Noninvasive detection of Zika virus in mosquito excreta sampled from wild mosquito populations in French Guiana.

Arboviruses can be difficult to detect in the field due to relatively low prevalence in mosquito populations. The discovery that infected mosquitoes can release viruses in both their saliva and excreta gave rise to low-cost methods for the detection of arboviruses during entomological surveillance. We implemented both saliva and excreta-based entomological surveillance during the emergence of Zika virus (ZIKV) in French Guiana in 2016 by trapping mosquitoes around households of symptomatic cases with confirmed ZIKV infection. ZIKV was detected in mosquito excreta and not in mosquito saliva in 1 trap collection out of 85 (1.2%). One female Ae. aegypti L. (Diptera: Culicidae) was found with a ZIKV systemic infection in the corresponding trap. The lag time between symptom onset in a ZIKV-infected individual living near the trap site and ZIKV detection in this mosquito was 1 wk. These results highlight the potential of detection in excreta from trapped mosquitoes as a sensitive and cost-effective method to non invasively detect arbovirus circulation.

Mortality Trend of Severe COVID-19 in Under-Vaccinated Population Admitted to ICU in French Amazonia.

(1) Background: Until December 2021, French Guiana (FG), located in South America, faced four consecutive COVID-19 epidemic waves. This study sought to analyze the mortality trend of severe COVID-19 patients admitted to the referral ICU of FG. (2) Methods: We conducted a prospective, observational, and non-interventional study in ICU at Cayenne Hospital. We included 383 patients older than 18 admitted with SARS-CoV-2-related pneumonia hospitalized from May 2020 to December 2021. The study covers three periods. Period 1 (Waves 1 and 2, original variant), period 2 (Wave 3, Gamma variant), and period 3 (Wave 4, Delta variant). (3) Results: The median age was 63 years (52-70). Frailty was diagnosed in 36 patients over 70 (32.4%). Only 4.8% of patients were vaccinated. The median ICU LOS was 10 days (6-19). Hospital mortality was 37.3%. It was 30.9% in period 1, 36.6% in period 2 (p = 0.329 vs. period 1), and 47.1% in period 3 (0.015 vs. period 1). In multivariate analysis, independent factors associated with hospital mortality included age greater than 40 years (]40-60 years] OR = 5.2, 95%CI: 1.4-19.5; (]60-70 years] OR = 8.5, 95%CI: 2.2-32; (]70+ years] OR = 17.9, 95%CI: 4.5-70.9), frailty (OR = 5.6, 95%CI: 2.2-17.2), immunosuppression (OR = 2.6, 95%CI: 1.05-6.7), and MV use (OR = 11, 95%CI: 6.1-19.9). This model had an overall sensitivity of 72%, a specificity of 80.4%, a positive predictive value of 68.7%, and a negative predictive value of 82.8%. (4) Conclusions: The mortality of severe COVID-19 patients in French Amazonia was higher during the Delta variant wave. This over-death could be explained by the virulence of the responsible SARS-CoV-2 variant and the under-vaccination coverage of the studied population.

Effect of the time to antivenom administration on recovery from snakebite envenoming-related coagulopathy in French Guiana.

BACKGROUND: Snakebite (SB) envenoming is an acute emergency requiring an early care delivery. We aimed to search for the time to reach healthcare facilities in various regions of French Guiana (FG) and to assess the impact of time to antivenom (AV) on the correction of coagulation parameters in these patients. METHODOLOGY: This is a prospective observational study conducted in Cayenne General Hospital between January 1st, 2016, and July 31st, 2022. We included all patients hospitalized for SB envenoming less than 48h after the bite, and receiving antivenom (AV). We assessed the time lapse between SB and medical attention and the time needed to return of the coagulation parameters to normal. PRINCIPAL FINDINGS: Overall, 119 patients were investigated, and 48.7% were from remote areas. The median time from SB to AV therapy was 09:15 h (05:32-17:47). The time was longer in patients from remote rural locations. AV was dispensed within the first six hours after the SB in 45 cases (37.8%). Time from SB to reaching normal plasma fibrinogen concentration was 23:27 h (20:00-27:10) in patients receiving AV≤6h vs. 31:23 h (24:00-45:05) in those receiving AV>6h (p<0.001). Whereas, the time from AV administration to reach normal fibrinogen dosage was similar in the two groups. CONCLUSIONS: Patients from rural settings in FG suffer from a delay in AV administration after SB envenoming leading to an extended time in which patients are coagulopathic. Once AV is administered, clotting parameters recover at a similar rate. Supplying remote healthcare facilities with AV and with medical teams trained on its use should be planned.

