Date: Thu 7 May 2009
Source: Eurosurveillance, Volume 14, Issue 18 [edited]
<http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=1919>
Age-specific infection and death rates for human A(H5N1) avian
influenza in Egypt. By J. P. Dudley, Science Applications
International Corporation, Modeling and Analysis Division, Rockville,
Maryland, United States
-----------------------------------------------
The age-specific infection and death profiles among confirmed human
cases of influenza A(H5N1) infection in Egypt differ markedly from
those recorded in other countries. The case fatality rate among human
H5N1 cases in Egypt is 34 percent, versus an average of 66 percent in
other countries. In Egypt, children younger than 10 years comprise 48
percent of reported cases, nearly twice the global average of
approximately 25 percent, and no H5N1 fatalities have been confirmed
among individuals in this age group as of 23 Apr 2009. Females
outnumber males among confirmed H5N1 cases by a factor of nearly 2:1,
and 90 percent of reported fatalities in Egypt have been females. The
evident age and sex biases in morbidity and mortality among H5N1
cases in Egypt are phenomena that warrant further investigation and analysis.
Introduction:
The 1st cases of human infection with avian influenza type A(H5N1)
were reported from Egypt in March 2006, and a cumulative total of 67
confirmed cases including 23 fatalities have been reported as of 23
Apr 2009 [1]. There are evident anomalies in the age distribution and
sex ratio of human mortality from influenza A(H5N1) in Egypt relative
to those reported from other countries that warrant detailed
investigation and analysis.
Methods:
Published information on human H5N1 cases in Egypt was analysed to
develop a 1st order comparative analysis of age-specific and
sex-specific infection and mortality patterns between human H5N1
cases in Egypt and those in other areas of the world. The age and
case history data of patients with confirmed influenza A(H5N1)
infection in Egypt used in this analysis were derived from reports
published by the United States Naval Medical Research Unit No. 3 in
Cairo, Egypt [2] and the World Health Organization (WHO), available
as of 23 Apr 2009 [1].
Results:
Human H5N1 cases in Egypt are most frequently reported among children
younger than 10 years, and approximately 80 percent of all reported
cases have occurred among individuals under the age of 30 years. In
Egypt, children under the age of 10 years comprise 48 percent of all
reported cases, nearly double the current global average of
approximately 25 percent [3]. A median age of 8 years has been
reported for human H5N1 cases in Egypt between March 2006 and March
2009 [2], versus a median age of 18 years for WHO-confirmed human
cases globally between November 2003 and November 2006 [4].
The age-specific infection and death profiles among confirmed human
A(H5N1) cases in Egypt differ markedly from those recorded in Asia
and Indonesia when compared to cumulative data for countries
worldwide other than Egypt, Nigeria, and Turkey [These data are
illustrated by 2 figures in the original text.]. The case fatality
rate from human H5N1 cases in Egypt confirmed as of 23 Apr 2009 is
only 34 percent (23 of 67), versus an average of 66 percent among
WHO-confirmed cases from all countries other than Egypt (234 of 354
cases as of 23 Apr 2009) [5].
Human mortality from H5N1 in Egypt is highly biased towards females
(90 percent: 21 females, 2 males), with confirmed mortality only
reported among individuals older than 9 years. Although the sex ratio
of cases in most countries is approximately 1:1, females outnumber
males among confirmed cases in Egypt by a factor of nearly 2:1 (43
females: 24 males). Although the average case fatality rate from H5N1
among children aged 0-9 years from all countries other than Egypt and
Turkey is 59 percent, no confirmed fatalities among 33 children in
this age cohort have been reported from Egypt as of 23 Apr 2009. A
similar pattern is evident for H5N1 cases in Turkey during January
2006; although 11 of 21 confirmed H5N1 cases in Turkey were children
in the age group 0-9 years, no confirmed fatalities were reported in
this age cohort [6].
Discussion:
There is increasing concern that undetected H5N1 cases may be
occurring in Egypt, given the evident anomalies in observed age-
specific and sex-specific case incidence and fatality rates. Although
there appears to be no compelling evidence for human-to-human
transmission of H5N1 in Egypt, family clusters have been observed in
Egypt, and H5N1 clusters involving highly probable human-to-human
transmission have been documented in China, Thailand, Viet Nam,
Indonesia, and Pakistan [7].
