Hide and Seek: The Interplay Between Zika Virus and the Host Immune Response.

Zika virus (ZIKV) received worldwide attention over the past decade when outbreaks of the disease were found to be associated with severe neurological syndromes and congenital abnormalities. Unlike most other flaviviruses, ZIKV can spread through sexual and transplacental transmission, adding to the complexity of Zika pathogenesis and clinical outcomes. In addition, the spread of ZIKV in flavivirus-endemic regions, and the high degree of structural and sequence homology between Zika and its close cousin Dengue have raised questions on the interplay between ZIKV and the pre-existing immunity to other flaviviruses and the potential immunopathogenesis. The Zika epidemic peaked in 2016 and has affected over 80 countries worldwide. The re-emergence of large-scale outbreaks in the future is certainly a possibility. To date, there has been no approved antiviral or vaccine against the ZIKV. Therefore, continuing Zika research and developing an effective antiviral and vaccine is essential to prepare the world for a future Zika epidemic. For this purpose, an in-depth understanding of ZIKV interaction with many different pathways in the human host and how it exploits the host immune response is required. For successful infection, the virus has developed elaborate mechanisms to escape the host response, including blocking host interferon response and shutdown of certain host cell translation. This review provides a summary on the key host factors that facilitate ZIKV entry and replication and the mechanisms by which ZIKV antagonizes antiviral innate immune response and involvement of adaptive immune response leading to immunopathology. We also discuss how ZIKV modulates the host immune response during sexual transmission and pregnancy to induce infection, how the cross-reactive immunity from other flaviviruses impacts ZIKV infection, and provide an update on the current status of ZIKV vaccine development.

From Mosquito Bites to Sexual Transmission: Evaluating Mouse Models of Zika Virus Infection.

Following the recent outbreak of Zika virus (ZIKV) infections in Latin America, ZIKV has emerged as a global health threat due to its ability to induce neurological disease in both adults and the developing fetus. ZIKV is largely mosquito-borne and is now endemic in many parts of Africa, Asia, and South America. However, several reports have demonstrated persistent ZIKV infection of the male reproductive tract and evidence of male-to-female sexual transmission of ZIKV. Sexual transmission may broaden the reach of ZIKV infections beyond its current geographical limits, presenting a significant threat worldwide. Several mouse models of ZIKV infection have been developed to investigate ZIKV pathogenesis and develop effective vaccines and therapeutics. However, the majority of these models focus on mosquito-borne infection, while few have considered the impact of sexual transmission on immunity and pathogenesis. This review will examine the advantages and disadvantages of current models of mosquito-borne and sexually transmitted ZIKV and provide recommendations for the effective use of ZIKV mouse models.

Sexual Abuse and Sexually-Transmitted HIV/AIDS in Jamaican Children and Adolescents Aged 6-19 Years.

INTRODUCTION: Risk factors and outcomes of sexually-acquired human immunodeficiency virus infection were characterized in Jamaican children and adolescents. METHODOLOGY: Management was carried out by multidisciplinary teams in Infectious Diseases clinics during August 2003 through February 2019 using modified World Health Organization HIV criteria. RESULTS: There were 78 clients, aged 6 to 19 years, with females:males = 4:1 (p < 0.05). Sexual-initiation occurred in 60%, 47 before < 16 years (median 13 years, with four < 10 years; females:males = 7:1). Sexual-initiation preceded HIV diagnosis in all cases (median 2 years). Secondary education 93% (69/77) and living with non-parental relatives 17% (13/78) were associated with early sexual-initiation (p < 0.042); as was later imprisonment in 6% (3/52). Other sexually transmitted infections 36% (19/53) were associated with sexual-initiation ≥ 16 years (p < 0.01). Risks for ongoing HIV-transmission included infrequent condom use 74% (39/53), body-piercings 50% (24/48), illicit drug use 37% (28/76), tattoos 36% (19/52), transactional sex 14% (7/53) and pregnancy 56% of girls. 77% (59/77) had Centres for Diseases Control's Category A HIV infection; 82% (61/75) initiated anti-retroviral therapy; 75% (56/75) had first-line drugs, with helper T lymphocyte counts ≥ 500 cells/µL in 61% (48/78) and HIV viral load of < 1,000 copies/µL in 63% (40/64). Complications included dermatological 39% (20/52), respiratory 25% (13/52) and neurological 15% (8/52). Early sexual initiation was associated with depression 43% (33/76; p < 0.004) and suicidal attempt or ideation 23% (18/77; p < 0.096). Four (5%) died. CONCLUSIONS: Sexually transmitted HIV/AIDS in children and adolescents should preempt prompt medical, legal and psychosocial interventions.

