectively (P = 0.29). Prior to school closure on February 14, three SARS-CoV-2 infected pupils attended three separate schools with no secondary cases in the following 14 days among pupils, teachers and non-teaching staff of the same schools. Familial clustering of cases was documented by the high proportion of antibodies among parents and relatives of infected pupils (36/59 = 61.0% and 4/9 = 44.4%, respectively). In children, disease manifestations were mild, and 24/58 (41.4%) of infected children were asymptomatic.Interpretation: In young children, SARS-CoV-2 infection was largely mild or asymptomatic and there was no evidence of onwards transmission from children in the school setting

Neutralising antibody responses to SARS-CoV-2 omicron among elderly nursing home residents following a booster dose of BNT162b2 vaccine: A community-based, prospective, longitudinal cohort study

International audienceBACKGROUND: 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 2(nd) and 3(rd) 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 23(rd), 2020 and April 29(th), 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

Cluster of COVID-19 in northern France: A retrospective closed cohort study

Posté sur MedRxiv le 23 avril 2020Background: The Oise department in France has been heavily affected by COVID-19 in early 2020.Methods: Between 30 March and 4 April 2020, we conducted a retrospective closed cohort study amongpupils, their parents and siblings, as well as teachers and non-teaching staff of a high-school located inOise. Participants completed a questionnaire that covered history of fever and/or respiratory symptomssince 13 January 2020 and had blood tested for the presence of anti-SARS-CoV-2 antibodies. Theinfection attack rate (IAR) was defined as the proportion of participants with confirmed SARS-CoV-2infection based on antibody detection. Blood samples from two blood donor centres collected between23 and 27 March 2020 in the Oise department were also tested for presence of anti-SARS-CoV-2antibodies.Findings: Of the 661 participants (median age: 37 years), 171 participants had anti-SARS-CoV-2antibodies. The overall IAR was 25.9% (95% confidence interval (CI) = 22.6-29.4), and the infectionfatality rate was 0% (one-sided 97.5% CI = 0 - 2.1). Nine of the ten participants hospitalised since midJanuary were in the infected group, giving a hospitalisation rate of 5.3% (95% CI = 2.4 –9.8). Anosmia and ageusia had high positive predictive values for SARS-CoV-2 infection (84.7% and 88.1%,respectively). Smokers had a lower IAR compared to non-smokers (7.2% versus 28.0%, P <0.001). Theproportion of infected individuals who had no symptoms during the study period was 17.0% (95% CI =11.2 – 23.4). The proportion of donors with anti-SARS-CoV-2 antibodies in two nearby blood banksof the Oise department was 3.0% (95% CI = 1.1 - 6.4).Interpretation: The relatively low IAR observed in an area where SARS-CoV-2 actively circulatedweeks before confinement measures indicates that establishing herd immunity will take time, and thatlifting these measures in France will be long and complex