The most characteristic presentation of humans with fatal H5N1 virus
infections is severe lower respiratory disease accompanied by
hypercytokinaemia of the alveolar tissues. The pathology of most
fatal H5N1 cases resembles those of fatal human severe acute
respiratory syndrome (SARS) infections, and a suspected SARS case in
China during November 2003 was subsequently confirmed as a fatal H5N1 case [8].
The existing anomalies with regard to age and sex may be attributable
in part to the existence of undetected fatal or non-fatal atypical or
asymptomatic human H5N1 infections. Although human infections with
the H5N1 virus are typically associated with respiratory symptoms,
the clinical spectrum of H5N1 infections in humans is extremely
broad, and H5N1 virus has been recovered from lung, brain, large
intestine, small intestine, cerebrospinal fluid, kidney, spleen,
liver, pharynx, blood, and placental tissues [9]. Fatal atypical
human H5N1 infections involving only gastrointestinal and
neurological symptoms have been documented from patients in Viet Nam
and Thailand [10]. Asymptomatic human infections with H5N1 have been
reported from China, Viet Nam, Japan, Thailand, and Korea [11].
Clinically mild illness from highly pathogenic avian influenza (HPAI)
H5N1 virus infection has been reported from children in most
countries, but the early detection and treatment of possible cases
may be a factor in the overall lower case fatality rate reported for
H5N1 cases in Egypt. Although a median time of 4 days from symptom
onset to hospitalization has been reported for H5N1 cases worldwide
[4], nearly 50 percent of confirmed cases in Egypt are admitted to
hospitals within 24 hours after the 1st onset of symptoms, and
approximately 70 percent are hospitalized within 72 hours after
symptom onset [2].
Conclusions:
The evident age and sex biases in the incidence of infection and
mortality among H5N1 cases from Egypt are phenomena that have not
been fully explained and merit further in-depth investigation and
analysis. Further research is needed to understand the immediate and
long-term health risks of avian influenzas for human populations and
to identify those members of exposed populations who are at greatest
risk of infection and serious disease from avian influenza viruses.
Although most cases in Egypt can be linked to contact with diseased
poultry, increasing numbers of confirmed human H5N1 cases with no
evident history of direct exposure to diseased poultry or birds are
being reported from China and Indonesia. Efforts need to be made to
evaluate potential background rates of asymptomatic and mild cases of
human avian influenza in communities where human H5N1 clusters have
been documented and to evaluate potential instances of human-to-human
transmission of H5N1 in Egypt.
References:
(1) World Health Organization. Epidemic and Pandemic Alert and
Response (EPR). Disease outbreaks by country. Egypt. Geneva: World
Health Organization; 2009 Apr 23. Available from:
<http://www.who.int/csr/don/2009_04_23a/en/index.html>.
(2) United States Naval Medical Research Unit No. 3. Influenza
Activities Report. February-March 2009. Egypt. Available from:
<http://www.geis.fhp.osd.mil/GEIS/SurveillanceActivities/Influenza/Reports/NAMRU3_March_2009.pdf>.
(3) World Health Organization Western Pacific Regional Office. Avian
Influenza A(H5N1) Cases by Age Group and Outcome. Geneva: World
Health Organization Western Pacific Regional Office; 2009 Mar 23.
Available from:
<http://www.wpro.who.int/NR/rdonlyres/FD4AC2FD-B7C8-4A13-A32C-6CF328A0C036/0/Slide4.jpg>.
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Geneva: World Health Organization; 2009 Apr 23. Available from:
<http://www.who.int/csr/disease/avian_influenza/country/cases_table_2009_04_23/en/index.html>.
(6) World Health Organization. Epidemic and Pandemic Alert and
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<http://www.who.int/csr/don/2006_01_18/en/index.html>.
(7) Nicoll A. (Yet) another human A/H5N1 influenza case and cluster -
when should Europe be concerned? Euro Surveill.
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<http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=18833>.
(8) Zhu QY, Qin ED, Wang W, Yu J, Liu BH, Hu Y, et al. Fatal
infection with influenza A (H5N1) virus in China. New Engl J Med.
2006;354(25): 2731-2. Available from:
<http://content.nejm.org/cgi/content/full/354/25/2731>.
(9) Ng WF, To KF. Pathology of human H5N1 infection: new findings.
Lancet 2007;370(9593):1106-8.
(10) de Jong MD, Hien TT. Avian influenza A (H5N1). J Clin Virol.
2006;35(1):2-13. Available from:
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(11) Dudley JP. Public health and epidemiological considerations for
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