Autochthonous Transmission Of Zika Virus Research Articles

Natural infection by Zika virus but not DNA vaccination consistently elicits antibodies that compete with two potently neutralising monoclonal antibodies targeting distinct epitopes

Autochthonous transmission of Zika virus (ZIKV) has been reported in 87 countries since 2015. Although most infections are mild, there is risk of Guillain-Barré syndrome and adverse pregnancy outcomes. Vaccines are urgently needed to prevent Zika, but sufficient understanding of humoral responses and tools to assess ZIKV-specific immunity are lacking. We developed a blockade-of-binding (BOB) ELISA using A9E and G9E, two strongly neutralising ZIKV-specific monoclonal antibodies, which do not react with dengue virus. Receiver operating characteristic curve analysis assessed A9E and G9E BOB serodiagnostic performance. BOB was then applied to samples from a surveillance cohort in Risaralda, Colombia, and phase 1 ZIKV vaccine trial samples, comparing results against traditional serologic tests. In the validation sample set (n=120), A9E BOB has a sensitivity of 93.5% (95% CI: 79.3, 98.9) and specificity 97.8 (95% CI: 92.2, 99.6). G9E BOB had a sensitivity of 100% (95% CI: 89.0, 100.0) and specificity 100% (95% CI: 95.9, 100). Serum from natural infections consistently tested positive in these assays for up to one year, and reactivity tracks well with ZIKV infection status among sera from endemic areas with complicated flavivirus exposures. Interestingly, a leading ZIKV vaccine candidate elicited minimal BOB reactivity despite generating neutralising antibody responses. In conclusion, A9E and G9E BOB assays are sensitive and specific assays for detecting antibodies elicited by recent or remote ZIKV infections. Given the additional ability of these BOB assays to detect immune responses that target different epitopes, further development of these assays is well justified for applications including flavivirus surveillance, translational vaccinology research and as potential serologic correlates of protective immunity against Zika. R21 AI129532 (PI: S. Becker-Dreps), CDCBAA 2017-N-18041 (PI: A. M. de Silva), Thrasher Fund (PI: M. H. Collins), K22 AI137306 (PI: M. H. Collins).

Methodological procedures explain observed differences in the competence of European populations of Aedes albopictus for the transmission of Zika virus

The risk of autochthonous transmission of Zika virus (ZIKV) in Europe greatly depends on the capacity of Aedes albopictus to transmit ZIKV. Experimental studies of the vector competence of European populations of this invasive mosquito species provided contrasting results, that may suggest differences between mosquito populations in ZIKV competence and/or differences in the methodological procedures used on the experimental studies. We systematically reviewed published studies of experimental mosquito infections and show that differences detected in the infection and transmission rates of Ae. albopictus are mostly due to differences between studies in the temperature, the viral load used to inoculate mosquitoes, and the number of days post-exposure (dpe) to the virus at which mosquitoes were analysed. In particular, the proportion of infected mosquitoes was affected by the viral load inoculated and the dpe, whereas the transmission rate was influenced by the viral load and temperature. Thus, the methodological differences used in these studies greatly affect the conclusions obtained regarding the role of Ae. albopictus in Europe as a competent vector for ZIKV and its epidemiological relevance.

Short Report: Asymptomatic Zika virus infections with low viral loads not likely to establish transmission in New Orleans Aedes populations.

Aedes aegypti and Aedes albopictus are both vectors of Zika virus and both are endemic to the New Orleans Metropolitan area. Fortunately, to date there has been no known autochthonous transmission of Zika virus in New Orleans. No studies of the vector competence of local populations of Ae. aegypti and Ae. albopictus for Zika virus transmission have been conducted. To determine if New Orleans Ae. aegypti and Ae. albopictus mosquitoes are competent for Zika virus, mosquitoes were reared to generation F3 from eggs collected in New Orleans during the 2018 mosquito season. Adults were fed an infectious blood meal and kept for 15 days in an environmental chamber. Transmission assays were conducted at 4, 10, and 15 days post exposure and RT-PCR was run on bodies and saliva to detect the presence of Zika virus RNA. We observed remarkably low susceptibility of both Ae. aegypti and Ae. albopictus from New Orleans to a Zika strain from Panama after oral challenge. These results suggest a limited risk of Zika virus transmission should it be introduced to the New Orleans area, and may partially explain why no transmission was detected in Louisiana during the 2016 epidemic in the Americas, despite multiple known travel associated introductions to New Orleans. Despite these results these mosquito populations are known to be competent vectors for some other mosquito-borne viruses and control measures should not be relaxed.

