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Zika Virus and Its Associated Diseases Zika is a mosquito-borne flavivirus that can cause congenital defects, including microcephaly. Although most Zika virus infections are asymptomatic, rash, fev...

Zika virus (ZIKV), a vector-borne virus similar to dengue virus, was responsible for a global epidemic between 2013 and 2017 and has emerged as a new agent responsible for severe fetopathies. We present a review to describe the risks and complications of maternal and subsequent fetal infection by ZIKV. The risk of ZIKV infection during pregnancy depends on the incidence of the disease, which is highly variable in different affected geographic areas (less than 1% to 75%). Among infected pregnant women, the risk of any adverse fetal/neonatal outcome was estimated at 5% to 42%, with 1% to 4% of fetal loss and 4% to 9% of suspected congenital Zika syndrome (CZS). The estimated rate of maternal-fetal transmission ranges between 7% and 26%, depending on the methodology of the study. Findings associated with CZS are microcephaly (33%-64%), ventriculomegaly (63%-92%), calcifications (71%-92%), malformations of cortical development (79%-82%), anomalies of the corpus callosum (71%-100%) and of the posterior fossa (21%-82%), arthrogryposis (10%-25%), eye abnormalities (25%), and extra-neurologic signs such as intra uterine growth restriction (14%), placentomegaly, transient hepatitis, mild anemia. Infants who present with CZS at birth suffer from motor abnormalities (77%-100%), epilepsy (9%-54%), hearing loss, and neurologic impairments. Prenatal ultrasound with advanced neurosonography and appropriate virological follow-up represent the state-of-the art approach to adequately monitor at-risk pregnancies, in order to diagnose early signs of CZS and to inform parents about the neonatal prognosis.

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International audience; Zika and chikungunya viruses were first detected in Fiji in 2015. Examining surveillance and phylogenetic and serologic data, we found evidence of low-level transmission of Zika and chikungunya viruses during 2013-2017, in contrast to the major outbreaks caused by closely related virus strains in other Pacific Island countries.

International audience; Congenital Zika virus syndrome consists of a large spectrum of neurologic abnormalities seen in infants infected with Zika virus in utero. However, little is known about the effects of Zika virus intrauterine infection on the neurocognitive development of children born without birth defects. Using a case-control study design, we investigated the temporal association of a cluster of congenital defects with Zika virus infection. In a nested study, we also assessed the early childhood development of children recruited in the initial study as controls who were born without known birth defects,. We found evidence for an association of congenital defects with both maternal Zika virus seropositivity (time of infection unknown) and symptomatic Zika virus infection during pregnancy. Although the early childhood development assessment found no excess burden of developmental delay associated with maternal Zika virus infection, larger, longer-term studies are needed.

Zika virus was discovered in East Africa in 1947 by the Rockefeller Foundation during investigations on the ecology of yellow fever. Although it was subsequently shown to have widespread distribution in Africa and Asia, it was not known to cause epidemics until 2007. This paper describes the history of the virus discovery, emergence and evolution as an epidemic virus, and the its evolving clinical spectrum.

Summary The epidemic history of Zika virus began in 2007, with its emergence in Yap Island in the western Pacific, followed in 2013–14 by a larger epidemic in French Polynesia, south Pacific, where the first severe complications and non-vector-borne transmission of the virus were reported. Zika virus emerged in Brazil in 2015 and was declared a national public health emergency after local researchers and physicians reported an increase in microcephaly cases. In 2016, WHO declared the recent cluster of microcephaly cases and other neurological disorders reported in Brazil a global public health emergency. Similar clusters of microcephaly cases were also observed retrospectively in French Polynesia in 2014. In 2015–16, Zika virus continued its spread to cause outbreaks in the Americas and the Pacific, and the first outbreaks were reported in continental USA, Africa, and southeast Asia. Non-vector-borne transmission was confirmed and Zika virus was established as a cause of severe neurological complications in fetuses, neonates, and adults. This Review focuses on important updates and gaps in the knowledge of Zika virus as of early 2017.