Emerging Maripa Hantavirus as a Potential Cause of a Severe Health Threat in French Guiana.

We describe the clinical parameters and management of nine confirmed cases of hantavirus pulmonary syndrome reported in French Guiana since 2008. All patients were admitted to Cayenne Hospital. Seven patients were men and the mean age was 48 years (range, 19-71 years). Two phases characterized the disease. The prodromal phase was characterized by fever (77.8%), myalgia (66.7%), and gastrointestinal symptoms (vomiting and diarrhea; 55.6%) starting, on average, 5 days before the illness phase, which was characterized by respiratory failure in all patients. Five patients died (55.6%) and the length of stay in the intensive care unit was 19 days (range, 11-28 days) for survivors. Detection of two back-to-back recent cases highlights the reason to screen for hantavirus infection during the nonspecific phase of the disease, in particular when concomitant pulmonary infection and digestive disorders are observed. Specific longitudinal serological surveys must also be used to identify other potential clinical forms of the disease in French Guiana.

Symptomatic Chikungunya Virus Infection and Pregnancy Outcomes: A Nested Case-Control Study in French Guiana.

During the Chikungunya epidemic in the Caribbean and Latin America, pregnant women were affected by the virus in French Guiana. The question of the impact of the virus on pregnancy was raised because of the lack of scientific consensus and published data in the region. Thus, during the Chikungunya outbreak in French Guiana, a comparative study was set up using a cohort of pregnant women. The objective was to compare pregnancy and neonatal outcomes between pregnant women with Chikungunya virus (CHIKV) infection and pregnant women without CHIKV. Of 653 mothers included in the cohort, 246 mothers were included in the case-control study: 73 had CHIKV fever during pregnancy and 173 had neither fever nor CHIKV during pregnancy. The study did not observe any severe clinical presentation of CHIKV in the participating women. There were no intensive care unit admissions. In addition, the study showed no significant difference between the two groups with regard to pregnancy complications. However, the results showed a potential excess risk of neonatal ICU admission of the newborn when the maternal infection occurred within 7 days before delivery. These results suggest that special attention should be paid to neonates whose mothers were infected with CHIKV shortly before delivery.

Characteristics of Snakebite-Related Infection in French Guiana.

Wound infection is frequently reported following snakebite (SB). This study is retrospective. It was conducted in the emergency department and the Intensive Care Unit (ICU) of Cayenne General Hospital between 1 January 2016 and 31 July 2021. We included 172 consecutive patients hospitalized for SB envenoming. All patients were monitored for wound infection. Sixty-three patients received antibiotics at admission (36.6%). The main antibiotic used was amoxicillin-clavulanate (92.1%). Wound infection was recorded in 55 cases (32%). It was 19% in grade 1, 35% in grade 2, and 53% in grade 3. It included abscess (69.1%), necrotizing fasciitis (16.4%), and cellulitis (21.8%). The time from SB to wound infection was 6 days (IQR: 3-8). The main isolated microorganisms were A. hydrophila and M. morganii (37.5% and 18.8% of isolated organisms). Surgery was required in 48 patients (28.1%), and a necrosectomy was performed on 16 of them (33.3%). The independent factors associated with snakebite-associated infection were necrosis (p < 0.001, OR 13.15, 95% CI: 4.04-42.84), thrombocytopenia (p = 0.002, OR: 3.37, 95% CI: 1.59-7.16), and rhabdomyolysis (p = 0.046, OR: 2.29, 95% CI: 1.02-5.19). In conclusion, wound infection following SB is frequent, mainly in grade 2 and 3 envenomed patients, especially those with necrosis, thrombocytopenia, and rhabdomyolysis. The main involved bacteria are A. hydrophila and M. morganii.

