High specificity and sensitivity of Zika EDIII-based ELISA diagnosis highlighted by a large human reference panel.

BACKGROUND: Zika virus (ZIKV) and Dengue virus (DENV) are often co-endemic. The high protein-sequence homology of flaviviruses renders IgG induced by and directed against them highly cross-reactive against their antigen(s), as observed on a large set of sera, leading to poorly reliable sero-diagnosis. METHODS: We selected Domain III of the ZIKV Envelope (ZEDIII) sequence, which is virus specific. This recombinant domain was expressed and purified for the specific detection of ZEDIII-induced IgG by ELISA from ZIKV-RT-PCR-positive, ZIKV-IgM-positive, flavivirus-positive but ZIKV-negative, or flavivirus-negative sera. We also assessed the reactivity of ZEDIII-specific human antibodies against EDIII of DENV serotype 4 (D4EDIII) as a specific control. Sera from ZEDIII-immunized mice were also tested. RESULTS: Cross-reactivity of IgG from 5,600 sera against total inactivated DENV or ZIKV was high (71.0% [69.1; 72.2]), whereas the specificity and sensitivity calculated using a representative cohort (242 sera) reached 90% [84.0; 95.8] and 92% [84.5; 99.5], respectively, using a ZEDIII-based ELISA. Moreover, purified human IgG against D2EDIII or D4EDIII did not bind to ZEDIII and we observed no D4EDIII reactivity with ZIKV-induced mouse polyclonal IgGs. CONCLUSIONS: We developed a ZEDIII-based ELISA that can discriminate between past or current DENV and ZIKV infections, allowing the detection of a serological scar from other flaviviruses. This could be used to confirm exposure of pregnant women or to follow the spread of an endemic disease.

Tracking Rift Valley fever: From Mali to Europe and other countries, 2016.

On 16 September 2016, the World Health Organization confirmed a Rift Valley fever (RVF) outbreak in Niger. Epidemiological surveillance was reinforced among the French Armed Forces deployed in Niger and bordering countries: Chad, Mali and Burkina Faso. On 26 October, a probable case of RVF was reported in a service member sampled in Mali 3 weeks earlier. At the time the result was reported, the patient was on vacation on Martinique. An epidemiological investigation was conducted to confirm this case and identify other cases. Finally, the case was not confirmed, but three suspected cases of RVF were confirmed using serological and molecular testing. RVF viral RNA was detectable in whole blood for 57 and 67 days after onset of symptoms for two cases, although it was absent from plasma and serum. At the time of diagnosis, these cases had already returned from Mali to Europe. The infectivity of other arboviruses in whole blood has already been highlighted. That RVF virus has been detected in whole blood that long after the onset of symptoms (67 days) raises the question of its potential prolonged infectivity. Because of exposure to tropical infectious diseases during deployment, military populations could import emerging pathogens to Europe.

Seroprevalence of West Nile virus antibodies in equids in the North-East of Algeria and detection of virus circulation in 2014.

West Nile fever (WNF) is a viral disease of wild birds transmitted by mosquitoes. Humans and equids can also be affected and suffer from meningoencephalitis. In Algeria, since the 1994 epidemic, no data on WNV circulation was available until 2012. In September 2012, a fatal human case of WNV neuro-invasive infection occurred in Jijel province. This study describes the first seroprevalence study of West Nile virus (WNV) antibodies conducted in the equine population in Algeria. During 2014, serum samples were collected from 293 equids (222 donkeys and 71 horses) asymptomatic and unvaccinated for WNV in three localities in Northeastern wetlands of Algeria. Antibodies against WNV were found in 51 samples (seroprevalence 17.4%) of sampled equids, distributed as follows: 19 (seroprevalence 26.8%) horses and 32 (seroprevalence 14.4%) donkeys. Moreover 7 horses coming from Blida, in the center of Algeria, were tested before and after an 8-months stay in North-East Algeria. We observe a seroconversion in 2 horses, showing WNV circulation in 2014 in this specific region of Algeria.

First Serological Evidence of West Nile Virus in Horses and Dogs from Corsica Island, France.