BACKGROUND Between October 2013 and March 2014, French Polynesia experienced the largest Zika virus (ZIKV) outbreak ever described before the emergence of ZIKV in the Americas in 2015. As arbovirus transfusion-transmitted (TT) infections have been previously reported, we hypothesized that transfusion of blood products could also transmit ZIKV. STUDY DESIGN AND METHODS Mitigation strategies to prevent ZIKV-TT infections included nonspecific measures and the implementation of a laboratory developed ZIKV-specific nucleic acid testing (NAT) assay. Donor sera were tested in pools of 3 and constitutive sera of ZIKV-reactive pools were tested individually. Donor sera were tested prospectively and retrospectively. A posttransfusion follow-up of a patient transfused with ZIKV RNA–reactive blood products was implemented. RESULTS NAT detected 42 blood donor sera as ZIKV RNA reactive of 1505 tested (2.8%). Thirty ZIKV RNA–reactive blood products collected before the implementation of NAT were transfused to 26 recipients. Posttransfusion investigations were conducted by the hemovigilance unit and data were available for 12 recipients. Symptomatic ZIKV-TT infections were not reported. CONCLUSION Predonation screening of blood donors, postdonation information, products discard, and quarantine of blood products were not effective enough to prevent transfusion of ZIKV RNA–reactive blood products. ZIKV NAT was an effective measure once implemented to prevent transfusion of ZIKV RNA–reactive blood products but it is difficult to evaluate the effectiveness of this measure to prevent ZIKV-TT infection, which is a rare event.

BACKGROUND The potential for Zika virus (ZIKV) transfusion-transmission (TT) has been demonstrated in French Polynesia and Brazil. Pathogen inactivation (PI) of blood products is a proactive strategy to inactivate TT pathogens including arboviruses. Inactivation of West Nile, dengue, Zika, and chikungunya viruses was previously demonstrated by photochemical treatment with amotosalen and ultraviolet A (UVA) illumination. In this study, we evaluated ZIKV inactivation in red blood cell (RBC) components by a chemical approach that uses amustaline (S-303) and glutathione (GSH). STUDY DESIGN AND METHODS RBC components were spiked with a high titer of ZIKV. Viral titers (infectivity) and ZIKV RNA loads (reverse transcription–polymerase chain reaction) were measured in spiked RBCs before and after S-303 and GSH treatment and confirmed using repetitive passages in cell culture. A mock-treated arm validated the approach by demonstrating stability of the virus (infectivity and RNA load) during the process. RESULTS The mean ZIKV infectivity titer and RNA load in RBCs were 5.99 ± 0.2 log 50% tissue culture infectious dose (TCID50)/mL and 7.75 ± 0.16 log genomic equivalents/mL before inactivation. No infectivity was detected immediately after S-303 and GSH treatment and after five serial passages in cell culture. CONCLUSION Complete ZIKV inactivation of more than 5.99 log TCID50/mL in RBCs was achieved using S-303 and GSH at levels higher than those found in asymptomatic ZIKV-infected blood donors. Therefore, the S-303 and GSH PI system is promising for mitigating the risk of ZIKV TT.

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Background: Differential diagnosis between acute-phase Zika and dengue is challenging because of a similar clinical presentation and the lack of available molecular diagnosis tools in most of endemic areas. Objectives: Our study aimed to evaluate the use of simple laboratory parameters to differentiate these infections. Methods: We retrospectively compared simple hematology and biochemistry values in 81 and 341 patients with confirmed Zika and dengue, respectively, collected from June 2013 to March 2014 during the French Polynesia outbreaks. Results: Thrombocytopenia, neutropenia, leukopenia, lymphopenia, and elevated aspartate aminotransaminases were significantly more frequent in dengue than in Zika (p < 0.001). Platelets 9/L, neutrophils 9/L, lymphocytes 9/L, and aspartate aminotransaminases >100 IU/mL were found in dengue but not in Zika. The positive predictive value of the ­association of leukocytes 9/L + lymphocytes 9/L + aspartate aminotransaminases >40 IU/mL for the diagnosis of dengue was 90%, with an accuracy of 82.4%. Conclusion: For the differential diagnosis between acute-phase Zika and dengue, there is no specific standard laboratory pattern. We identified cutoff values and a combination of laboratory parameters that are a strong argument against Zika and in favor of dengue.

