A Comparison of Clinical and Epidemiological Characteristics of Fatal Human Infections with H5N1 and Human Influenza Viruses in Thailand, 2004–2006

Shinde, Vivek; Hanshaoworakul, Wanna; Simmerman, James Mark; Narueponjirakul, Ubolrat; Sanasuttipun, Wiwan; Kaewchana, Suchada; Areechokechai, Darin; Ungchusak, Kumnuan; Fry, Alicia M.

doi:10.1371/journal.pone.0014809

Cited by 24 publications

(27 citation statements)

References 18 publications

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“…One typical laboratory finding in human cases of H5N1 is marked lymphopenia. Comparison of the lymphocyte count of fatal and nonfatal cases of H5N1-infected patients has shown significantly lower lymphocyte counts in fatal cases [8]. Decreased lymphocyte count is correlated with impaired viral clearance as well as a longer course of disease.…”

Section: Discussionmentioning

confidence: 99%

The presence of monocytes enhances the susceptibility of B cells to highly pathogenic avian influenza (HPAI) H5N1 virus possibly through the increased expression of α2,3 SA receptor

Lersritwimanmaen

Na-Ek

Thanunchai

et al. 2015

Biochemical and Biophysical Research Communications

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Section: Discussionmentioning

confidence: 99%

The presence of monocytes enhances the susceptibility of B cells to highly pathogenic avian influenza (HPAI) H5N1 virus possibly through the increased expression of α2,3 SA receptor

Lersritwimanmaen

Na-Ek

Thanunchai

et al. 2015

Biochemical and Biophysical Research Communications

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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%

“…Fatal infection with H5N1 has been associated with acute respiratory distress syndrome (ARDS) (9)(10)(11), multiple organ failure (12)(13)(14)(15)(16)(17)(18), and encephalitis (19), but overall, few human autopsies have been conducted and it is difficult to determine the contribution of systemic infection to case fatality rates. 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).…”

mentioning

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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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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“…The median duration between admission and death was shorter than that reported in Indonesia, (one compared to three days), with more patients dying on the day of admission (44% in Cambodia versus 12% in Indonesia) [23]. This contrasts with Thailand where fatal cases were hospitalised for a median of six days before death [24]. The death of the majority of patients within two days of hospitalisation suggests that, like those patients in Indonesia, the Cambodian cases had progressed to a stage when treatment was unlikely to impact on clinical outcome [23].…”

Section: Discussionmentioning

confidence: 99%

Human H5N1 influenza infections in Cambodia 2005–2011: case series and cost-of-illness

Humphries-Waa¹,

Drake²,

Huszar³

et al. 2013

BMC Public Health

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BackgroundSoutheast Asia has been identified as a potential epicentre of emerging diseases with pandemic capacity, including highly pathogenic influenza. Cambodia in particular has the potential for high rates of avoidable deaths from pandemic influenza due to large gaps in health system resources. This study seeks to better understand the course and cost-of-illness for cases of highly pathogenic avian influenza in Cambodia.MethodsWe studied the 18 laboratory-confirmed cases of avian influenza subtype H5N1 identified in Cambodia between January 2005 and August 2011. Medical records for all patients were reviewed to extract information on patient characteristics, travel to hospital, time to admission, diagnostic testing, treatment and disease outcomes. Further data related to costs was collected through interviews with key informants at district and provincial hospitals, the Ministry of Health and non-governmental organisations. An ingredient-based approach was used to estimate the total economic cost for each study patient. Costing was conducted from a societal perspective and included both financial and opportunity costs to the patient or carer. Sensitivity analysis was undertaken to evaluate potential change or variation in the cost-of-illness.ResultsOf the 18 patients studied, 11 (61%) were under the age of 18 years. The majority of patients (16, 89%) died, eight (44%) within 24 hours of hospital admission. There was an average delay of seven days between symptom onset and hospitalisation with patients travelling an average of 148 kilometres (8-476 km) to the admitting hospital. Five patients were treated with oseltamivir of whom two received the recommended dose. For the 16 patients who received all their treatment in Cambodia the average per patient cost of H5N1 influenza illness was US$300 of which 85.0% comprised direct medical provider costs, including diagnostic testing (41.2%), pharmaceuticals (28.4%), hospitalisation (10.4%), oxygen (4.4%) and outpatient consultations (0.6%). Patient or family costs were US$45 per patient (15.0%) of total economic cost.ConclusionCases of avian influenza in Cambodia were characterised by delays in hospitalisation, deficiencies in some aspects of treatment and a high fatality rate. The costs associated with medical care, particularly diagnostic testing and pharmaceutical therapy, were major contributors to the relatively high cost-of-illness.

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A Comparison of Clinical and Epidemiological Characteristics of Fatal Human Infections with H5N1 and Human Influenza Viruses in Thailand, 2004–2006

Cited by 24 publications

References 18 publications

The presence of monocytes enhances the susceptibility of B cells to highly pathogenic avian influenza (HPAI) H5N1 virus possibly through the increased expression of α2,3 SA receptor

The presence of monocytes enhances the susceptibility of B cells to highly pathogenic avian influenza (HPAI) H5N1 virus possibly through the increased expression of α2,3 SA receptor

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

Human H5N1 influenza infections in Cambodia 2005–2011: case series and cost-of-illness

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