Do Not Neglect the Covid-19 Transmission Through Sexual Intercourse.

INTRODUCTION: Given the important role of sexual activity in most people's lives, in response to the question of whether the coronavirus is transmitted through sexual contact, this study was conducted to investigate the association of coronavirus transition with sexual contact. METHODS: Based on the PRISMA checklist, we review published articles on sexual contact with the Corona virus until 15 February 2021. Electronic databases based on search strategy including PubMed, Scopus, Web of Science was searched to identify relevant papers in English language. RESULTS: Retrieved from 4671, 29 titles and abstracts articles screened, eight were excluded. There were 21 articles in the selection criteria. Of the 21 studies whose full text was read, only 5 studies stated that coronavirus was not transmitted through sexual contact, and 16 articles argued that sexual transmission of the virus could not be ignored. Most studies have confirmed the transmission of the virus through semen, but its transmission through vaginal secretions is unknown. CONCLUSION: Transmission of the virus through semen should be taken seriously in patients and the necessary education should be given to men and their sexual partners. Health care providers need to increase their knowledge and awareness to provide the best practices to reduction the risks related to Covid-19 sexual transmission through counseling and appropriate approaches.

Viral Venereal Diseases of the Skin.

Viral venereal diseases remain difficult to treat. Human papilloma virus (HPV) and herpes simplex virus (HSV) are two common viral venereal diseases. HPV infections are characterized by anogenital warts and less commonly by premalignant or malignant lesions. HSV infections classically present as grouped vesicles on an erythematous base with associated burning or pain; however, immunosuppressed patients may have atypical presentations with nodular or ulcerative lesions. This review discusses the epidemiology, diagnosis, and management of anogenital HPV and HSV infections with an emphasis on treatment modalities for the practicing dermatologist. Diagnosis of these diseases typically relies on clinical assessment, although multiple diagnostic techniques can be utilized and are recommended when diagnosis is uncertain or evaluating an individual with increased risk of malignancy. Management of HPV and HSV infections involves appropriate counseling, screening, and multiple treatment techniques. Particularly for HPV infections, a practitioner may need to use a combination of techniques to achieve the desired outcome.

Persistence of Zika virus RNA in the epididymis of the murine male reproductive tract.

Zika virus (ZIKV) can infect developing fetuses in utero and cause severe congenital defects independent of route of maternal infection. Infected men can shed ZIKV RNA in semen for over six months. Whether prolonged viral RNA shedding in semen indicates a persistent infection in the male reproductive tract is unknown. We hypothesized that if ZIKV establishes a persistent infection in the male reproductive tract (MRT), then immunosuppressant treatment should stimulate ZIKV replication and seminal shedding. Male mice were infected with ZIKV and immunosuppressed when they shed viral RNA but not infectious virus in ejaculates. Following immunosuppression, we did not detect infectious virus in ejaculates. However, we did detect ZIKV positive and negative sense RNA in the epididymal lumens of mice treated with cyclophosphamide, suggesting that ZIKV persists in the epididymis. This study provides insight into the mechanisms behind ZIKV sexual transmission, which may inform public health decisions regarding ZIKV risks.

Epididymal epithelium propels early sexual transmission of Zika virus in the absence of interferon signaling.