Rationale for reviewYoung adults of childbearing age and pregnant women are travelling more frequently to tropical areas, exposing them to specific arboviral infections such as dengue, zika and chikungunya viruses, which may impact ongoing and future pregnancies. In this narrative review, we analyse their potential consequences on pregnancy outcomes and discuss current travel recommendations.Main findingsDengue virus may be associated with severe maternal complications, particularly post-partum haemorrhage. Its association with adverse fetal outcomes remains unclear, but prematurity, growth retardation and stillbirths may occur, particularly in cases of severe maternal infection. Zika virus is a teratogenic infectious agent associated with severe brain lesions, with similar risks to other well-known TORCH pathogens. Implications of chikungunya virus in pregnancy are mostly related to intrapartum transmission that may be associated with severe neonatal infections and long-term morbidity.Travel recommendationsFew agencies provide specific travel recommendations for travelling pregnant patients or couples trying to conceive and discrepancies exist, particularly regarding Zika virus prevention. The risks significantly depend on epidemiological factors that may be difficult to predict. Prevention relies principally on mosquito control measures. Couples trying to conceive and pregnant women should receive adequate information about the potential risks. It seems reasonable to advise pregnant women to avoid unnecessary travel to Aedes spp. endemic regions. The current rationale to avoid travel and delay conception is debatable in the absence of any epidemic. Post-travel laboratory testing should be reserved for symptomatic patients.

BACKGROUND Zika virus (ZIKV) is an emerging mosquito-borne Flavivirus of major public health concern. The potential for ZIKV transmission by blood transfusion has been demonstrated; however, inactivation or removal of ZIKV during the manufacture of plasma-derived medicinal products has not been specifically investigated. STUDY DESIGN AND METHODS Inactivation of ZIKV by pasteurization and solvent/detergent (S/D) treatment was investigated by spiking high-titer ZIKV stocks into human serum albumin and applying either heat or adding different mixtures of S/D reagents and assaying for infectious virus particles. Removal of ZIKV was evaluated using filters of differing pore sizes (75, 40, 35, and 19 nm), assaying for infectious virus and RNA. Electron microscopy was performed to determine the size of ZIKV particles. Neutralization of virus infectivity by immunoglobulins was investigated. RESULTS ZIKV was effectively and rapidly inactivated by liquid heat treatment as well as by various mixtures of S/D reagents with reduction factors more than 4 log, in each case. Effective reduction of ZIKV infectivity was demonstrated for virus filtration for filters with average pore sizes of not more than 40 nm, although a significant proportion of virus RNA was detected in the 40- to 35-nm filtrates likely due to the presence of subviral particles observed by electron microscopy. None of the immunoglobulin preparations investigated neutralized ZIKV infectivity. CONCLUSIONS Pasteurization and S/D treatment very rapidly inactivated ZIKV and filters with a pore size of not more than 40 nm removed all infectious ZIKV, demonstrating the effectiveness of these virus reduction strategies used during the manufacture of plasma-derived medicinal products.

SUMMARY Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the genus Flavivirus and the family Flaviviridae . ZIKV was first isolated from a nonhuman primate in 1947 and from mosquitoes in 1948 in Africa, and ZIKV infections in humans were sporadic for half a century before emerging in the Pacific and the Americas. ZIKV is usually transmitted by the bite of infected mosquitoes. The clinical presentation of Zika fever is nonspecific and can be misdiagnosed as other infectious diseases, especially those due to arboviruses such as dengue and chikungunya. ZIKV infection was associated with only mild illness prior to the large French Polynesian outbreak in 2013 and 2014, when severe neurological complications were reported, and the emergence in Brazil of a dramatic increase in severe congenital malformations (microcephaly) suspected to be associated with ZIKV. Laboratory diagnosis of Zika fever relies on virus isolation or detection of ZIKV-specific RNA. Serological diagnosis is complicated by cross-reactivity among members of the Flavivirus genus. The adaptation of ZIKV to an urban cycle involving humans and domestic mosquito vectors in tropical areas where dengue is endemic suggests that the incidence of ZIKV infections may be underestimated. There is a high potential for ZIKV emergence in urban centers in the tropics that are infested with competent mosquito vectors such as Aedes aegypti and Aedes albopictus .

International audience; Introduction: Zika virus (ZIKV) recently emerged as a global public health emergency of international concern. ZIKV is responsible for severe neurological complications in adults and infection during pregnancy and can lead to congenital Zika syndrome. There is no licensed vaccine or drug to prevent or treat ZIKV infection.Areas covered: The aim of this article is to provide an overview and update of the progress of research on anti-ZIKV vaccine and medications until the end of 2017, with a special emphasis on drugs that can be used during pregnancy.Expert commentary: Development of new vaccines and drugs is challenging and several points particular to ZIKV infections augment this difficulty: (1) Cross-reactions between ZIKV and other flaviviruses, the impact of ZIKV vaccination on subsequent flavivirus infections, and vice-versa, is unknown, (2) Drugs against ZIKV should be safe in pregnant women, and (3) Evaluation of the efficacy of vaccine and drugs against ZIKV in clinical trials phase II-IV will be complicated due to the decline of ZIKV circulation.

