Clinical Features of Human Influenza A (H5N1) Infection in Vietnam: 2004–2006

Liêm, Nguyễn Thanh; Tùng, Cao Việt; Hiền, Nguyễn Đức; Hien, Tran Tinh; Chau, Ngo Quy; Long, Hoang Thuy; Hiển, Nguyễn Trần; Quynh, Lê; Taylor, Walter; Wertheim, Heiman; Farrar, Jeremy; Kháng, Đinh Duy; Horby, Peter

doi:10.1086/599031

Cited by 126 publications

(147 citation statements)

References 41 publications

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“…An acute respiratory disease characterizes H5N1 influenza virus infection in humans (1,5,13). The respiratory tract is the site of virus replication, and a combination of host-virus interactions modulates the severity and outcome of the disease.…”

Section: Resultsmentioning

confidence: 99%

Intranasal Delivery of an IgA Monoclonal Antibody Effective against Sublethal H5N1 Influenza Virus Infection in Mice

Shao

Hickman

et al. 2010

Clin Vaccine Immunol

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Section: Resultsmentioning

confidence: 99%

Intranasal Delivery of an IgA Monoclonal Antibody Effective against Sublethal H5N1 Influenza Virus Infection in Mice

Shao

Hickman

et al. 2010

Clin Vaccine Immunol

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“…Some autopsy reports indicate that infection was limited to the respiratory and gastrointestinal tracts (9, 20), while others have isolated virus from the brain and gastrointestinal tract (21) or serum and cerebrospinal fluid (CSF) (22)(23)(24) or detected viral mRNA in the brain (21, 25). Measurements from blood samples taken early during the infectious period link severe disease outcomes with lymphopenia and hypercytokinemia (2,10,14,26), while the presence of high loads of negative-sense …”

mentioning

confidence: 99%

“…During an H5N1 outbreak, when the supply of oseltamivir may be limited, its prescription may be prioritized to individuals in high-risk exposure groups; for example, people who have had close contact with H5N1 virusinfected birds or patients (28). For a better-informed decision when prioritizing oseltamivir treatment, a more precise understanding of what constitutes high-risk groups is required, because for natural exposure, the source of virus is ambiguous, usually based on an anecdote provided by the patient or the patient's family (26). Furthermore, the characterization of high-risk exposure is based on the assumption that all mucosal sites of initial viral deposition are equally permissive to infection; however, differences between mucosal sites, such as receptor distribution, temperature, and pH, may contradict this assumption.…”

mentioning

confidence: 99%

“…However, some differences between the two species in response to H5N1 have been noted. Infected humans frequently show progression to ARDS, but neurological disease is rarely manifested (2,13,14,19,21,26,32,33), while detection of virus in the brain and neurological disease are common in ferrets experimentally infected by the total respiratory tract (TRT) route (34,35). H5N1 virus spread outside the respiratory tract in ferrets has enabled this model to be employed as a means to study the anatomical pathways of viral dissemination.…”

mentioning

confidence: 99%

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Predicting Disease Severity and Viral Spread of H5N1 Influenza Virus in Ferrets in the Context of Natural Exposure Routes

Edenborough

Lowther

Laurie

et al. 2016

J Virol

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Although avian H5N1 influenza virus has yet to develop the capacity for human-to-human spread, the severity of the rare cases of human infection has warranted intensive follow-up of potentially exposed individuals that may require antiviral prophylaxis. For countries where antiviral drugs are limited, the World Health Organization (WHO) has developed a risk categorization for different levels of exposure to environmental, poultry, or human sources of infection. While these take into account the infection source, they do not account for the likely mode of virus entry that the individual may have experienced from that source and how this could affect the disease outcome. Knowledge of the kinetics and spread of virus after natural routes of exposure may further inform the risk of infection, as well as the likely disease severity. Using the ferret model of H5N1 infection, we compared the commonly used but artificial inoculation method that saturates the total respiratory tract (TRT) with virus to upper respiratory tract (URT) and oral routes of delivery, those likely to be encountered by humans in nature. We show that there was no statistically significant difference in survival rate with the different routes of infection, but the disease characteristics were somewhat different. Following URT infection, viral spread to systemic organs was comparatively delayed and more focal than after TRT infection. By both routes, severe disease was associated with early viremia and central nervous system infection. After oral exposure to the virus, mild infections were common suggesting consumption of virus-contaminated liquids may be associated with seroconversion in the absence of severe disease. IMPORTANCERisks for human H5N1 infection include direct contact with infected birds and frequenting contaminated environments. We used H5N1 ferret infection models to show that breathing in the virus was more likely to produce clinical infection than swallowing contaminated liquid. We also showed that virus could spread from the respiratory tract to the brain, which was associated with end-stage disease, and very early viremia provided a marker for this. With upper respiratory tract exposure, infection of the brain was common but hard to detect, suggesting that human neurological infections might be typically undetected at autopsy. However, viral spread to systemic sites was slower after exposure to virus by this route than when virus was additionally delivered to the lungs, providing a better therapeutic window. In addition to exposure history, early parameters of infection, such as viremia, could help prioritize antiviral treatments for patients most at risk of succumbing to infection. Since the emergence of highly pathogenic avian influenza H5N1 in humans in 1997, outbreaks have occurred sporadically, primarily in populations associated with direct contact with sick birds (1-4). Currently, outbreaks occur in regions where H5N1 is endemic in migratory birds and where a large proportion of the population rear backyard poultry ...

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“…A large number of H5N1 patients present with diarrhea. In fact, one retrospective report documenting the clinical features of H5N1 in Vietnam found that diarrhea was more common in fatal than nonfatal H5N1 cases [23].…”

Section: H5n1mentioning

confidence: 99%

NS1 of H5N1 Interacts with SAP-97 in a PDZ-dependent Manner to Disrupt Epithelial Barrier Integrity

Conoley¹

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Clinical Features of Human Influenza A (H5N1) Infection in Vietnam: 2004–2006

Abstract: In cases of infection with Influenza A (H5N1), the presence of both neutropenia and raised serum transaminase levels predicts a poor outcome. Oseltamivir treatment shows benefit, but treatment with corticosteroids is associated with an increased risk of death.

Cited by 126 publications

References 41 publications

Intranasal Delivery of an IgA Monoclonal Antibody Effective against Sublethal H5N1 Influenza Virus Infection in Mice

Intranasal Delivery of an IgA Monoclonal Antibody Effective against Sublethal H5N1 Influenza Virus Infection in Mice

Predicting Disease Severity and Viral Spread of H5N1 Influenza Virus in Ferrets in the Context of Natural Exposure Routes

NS1 of H5N1 Interacts with SAP-97 in a PDZ-dependent Manner to Disrupt Epithelial Barrier Integrity

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