Recognition of Zika virus (ZIKV) sexual transmission (ST) among humans challenges our understanding of the maintenance of mosquito-borne viruses in nature. Here we dissected the relative contributions of the components of male reproductive system (MRS) during early male-to-female ZIKV transmission by utilizing mice with altered antiviral responses, in which ZIKV is provided an equal opportunity to be seeded in the MRS tissues. Using microRNA-targeted ZIKV clones engineered to abolish viral infectivity to different parts of the MRS or a library of ZIKV genomes with unique molecular identifiers, we pinpoint epithelial cells of the epididymis (rather than cells of the testis, vas deferens, prostate, or seminal vesicles) as a most likely source of the sexually transmitted ZIKV genomes during the early (most productive) phase of ZIKV shedding into the semen. Incorporation of this mechanistic knowledge into the development of a live-attenuated ZIKV vaccine restricts its ST potential.

Effects of COVID-19 on male sex function and its potential sexual transmission.

INTRODUCTION: Severe Acute Respiratory Syndrome Coronavirus 2, (SARS-CoV-2) was first identified by the Chinese Centers for Disease Control and Prevention on January 8, 2020 and was declared as a global pandemic on March 11, 2020 by WHO. SARS-CoV-2 uses the Angiotensin-converting enzyme 2 (ACE2) receptor as an entry route, associated with the transmembrane serine protease protein (TMPRSS2), which makes the testis and particularly spermatogenesis potentially vulnerable, since this tissue has high expression of ACE2. MATERIAL AND METHODS: We performed a systematic literature review by electronic bibliographic databases in Pubmed, Scopus and ScienceDirect up to August 2020 about the effect of SARS-CoV-2 on male sexual function and its transmission, to assess possible repercussions on sex organs and the existence of a sexual transmission path. RESULTS: Although SARS-CoV-2 presence has not been found in testicle samples, it has been demonstrated that it causes histological changes compatible with orchitis, and sex hormone disturbances. TMPRSS2 is up-regulated in prostate cancer where it supports tumor progression, thus these patients may have a higher risk of SARS-CoV-2 infection. TMPRSS2 inhibitors may be useful for the treatment or prevention of COVID-19. No viral material has been found in blood or semen, however it has been proven to be present in stool and saliva. CONCLUSION: The male reproductive system would be highly vulnerable and susceptible to infection by SARS-CoV-2 given the expression of the ACE2 receptor in somatic and germ cells. The seminal fluid would remain free of viral presence in patients with COVID-19. Regardless, non-genital sex could be an important source of viral transmission. In assisted reproduction techniques all necessary tests must be carried out to ensure the donor is free of the virus at the time of collection and handling of the seminal sample.

COVID-19 and human spermatozoa-Potential risks for infertility and sexual transmission?

As COVID-19 infections wreak havoc across the globe, attention has rightly been focused on the vital organ systems (lung, kidney and heart) that are vulnerable to viral attack and contribute to the acute pathology associated with this disease. However, we should not lose sight of the fact that COVID-19 will attack any cell type in the body expressing ACE2 - including human spermatozoa. These cells possess the entire repertoire of receptors (AT1R, AT2R, MAS) and ligand processing enzymes (ACE1 and ACE2) needed to support the angiotensin signalling cascade. The latter not only provides COVID-19 with a foothold on the sperm surface but may also promote integration, given the additional presence of a range of proteases (TMPRSS2, TMPRSS11B, TMPRSS12, furin) capable of promoting viral fusion. This article reviews the roles played by these various cellular constituents in maintaining the vitality of human spermatozoa and their competence for fertilization. The reproductive consequences of a viral attack on these systems, in terms of fertility and the risk of sexual transmission, are currently unknown. However, we should be alive to the possibility that there may be reproductive consequences of COVID-19 infection in young males that go beyond their capacity to survive a viral attack.

It is currently unknown whether SARS-CoV-2 is viable in semen or whether COVID-19 damages spermatozoa.

