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Archive Number 20100128.0306
Published Date 28-JAN-2010
Subject PRO/AH/EDR> Avian influenza, human (07): Egypt, case analysis

AVIAN INFLUENZA, HUMAN (07): EGYPT, CASE ANALYSIS
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Date: Thu 28 Jan 2010
Source: Eurosurveillance, Vol. 15, Issue 4 [edited]
<http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19473>


Surveillance and outbreak report: Avian influenza A(H5N1) in humans; 
Lessons from Egypt. By: F O Fasina, V I Ifende, Ajibade At the 
National Veterinary Research Institute, Vom, Plateau State, Nigeria
---------------------------------------
Highly pathogenic avian influenza A(H5N1) has ravaged the Egyptian 
poultry population. 90 human cases, including 27 fatalities, have 
been recorded by 30 Dec 2009. However, epidemiological information on 
the infection in humans in Egypt is scarce. We analysed the 1st 3 
years of highly pathogenic avian influenza A(H5N1) in Egypt between 
20 Mar 2006 and 31 Aug 2009 and found that more cases occurred in 
females than males, especially in 2006 and 2007. Women in the age 
group 20-39 years had the greatest tendency to be infected. It took 
an average of one day and 18 hours to seek medical assistance in 
patients who recovered and of 6 days in fatal cases. Children sought 
treatment much earlier than adults. On average, a patient died 11 
days after the onset of symptoms. Exposure to infected poultry 
remained the most important risk factor.

Introduction
On 17 Feb 2006, highly pathogenic avian influenza A(H5N1) was 1st 
reported in the poultry population in Egypt [1]. Since that time, the 
infection had affected at least 21 governorates, forcing over 1.5 
million individuals to loose their source of livelihood [1]. Overall, 
370 backyard poultry flocks, 850 farms, and 4 zoos have been 
affected, and more than 36 million birds (mainly chickens) have died 
or have been culled in Egypt at an enormous cost to the country [1]. 
Currently, the virus is endemic in the Egyptian poultry population.

The 1st human case of avian influenza A(H5N1) in Egypt occurred on 17 
Mar 2006 [2], and to date (30 Dec 2009), the statistics of human 
infection and fatalities continue to rise. Specifically, 90 human 
cases (approximately 1/5th of the total global count), including 27 
fatalities (around 1/11th of the global count) have been recorded in 
Egypt as of 30 Dec 2009 [2]. These numbers rank Egypt 3rd in the list 
of recorded human cases and fatalities in the world, after Indonesia 
and Viet Nam, and remain, by far, the highest in Africa. The World 
Health Organization (WHO) had previously stated that "countries 
around the world had improved their defenses against bird flu, but 
the situation remained critical in Egypt and Indonesia, where the 
risk of the H5N1 virus mutating into a major human threat remains high" [3].

Worrisome with the situation in Egypt is the frequency with which 
women and young people are being infected and the very current trend 
of rising infections in children: in 2009 alone, 79 percent of all 
infected individuals were under 10 years old. Between January and 
December 2009, 17 of the 34 recorded cases involved children between 
12 and 30 months-old. Similarly, at the time of this report, human 
cases of 2009 pandemic influenza A(H1N1) had also been confirmed in 
the Egyptian population, which raises the possibility of co-infection 
and the emergence of reassortant viruses.

While the situation in Egypt remains critical, empirical evaluation 
of its peculiarities seem to be lacking, except for a very recent 
report by Dudley [4]. Assessment of the scientific literature and 
epidemiological data returned little or no concrete evidence from 
Egypt. However, the country has provided adequate records to 
international organisations like the WHO and the World Organisation 
for Animal Health (OIE), and these reports have improved 
significantly since the 1st submission in terms of spatial and 
temporal data and clinical records of affected persons. In this 
study, we analysed the records on avian influenza A(H5N1) in Egypt 
between 20 Mar 2006 and 31 Aug 2009 and explain the epidemiological 
significance of our findings.

Materials and Methods
The Egyptian government reports to the WHO, available on the WHO 
website [2], were the primary source of data for these analyses. We 
considered all laboratory-confirmed human cases of avian influenza 
A(H5N1) reported to the WHO from Egypt between 20 Mar 2006 and 31 Aug 
2009. All positive samples reported and used in these analyses had 
earlier been confirmed by microneutralisation assay on serum or by 
PCR on respiratory tract specimens as reported [5]. Similar 
confirmatory tests were done in the Egyptian national reference 
laboratory and at the WHO reference laboratories for diagnosis of 
influenza A(H5) infection, including the United States Naval Medical 
Research Unit 3 in Cairo, Egypt [4].