Mayaro virus infection in French Guiana, a cross sectional study 2003-2019.

Mayaro Virus is an emerging arbovirus which can be responsible of important outbreaks in tropical regions. A retrospective study was performed in French Guiana, an ultraperipheral region of Europe in Amazonia. We identified 17 human cases between 2003 and 2019. The clinical and biological picture was close to Chikungunya with fever and arthralgia. One patient had acute meningo-encephalitis, and 4 had persistent arthralgia. Physicians should be aware of this virus, as imported cases in Europe have already occurred. AUTHOR SUMMARY: Latin America has experienced several epidemics of arboviruses in recent years, some known for a long time, such as the dengue virus, and others of more recent introduction such as the chikungunya or Zika viruses. There are other arboviruses for the moment more discreet which are rife with low noise in several countries of the continent, such as the Mayaro virus. This alphavirus, with a presentation similar to that of the chikungunya virus, is currently confined to transmission by forest mosquitoes, but its potential to be transmitted by coastal mosquitoes such as Aedes aegypti, make it a potential candidate for a continent-wide epidemic. It therefore seems necessary to know this virus as well as possible in order to anticipate the occurrence of a possible new epidemic. We present here a both demographic and clinical study of this endemic arbovirus disease in French Guiana.

Evaluation of the diagnostic capacities for emerging arboviral diseases in the international network MediLabSecure from 2014 to 2018 - Importance of external quality assessments.

BACKGROUND: Emerging infectious diseases pose an increasing threat to all nations around the world, including to developed countries. By definition, because they are rare or unknown, public health systems are not well prepared against these emerging diseases. To be fully prepared, countries must have implemented surveillance systems to monitor rare or unusual sanitary events. METHODS: The capacity of diagnostic laboratories is a key component of surveillance systems since they are in charge of identifying the pathogens responsible for outbreaks in a timely manner. The MediLabSecure project aims at implementing a comprehensive surveillance system for vector-borne diseases around the Mediterranean and Black Sea regions. From 2014 to 2018, the human-virology group of MediLabSecure notably supported the implementation of molecular diagnostic capacities for eight arboviruses and one coronavirus in 19 laboratories of its network through sharing of protocols and reagents, and technical training of the scientific staff of beneficiary laboratories. RESULTS: We report the results of External Quality Assessments for four of these viruses to assess the efficiency of the diagnostic for these threats emerging in the geographic area. The results for these EQA demonstrate the success of the project in the implementation of diagnostic technics for the identification of Dengue, Chikungunya, Zika, and West Niles viruses in laboratories that did not have the capacity before. However, results also show that some work is still to be done to strengthen the newly acquired capacity. CONCLUSION: The MediLabSecure project deployed an effort to build an efficient capacity in identifying and survey the emergence of arboviruses in the Mediterranean area. Diagnostic technics were successfully implemented in many of the laboratories of the network, but the effort must be maintained over time to strengthen these capacities.

Impact of Antibiotic Consumption on the Acquisition of Extended-Spectrum ß-Lactamase Producing Enterobacterales Carriage during the COVID-19 Crisis in French Guiana.

