Dataset Information

Ocular Findings in Yellow Fever Infection.

ABSTRACT:

Importance

Yellow fever virus (YFV) is a reemerging, potentially lethal arboviral disease that has been occurring recently in Africa and South America. Poor levels of immunization have facilitated the viral spread in southeastern Brazil, leading to an unprecedented outbreak that started in late 2016. Although human cases have been linked to sylvatic mosquitoes, the concern is that YFV may spread to urban centers infested with Aedes aegypti and Aedes albopictus mosquitoes and start a true urban cycle.

Objective

To describe the ocular findings in patients with acute YFV infection.

Design, setting, participants

Two adults with an acute YFV infection in southeastern Brazil underwent an ophthalmologic and ocular ultrasonographic examination in early 2018.

Main outcomes and measures

Ocular findings in patients with acute YFV infection.

Results

Both patients presented with increased choroidal thickness bilaterally seen on ocular ultrasonography. A man in his late 50s who had not been vaccinated previously also presented with bilateral, midperipheral, 360° choroidal detachment and yellowish subretinal lesions. After clinical deterioration and liver transplant, the man died. A woman in her early 30s who had been vaccinated previously for YFV presented with increased retinal venous congestion bilaterally. She was discharged with mild conjunctival chemosis and icterus.

Conclusions and relevance

These reports describe different patterns of ocular findings associated with YFV acute infection. However, the exact mechanism involved in the retinal and choroidal findings remains unclear.

SUBMITTER: Vianello S

PROVIDER: S-EPMC6439724 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ocular Findings in Yellow Fever Infection.

Vianello Silvana S Silva de Souza Gláucio G Maia Maurício M Belfort Rubens R de Oliveira Dias João Rafael JR

JAMA ophthalmology 20190301 3

<h4>Importance</h4>Yellow fever virus (YFV) is a reemerging, potentially lethal arboviral disease that has been occurring recently in Africa and South America. Poor levels of immunization have facilitated the viral spread in southeastern Brazil, leading to an unprecedented outbreak that started in late 2016. Although human cases have been linked to sylvatic mosquitoes, the concern is that YFV may spread to urban centers infested with Aedes aegypti and Aedes albopictus mosquitoes and start a true ...[more]

PMID: 30629101

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Project description:Zika virus (ZIKV) emerged as an important infectious disease agent in Brazil in 2016. Infection usually leads to mild symptoms, but severe congenital neurological disorders and Guillain-Barré syndrome have been reported following ZIKV exposure. Creating an effective vaccine against ZIKV is a public health priority. We describe the protective effect of an already licensed attenuated yellow fever vaccine (YFV, 17DD) in type-I interferon receptor knockout mice (A129) and immunocompetent BALB/c and SV-129 (A129 background) mice infected with ZIKV. YFV vaccination provided protection against ZIKV, with decreased mortality in A129 mice, a reduction in the cerebral viral load in all mice, and weight loss prevention in BALB/c mice. The A129 mice that were challenged two and three weeks after the first dose of the vaccine were fully protected, whereas partial protection was observed five weeks after vaccination. In all cases, the YFV vaccine provoked a substantial decrease in the cerebral viral load. YFV immunization also prevented hippocampal synapse loss and microgliosis in ZIKV-infected mice. Our vaccine model is T cell-dependent, with AG129 mice being unable to tolerate immunization (vaccination is lethal in this mouse model), indicating the importance of IFN-γ in immunogenicity. To confirm the role of T cells, we immunized nude mice that we demonstrated to be very susceptible to infection. Immunization with YFV and challenge 7 days after booster did not protect nude mice in terms of weight loss and showed partial protection in the survival curve. When we evaluated the humoral response, the vaccine elicited significant antibody titers against ZIKV; however, it showed no neutralizing activity in vitro and in vivo. The data indicate that a cell-mediated response promotes protection against cerebral infection, which is crucial to vaccine protection, and it appears to not necessarily require a humoral response. This protective effect can also be attributed to innate factors, but more studies are needed to strengthen this hypothesis. Our findings open the way to using an available and inexpensive vaccine for large-scale immunization in the event of a ZIKV outbreak.

Project description:Mosquito-borne yellow fever virus (YFV) causes highly lethal, viscerotropic disease in humans and non-human primates. Despite the availability of efficacious live-attenuated vaccine strains, 17D-204 and 17DD, derived by serial passage of pathogenic YFV strain Asibi, YFV continues to pose a significant threat to human health. Neither the disease caused by wild-type YFV, nor the molecular determinants of vaccine attenuation and immunogenicity, have been well characterized, in large part due to the lack of a small animal model for viscerotropic YFV infection. Here, we describe a small animal model for wild-type YFV that manifests clinical disease representative of that seen in primates without adaptation of the virus to the host, which was required for the current hamster YF model. Investigation of the role of type I interferon (IFN-alpha/beta) in protection of mice from viscerotropic YFV infection revealed that mice deficient in the IFN-alpha/beta receptor (A129) or the STAT1 signaling molecule (STAT129) were highly susceptible to infection and disease, succumbing within 6-7 days. Importantly, these animals developed viscerotropic disease reminiscent of human YF, instead of the encephalitic signs typically observed in mice. Rapid viremic dissemination and extensive replication in visceral organs, spleen and liver, was associated with severe pathologies in these tissues and dramatically elevated MCP-1 and IL-6 levels, suggestive of a cytokine storm. In striking contrast, infection of A129 and STAT129 mice with the 17D-204 vaccine virus was subclinical, similar to immunization in humans. Although, like wild-type YFV, 17D-204 virus amplified within regional lymph nodes and seeded a serum viremia in A129 mice, infection of visceral organs was rarely established and rapidly cleared, possibly by type II IFN-dependent mechanisms. The ability to establish systemic infection and cause viscerotropic disease in A129 mice correlated with infectivity for A129-derived, but not WT129-derived, macrophages and dendritic cells in vitro, suggesting a role for these cells in YFV pathogenesis. We conclude that the ability of wild-type YFV to evade and/or disable components of the IFN-alpha/beta response may be primate-specific such that infection of mice with a functional IFN-alpha/beta antiviral response is attenuated. Consequently, subcutaneous YFV infection of A129 mice represents a biologically relevant model for studying viscerotropic infection and disease development following wild-type virus inoculation, as well as mechanisms of 17D-204 vaccine attenuation, without a requirement for adaptation of the virus.

Dataset Information

Ocular Findings in Yellow Fever Infection.

Importance

Objective

Design, setting, participants

Main outcomes and measures

Results

Conclusions and relevance

Publications

Ocular Findings in Yellow Fever Infection.

Similar Datasets

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