West Nile virus (WNV) is widely distributed over the world, including Europe, Africa, and Asia and spread over the past two decades to North and South America. In the south of France, sporadic cases are frequently described and the virus is endemic in Italy with frequent cases and outbreaks. The aim of this study was to identify a possible WNV circulation in Corsica (French island in the Mediterranean Sea) in sheep, horses, and dogs as sentinel animals for the virus surveillance. In 2014, 386 blood samples were collected from 219 sheep, 96 horses, and 71 dogs, in 12 localities in Corsica, in the oriental coast of Corsica. Each sample was systematically tested for WNV immunoglobulin G using an in-house enzyme-linked immunosorbent assay (ELISA) with inactivated WNV as antigen. The result of the ELISA for the WNV antibody test on the sheep sera was all negative, whereas 9 of 96 horses (9.4%) and 6 of 71 dogs (8.4%) presented WNV antibodies. All the positive samples from horses and dogs were confirmed by serum neutralization test. Although no clinical case in humans and horses was reported to date, this report highlights the necessity to improve WNV surveillance in animals and humans, as well as in blood donors in Corsica.

Serological Survey of West Nile Virus in Domestic Animals from Northwest Senegal.

In Africa, infection with West Nile virus (WNV) is frequent but almost always asymptomatic in humans and equids. The aim of this study was to identify whether any other domestic animal living in the same enzootic locality may be the sentinel of WNV circulation. In northwest Senegal, blood samples were collected from 283 adult domestic animals (136 sheep, 64 horses, 29 donkeys, 29 goats, 14 cattle, and 11 dogs), in three localities near Keur Momar Sarr. Each serum was tested for WNV immunoglobulin G using enzyme-linked immunosorbent assay. The prevalence among donkeys, horses, dogs, goats, cattle, and sheep was 86.2%, 68.7%, 27.3%, 6.9%, 0%, and 0%, respectively. This survey confirms that equids and dogs could be the best sentinel animals for surveillance of WNV. The ruminants do not play a role in WNV epidemiology.

Aedes albopictus mosquito: the main vector of the 2007 Chikungunya outbreak in Gabon.

The primary vector at the origin of the 2007 outbreak in Libreville, Gabon is identified as Aedes albopictus, trapped around the nearby French military camp. The Chikungunya virus was isolated from mosquitoes and found to be identical to the A226V circulating human strain. This is the first field study showing the role of the recently arrived species Aedes albopictus in Chikungunya virus transmission in Central Africa, and it demonstrates this species' role in modifying the epidemiological presentation of Chikungunya in Gabon.

Circulation of Chikungunya virus in Gabon, 2006-2007.

This study reports the first isolation and partial genetic characterization of Chikungunya virus (CHIKV) from patients during a 2006-2007 dengue-like syndrome outbreak in Gabon. The isolated viruses were phylogenetically close to strains isolated in the Democratic Republic of the Congo 7 years ago and to strains isolated more recently in Cameroon. These results indicate a continuing circulation of a genetically stable CHIKV population during 7 years in Central Africa.

O'nyong-nyong Virus, Chad.

We report the first laboratory-confirmed human infection with O'nyong-nyong virus in Chad. This virus was isolated from peripheral blood mononuclear cells of a patient with evidence of a seroconversion to a virus related to Chikungunya virus. Genome sequence was partly determined, and phylogenetic studies were conducted.

West Nile Virus in horses, sub-Saharan Africa.

To evaluate the presence and extension of West Nile virus where French soldiers are stationed in Africa, specific antibody prevalence was determined by using ELISA and Western blot. Among 245 horses living in close proximity to the soldiers, seroprevalence was particularly high in Chad (97%) and Senegal (92%).

Dengue type 3 virus, Saint Martin, 2003-2004.

We describe the spread of a dengue virus during an outbreak in Saint Martin island (French West Indies) during winter 2003-2004. Dengue type 3 viruses were isolated from 6 patients exhibiting clinical symptoms. This serotype had not been detected on the island during the preceding 3 years. Genome sequence determinations and analyses showed a common origin with dengue type 3 viruses isolated in Martinique 2 years earlier.