Risk assessment and genomic characterization of Zika virus in China and its surrounding areas.

Zika virus (ZIKV) has emerged as a global pathogen causing significant public health concerns. China has reported several imported cases where ZIKV were carried by travelers who frequently travel between China and ZIKV-endemic regions. To fully characterize the ZIKV strains isolated from the cases reported in China and assess the risk of ZIKV transmission in China, comprehensive phylogenetic and genetic analyses were performed both on all ZIKV sequences of China and on a group of scientifically selected ZIKV sequences reported in some of the top interested destinations for Chinese travelers. ZIKV genomic sequences were retrieved from the National Center for Biotechnology Information database through stratified sampling. Recombination event detection, maximum likelihood (ML) phylogenetic analysis, molecular clock analysis, selection pressure analysis, and amino acid substitution analysis were used to reconstruct the epidemiology and molecular transmission of ZIKV. The present study investigated 18 ZIKV sequences from China and 70 sequences from 16 selected countries. Recombination events rarely happens in all ZIKV Asian lineage. ZIKV genomes were generally undergone episodic positive selection (17 sites), and only one site was under pervasive positive selection. All ZIKV imported into China were Asian lineage and were assigned into two clusters: Venezuela-origin (cluster A) and Samoa-origin cluster (cluster B) with common ancestor from French Polynesia. The time of most recent common ancestors of Cluster A dated to approximately 2013/11 (95% highest posterior density [HPD] 2013/06, 2014/03) and cluster B dated to 2014/08 (95% HPD 2014/02, 2015/01). Cluster B is more variable than Cluster A in comparison with other clusters, but no varied site of biological significance was revealed. ZIKV strains in Southeast Asia countries are independent from strains in America epidemics. The genetic evolution of ZIKV is conservative. There are two independent introductions of ZIKV into China and China is in danger of autochthonous transmission of ZIKV because of high-risk surrounding areas. Southeast Asia areas have high risk of originating the next large-scale epidemic ZIKV strains.

The Zika Virus Epidemic Four Years After: Where are We?

Zika virus (ZIKV), an emerging arthropod-borne, single-stranded RNA virus, member of the Spondweni serocomplex (genus Flavivirus, family Flaviviridae), was first isolated in 1947 from a sentinel (monkeys held captive with the purpose of identifying yellow fever activity) rhesus monkey in a forest in Uganda. After its discovery, ZIKV was associated only with few sporadic mild cases in humans in Africa and Asia over the next 60 years.[1] However, since 2007, when the first outbreak of ZIKV outside Africa and Asia was reported in the Federated States of Micronesia (Yap), it has been identified in subsequent outbreaks in French Polynesia, Pacific islands, and more recently, from 2015, Brazil was the first country in the Western Hemisphere to confirm autochthonous transmission of ZIKV associated with an outbreak of “dengue-like syndrome” cases.[2]

Limited risk of Zika virus transmission by five Aedes albopictus populations from Spain