Research is needed to understand the presence of the SARS-CoV-2 virus in semen, sexual transmissibility, and impact on sperm quality. Several studies have examined men recovering from COVID-19, but large-scale community-based testing is needed to ascertain the effects on the male reproductive tract, and the potential for prolonged transmission.

Follow-Up Household Serosurvey in Northeast Brazil for Zika Virus: Sexual Contacts of Index Patients Have the Highest Risk for Seropositivity.

BACKGROUND: Zika virus (ZIKV) is a mosquito-borne virus that is also transmitted sexually; however, the epidemiological relevance of ZIKV sexual transmission in endemic regions is unclear. METHODS: We performed a household-based serosurvey in Northeast Brazil to evaluate the differential exposure to ZIKV and chikungunya virus (CHIKV) among households. Individuals who participated in our previous arboviral disease cohort (indexes) were recontacted and enrolled, and their household members were newly enrolled. RESULTS: The relative risk of sexual partners being ZIKV-seropositive when living with a ZIKV-seropositive index participant was significantly higher, whereas this was not observed among nonsexual partners of the index. For CHIKV, both sexual and nonsexual partner household members living with a CHIKV-seropositive index had a significantly higher risk of being seropositive. In the nonindex-based dyadic and generalized linear mixed model analyses, the odds of sexual dyads having a concordant ZIKV plaque reduction neutralization test result was significantly higher. We have also analyzed retrospective clinical data according to the participants' exposure to ZIKV and CHIKV. CONCLUSIONS: Our data suggest that ZIKV sexual transmission may be a key factor for the high ZIKV seroprevalence among households in endemic areas and raises important questions about differential disease from the 2 modes of transmission.

Sexual transmission of SARS-CoV-2 virus and its role in the spread of COVID-19: A living systematic review protocol.

OBJECTIVE: To provide a review of the literature on the presence of SARS-CoV-2 in the sexual fluids of patients with COVID-19 and to observe its possible sexual transmission in a timely, rigorous, and continuously updated manner. DATA SOURCES: We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature, and a centralized repository in L·OVE (Living OVerview of Evidence). L·OVE is a platform that maps PICO questions to evidence from the Epistemonikos database. In response to the COVID-19 emergency, L·OVE was adapted to expand the range of evidence it covers and customized to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS: We adapted an already published standard protocol for multiple parallel systematic reviews to the specificities of this question. We will include randomized trials evaluating the sexual transmission of the SARS-CoV-2 virus. Randomized trials evaluating the sexual transmission of other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomized studies in COVID-19 will be searched if no direct evidence from randomized trials is found or if the direct evidence provides a low to a very low level of certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit the review if the conclusions change or if there are substantial updates. PROSPERO REGISTRATION: (CRD42020189368).

OBJETIVO: Proporcionar una revisión de la literatura sobre la presencia de SARS-CoV-2 en los fluidos sexuales de pacientes con COVID-19 y su posible transmisión sexual de manera oportuna, rigurosa y continuamente actualizada. FUENTES DE DATOS: Realizaremos búsquedas en PubMed / Medline, Embase, Registro Cochrane Central de Ensayos Controlados (CENTRAL), literatura gris y en un repositorio centralizado en L · OVE (Living OVerview of Evidence). L · OVE es una plataforma que mapea las preguntas PICO a la evidencia de la base de datos Epistemonikos. En respuesta a la emergencia de COVID-19, L · OVE se adaptó para ampliar el rango de evidencia que cubre y se personalizó para agrupar todas las pruebas de COVID-19 en un solo lugar. La búsqueda cubrirá el período hasta el día anterior al envío a una revista. CRITERIOS DE ELEGIBILIDAD PARA LA SELECCIÓN DE ESTUDIOS Y MÉTODOS: Adaptamos un protocolo común ya publicado para múltiples revisiones sistemáticas paralelas a las especificidades de esta pregunta. Incluiremos ensayos aleatorios que evalúen la transmisión sexual del virus SARS-CoV-2. Se buscarán ensayos aleatorizados que evalúen la transmisión sexual de otros coronavirus, como MERS-CoV y SARS-CoV, y estudios no aleatorizados en COVID-19 en caso de que no se encuentre evidencia directa de ensayos aleatorizados, o si la evidencia directa proporciona una - o certeza muy baja para resultados críticos. Dos revisores evaluarán de forma independiente la elegibilidad de cada estudio, extraerán datos y evaluarán el riesgo de sesgo. Realizaremos metanálisis de efectos aleatorios y utilizaremos GRADE para evaluar la certeza de la evidencia para cada resultado. Una versión viva basada en la web de esta revisión estará disponible abiertamente durante la pandemia de COVID-19. Lo volveremos a enviar si las conclusiones cambian o hay actualizaciones sustanciales. REGISTRO PROSPERO: (CRD42020189368).