The unexpected emergence of Zika virus (ZIKV) in the Pacific Islands and Latin America and its association with congenital Zika virus syndrome (CZVS) (which includes microcephaly) and Guillain-Barré syndrome (GBS) have stimulated wide-ranging research. High densities of susceptible Aedes spp., immunologically naive human populations, global population growth with increased urbanization, and escalation of global transportation of humans and commercial goods carrying vectors and ZIKV undoubtedly enhanced the emergence of ZIKV. However, flavivirus mutations accumulate with time, increasing the likelihood that genetic viral differences are determinants of change in viral phenotype. Based on comparative ZIKV complete genome phylogenetic analyses and temporal estimates, we identify amino acid substitutions that may be associated with increased viral epidemicity, CZVS, and GBS. Reverse genetics, vector competence, and seroepidemiological studies will test our hypothesis that these amino acid substitutions are determinants of epidemic and neurotropic ZIKV emergence.

BACKGROUND Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) transmitted by mosquitoes. The potential for ZIKV transmission through blood transfusion was demonstrated during the ZIKV outbreak that occurred in French Polynesia from October 2013 to April 2014. Pathogen inactivation of blood products is a proactive strategy that provides the potential to reduce transfusion-transmitted diseases. Inactivation of arboviruses by amotosalen and ultraviolet A (UVA) illumination was previously demonstrated for chikungunya, West Nile, and dengue viruses. We report here the efficiency of this process for ZIKV inactivation of human plasma. STUDY DESIGN AND METHODS Plasma units were spiked with ZIKV. Viral titers and RNA loads were measured in plasma before and after amotosalen and UVA photochemical treatment. RESULTS The mean ZIKV titers and RNA loads in plasma before inactivation were respectively 6.57 log TCID50/mL and 10.25 log copies/mL. After inactivation, the mean ZIKV RNA loads was 9.51 log copies/mL, but cell cultures inoculated with inactivated plasma did not result in infected cells and did not produce any replicative virus after one passage, nor detectable viral RNA from the second passage. CONCLUSION In this study we demonstrate that amotosalen combined with UVA light inactivates ZIKV in fresh-frozen plasma. This inactivation process is of particular interest to prevent plasma transfusion-transmitted ZIKV infections in areas such as French Polynesia, where several arboviruses are cocirculating.

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While Zika virus (ZIKV) circulated for decades (African lineage strains) without report of outbreaks and severe complications, its emergence in French Polynesia and subsequently in the Americas (Asian lineage strains) was associated with description of severe neurological defects in newborns/neonates and adults. With the aim to identify virus lineage-dependent factors, we compared cell susceptibility, virus replication, cell death and innate immune responses following infection with two African and three contemporary Asian lineage strains of ZIKV. To this end, we used green monkey Vero and Aedes albopictus C6/36 cells and human monocyte-derived dendritic cells (DCs). The latter are involved in the pathogenesis of several mosquito-borne Flavivirus infections. In Vero and C6/36 cells, we observed strain- but not lineage-dependent differences in infection profiles. Nevertheless, in human DCs, no significant differences in susceptibility and virus replication were found between lineages and strains. ZIKV induced antiviral interferon type I/III in a limited fashion, with the exception of one African strain. None of the strains induced cell death or DC maturation in terms of MHC II, CD40, CD80/86 or CCR7 expression. Taken together, our data suggest that a large collection of virus isolates needs to be investigated before conclusions on lineage differences can be made.

International audience; Based on serological evidence and viral isolation, Zika virus (ZIKV) has circulated for many years relatively benignly in a sylvatic cycle in Africa and an urban cycle in South East Asia (SEA). With the recent availability of limited but novel Indian ZIKV sequences to add to the plethora of SEA sequences, we traced the phylogenetic history and spatio-temporal dispersal pattern of ZIKV in Asia prior to its explosive emergence in the Pacific region and the Americas. These analyses demonstrated that the introduction and dispersal of ZIKV on the Pacific islands were preceded by an extended period of relatively silent transmission in SEA, enabling the virus to expand geographically and evolve adaptively before its unanticipated introduction to immunologically naive populations on the Pacific islands and in the Americas. Our findings reveal new features of the evolution and dispersal of this intriguing virus and may benefit future disease control strategies.

