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Contact: Stephen M. Apatow, Director of Research and Development, Humanitarian University Consortium GraduateStudies Center for Medicine, Veterinary Medicine and Law.  Email:

Archive Number:  20060905.2522
Published Date: 05-SEP-2006
Subject: PRO/AH> Avian influenza, human (140): atypical infections

A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases

Date: Mon 4 Sep 2006
From: Stephen M. Apatow <>

Comments on WHO Case Definitions and Atypical H5N1 Infections
In the context of the WHO case definitions for human infections with influenza A(H5N1) virus, it appears that atypical infections continue to be excluded from the potential clinical spectrum of challenge:

See: <> (29 Aug 2006), or  ProMED-mail post "Avian influenza, human (133): WHO case definitions" 20060830.2467.

WHO has defined a suspect case as: A person presenting with unexplained acute lower respiratory illness with fever (>38 C [100.4 F]) and cough, shortness of breath or difficulty breathing. And one or more of the following exposures in the 7 days prior to symptom onset:

a. Close contact (within 1 metre) with a person (e.g. caring for, speaking with, or touching) who is a suspected, probable, or confirmed H5N1 case;
b. Exposure (e.g. handling, slaughtering, defeathering, butchering, preparation for consumption) to poultry or wild birds or their remains or to environments contaminated by their faeces in an area where H5N1 infections in animals or humans have been suspected or confirmed in the last month;
c. Consumption of raw or undercooked poultry products in an area where H5N1 infections in animals or humans have been suspected or confirmed in the last month;
d. Close contact with a confirmed H5N1 infected animal other than poultry or wild birds (e.g. cat or pig);
e. Handling samples (animal or human) suspected of containing H5N1 virus in a laboratory or other setting.

However, the following references indicate that atypical infections (encephalitis, diarrheal, gastrointestinal illness) are a serious concern associated with outbreaks of avian influenza A subtype H5N1 worldwide (See: <>: Emerging Infectious Diseases, Vol. 10, No. 7, July 2004; and <>, NEJM, Volume 352:686-691, 17 Feb 2005, Number 7).

Furthermore, European researchers have reported what they call the first evidence that low-pathogenic avian influenza (LPAI) viruses, and not just highly pathogenic (HPAI) strains like H5N1, can infect humans. The finding, in a study of Italian poultry workers, suggests that avian influenza viruses have more chances than previously suspected to mix with human influenza viruses, potentially creating hybrids that could trigger a human influenza pandemic, according to a report published online by the Journal of Infectious Diseases (See: Low-pathogenic Avian Influenza (LPAI) Viruses Can Infect Humans <>, and ProMED-mail post "Avian influenza, human: LPAI susceptibility" 20050918.2759).

Diarrhea and the detection of viral RNA in most fecal samples tested has been a frequent observation suggesting that H5N1 virus may replicate in the human gastrointestinal tract. This raises the question of whether human feces could be a source of transmission. (See the Editorial Commentary on the Puzelli et al. paper by
Frederick Hayden and Alice Croisier in the journal of Infectious Diseases, 15 Oct 2005

Examples of Asymptomatic Human Infection
(1) Four South Koreans were infected with the H5N1 strain of bird flu in late 2003 and early 2004, but none of them developed any serious illness, an official said 24 Feb 2006. (See: <>).

(2) Three asymptomatic infections have been documented among close contacts of confirmed cases in Viet Nam suggesting that milder H5N1 infections are occurring. Four persons who culled H5N1 infected birds in Japan and 2 animal attendants caring for infected tigers in Thailand also have antibodies to H5 virus. Asymptomatic infections were also detected retrospectively in Hong Kong following the 1997 outbreak. (See: <>).

(3) On 9 Mar 2005 Vietnamese health authorities released information about 2 such cases. Nguyen Tran Hien, director of the National Institute for Hygiene and Epidemiology, confirmed that lab tests showed that a 61-year-old woman from northern Thai Binh province had contracted the H5N1 virus but was not showing any symptoms. (See: <>).

(4) Two elderly relatives of people in Vietnam who died of bird influenza have tested positive for the disease, despite having no symptoms. Samples from another 7 cases that originally tested negative in Viet Nam in January were re-tested in Tokyo and found to carry the virus, according to the World Health Organization. (See: <>).

(5) Dr Charoen Chuchottaworn, a bird-flu expert at the [Thai] Public Health Ministry's Department of Medical Services, said doctors concluded after reviewing the history of the past 2 cases that bothvictims presented very mild symptoms of avian influenza and neither had any physical contact with chickens or birds. (See: <>.

While much has been made of the fulminant cases of presumed viral pneumonia in 1918, Dr. Brundage's research indicates that the majority of pneumonia cases, even in 1918, were either secondary bacterial pneumonias following an influenza infection or mixed viral and bacterial pneumonias. In the pre-antibiotic era, these cases of
bacterial pneumonia carried a very high mortality rate; however, with appropriate antibiotic therapy, many such patients may be saved.

Stephen M. Apatow

[There is still a deficit of comprehensive seroprevalence data to establish the true frequency of subclinical infections and the relevance of these sporadic accounts of atypical infections listed above. For a discussion of this topic and an evaluation of some published seroprevalence studies, the reader is referred to the ProMED-mail posts archived as Avian influenza, human - Eurasia (41): multicountry 20060130.0290 and Avian influenza, human - East Asia (195): China 20051208.3538. - Mod.CP]

[see also:
Avian influenza, human (133): WHO case definitions 20060830.2467
Avian influenza, human - Eurasia (41): multicountry 20060130.0290
Avian influenza, human - East Asia (195): China 20051208.3538
Avian influenza, human: LPAI susceptibility 20050918.2759]


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