(1) Background: During the COVID-19 outbreak, several studies showed an increased prevalence of extended-spectrum ß-lactamase producing Enterobacterales (ESBL-PE) carriage in intensive care units (ICUs). Our objective was to assess the impact of antibiotic prescriptions on the acquisition of ESBL-PE in ICUs during the COVID-19 crisis. (2) Methods: We conducted an observational study between 1 April 2020, and 31 December 2021, in the medical-surgical ICU of the Cayenne General Hospital. We defined two periods: Period 1 with routine, empirical antibiotic use, and Period 2 with no systematic empiric antibiotic prescription. (3) Results: ICU-acquired ESBL-PE carriage was 22.8% during Period 1 and 9.4% during Period 2 (p = 0.005). The main isolated ESBL-PE was Klebsiella pneumoniae (84.6% in Period 1 and 58.3% in Period 2). When using a generalized linear model with a Poisson family, exposure to cefotaxime was the only factor independently associated with ESBL-PE acquisition in ICU (p = 0.002, IRR 2.59 (95% IC 1.42-4.75)). The propensity scores matching estimated the increased risk for cefotaxime use to acquire ESBL-PE carriage at 0.096 (95% CI = 0.02-0.17), p = 0.01. (4) Conclusions: Exposure to cefotaxime in patients with severe COVID-19 is strongly associated with the emergence of ESBL-PE in the context of maximal infection control measures.

Prolonged Maternal Zika Viremia as a Marker of Adverse Perinatal Outcomes.

Whether prolonged maternal viremia after Zika virus infection represents a risk factor for maternal-fetal transmission and subsequent adverse outcomes remains unclear. In this prospective cohort study in French Guiana, we enrolled Zika virus-infected pregnant women with a positive PCR result at inclusion and noninfected pregnant women; both groups underwent serologic testing in each trimester and at delivery during January-July 2016. Prolonged viremia was defined as ongoing virus detection >30 days postinfection. Adverse outcomes (fetal loss or neurologic anomalies) were more common in fetuses and neonates from mothers with prolonged viremia (40.0%) compared with those from infected mothers without prolonged viremia (5.3%, adjusted relative risk [aRR] 7.2 [95% CI 0.9-57.6]) or those from noninfected mothers (6.6%, aRR 6.7 [95% CI 3.0-15.1]). Congenital infections were confirmed more often in fetuses and neonates from mothers with prolonged viremia compared with the other 2 groups (60.0% vs. 26.3% vs. 0.0%, aRR 2.3 [95% CI 0.9-5.5]).

Modeling intra-mosquito dynamics of Zika virus and its dose-dependence confirms the low epidemic potential of Aedes albopictus.

Originating from African forests, Zika virus (ZIKV) has now emerged worldwide in urbanized areas, mainly transmitted by Aedes aegypti mosquitoes. Although Aedes albopictus can transmit ZIKV experimentally and was suspected to be a ZIKV vector in Central Africa, the potential of this species to sustain virus transmission was yet to be uncovered until the end of 2019, when several autochthonous transmissions of the virus vectored by Ae. albopictus occurred in France. Aside from these few locally acquired ZIKV infections, most territories colonized by Ae. albopictus have been spared so far. The risk level of ZIKV emergence in these areas remains however an open question. To assess Ae. albopictus' vector potential for ZIKV and identify key virus outbreak predictors, we built a complete framework using the complementary combination of (i) dose-dependent experimental Ae. albopictus exposure to ZIKV followed by time-dependent assessment of infection and systemic infection rates, (ii) modeling of intra-human ZIKV viremia dynamics, and (iii) in silico epidemiological simulations using an Agent-Based Model. The highest risk of transmission occurred during the pre-symptomatic stage of the disease, at the peak of viremia. At this dose, mosquito infection probability was estimated to be 20%, and 21 days were required to reach the median systemic infection rates. Mosquito population origin, either temperate or tropical, had no impact on infection rates or intra-host virus dynamic. Despite these unfavorable characteristics for transmission, Ae. albopictus was still able to trigger and yield large outbreaks in a simulated environment in the presence of sufficiently high mosquito biting rates. Our results reveal a low but existing epidemic potential of Ae. albopictus for ZIKV, that might explain the absence of large scale ZIKV epidemics so far in territories occupied only by Ae. albopictus. They nevertheless support active surveillance and eradication programs in these territories to maintain the risk of emergence to a low level.