BackgroundAedes albopictus, the Asian tiger mosquito, is an exotic invasive species in Europe. It has substantial public health relevance due to its potential role in transmitting several human pathogens. Out of the European countries, Spain has one of the highest risk levels of autochthonous arbovirus transmission due to both the high density of Ae. albopictus and the extensive tourist influx from vector-endemic areas. This study aims to investigate the susceptibility of five Ae. albopictus populations from mainland Spain and the Balearic Islands to a Brazilian Zika virus (ZIKV) strain.MethodsThe F1 generation of each Ae. albopictus population was orally challenged with a ZIKV-infected blood meal (1.8 × 106 PFU/ml). At 7 and 14 days post-infection (dpi), mosquito bodies (thorax and abdomen) and heads were individually analysed through RT-qPCR to determine the infection rate (IR) and dissemination rate (DR), respectively. The saliva of infected mosquitoes was inoculated in Vero cells and the transmission rate was assessed by plaque assay or RT-qPCR on ~33 individuals per population.ResultsThe IR and DR ranged between 12–88%, and 0–60%, respectively, suggesting that ZIKV is capable of crossing the midgut barrier. Remarkably, no infectious viral particle was found in saliva samples, indicating a low ability of ZIKV to overcome the salivary gland barrier. A subsequent assay revealed that a second non-infective blood meal 48 h after ZIKV exposure did not influence Ae. albopictus vector competence.ConclusionsThe oral experimental ZIKV infections performed here indicate that Ae. albopictus from Spain become infected and disseminate the virus through the body but has a limited ability to transmit the Brazilian ZIKV strain through biting. Therefore, the results suggest a limited risk of autochthonous ZIKV transmission in Spain by Ae. albopictus.

United States Travelers' Concern about Zika Infection and Willingness to Receive a Hypothetical Zika Vaccine.

.The ongoing Zika pandemic has affected many countries that are common travel destinations. We assessed the willingness to receive a prophylactic Zika virus (ZIKV) vaccine, currently under development, among travelers to areas with reported autochthonous ZIKV transmission. We surveyed United States (U.S.) residents aged 18–44 years who had ever heard of ZIKV and planned to travel to Florida and/or Texas (N = 420) or a U.S. territory or foreign country (N = 415) in 2017, using a nationally representative internet panel. Travelers to Florida and/or Texas reported less concern about ZIKV infection than travelers to other destinations (27% versus 36%, P = 0.01). Female sex, Hispanic ethnicity, discussing ZIKV with medical professionals, ZIKV risk perception, and self-efficacy for ZIKV prevention predicted concern about ZIKV infection in both groups. Travelers to Florida and/or Texas (43%) and other destinations (44%) were equally willing to receive a ZIKV vaccine. Hispanic ethnicity, discussing ZIKV with medical professionals, and concern about ZIKV infection predicted vaccine willingness in both groups. Likelihood of using existing ZIKV prevention methods, confidence in the U.S. government to prevent ZIKV spread, self-efficacy for ZIKV prevention, and knowledge about ZIKV symptoms further predicted vaccine willingness in travelers to other destinations. In multivariable analyses, only concern about ZIKV infection was associated with vaccine willingness in both groups (prevalence ratio [95% confidence interval]: Florida and/or Texas: 1.34 [1.06, 1.69]; other: 1.82 [1.44, 2.29]). Targeted communications can educate travelers, particularly travelers who are pregnant or may become pregnant, about ZIKV risk to generate ZIKV vaccine demand.

Sleep EEG of Microcephaly in Zika Outbreak

ABSTRACTMicrocephaly (MC), previously considered rare, is now a health emergency of international concern because of the devastating Zika virus pandemic outbreak of 2015. The authors describe the electroencephalogram (EEG) findings in sleep EEG of epileptic children who were born with microcephaly in areas of Brazil with active Zika virus transmission between 2014 and 2017. The authors reviewed EEGs from 23 children. Nine were females (39.2%), and the age distribution varied from 4 to 48 months. MC was associated with mother positive serology to toxoplasmosis (toxo), rubella (rub), herpes, and dengue (1 case); toxo (1 case); chikungunya virus (CHIKV) (1 case); syphilis (1 case); and Zika virus (ZIKV) (10 cases). In addition, 1 case was associated with perinatal hypoxia and causes of 9 cases remain unknown. The main background EEG abnormality was diffuse slowing (10 cases), followed by classic (3 cases) and modified (5 cases) hypsarrhythmia. A distinct EEG pattern was seen in ZIKV (5 cases), toxo (2 cases), and undetermined cause (1 case). It was characterized by runs of frontocentrotemporal 4.5–13 Hz activity (7 cases) or diffuse and bilateral runs of 18–24 Hz (1 case). In ZIKV, this rhythmic activity was associated with hypsarrhythmia or slow background. Further studies are necessary to determine if this association is suggestive of ZIKV infection. The authors believe that EEG should be included in the investigation of all newly diagnosed congenital MC, especially those occurring in areas of autochthonous transmission of ZIKV.