Recommendations for reducing the risk of viral transmission during fertility treatment with the use of autologous gametes: a committee opinion.

Sexually transmitted infections are of major concern to reproductive specialists. Heading the list are human immunodeficiency virus types 1 and 2 and hepatitis B and C viruses. These pathogens, which may cause incurable chronic infections, can be transmitted through assisted reproductive technologies and from infected mothers to the fetus or newborn. This document replaces the document of the same name last published in 2013 (Fertil Steril 2013;99:340-6).

Transmisión sexual del virus SARS-CoV-2 y su rol en la propagación de COVID-19: protocolo de una revisión sistemática viva / Sexual transmission of SARS-CoV-2 virus and its role in the spread of COVID-19: a living systematic review protocol

Objetivo Proporcionar una revisión de la literatura sobre la presencia de SARS-CoV-2 en los fluidos sexuales de pacientes con COVID-19 y su posible transmisión sexual de manera oportuna, rigurosa y continuamente actualizada. Fuentes de datos Realizaremos búsquedas en PubMed / Medline, Embase, Registro Cochrane Central de Ensayos Controlados (CENTRAL), literatura gris y en un repositorio centralizado en L · OVE (Living OVerview of Evidence). L · OVE es una plataforma que mapea las preguntas PICO a la evidencia de la base de datos Epistemonikos. En respuesta a la emergencia de COVID-19, L · OVE se adaptó para ampliar el rango de evidencia que cubre y se personalizó para agrupar todas las pruebas de COVID-19 en un solo lugar. La búsqueda cubrirá el período hasta el día anterior al envío a una revista. Criterios de elegibilidad para la selección de estudios y métodos Adaptamos un protocolo común ya publicado para múltiples revisiones sistemáticas paralelas a las especificidades de esta pregunta. Incluiremos ensayos aleatorios que evalúen la transmisión sexual del virus SARS-CoV-2. Se buscarán ensayos aleatorizados que evalúen la transmisión sexual de otros coronavirus, como MERS-CoV y SARS-CoV, y estudios no aleatorizados en COVID-19 en caso de que no se encuentre evidencia directa de ensayos aleatorizados, o si la evidencia directa proporciona una - o certeza muy baja para resultados críticos. Dos revisores evaluarán de forma independiente la elegibilidad de cada estudio, extraerán datos y evaluarán el riesgo de sesgo. Realizaremos metanálisis de efectos aleatorios y utilizaremos GRADE para evaluar la certeza de la evidencia para cada resultado. Una versión viva basada en la web de esta revisión estará disponible abiertamente durante la pandemia de COVID-19. Lo volveremos a enviar si las conclusiones cambian o hay actualizaciones sustanciales Registro PROSPERO (CRD42020189368).

Review on the molecular epidemiology of sexually acquired hepatitis C virus infection in the Asia-Pacific region.