The parameters included in our analysis were: date of exposure, date 
of onset, course of symptoms, and time from hospitalisation until 
death/recovery, as listed in the WHO situation reports on avian 
influenza [6]. In the absence of complete information, reports were 
based on approximate dates and times from the reports. However, in 
cases of ambiguity arising from the records, such data were excluded 
from the calculations. In total, 85 confirmed cases were reported 
during the study period, of which 27 were fatal. After the exclusion 
of ambiguous data, only 63 of the 85 reported cases and 20 of the 27 
fatal cases were evaluated for symptoms and hospitalization; and 44 
of the 58 cases who recovered or were stable were analysed for 
symptoms and recovery. Analyses were performed using StatGraphics 
v2.0. Distributions were compared using chi-square test, and medians 
were compared using Fisher's exact test.

Results
In the period under analyses, 85 cases were evaluated, 32 of whom 
were male and 53 were female. 18 cases had been reported in 2006, 25 
in 2007, 8 in 2008 and 34 to date (31 Aug) in 2009, including a total 
of 27 human fatalities over the 3.5-year period.

The youngest cases were one year of age (2 boys), and the oldest case 
was a 75 year-old woman. The median age of all confirmed cases was 6 
years. The age of the cases (n=85) ranged from 12 months to 75 years, 
with a mean of 13 years and 2 months. The median age of all 
fatalities (n=27) was 25 years (range: 4 to 75 years), and the mean 
was 26 years and 3 months. The median age of the female cases (n=53) 
was 15 years, (range: 14 months to 75 years), and the mean was 16 
years and 10 months, while the median age of the male cases (n=32) 
was 4 years (range: 2 months to 32 years) and the mean 7 years and 2 
months. [These data are tabulated and displayed graphically in the 
original text].

The overall sex ratio (male:female) was 0.6, and the annual sex 
ratios were 0.4 (2006), 0.4 (2007), 1.0 (2008) and 0.9 (2009). By 
age, the sex ratios (male:female) were 1.1 (less than 10 years), 0.3 
(10-19 years), 0.1 (20-29 years), 0.2 (30-39 years), 0 (40-49 years; 
no case) and 0 (greater than 50 years; all cases female), with 
E=11.87 in Pearson's chi-square test, p=0.001 in Fisher's exact test, 
and degree of freedom (DF)=1 (see Table).

The number of days from onset of symptoms to hospitalisation (S-H) 
for all cases was calculated for 63 of the 85 cases. The median was 2 
days (range: 12 hours to 11 days), the mean was 2 days and 19 hours. 
For the fatal cases (17 of 27 were included in the analysis), the 
median (S-H) was 6 days (range: 2 to 11 days) with a mean of 6 days. 
Among the recovered cases (47 of 58 were included in the analysis), 
the median (S-H) was one day (range: 12 hours to 5 days), and the 
mean was one day and 18 hours.

The time from onset of symptoms to death had a median of 9 days 
(range: 5 to 30 days) and a mean of 11 days, while the time from 
hospitalisation to death had a median of 4 days (range: one to 25 
days) and a mean of 6 days. The S-H in children and teenagers between 
the ages of 10 and 19 years (n=51) had a median of one day (range: 12 
hours to 8 days) and a mean of 2 days and 12 hours, in contrast to 
the adults over 20 years of age (n=12), in whom the median was 4 days 
(range: 12 hours to 11 days) and the mean was 4 days. Many (19) of 
the adults did not present with full hospital records and were not 
included in the analysis for hospitalisation.

The overall case fatality rate was 32 percent (27/85). It was much 
lower in male (3/32) than in female (24/53) cases. According to age, 
the case fatality was 2 of 49 in the under 10-year-olds, 8 of 13 in 
the 10-19-year-olds, 7 of 9 in the 20-29-year-olds, 8 of 12 in the 
30-39-year-olds, and 2 of 2 in the over 50-year-olds (there were no 
cases among the 40-49-year-olds). In the years under review, the case 
fatality was 10 of 18 for 2006, 9 of 25 for 2007, 4 of 8 for 2008 and 
4 of 34 for 2009, with E=10.81 in Pearson's chi-square test and DF=4).

Discussion
This study is subject to some limitations. We conducted our analyses 
based on the limited data available for scrutiny. We suspect that 
cases have been missed because of the current surveillance system in 
humans which targets only severe infections backed by laboratory 
confirmation [7]. If this is so, Egypt may have had many more cases 
and possibly fatalities than reported and used in this work. People 
trying to avoid hospitalisation, especially among the adults, may 
also have contributed to underreporting.