Zika in travellers 1947-2017: a systematic review.

Travellers contributed substantially to the rapid spread of Zika virus (ZIKV). They act as sentinel and may unmask ongoing ZIKV transmission in countries where outbreaks have not yet been reported. Our objectives were to (i) describe the burden of ZIKV infections in international travellers over time; (ii) estimate the proportion of birth defects as a result of maternal ZIKV infection in travellers; (iii) track the extent of sexual transmission; (iv) summarize ZIKV infections in returning travellers as reported by the GeoSentinel network; and (v) identify countries without reports on local ZIKV transmission where travellers served as sentinel. We performed a systematic review from 1947 to April 2017 on travel-associated ZIKV infections. We also compared published reports on autochthonous ZIKV transmission in Asia with published reports on exportations from travellers in Asia. Of 314 papers that fit the inclusion criteria, 61 were eligible for final analysis. There was an exponential increase in the number of reported ZIKV infected travellers from the years 2013 to 2016, which declined in 2017. Amongst pregnant women with ZIKV infection, (5%) resulted in a fetus or infant with ZIKV-associated birth defects. An estimated 1% of the total number of ZIKV cases reported in the USA and Europe were acquired through sexual transmission. Through the GeoSentinel network, five countries (Indonesia, Philippines, Thailand, Vietnam, Cameroon) were identified as sentinel markers where ZIKV was exported despite the absence of reported local transmission. Mobility patterns and travel volumes can help to identify the most likely origin of importation, and also in predicting further propagation. Studies on pregnant returning travellers have contributed to a better understanding of the risk estimates of congenital Zika syndrome/microcephaly as a result of maternal ZIKV infection, and the relative contribution of sexual transmisison.

Returning ex-patriot Chinese to Guangdong, China, increase the risk for local transmission of Zika virus

Fast expansion and linkage to microcephaly and Guillain Barre syndrome have made Zika virus (ZIKV) track attention of global health authority concerns. The epidemiology, virological characteristics and genetic evolution of introduced ZIKV to Guangdong, China, were investigated. Analyses of the epidemiological characteristics and genetic diversity of ZIKV isolates were performed. A total of twenty-eight confirmed ZIKV infection cases were imported into China in 2016, of which 19 were imported into Guangdong, China from Venezuela (16), the Samoa Islands (1), Suriname (1) and Guatemala (1). Serial sampling studies of the cases indicated longer shedding times of ZIKV particles from urine and saliva samples than from serum and conjunctiva swab samples. Seven ZIKV strains were successfully isolated from serum, urine and conjunctiva swab samples using cell culture and neonatal mouse injection methods. Genomic analysis indicated that all viruses belonged to the Asian lineage but had different evolutionary transmission routes with different geographic origins. The molecular clock phylogenetic analysis of the ZIKV genomes indicated independent local transmission that appeared to have been previously established in Venezuela and Samoa. Additionally, we found 7 unique non-synonymous mutations in the genomes of ZIKV that were imported to China. The mutations may indicate that ZIKV has undergone independent evolutionary history not caused by sudden adaptation to Chinese hosts. The increasing number of ex-patriot Chinese returning from ZIKV hyper-endemic areas to Guangdong combined with the presence of a variety of Aedes species indicate the potential for autochthonous transmission of ZIKV in Guangdong.

Five cases of acute Zika virus infection in French women of reproductive age returning from Central and South America

IntroductionThe favorable season for Aedes albopictus circulation has started in Europe and may lead to autochthonous transmission of Zika virus. Health care providers should be familiar with evocative clinical presentations and able to give updated information to women of reproductive age infected by Zika virus. ObservationsWe report five laboratory-confirmed Zika virus infections imported to metropolitan France from Central and South America between January and April, 2016. The five young women were not connected and not pregnant; common presentation combined a rash with persistent arthralgia. Zika virus was identified by RT-PCR from serum or urines, between two and eight days after the onset of the symptoms. ConclusionAs the duration of potential materno-foetal infectivity is still unknown, we were unable to answer with certitude to the patients’ questions about the time interval to respect before attempting a pregnancy: one of them became pregnant one month after the diagnosis.