INTRODUCTION: Sexual acquisition has emerged as a transmission route for hepatitis C virus (HCV) of growing importance among human immunodeficiency virus (HIV)-positive populations. In Western countries, HCV epidemics have been increasingly detected among men who have sex with men (MSM). This review describes the molecular epidemiology of sexually acquired HCV infection in the Asia-Pacific region. METHODS: A systematic search was performed on PubMed in March 2019. Either abstract or full-text of each publication in the search results was screened for eligibility. Studies from different countries/cities involving eligible cases, who acquired HCV sexually with identified subtype, were synthesized for the evaluation of molecular epidemiology in the Asia-Pacific region. Two large-scale systematic reviews on the genotype distribution of HCV at a population level and among PWID were used as references for comparison. RESULTS AND DISCUSSION: Overall, 13 full-text articles with 549 subjects originating from nine countries/cities were reviewed. A total of five genotypes and 14 subtypes were identified, dominated by subtypes 1b (23.0%), 2a (19.1%) and 3a (29.5%). A majority of the infected cases occurred in HIV-positive MSM. In some places, notably Hong Kong, India and Indonesia, the predominant subtype in sexually acquired HCV infection in MSM was different from that circulating in the general population. Shared transmission networks between people who inject drugs (PWID) and MSM were shown in Australia and New Zealand, whereas overlapping risk elicited from a small number of subjects existed in Tokyo, Taipei and Guangxi. MSM-specific clusters were identified in Hong Kong, Taipei and Hubei. CONCLUSIONS: The distribution of sexually acquired HCV was sparsely scattered across countries/cities in the Asia-Pacific region. The threat of overlapping risk differed by locations, whereas transnational outbreaks remained uncommon. The paucity of information has hindered progress with comprehensive assessment in the Asia-Pacific region, where seroprevalence of HCV among HIV-positive MSM was relatively high.

Can a health care worker have sex in the time of COVID-19?

Covid-19 is not transmitted by sex but close proximity during the act could aide in spread of the disease. Health care workers by virtue of the nature of their work have higher chances of exposure to the virus and them indulging in sex needs risk reduction strategies.

Twenty-First Century Viral Pandemics: A Literature Review of Sexual Transmission and Fertility Implications in Men.

INTRODUCTION: The 21st century has seen a series of viral pandemics that have collectively infected millions of individuals. To understand factors that may contribute to viral spread and address long-term health sequelae for survivors, it is important to review evidence regarding viral presence in semen, sexual transmission potential, and possible effects on fertility. AIM: To review the current literature regarding the sexual transmissibility of recent viral pandemics and their effects on semen parameters and fertility. We review evidence for the following viruses: Ebola, Zika, West Nile, pandemic influenza, severe acute respiratory syndrome (SARS), and SARS-corona virus-2 (SARS-CoV-2). METHODS: A literature search was conducted to identify relevant studies. Titles and abstracts were reviewed for relevance. References from identified articles were searched and included, if appropriate. MAIN OUTCOME MEASURES: The main outcome measure of this study was reviewing of peer-reviewed literature. RESULTS: Both the Ebola virus and Zika virus are present in semen, but only the Zika virus shows consistent evidence of sexual transmission. Current evidence does not support the presence of the West Nile virus, pandemic influenza, SARS, and SARS-CoV-2 in semen. The Zika virus appears to alter semen parameters in a way that diminishes fertility, but the effect is likely time limited. The West Nile virus and SARS have been associated with orchitis in a small number of case reports. Viruses that cause febrile illness, such as pandemic influenza, SARS, and SARS-CoV-2, are associated with decreased sperm count and motility and abnormal morphology. SARS and SARS-CoV-2 may interact with angiotensin-converting enzyme 2 receptors present in the testes, which could impact spermatogenesis. CONCLUSIONS: We have reported the presence in semen, sexual transmission potential, and fertility side effects of recent viral pandemics. Overall, semen studies and fertility effects are highly understudied in viral pandemics, and rigorous study on these topics should be undertaken as novel pandemics emerge. Payne K, Kenny P, Scovell JM, et al. Twenty-First Century Viral Pandemics: A Literature Review of Sexual Transmission and Fertility Implications for Men. Sex Med Rev 2020;8:518-530.

Estimation of mosquito-borne and sexual transmission of Zika virus in Australia: Risks to blood transfusion safety.