Rapid Genomic Characterization of SARS-CoV-2 by Direct Amplicon-Based Sequencing Through Comparison of MinION and Illumina iSeq100TM System.

Global human health is increasingly challenged by emerging viral threats, especially those observed over the last 20 years with coronavirus-related human diseases, such as the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome (MERS). Recently, in late December 2019, a novel Betacoronavirus, SARS-CoV-2, originating from the Chinese city of Wuhan, emerged and was then identified as the causative agent of a new severe form of pneumonia, COVID-19. Real-time genome sequencing in such viral outbreaks is a key issue to confirm identification and characterization of the involved pathogen and to help establish public health measures. Here, we implemented an amplicon-based sequencing approach combined with easily deployable next-generation sequencers, the small and hand-held MinION sequencer and the latest most compact Illumina sequencer, the iSeq100TM system. Our results highlighted the great potential of the amplicon-based approach to obtain consensus genomes of SARS-CoV-2 from clinical samples in just a few hours. Both these mobile next-generation sequencers are proven to be efficient to obtain viral sequences and easy to implement, with a minimal laboratory environment requirement, providing useful opportunities in the field and in remote areas.

First report of human Leptospira santarosai infection in French Guiana.

Leptospirosis is a zoonotic disease with worldwide distribution. In French Guiana, a French overseas department of South America, this bacterial infection is endemic with the increase of human cases since the last 5 years. Nevertheless, the epidemiological data on the circulating infecting strain remains scarce due to the lack of specific symptoms and the used diagnostic approaches. We report a severe case of leptospirosis in a 52-years-old male, working as a street cleaner, hospitalized at the Intensive Care Unit of city capital hospital of French Guiana because of hemodynamic, neurological, renal, and respiratory failure. At ICU admission, the patient was comatose, his temperature was 37.3°C, heart rate 104 beats per minute, blood pressure 84/45mmHg, and oxygen saturation 95% while under mechanical ventilation. Retrospective exploration using molecular and serological approaches from the samples allowed reporting an infection by Leptospira santarosai serogroup Sejroe serovar Hardjo. To our knowledge, this is the first human case infected with this species in French Guiana. Through these analyses, this report provides new epidemiological information about the Leptospira strains circulating in French Guiana. In particular, this emphasizes the importance of accurate diagnosis to characterize with more precision the circulating Leptospira strains in this department.

ZIKA Virus infection in pregnant women in French Guiana: More precarious-more at risk.

BACKGROUND: A recent study in French Guiana suggested that populations living in precarious neighborhoods were more at risk for Chikungunya CHIKV than those living in more privileged areas. The objective of the present study was to test the hypothesis that Zika virus (ZIKV) infection was more frequent in precarious pregnant women than in non-precarious pregnant women, as reflected by their health insurance status. METHODS: A multicentric cross-sectional study was conducted in Cayenne hospital including ZIKV pregnant women with serological or molecular proof of ZIKV during their pregnancy between January and December 2016. Health insurance information was recorded at delivery, which allowed separating women in: undocumented foreigners, precarious but with residence permit, and non-precarious. RESULTS: A total of 6654 women were included. Among them 1509 (22,7%) had confirmed ZIKV infection. Most women were precarious (2275/3439) but the proportion of precarious women was significantly greater in ZIKV-confirmed 728/906 (80.4%) than the ZIKV-negatives 1747/2533 (69.0%), p<0.0001. There were 1142 women classified as non-precarious, 1671 were precarious legal residents, and 1435 were precarious and undocumented. Precariousness and undocumented status were associated with a higher prevalence of ZIKV during pregnancy (adjusted prevalence ratio = 1.59 (95%CI = 1.29-1.97), p<0.0001), (adjusted prevalence ratio = 1.5 (95%CI = 1.2-1.8), p<0.0001), respectively. CONCLUSIONS: These results illustrate that in French Guiana ZIKV transmission disproportionately affected the socially vulnerable pregnant women, presumably because of poorer housing conditions, and lack of vector control measures in poor neighborhoods.