Zika virus: Vaccine initiatives and obstacles

Over 130,000 humans in Brazil are infected with Zika virus (ZIKV) since March 2015, and presently 29 countries in Americas have reported local autochthonous ZIKV transmission. Besides the associated clinical features, Brazil has also reported a temporal and spatial association of ZIKV with Guillain-Barre syndrome (GBS) and Zika fetal syndrome. ZIKV vaccine approaches include purified inactivated virus, nucleic acid-based vaccines (DNA, RNA), live vector vaccines, subunit vaccines, virus-like particle technologies, and live recombinant vaccines similar to the technologies used against other human flaviviruses. At present, 15 commercial entities are involved in the development of ZIKV vaccine. Vaccines developed through different approaches would have their own inherent advantages and disadvantages. The presentation of disease in different populations and lack of clarity on the pathogenesis and complications is the most important obstacle. Second, Zika belongs to a genus that is notorious for the antibody-mediated enhancement of infection, which proved to be a stumbling block during the development of the dengue vaccine. Identifying large naive and yet uninfected at-risk populations may be an obstacle to demonstrating efficacy. Next, the association of Zika with GBS is being researched since the vaccine may have the potential to provoke similar neuropathophysiologic mechanisms. Zika's association with adverse fetal outcomes necessitates that pregnant women and women of childbearing age are considered for evaluating vaccines, which form a vulnerable group for vaccine trials.

Estimating the subcritical transmissibility of the Zika outbreak in the State of Florida, USA, 2016.

BackgroundFlorida State has reported autochthonous transmission of Zika virus since late July 2016. Here we assessed the transmissibility associated with the outbreak and generated a short-term forecast.MethodsTime-dependent dynamics of imported cases reported in the state of Florida was approximated by a logistic growth equation. We estimated the reproduction number using the renewal equation in order to predict the incidence of local cases arising from both local and imported primary cases. Using a bootstrap method together with the logistic and renewal equations, a short-term forecast of local and imported cases was carried out.ResultsThe reproduction number was estimated at 0.16 (95 % Confidence Interval: 0.13, 0.19). Employing the logistic equation to capture a drastic decline in the number of imported cases expected through the course of 2016, together with the low estimate of the local reproduction number in Florida, the expected number of local reported cases was demonstrated to show an evident declining trend for the remainder of 2016.ConclusionsThe risk of local transmission in the state of Florida is predicted to dramatically decline by the end of 2016.

Detecting Guillain-Barré syndrome caused by Zika virus using systems developed for polio surveillance.

