Risk Factors Associated with Subclinical Human Infection with Avian Influenza A (H5N1) Virus—Cambodia, 2006

Vong, Sirenda; Ly, Sowath; Kerkhove, Maria D. Van; Achenbach, Jenna E.; Holl, Davun; Buchy, Philippe; Sorn, San; Heng, Seng; Uyeki, Timothy M.; Touch, Sok; Katz, Jacqueline M.

doi:10.1086/599208

Cited by 90 publications

(91 citation statements)

References 29 publications

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“…TRT infections were performed by administering 500 l of phosphatebuffered saline (PBS) containing 10 6 50% egg infectious doses (EID 50 ) to the nares of sedated ferrets in a dropwise manner as previously described (41). Administering Evans blue dye in this manner demonstrated that the TRT infection method dispersed the inoculum throughout the nasal and oral cavities, the trachea, the lungs, and the esophagus.…”

Section: Virusmentioning

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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Section: Virusmentioning

confidence: 99%

“…An additional experiment infecting ferrets with 10 3.5 50% tissue culture infective doses (TCID 50 ) of A/Port Chalmers/1/73 virus as a TRT infection was also performed.…”

Section: Virusmentioning

confidence: 99%

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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“…It was also likely that both cases inhaled dust while sitting, playing, crawling, or working on the ground. Direct hand contact with environments or inhalation of dust contaminated by A(H5N1) virus during poultry outbreaks have been previously identified as risk factors for A(H5N1) virus infection in humans in Cambodia [36,37]. However, due to the lack of environmental sampling in this investigation, this route of transmission to the cases could not be confirmed.…”

Section: Discussionmentioning

confidence: 70%

Two clustered cases of confirmed influenza A(H5N1) virus infection, Cambodia, 2011

Chea¹,

Rith

et al. 2014

Eurosurveillance

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“…Factors that may contribute to undercounting are the diffi culty of obtaining virologic confi rmation or of storing and transporting samples in resource-poor settings and reluctance by relatives to consent to autopsy. Another reason to believe that less fulminant cases may go unreported is the occurrence in Pakistan, and elsewhere, of clinically mild and asymptomatic cases (5,(8)(9)(10)(11)(12)(13)(14), indicating that infl uenza (H5N1) virus may cause a spectrum of illness. The demonstration during the 1997 Hong Kong outbreak of infl uenza (H5N1) with seroconversion in apparently asymptomatic health care workers and social contacts suggests human-to-human transmission, although in Hanoi, no transmission to health care workers was detected (8,13,15).…”

Section: Discussionmentioning

confidence: 99%

Human Infection with Avian Influenza Virus, Pakistan, 2007

Zaman¹,

Ashraf²,

Dreyer³

et al. 2011

Emerg. Infect. Dis.

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Human infection with avian infl uenza (H5N1) virus raises concern for the possibility of a pandemic. We report 20 cases, which ranged from asymptomatic to fatal, in Pakistan in 2007. These cases indicate human-to-humanto-human transmission of this virus, and the number of cases may be higher than realized. 2). We report a larger set of 20 cases during this outbreak in Pakistan, supporting human-to-human-to-human transmission. The CasesRecords were examined from all hospitals that treated patients with infl uenza (H5N1) virus in Northwest Frontier Province during 2007. Data were rendered anonymous and entered into a secure database with predetermined clinical and epidemiologic fi elds. Cases matching predefi ned criteria (Table 1) were classifi ed as laboratory confi rmed, likely, or possible. Cases not meeting classifi cation criteria were excluded. We slightly modifi ed WHO criteria to resemble criteria that clinicians might adopt during an actual outbreak, especially in a resource-poor setting (3).We identifi ed 20 cases-4 laboratory confi rmed, 7 likely, and 9 possible-resulting in a ratio of 4 likely/ possible cases for each laboratory-confi rmed case. Median age was 29 years (range 7-60 years) for all patients and 30 years (range 23-35 years) for confi rmed case-patients; 16 (80%) patients were male. The infecting exposure could not be established for all patients because multiple exposures, human and avian, were recorded for some. Of the 4 patients with laboratory-confi rmed cases, 3 were treated with oseltamivir (2 [67%] of whom survived), and 1 had asymptomatic disease and received no antiviral treatment.

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Risk Factors Associated with Subclinical Human Infection with Avian Influenza A (H5N1) Virus—Cambodia, 2006

Abstract: Avian-to-human transmission of influenza H5N1 virus remains low, despite extensive poultry contact. Exposure to a potentially contaminated environment was a risk factor for human infection.

Cited by 90 publications

References 29 publications

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

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

Two clustered cases of confirmed influenza A(H5N1) virus infection, Cambodia, 2011

Human Infection with Avian Influenza Virus, Pakistan, 2007

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