Objectives Zika virus (ZIKV) transmission through semen donation has never been reported but the risk is supported by the detection of ZIKV in semen and the demonstration of ZIKV sexual transmission. The potential impact of ZIKV on assisted reproductive procedures should be evaluated. Methods We tested longitudinally collected semen samples provided by asymptomatic blood donors who tested positive for ZIKV RNA in plasma during ZIKV outbreaks in Puerto Rico and Florida in 2016. Results Five of the 14 (35.7%) asymptomatic blood donors provided semen samples that tested positive for ZIKV RNA, with ZIKV RNA loads ranging from 8.03 × 10 3 to 2.55 × 10 6 copies/mL. Plasma collected at the same time as the semen tested negative for ZIKV RNA for most ZIKV RNA-positive semen collections; all corresponding plasma samples tested positive or equivocal for anti-ZIKV IgG antibodies and all except one tested positive for ZIKV IgM antibodies. The rate of detection of ZIKV RNA in semen in asymptomatic donors is not significantly different from the rate previously reported for symptomatic patients. Conclusions Our results that show a high percentage of detection of ZIKV RNA in the semen of asymptomatic men confirm that ZIKV is a new threat for reproductive medicine and should have important implications for assisted reproductive technology. We recommend that semen donations from men at risk for ZIKV infection should be tested for ZIKV RNA, regardless of symptoms of ZIKV infection.

Concerned over the risk of Zika virus (ZIKV) transfusion transmission, public health agencies recommended the implementation of mitigation strategies for its prevention. Those strategies included the use of pathogen inactivation for the treatment of plasma and platelets. The efficacy of amotosalen/ultraviolet A to inactivate ZIKV in plasma had been previously demonstrated, and the efficacy of inactivation in platelets with the same technology was assumed. These studies quantify ZIKV inactivation in platelet components using amotosalen/ultraviolet A.Platelet components were spiked with ZIKV, and ZIKV infectious titers and RNA loads were measured by cell culture-based assays and real-time polymerase chain reaction in spiked platelet components before and after photochemical treatment using amotosalen/ultraviolet A.The mean ZIKV infectivity titers and RNA loads in platelet components before inactivation were either 4.9 logAs previously demonstrated for plasma, robust levels of ZIKV inactivation were achieved in platelet components. With inactivation of higher levels of ZIKV than those reported in asymptomatic, RNA-reactive blood donors, the pathogen-inactivation system using amotosalen/ultraviolet A offers the potential to mitigate the risk of ZIKV transmission by plasma and platelet transfusion.

In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia, and ZIKV was isolated from his semen. ZIKV transmission by sexual intercourse has been previously suspected. This observation supports the possibility that ZIKV could be transmitted sexually.

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International audience; The Zika virus crisis exemplified the risk associated with emerging pathogens and was a reminder that preparedness for the worst-case scenario, although challenging, is needed. Herein, we review all data reported during the unexpected emergence of Zika virus in French Polynesia in late 2013. We focus on the new findings reported during this outbreak, especially the first description of severe neurological complications in adults and the retrospective description of CNS malformations in neonates, the isolation of Zika virus in semen, the potential for blood-transfusion transmission, mother-to-child transmission, and the development of new diagnostic assays. We describe the effect of this outbreak on health systems, the implementation of vector-borne control strategies, and the line of communication used to alert the international community of the new risk associated with Zika virus. This outbreak highlighted the need for careful monitoring of all unexpected events that occur during an emergence, to implement surveillance and research programmes in parallel to management of cases, and to be prepared to the worst-case scenario.

The potential for Zika virus (ZIKV) transfusion-transmission (TT) has been demonstrated in French Polynesia and Brazil. Pathogen inactivation (PI) of blood products is a proactive strategy to inactivate TT pathogens including arboviruses. Inactivation of West Nile, dengue, Zika, and chikungunya viruses was previously demonstrated by photochemical treatment with amotosalen and ultraviolet A (UVA) illumination. In this study, we evaluated ZIKV inactivation in red blood cell (RBC) components by a chemical approach that uses amustaline (S-303) and glutathione (GSH).RBC components were spiked with a high titer of ZIKV. Viral titers (infectivity) and ZIKV RNA loads (reverse transcription-polymerase chain reaction) were measured in spiked RBCs before and after S-303 and GSH treatment and confirmed using repetitive passages in cell culture. A mock-treated arm validated the approach by demonstrating stability of the virus (infectivity and RNA load) during the process.The mean ZIKV infectivity titer and RNA load in RBCs were 5.99 ± 0.2 log 50% tissue culture infectious dose (TCIDComplete ZIKV inactivation of more than 5.99 log TCID

As a lot of reviews are available on Zika virus (ZIKV), in this short commentary, we will focus on the recent advances and gaps in knowledge regarding our understanding of ZIKV infections and on the reaction to the “ZIKV crisis.”