Discriminating Tonate Virus from Dengue Virus Infection: A Matched Case-Control Study in French Guiana, 2003-2016.

Tonate virus (TONV) is an arbovirus discovered in 1973 in French Guiana (FG) belonging to the Venezuelan equine encephalitis virus complex, Alphavirus genus. Only few publications and cases have been reported in FG. The objectives of the present study were to describe the clinical picture of TONV and to compare its presentation with that of dengue virus (DENV). A retrospective study was performed in Cayenne hospital from 2003 to 2016 including all patients exclusively positive for TONV IgM and not for other alphaviruses. They were classified as high probability: typical clinical picture of arbovirus infection (i.e., fever, chills, headaches, muscle, and joint pains) and IgM seroconversion; medium probability: typical clinical picture + single positive IgM on a unique serum sample without control; and low probability: atypical clinical picture of infection and single positive IgM. Only patients with high and medium probability were included in the analysis and compared with a gender- and age-matched control group of DENV diagnosed by NS1 antigen (two controls per case). During the study period, 45 cases of TONV were included and compared with 90 cases of DENV. Twenty-eight (62.2%) were men; the median age was 34 years (IQ [22-49]). In the bivariate analysis, variables significantly associated with TONV versus DENV were the presence of cough (33.3% versus 10.3%) and anemia (32.5% versus 11.1%) and the absence of nausea (4.4% versus 32.2%), rash (2.2% versus 27.4%), fatigue (17.8% versus 41.0%), anorexia (6.7% versus 30.1%), muscle pain (42.2% versus 61.4%), headache (53.3% versus 70.8%), leukopenia (9.8% versus 44.4), and lymphopenia (42.5% versus 89.9%). There were no cases with severe neurological involvement, and there were no deaths. Tonate virus may be evoked as a cause of fever in patients living or returning from the Amazonian area. Positive TONV IgM does not prove the diagnosis and should not preclude from searching for alternative infectious diagnoses.

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.

Performance of 2 Commercial Serologic Tests for Diagnosing Zika Virus Infection.

Reliable serologic tests are needed for diagnosis and surveillance of Zika virus infection. We evaluated the Euroimmun and Dia.Pro serologic tests for detection of Zika virus IgM and IgG by using a panel of 199 samples from a region endemic for flaviviruses. Kinetics of Zika virus antibodies were monitored from 300 sequential specimens sampled over a period of 10 months after infection. We observed suboptimal performance; sensitivity for Zika virus IgM was low, especially in the Euroimmun assay (49%), whereas IgM could be detected for months with the Dia.pro assay. The specificity of the Zika virus IgG assays was also low, especially that of Dia.Pro (62%); findings were strongly influenced by the epidemiologic context. These results highlight the complexity of serologic diagnosis of Zika virus infection in regions endemic for flaviviruses. Accurate analysis of the performance of assays is required to adapt and interpret algorithms.

Capillary leak-syndrome triggered by Maripa virus in French Guiana: case report and implication for pathogenesis.

BACKGROUND: We report hereby a severe case of Hantavirus Pulmonary Syndrome" (HPS) induced by Maripa virus in French Guiana and describe the mechanism of severity of the human disease. CASE PRESENTATION: A 47-year- old patient started presenting a prodromic period with fever, dyspnea, cough and head ache. This clinical presentation was followed by a rapid respiratory, hemodynamic and renal failure leading to admission in the ICU. Biological exams revealed an increased haematocrit level with a paradoxical low protein level. Echocardiographic and hemodynamic monitoring showed a normal left ventricular function with low filling pressures, an elevated extravascular lung water index and pulmonary vascular permeability index. These findings were compatible with a capillary leak-syndrome (CLS). CONCLUSIONS: The severity of HPS caused by the virus Maripa in French Guiana can be explained by the tropism of hantavirus for the microvascular endothelial cell leading to a CLS.