BACKGROUND: Since 2015, Zika virus (ZIKV) outbreaks have occurred in the Americas and the Pacific involving mosquito-borne and sexual transmission. ZIKV has also emerged as a risk to global blood transfusion safety. Aedes aegypti, a mosquito well established in north and some parts of central and southern Queensland, Australia, transmits ZIKV. Aedes albopictus, another potential ZIKV vector, is a threat to mainland Australia. Since these conditions create the potential for local transmission in Australia and a possible uncertainty in the effectiveness of blood donor risk-mitigation programs, we investigated the possible impact of mosquito-borne and sexual transmission of ZIKV in Australia on local blood transfusion safety. METHODOLOGY/PRINCIPAL FINDINGS: We estimated 'best-' and 'worst-' case scenarios of monthly reproduction number (R0) for both transmission pathways of ZIKV from 1996-2015 in 11 urban or regional population centres, by varying epidemiological and entomological estimates. We then estimated the attack rate and subsequent number of infectious people to quantify the ZIKV transfusion-transmission risk using the European Up-Front Risk Assessment Tool. For all scenarios and with both vector species R0 was lower than one for ZIKV transmission. However, a higher risk of a sustained outbreak was estimated for Cairns, Rockhampton, Thursday Island, and theoretically in Darwin during the warmest months of the year. The yearly estimation of the risk of transmitting ZIKV infection by blood transfusion remained low through the study period for all locations, with the highest potential risk estimated in Darwin. CONCLUSIONS/SIGNIFICANCE: Given the increasing demand for plasma products in Australia, the current strategy of restricting donors returning from infectious disease outbreak regions to source plasma collection provides a simple and effective risk management approach. However, if local transmission was suspected in the main urban centres of Australia, potentially facilitated by the geographic range expansion of Ae. aegypti or Ae. albopictus, this mitigation strategy would need urgent review.

Modeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey.

Mosquito-borne and sexual transmission of Zika virus (ZIKV), a TORCH pathogen, recently initiated a series of large epidemics throughout the Tropics. Animal models are necessary to determine transmission risk and study pathogenesis, as well screen antivirals and vaccine candidates. In this study, we modeled mosquito and sexual transmission of ZIKV in the African green monkey (AGM). Following subcutaneous, intravaginal or intrarectal inoculation of AGMs with ZIKV, we determined the transmission potential and infection dynamics of the virus. AGMs inoculated by all three transmission routes exhibited viremia and viral shedding followed by strong virus neutralizing antibody responses, in the absence of clinical illness. All four of the subcutaneously inoculated AGMs became infected (mean peak viremia: 2.9 log10 PFU/mL, mean duration: 4.3 days) and vRNA was detected in their oral swabs, with infectious virus being detected in a subset of these specimens. Although all four of the intravaginally inoculated AGMs developed virus neutralizing antibody responses, only three had detectable viremia (mean peak viremia: 4.0 log10 PFU/mL, mean duration: 3.0 days). These three AGMs also had vRNA and infectious virus detected in both oral and vaginal swabs. Two of the four intrarectally inoculated AGMs became infected (mean peak viremia: 3.8 log10 PFU/mL, mean duration: 3.5 days). vRNA was detected in oral swabs collected from both of these infected AGMs, and infectious virus was detected in an oral swab from one of these AGMs. Notably, vRNA and infectious virus were detected in vaginal swabs collected from the infected female AGM (peak viral load: 7.5 log10 copies/mL, peak titer: 3.8 log10 PFU/mL, range of detection: 5-21 days post infection). Abnormal clinical chemistry and hematology results were detected and acute lymphadenopathy was observed in some AGMs. Infection dynamics in all three AGM ZIKV models are similar to those reported in the majority of human ZIKV infections. Our results indicate that the AGM can be used as a surrogate to model mosquito or sexual ZIKV transmission and infection. Furthermore, our results suggest that AGMs are likely involved in the enzootic maintenance and amplification cycle of ZIKV.