The unexpected emergence of Zika virus (ZIKV) in the Pacific Islands and Latin America and its association with congenital Zika virus syndrome (CZVS) (which includes microcephaly) and Guillain-Barré syndrome (GBS) have stimulated wide-ranging research. High densities of susceptible Aedes spp., immunologically naive human populations, global population growth with increased urbanization, and escalation of global transportation of humans and commercial goods carrying vectors and ZIKV undoubtedly enhanced the emergence of ZIKV. However, flavivirus mutations accumulate with time, increasing the likelihood that genetic viral differences are determinants of change in viral phenotype. Based on comparative ZIKV complete genome phylogenetic analyses and temporal estimates, we identify amino acid substitutions that may be associated with increased viral epidemicity, CZVS, and GBS. Reverse genetics, vector competence, and seroepidemiological studies will test our hypothesis that these amino acid substitutions are determinants of epidemic and neurotropic ZIKV emergence.

Background Zika virus (ZIKV) viremia is reported as low and transient, however, these estimates rely on limited data. We report RNA loads in sera collected from symptomatic patients during the 2013-2014 French Polynesian ZIKV outbreak. Methods We performed molecular detection of ZIKV RNA in sera from 747 patients presenting with suspected acute phase ZIKV infection. Among patients with confirmed infection, we analyzed the duration of viremia, assessed viral RNA loads and recorded the main clinical symptoms. Results A total of 210/747 (28.1%) sera tested positive using a ZIKV-specific RT-PCR. Viral RNA loads in symptomatic patients that ranged from 5 to 3.7 × 106 copies/mL (mean 9.9 × 104 copies/mL) were not related to a particular clinical presentation, and were significantly lower than those previously obtained from asymptomatic ZIKV infected blood donors. Conclusions The rate of detection of ZIKV RNA in sera from suspected cases of acute phase ZIKV infection was low. ZIKV RNA loads were lower in symptomatic patients compared to asymptomatic blood donors and were lower than RNA loads usually reported in dengue infections. As there is no abrupt onset of symptoms in ZIKV infections, we suggest that infected patients sought for medical attention when viremia was already decreasing or had resolved. This article is protected by copyright. All rights reserved

Background Saliva and urine have been used for arthropod-borne viruses molecular detection but not yet for chikungunya virus (CHIKV). We investigated the use of saliva and urine for molecular detection of CHIKV during the French Polynesian outbreak. Methods During the French Polynesian chikungunya outbreak (2014–2015), we collected the same day blood and saliva samples from 60 patients with probable chikungunya (47 during the 1st week post symptoms onset and 13 after), urine was available for 39 of them. All samples were tested using a CHIKV reverse-transcription PCR. Results Forty eight patients had confirmed chikungunya. For confirmed chikungunya presenting during the 1st week post symptoms onset, CHIKV RNA was detected from 86.1 % (31/36) of blood, 58.3 % (21/36) of saliva and 8.3 % (2/24) of urine. Detection rate of CHIKV RNA was significantly higher in blood compared to saliva. For confirmed chikungunya presenting after the 1st week post symptoms onset, CHIKV RNA was detected from 8.3 % (1/12) of blood, 8.3 % (1/12) of saliva and 0 % (0/8) of urine. Conclusions In contrast to Zika virus (ZIKV), saliva did not increased the detection rate of CHIKV RNA during the 1st week post symptoms onset. In contrast to ZIKV, dengue virus and West Nile virus, urine did not enlarged the window of detection of CHIKV RNA after the 1st week post symptoms onset. Saliva can be used for molecular detection of CHIKV during the 1st week post symptoms onset only if blood is impossible to collect but with a lower sensitivity compared to blood.

Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barré syndrome.In this case-control study, cases were patients with Guillain-Barré syndrome diagnosed at the Centre Hospitalier de Polynésie Française (Papeete, Tahiti, French Polynesia) during the outbreak period. Controls were age-matched, sex-matched, and residence-matched patients who presented at the hospital with a non-febrile illness (control group 1; n=98) and age-matched patients with acute Zika virus disease and no neurological symptoms (control group 2; n=70). Virological investigations included RT-PCR for Zika virus, and both microsphere immunofluorescent and seroneutralisation assays for Zika virus and dengue virus. Anti-glycolipid reactivity was studied in patients with Guillain-Barré syndrome using both ELISA and combinatorial microarrays.42 patients were diagnosed with Guillain-Barré syndrome during the study period. 41 (98%) patients with Guillain-Barré syndrome had anti-Zika virus IgM or IgG, and all (100%) had neutralising antibodies against Zika virus compared with 54 (56%) of 98 in control group 1 (p0.0001). 39 (93%) patients with Guillain-Barré syndrome had Zika virus IgM and 37 (88%) had experienced a transient illness in a median of 6 days (IQR 4-10) before the onset of neurological symptoms, suggesting recent Zika virus infection. Patients with Guillain-Barré syndrome had electrophysiological findings compatible with acute motor axonal neuropathy (AMAN) type, and had rapid evolution of disease (median duration of the installation and plateau phases was 6 [IQR 4-9] and 4 days [3-10], respectively). 12 (29%) patients required respiratory assistance. No patients died. Anti-glycolipid antibody activity was found in 13 (31%) patients, and notably against GA1 in eight (19%) patients, by ELISA and 19 (46%) of 41 by glycoarray at admission. The typical AMAN-associated anti-ganglioside antibodies were rarely present. Past dengue virus history did not differ significantly between patients with Guillain-Barré syndrome and those in the two control groups (95%, 89%, and 83%, respectively).This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome. Because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillain-Barré syndrome.Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.

The global spread of epidemic Zika virus (ZIKV) began in Micronesia in 2007, followed by epidemics in French Polynesia in 2013-14, other South Pacific islands in 2014-15, and the Americas in 2015-16. A dramatic increase in severe congenital malformations (microcephaly) potentially associated with ZIKV in Brazil, combined with the rapid geographical spread, led the World Health Organization to declare ZIKV epidemic a Public Health Emergency of International Concern. Although ZIKV was first isolated nearly 70 years ago, very little is known about the biology, epidemiology and clinical manifestations because transmission has been sporadic and silent for most of that time. Here we review what is and is not known about ZIKV, with emphasis on the gaps in knowledge about ZIKV and the possible inaccurate assumptions made based on what we know about related viruses.