Evolution of symptoms and quality of life during Zika virus infection: A 1-year prospective cohort study.

BACKGROUND: Although the complications of Zika virus infection have been well described, the clinical pattern has not been reported in enough detail to differentiate this infection from those with other arboviroses, and no longitudinal study has yet been published on the persistence of symptoms and quality of life. OBJECTIVES: were to describe bio-clinical pattern and quality of life during ZIKV infection, and their evolution. STUDY DESIGN: We present a 1-year clinical follow-up of 49 people infected with Zika virus in French Guiana, for whom the diagnosis was confirmed by RT-PCR in serum or urine. RESULTS: Fever was inconsistent (95% confidence interval (CI), 39-67). Exanthema (CI, 84-100) was maculopapular, with pruritus and conjunctivitis, variable over time and disappeared 12 days after the onset of symptoms (CI, 10-14). Joint pain (CI, 39-67) occurred mainly in the hands, wrists, knees and ankles and lasted for 10 days (CI, 7-13). Asthenia (CI, 61-85) scored low (3/10) but lasted for 19 days (CI, 16-22). The last two symptoms strongly limited patients' activities in the acute stage of the disease (RAPID-3 score, CI, 5-8). None of the patients had neurological complications, but 41% (CI, 27-55) had areflexia during the first month. CONCLUSIONS: We found no real chronic evolution or decreased quality of life, function or ability to work from the first month after symptom onset.

Maternal-fetal transmission and adverse perinatal outcomes in pregnant women infected with Zika virus: prospective cohort study in French Guiana.

OBJECTIVES: To estimate the rates of maternal-fetal transmission of Zika virus, adverse fetal/neonatal outcomes, and subsequent rates of asymptomatic/symptomatic congenital Zika virus infections up to the first week of life. DESIGN: Cohort study with prospective data collection and subsequent review of fetal/neonatal outcomes. SETTINGS: Referral centre for prenatal diagnosis of the French Guiana Western Hospital. PARTICIPANTS: Pregnant women at any stage of pregnancy with a laboratory confirmed symptomatic or asymptomatic Zika virus infection during the epidemic period in western French Guiana. The cohort enrolled 300 participants and prospectively followed their 305 fetuses/newborns. MAIN OUTCOME MEASURES: Rate of maternal-fetal transmission of Zika virus (amniotic fluid, fetal and neonatal blood, urine, cerebrospinal fluid, and placentas); clinical, biological, and radiological outcomes (blindly reviewed); and adverse outcomes defined as moderate signs potentially related to congenital Zika syndrome (CZS), severe complications compatible with CZS, or fetal loss. Associations between a laboratory confirmed congenital Zika virus infection and adverse fetal/neonatal outcomes were evaluated. RESULTS: Maternal-fetal transmission was documented in 26% (76/291) of fetuses/newborns with complete data. Among the Zika virus positive fetuses/newborns, 45% (34/76) presented with no signs/complications at birth, 20% (15/76) with moderate signs potentially related to CZS, 21% (16/76) with severe complications compatible with CZS, and 14% (11/76) with fetal loss. Compared with the Zika virus positive fetuses/neonates, those that were identified as negative for Zika virus (215/291) were less likely to present with severe complications (5%; 10/215) or fetal loss (0.5%; 1/215; relative risk 6.9, 95% confidence interval 3.6 to 13.3). Association between a positive Zika virus test and any adverse fetal/neonatal outcome was also significant (relative risk 4.4, 2.9 to 6.6). The population attributable fraction estimates that a confirmed congenital Zika virus infection contributes to 47% of adverse outcomes and 61% of severe adverse outcomes observed. CONCLUSION: In cases of a known maternal Zika virus infection, approximately a quarter of fetuses will become congenitally infected, of which a third will have severe complications at birth or fetal loss. The burden of CZS might be lower than initially described in South America and may not differ from other congenital infections.