Didier Musso

Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study

BACKGROUND 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. METHODS 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. FINDINGS 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 (p<0.0001). 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). INTERPRETATION 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. FUNDING Labex Integrative Biology of Emerging Infectious Diseases, EU 7th framework program PREDEMICS. and Wellcome Trust.

Potential Sexual Transmission of Zika Virus

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.

Zika virus infection complicated by Guillain-Barre syndrome--case report, French Polynesia, December 2013.

Zika fever, considered as an emerging disease of arboviral origin, because of its expanding geographic area, is known as a benign infection usually presenting as an influenza-like illness with cutaneous rash. So far, Zika virus infection has never led to hospitalisation. We describe the first case of Guillain-Barré syndrome (GBS) occurring immediately after a Zika virus infection, during the current Zika and type 1 and 3 dengue fever co-epidemics in French Polynesia.

Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014.

Since October 2013, French Polynesia has experienced the largest documented outbreak of Zika virus (ZIKAV) infection. To prevent transmission of ZIKAV by blood transfusion, specific nucleic acid testing of blood donors was implemented. From November 2013 to February 2014: 42 (3%) of 1,505 blood donors, although asymptomatic at the time of blood donation, were found positive for ZIKAV by PCR. Our results serve to alert blood safety authorities about the risk of post-transfusion Zika fever.

Rapid spread of emerging Zika virus in the Pacific area

Zika virus (ZIKV) is an emerging arthropod-borne virus (arbovirus) belonging to the family Flaviviridae and genus Flavivirus. ZIKV was first isolated from a monkey in the Zika forest of Uganda in 1947 [1]. Subsequently, sporadic human infections were reported in Africa and Asia. In 2007, the first large documented ZIKV outbreak was reported from Yap State, Federated States of Micronesia [2]. No further transmission was identified in the Pacific until October 2013, when French Polynesia (FP) reported the first cases; a subsequent explosive outbreak resulted in an estimated 28 000 cases seeking medical care (approximately 11% of the population) [3,4]. Phylogenetic analyses demonstrated that the FP strain was closely related to Cambodia 2010 and Yap State 2007 strains, corroborating previous findings of the expansion of the ZIKV Asian lineage [3]. During the FP outbreak, most clinical cases presented with mild disease characterized by low-grade fever, maculopapular rash, arthralgia, and conjunctivitis. In November, a patient presented with Guillain–Barre syndrome (GBS), an autoimmune disease causing acute or subacute flaccid paralysis, 1 week after a confirmed acute ZIKV infection [5]. Subsequent GBS cases were identified, correlating temporally with the ZIKV outbreak. The incidence rate of GBS cases during the ZIKV outbreak was approximately 20-fold higher than expected given the size of the FP population and the established incidence rates of GBS (1–2/ 100 000 population per year) [6]. No severe disease resulting from ZIKV infection had been reported prior to the FP outbreak, but previous clinical characterization was based on a limited number of confirmed cases. The recent temporal and spatial association between the FP ZIKV outbreak and the highly unusual GBS cluster is very

Detection of Zika virus in saliva

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).

Zika virus: following the path of dengue and chikungunya?

On May 7, 2015, the Pan American Health Organization issued an alert about potential Zika virus (ZIKV) transmission in northeast Brazil. This has now been confi rmed with wide spread of the disease, underscoring the potential for ZIKV to spread globally, similar to dengue (DENV) and chikungunya (CHIKV) viruses. ZIKV is an emerging arthropodborne virus (arbovirus) that was fi rst isolated from a Rhesus monkey in Uganda, in 1947. This arbovirus is related to DENV and they have similar epidemiology and transmission cycle in urban environments. Until recently, only sporadic human ZIKV infections were reported. In 2007, ZIKV emerged outside of Asia and Africa for the fi rst time and caused an epidemic on Yap Island in the Federated States of Micronesia, which was followed by a large epidemic in French Polynesia in 2013–14. Subsequently, ZIKV spread to several countries in Oceania (fi gure). The clinical presentation of ZIKV infection is not specific (mild fever, rash, arthralgia, and conjunctivitis) and can be confused with other diseases, especially dengue and

Culture of previously uncultured members of the human gut microbiota by culturomics

Metagenomics revolutionized the understanding of the relations among the human microbiome, health and diseases, but generated a countless number of sequences that have not been assigned to a known microorganism1. The pure culture of prokaryotes, neglected in recent decades, remains essential to elucidating the role of these organisms2. We recently introduced microbial culturomics, a culturing approach that uses multiple culture conditions and matrix-assisted laser desorption/ionization–time of flight and 16S rRNA for identification2. Here, we have selected the best culture conditions to increase the number of studied samples and have applied new protocols (fresh-sample inoculation; detection of microcolonies and specific cultures of Proteobacteria and microaerophilic and halophilic prokaryotes) to address the weaknesses of the previous studies3–5. We identified 1,057 prokaryotic species, thereby adding 531 species to the human gut repertoire: 146 bacteria known in humans but not in the gut, 187 bacteria and 1 archaea not previously isolated in humans, and 197 potentially new species. Genome sequencing was performed on the new species. By comparing the results of the metagenomic and culturomic analyses, we show that the use of culturomics allows the culture of organisms corresponding to sequences previously not assigned. Altogether, culturomics doubles the number of species isolated at least once from the human gut.

Emerging arboviruses in the Pacific

Dengue virus is the causal agent of dengue fever and is typically characterised by fever, myalgia, arthralgia, rash, and sometimes severe and life-threatening clinical symptoms. This virus is regarded as the greatest threat to global public health of arthopod-borne viruses (arboviruses). However, during the past decade additional mosquito-borne viruses, including chikungunya virus, which causes fever and acute polyarthralgia, have successfully expanded to geographical areas where only dengue epidemics used to be reported, particularly to the tropical oceanic regions. In 2005, chikungunya virus was recorded in the Indian Ocean islands, and from the end of 2013, reached the Caribbean. In 2014, concomitant outbreaks have happened in the Pacific due to dengue virus, chikungunya virus, and Zika virus— another mosquito-borne virus that mostly causes mild fever, joint pain, conjunctivitis, and rash. Substantial changes in epidemiology of mosquito-borne diseases in tropical oceanic regions are probably caused by many and difficult to address factors. However, a review of the epidemiological situation in the Pacifi c from the past several years shows that the present crisis could be the product of a gradual process. In the Pacifi c the situation worsened during a 7-year period; the predominant circulation of a single dengue virus serotype (dengue virus serotype [DENV]-1) changed to co-circulation of several virus serotypes (DENV-4 in 2007, then also with DENV-2, which caused some sporadic outbreaks, and co-circulation of DENV-3 in 2013), and concurrent emergence of mosquito-borne viruses not previously reported in the region (fi gure). In 2007, the Yap State, the Federated States of Micronesia reported the first outbreak of Zika virus outside of Africa and Asia. Subsequent infections of Zika virus in other Pacifi c islands were not reported until 2013, when this virus reappeared in French Polynesia and then disseminated throughout the Pacific. The first autochthonous chikungunya infections in the region were reported in 2011 in New Caledonia. Chikungunya outbreaks occurred in Papua New Guinea in 2012, the Yap State in 2013, and Tonga, American Samoa, Samoa, and Tokelau in 2014. Tropical oceanic regions host potential vectors for many arboviruses that local populations are mostly naive for, making these regions an

Inactivation of Zika virus in plasma with amotosalen and ultraviolet A illumination.

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.