To the Editor: Chikungunya virus (CHIKV), an arthropod-borne virus (arbovirus) of the family Togaviridae, genus Alphavirus, is transmitted by mosquitoes of the Aedes genus, especially Ae. aegypti and Ae. albopictus (1). The main clinical manifestations of CHIKV infections are sudden high fever, headache, back pain, myalgia, arthralgia affecting mainly the extremities, and rash. CHIKV emerged in the Pacific region in New Caledonia in March 2011. Additional outbreaks occurred in Papua New Guinea in June 2012; Yap State (Federated States of Micronesia) in August 2013; Tonga in April 2014; and American Samoa, Samoa, and Tokelau in July 2014 (2). Phylogenetic analysis of CHIKV strains showed the existence of 3 lineages: West African, Asian, and East/Central/South African (1). French Polynesia is a French territory in the South Pacific, with 270,000 inhabitants living on 5 archipelagoes. Arboviruses are a common cause of outbreaks in French Polynesia: the last dengue virus (DENV) outbreaks caused by DENV-1 and DENV-3 occurred in 2013 (3), and DENV-1 still circulates. French Polynesia also experienced the largest Zika virus (ZIKV) outbreak ever reported during October 2013–April 2014 (4). In May 2014, CHIKV infection was detected for the first time in French Polynesia in a traveler returning from Guadeloupe, (5) where a chikungunya outbreak was ongoing (6). In late September 2014, an increasing number of patients with fever and rash who tested negative for DENV and ZIKV by real-time reverse transcription PCR (RT-PCR) were recorded by the French Polynesia Department of Health on the south coast of Tahiti, French Polynesia’s main island. Serum samples collected from 19 of these patients were tested for CHIKV by RT-PCR using previously reported primers and a probe (7). Seven of the 19 (37%) were positive; all 7 were autochthonous. The first specimen that tested positive for CHIKV had been collected from a patient on September 25, and by October 25, a total of 318 patients were confirmed by RT-PCR to be infected by CHIKV. Nearly all districts of Tahiti were affected, and cases were reported on 4 of French Polynesia’s 5 archipelagoes. Partial sequencing of the CHIKV E1 gene of a strain isolated from a patient and collected on September 29 (strain PF14-290914-16, GenBank accession no. {"type":"entrez-nucleotide","attrs":{"text":"KM985619","term_id":"807059694","term_text":"KM985619"}}KM985619) was performed as previously reported (8). Phylogenetic analysis showed that French Polynesia’s CHIKV strain belongs to the Asian lineage and is more closely related to a strain collected in the British Virgin Islands in 2014 (VG14/99659) and to the French Polynesian strain imported from Guadeloupe in May 2014 (PF14-270514-51impGP), with 99.9% homology, than to the strains that recently circulated in Yap State (FM13/3807), Tonga (TO14-080414-3007 and TO14-080414-3042), and New Caledonia (NC11-568) (Figure). Figure Phylogenetic analysis of chikungunya virus strain isolated in French Polynesia on September 29, 2014. The evolutionary history was inferred by using the maximum-likelihood method based on the Kimura 2-parameter model. The percentage of trees in which ... No cases of CHIKV infection were reported in French Polynesia within the 4 months after the imported case detected on May 25, 2014. Because of the active, ongoing circulation of CHIKV in the Pacific, introduction of this virus in French Polynesia was expected from other Pacific islands, especially from New Caledonia, because of extensive travel between the 2 French territories. The fact that the CHIKV strain circulating in French Polynesia is closely related to the strains currently circulating in the Caribbean suggests that the French Polynesia outbreak is a result of the introduction of CHIKV from the Caribbean rather than from another Pacific island. The delay between the current outbreak and the first infected patient detected in 2014 also suggests a new introduction rather than a circulation of the strain introduced in May. However, an undetected low-level circulation of CHIKV during the cooler and drier low transmission season, simultaneously with DENV-1 circulation, cannot be excluded. The introduction of arboviruses into French Polynesia from other French overseas territories rather than from other Pacific islands was previously reported for DENV. In 2013, DENV-3 reappeared in French Polynesia 3 months after the Solomon Islands had declared a DENV-3 outbreak. However, epidemiologic and phylogenetic investigations revealed that the DENV-3 strain that caused the outbreak in French Polynesia had been introduced by a traveler returning from French Guiana and belonged to a different genotype than the one that was circulating in the Solomon Islands (3). Several conditions are favorable to a large chikungunya outbreak in French Polynesia. First, because CHIKV has never been previously reported in French Polynesia, the entire population is thought to be immunologically naive for CHIKV infection. Second, 2 potential vectors for CHIKV are present in French Polynesia: Ae. aegypti (1) and Ae. polynesiensis mosquitoes (9). Third, in French Polynesia the hot and rainy season that lasts from October through March is conducive to the proliferation of mosquitoes. We have the experience of the French Polynesian ZIKV outbreak that started with the same favorable conditions in October 2013 and was responsible for 28,000 estimated symptomatic cases from October 2013 through April 2014 (10). This new outbreak corroborates the recent observation that the expansion of arboviruses in the Pacific is ongoing and inevitable (2).

International audience

In the last few years, the transfusion medicine community has been paying special attention to emerging vector-borne diseases transmitted by arboviruses. Zika virus is the latest of these pathogens and is responsible for major outbreaks in Africa, Asia and, more recently, in previously infection-naïve territories of the Pacific area. Many issues regarding this emerging pathogen remain unclear and require further investigation. National health authorities have adopted different prevention strategies. The aim of this review article is to discuss the currently available, though limited, information and the potential impact of this virus on transfusion medicine.

Background During the largest Zika virus (ZIKV) outbreak ever reported that occurred from October 2013 to March 2014 in French Polynesia, we observed that several patients presenting the symptoms of acute phase Zika fever were tested negative in blood by ZIKV real-time PCR (RT-PCR). Objectives As we have previously detected ZIKV RNA in the saliva of a young child, we investigated the use of saliva as an alternative sample for routine ZIKV RNA detection. Study design Over a 6 month period, 1,067 samples collected from 855 patients presenting symptoms of Zika fever (saliva only, blood only or both samples) were tested using a specific ZIKV RT-PCR. A medical questionnaire was available for most of the patients. Results ZIKV was more frequently detected in saliva compared to blood. For the 182 patients with both samples collected, tests were positive for 35 (19.2%) in saliva while negative in blood and tests were positive for 16 (8.8%) in blood while negative in saliva; the difference in mean days after symptoms onset and the percentage of the main symptoms of Zika fever for patients only positive in saliva or in blood was not significant. Conclusion The use of saliva sample increased the rate of molecular detection of ZIKV at the acute phase of the disease but did not enlarge the window of detection of ZIKV RNA. Saliva was of particular interest when blood was difficult to collect (children and neonates especially).