In this analysis, the female cases had a wider age window (14 months 
to 75 years) than the male cases (12 months to 32 years). Since 
exposure to poultry remains the most important risk factor for human 
infection in Egypt, this may reflect the fact that across all age 
groups, more women than men are involved in poultry-related 
activities. All infected individuals with the exception of 3 (whose 
exposure status was uncertain) had been exposed to infected poultry 
or poultry products or to slaughtered or defeathered infected birds. 
In children and young adults, however, infection was more prevalent 
among males, although it is not clear why. Although infections in 
children peaked in the years 2007 and 2009, the reason for this is 
not yet clearly understood. Strong peaks of infection usually appear 
to follow periods of relaxation of preventative measures [7].

It also appears that especially in the group of the 20-39-year-olds, 
women had a greater tendency to be infected, and more women died post 
infection. 15 of 21 infected women in this age group died. These 
groups face the highest risk of exposure, as it is mainly they who 
are involved in home slaughtering and defeathering of chickens and 
preparation of food, farm work and visits to infected farms. A recent 
study has analysed the age and sex bias with regards to the situation 
in Egypt [4], and it has been reported that farmers from other 
infected African countries believe that there is little or no risk of 
infection from culling, defeathering, home slaughtering and visit to 
infected premises [8,9]. In addition, failure of the government to 
pay compensation in Egypt for culled birds and the practice of 
keeping poultry on rooftops and in close association with humans may 
have played a role. Although no association has yet been established 
between the level of exposure to avian influenza A(H5N1) and 
fatalities in Egypt, reports on workers in Asia showed that a high 
prevalence of infection in the poultry population is associated with 
a higher incidence of infection in humans and that controlling such 
outbreaks of H5N1 influenza in the poultry flocks can stop human 
infection [7,10,11]. In addition, genetic characterisation of viruses 
from both the human and avian populations in Asia revealed that the 
viruses from both species were very similar [9,10].

According to our analysis, early hospitalisation following infection 
increased the chances of recovery. Children tend to be hospitalised 
earlier than adults, and this may have contributed to the 
significantly lower death rate in the children (only 2 cases in 
children under the age of 10 years were fatal). Similarly, although 
62 of the 85 cases were under-19-year-olds, this does not represent 
national demography, since only approximately 32 percent of the 
population are 15 years and younger [12]. In most parts of Africa, 
people are known to visit a hospital less frequently as they advance 
in age, and supposedly non life-threatening conditions such as 
seasonal influenza are often treated at home and therefore underreported [8].

The overall case fatality in this study was 32 percent (27/85). This 
percentage may appear small when compared with statistics from other 
places, for example 82 percent in Indonesia (115/141), 68 percent in 
Thailand (17/25), 66 percent in China (25/38) and 50 percent in Viet 
Nam (56/111). Nevertheless, with the exceptional surge in number of 
cases (especially in children) arising in Egypt in 2009 and the 
recent reoccurrence of human cases of avian influenza A(H5N1) in 
China and Viet Nam, despite an intensive control programme in the 
poultry populations, the pandemic potential of this virus is still 
very evident. Case fatality was significantly higher in females 
compared with males, but whether this is related to exposure dose 
cannot be confirmed in this analysis.

As previously suggested by Briand and Fukuda [9], public health 
guidelines in Egypt will need to be tailored to meet the local 
situation, taking into consideration the agricultural practices and 
the people's perceptions. It will also be necessary to conduct more 
studies on human H5N1 influenza infection in Africa to evaluate the 
situation of asymptomatic carriers and unreported cases.

Finally, as evident in this analysis, exposure to infected poultry 
remains the only common denominator and an important risk factor for 
the spread of avian influenza A(H5N1) in humans in Egypt. Other 
workers had identified and reported the same risk factor -- exposure 
to sick poultry -- previously [10,11].