Zika virus disease is caused by a ribonucleic acid (RNA) virus, which is transmitted to humans by mosquitoes of the Aedes aegypti species. Around 80% of infections are asymptomatic. (1) Symptomatic infections are characterized by mild fever lasting from four to seven days, associated with maculopapular rash, arthralgia, conjunctivitis, muscle pain and headache. Until recently, Zika virus disease has never been associated with deaths, intrauterine infections, or congenital anomalies. In 2013 and 2014, during an outbreak in French Polynesia, the disease was linked with GuillainBarre syndrome. (2) Zika infection can be established by detection of Zika virus RNA or specific viral antigens in human clinical samples. It is suspected that over 40 countries had autochthonous Zika virus transmission in 2015 and early 2016. (3,4) In some countries, there is a temporal association of Zika virus infections with severe clinical manifestations, particularly Guillain-Barre syndrome and congenital neurological malformations. (3,4) In December 2015, officials from the Brazilian Ministry of Health reported 76 patients diagnosed with neurological syndromes, of whom 42 (55%) were confirmed as having Guillain-Barre syndrome. (4) Similarly, between December 2015 and January 2016, Salvadorian health officials reported 46 patients with Guillain-Barre syndrome, more than 50% of whom had febrile illness lasting between seven to 15 days before onset of the syndrome. (4) A case-control study conducted in 2013 and 2014 in French Polynesia has shown evidence of Zika virus infections causing Guillain-Barre syndrome. (2) The French Polynesia study found, in most of the patients, neurological symptoms following Zika virus infections lasted a median of six days. (2) With increasing evidence of linkages between Guillain-Barre syndrome and Zika virus infection, (2-4) it is imperative to enhance Guillain-Barre syndrome surveillance. This can be done using existing surveillance systems like the one for acute flaccid paralysis (AFP) used by polio eradication programmes. (5) Scientists warn that in view of outbreaks that occurred in Africa, south-east Asia, the Pacific Islands, and the Americas, the disease now has pandemic potential. (6) In February 2016, the World Health Organization (WHO) declared that the reported clusters of microcephaly and other neurological disorders from the WHO Region of the Americas constituted a Public Health Emergency of International Concern and recommended to enhance surveillance for Zika virus infection. (7) The Aedes species of mosquitoes that transmits the Zika virus and other infections like dengue, chikungunya and yellow fever exists worldwide, posing a high risk for global transmission. (6) A 2016 modelling study looking at the potential for Zika virus spread predicted substantial international spread by travellers from Brazil to the rest of the world. (8) Many cases of microcephaly and Guillain-Barre syndrome are now being reported from countries affected by Zika. (2,4) Surveillance for timely detection and monitoring of Zika infection and screening for microcephaly and Guillain-Barre syndrome will be essential to guide the public health response. Governments and other stakeholders use existing AFP surveillance systems in countries to monitor progress towards a global polio eradication goal. (9) Currently, 91% (177 out of 194) of WHO Member States conduct AFP surveillance. Reporting of AFP in children younger than 15 years is followed by laboratory diagnosis of stool specimens to either confirm polio or identify nonpolio AFP cases. Guillain-Barre syndrome cases are classified as non-polio AFP cases. Guillain-Barre syndrome is the most common non-polio cause for AFP. Most countries achieve or surpass the global standard of an annual rate of at least one case of non-polio AFP per 100000 population of children younger than 15 years. In 2015, globally, 99 582 AFP cases among children younger than 15 years, including 72 laboratory-confirmed wild poliovirus cases, were reported. …

Epidemia do vírus Zika: a mais nova emergência internacional

Epidemia do vírus Zika: a mais nova emergência internacional

First detection of autochthonous Zika virus transmission in a HIV-infected patient in Rio de Janeiro, Brazil

Since May 2015, Brazil’s Ministry of Health has reported autochthonous transmission of Zika virus (ZIKV) in some states of the country. Simultaneous circulation of Dengue, Chikungunya and ZIKV in the country hinder both the diagnosis and the therapeutic approach of patients seeking care with acute febrile illnesses especially in patients with comorbidities. The association between HIV infection and endemic diseases has been described especially in tropical regions with varying levels of complications, although there has been no report of ZIKV in HIV-infected patients. We report the first autochthonous case of laboratory confirmed ZIKV infection in a HIV-infected patient in Rio de Janeiro, Brazil. He evolved with only mild symptoms and recovered well without major laboratory abnormalities. Phylogenetic analysis of the ZIKV detected in the patient sera clustered within the Asian clade. To the best of our knowledge, this is the first time that Zika virus co-infection is reported in a HIV-infected patient.

First report of autochthonous transmission of Zika virus in Brazil.

In the early 2015, several cases of patients presenting symptoms of mild fever, rash, conjunctivitis and arthralgia were reported in the northeastern Brazil. Although all patients lived in a dengue endemic area, molecular and serological diagnosis for dengue resulted negative. Chikungunya virus infection was also discarded. Subsequently, Zika virus (ZIKV) was detected by reverse transcription-polymerase chain reaction from the sera of eight patients and the result was confirmed by DNA sequencing. Phylogenetic analysis suggests that the ZIKV identified belongs to the Asian clade. This is the first report of ZIKV infection in Brazil.