References
(1) Samaha H. Highly pathogenic avian influenza in Egypt. HPAI 
Technical Meeting; 27-29 June 2007; Rome, Italy. Available from: 
<http://www.fao.org/avianflu/en/conferences/june2007/documents/Day_1/3-1-a_Egypt_Dr_Samaha.ppt> 
[accessed on 31 Mar 2009].
(2) World Health Organization. Cumulative Number of Confirmed Human 
Cases of Avian Influenza A/(H5N1) Reported to WHO. Geneva: WHO; 30 
Dec 2009 Available from: 
<http://www.who.int/csr/disease/avian_influenza/country/cases_table_2009_12_30/en/index.html>.
(3) Egypt reports new bird flu death. Agence France-Presse; 5 Apr 
2008. Available from: 
<http://afp.google.com/article/ALeqM5iVjvSXt4M04X8fBKsqIZ89GFqrnA>.
(4) Dudley JP. Age-specific infection and death rates for human A 
(H5N1) avian influenza in Egypt. Euro Surveill. 
2009;14(18):pii=19198. Available from: 
<http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19198>.
(5) World Health Organisation. Update: WHO-confirmed human cases of 
avian influenza A(H5N1) infection, 25 Nov 2003-24 Nov 2006. Wkly 
Epidemiol Rec. 2007;82(6):41-8.
(6) World Health Organization. WHO Global Alert and 
Response-Archives-Situation reports and Updates (2006-2009). 
Available from: 
<http://www.who.int/csr/disease/avian_influenza/updates/en/index.html> 
[accessed on 22 Jan 2010].
(7) Fasina FO, Bisschop SPR, Webster RG. Avian influenza H5N1 in 
Africa: an epidemiological twist. Lancet Infect Dis. 2007;7(11):696-7.
(8) Fasina FO, Bisschop SPR, Ibironke AA, Meseko CA. Avian influenza 
risk perception among poultry workers, Nigeria. Emerg Infect Dis. 
2009;15(4):616-7.
(9) Briand S, Fukuda K. Avian influenza A (H5N1) virus and 2 
fundamental questions. J Infect Dis. 2009;199(12):1717-9.
(10) Vong S, Ly S, Van Kerkhove MD, Achenbach J, Holl D, Buchy P, et 
al. Risk factors associated with subclinical human infection with 
avian influenza A (H5N1) virus-Cambodia, 2006. J Infect Dis. 
2009;199(12):1744-52.
(11) Zhou L, Liao Q, Dong L, Huai Y, Bai T, Xiang N, et al. Risk 
factors for human illness with avian influenza A (H5N1) virus 
infection in China. J Infect Dis. 2009;199(12):1726-34.
(12) Egypt State Information Service. National Population Conference, 
June, 2008: Population Distribution according to age. Available from: 
<http://new.sis.gov.eg/En/LastPage.aspx?Category_ID=19> [accessed on 
15 Jul 2009].

--
Communicated by:
ProMED-mail <promed@promedmail.org>

[The moderator has commented previously that the mortality from avian 
influenza (H5N1) virus infection in Egypt has declined during the 
period 2009/2010. By contrast, from 2006 to 2008, there were 47 cases 
and 23 deaths (48.9 percent mortality), whereas in 2009/2010 so far, 
there have been only 4 fatalities among 43 cases (9.3 percent 
mortality). In the preceding analysis of Fasina and colleagues, it 
was observed that it took an average of one day and 18 hours to seek 
medical assistance in patients who recovered and of 6 days in fatal 
cases. This suggests that the decline in mortality may be a 
consequence of more rapid diagnosis and hospitalisation of patients 
and early initiation of Tamiflu treatment as practised by the 
Egyptian authorities.

The WHO Table of confirmed human cases of avian influenza (H5N1) 
virus infection updated to 28 Jan 2010 is available at: 
<http://www.who.int/csr/disease/avian_influenza/country/cases_table_2010_01_28/en/index.html>. 
- Mod.CP]

[see also:
Avian influenza human (06): Egypt, who (to be archived)
Avian influenza, human (05): Egypt, 92nd - 94th cases 20100127.0294
Avian influenza, human (04): Egypt, 91st case 20100120.0227
2009
----
Avian influenza, human (123): Egypt, 90th case, WHO 20091221.4302
Avian influenza, human (117): Egypt, 89th case, WHO 20091127.4070
Avian influenza, human (116): Egypt, 88th case 20091118.3982
Avian influenza, human (114): Egypt, 86th & 87th cases, WHO 20090924.3350
Avian influenza, human (113): Egypt, 86th case 20090921.3321
Avian influenza, human (111): Egypt, 84th & 85th cases, WHO 20090901.3079
Avian influenza, human (110): Egypt, 85th case 20090830.3051
Avian influenza, human (109): Egypt, 84th case 20090830.3047
Avian influenza, human (108): Egypt, cases 82/83, WHO 20090811.2868
Avian influenza, human (104): Egypt, cases 79-81, WHO 20090702.2385
Avian influenza, human (101): Egypt, 79th, 80th cases 20090609.2123
Avian influenza, human (100): Egypt, 78th case, WHO conf. 20090603.2058
Avian influenza, human (99): Egypt (KS) 78th case 20090602.2055
Avian influenza, human (98): Egypt, 77th case, WHO conf. 20090602.2046
Avian influenza, human (97): Egypt 77th case 20090531.2024
Avian influenza, human (96): Egypt, WHO 20090528.1988
Avian influenza, human (95): Egypt (SA) 75th,76th cases 20090527.1977
Avian influenza, human (94): Egypt, WHO 20090523.1922
Avian influenza, human (92): Egypt (DQ) 73rd, (SJ) 74th 20090521.1901
Avian influenza, human (91): Egypt (DQ) 72nd case, 27th death 20090519.1876
Avian influenza, human (90): Egypt (GH), 71st case 20090518.1855
Avian influenza, human (89): Egypt, WHO 20090516.1827
Avian influenza, human (88): Egypt (SA), 70th case 20090514.1814]
.................................................................cp/msp/dk

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