26 Mar 2007

The following Article was lifted from the HNiman Website

Mild H5N1 in Aswan Egypt.



The case is a female child, three years old. The illness started on the 22nd of March and admitted to the hospital on the 24th where they put her on tamiflu. The samples were taken on the 24th and confirmed positive for H5N1 on 25 March 2007. The patient had a history of contact with backyard poultry. The patient is still in a good health condition and is not epidemiologically linked to the previous two human cases in Aswan.

The above comments (emphasis added) from the WHO Eastern Mediterranean Regional Office supports media reports indicating the three confirmed H5N1 cases in Aswan were mild.  Media reports indicate the two earlier cases (10F and 2M) were briefly hospitalized and have been discharged.  The above comments indicate the most recent case �is still in a good health condition.�  These comments support media reports indicating that the patients had a high fever and �cold� symptoms.  None of the reports indicated the patients developed pneumonia, and the short hospital stay supports a mild presentation.

The descriptions are similar to earlier reports in 2005 on cases in central and northern Vietnam.  These earlier re[ports included 195 suspect cases in central Vietnam as well as a family of five in Haiphong.  All five family members developed symptoms at the same time, were H5N1 confirmed, and were briefly hospitalized.  Although serum samples from these patients were tested repeatedly in Vietnam, the United States, and Japan, there was no official reports on the conflicting test reports.  Media reports indicated positive results were seen by the CDC in the United States as well as Hanoi.

The three cases in Aswan were hospitalized within nine days of each other and confirmed to be H5N1 positive.  However, it seems likely that the number of cases in Aswan could be markedly higher, since the symptoms appear to be similar to those of a bad cold, and many patients with such symptoms would not seek medical attention or be tested.

Like Vietnam, the milder cases were associated with a change in the HA cleavage site.  In northern Vietnam in 2005, the cleavage site lost an R, changing from RERRRKKR to RERRKKR.  In Aswan in southern Egypt, the Qinghai HA cleavage site changed a K to an R resulting in GERRRRKR from GERRRKKR.  In both instances the new cleavage site had been reported earlier in birds, and in each case the previously reported cleavage site appeared on a regional specific genetic background.

In Egypt, the altered cleavage site was also associated with reassortment.  The NA sequence in southern Egypt is almost identical to sequences from fatally infected patients from central Egypt.  However, the HA sequences in central and southern Egypt were readily distinguished.  The cases in the north had a 3 nucleotide deletion and the consensus Qinghai cleavage site, while the cases in the south had no deletion, but had the novel cleavage site which had been previously reported in swans in Mongolia.

The presence of a lethal H5N1 in central Egypt, and a mild H5N1 in southern Egypt is cause for concern.  Mild cases of H5N1 are more likely to be transmitted because the host is more mobile and cold symptoms are not as alarming as severe flu symptoms followed by pneumonia.  The altered cleavage site may increase transmission, as evidence by three confirmed cases in nine days.  Thus far there are no reports of H5N1 in contacts, but detection may be liked to high fevers, and lower levels of H5N1 may produce milder symptoms which may limit testing and/or detection.  Therefore, increased efficiency of infection may not be evident. 

Antibody testing of contacts with these children would be useful.

Co-circulation of an efficiently transmitted H5N1, with a highly lethal H5N1 could result in further recombination and/or reassortment to produce an efficiently transmitted lethal Qinghai H5N1.

Thank you Ross. This is surely something that bears watching.

That's the GOOD news?

As my daughters think I am crazy for even thinking about this - maybe you have a point!

Copied from the H.Niman website
28 Mar 2007

Mr. H. Niman suggests in the following article that

1.  There may be many more as yet unrecognised mild H5N1 infections
     in Egypt.

2.  Suggests that the screening of Passengers in the flight from
     H.K.  to montreal was inadequate given the apparent  existence
     of Mild H5N1 in Egypt.



Two More Confirmed H5N1 Infected Children in Egypt
 
The Ministry of Health and Population of Egypt has reported two new human cases of avian influenza on 26 March 2007 at 11:50 pm. One case is a boy 5 years old from Menia and another is a girl 6 years old from Qena. Both were given oseltaminvir within 24 hours after onset of symptoms. They are in good health condition and will be referred to El Bakry hospital in Cairo.

The above comments from the WHO Eastern Mediterranean Regional Office describe two more H5N1 confirmed children in Egypt.  Like the most recent case from Aswan, the patients are described as being �in good health condition�.  The Aswan case (3F) was confirmed yesterday and was the third child (10F and 2M) confirmed in Aswan who were hospitalized over a nine day period.

US NAMRU-3 has sequenced the HA and NA from the first two Aswan cases.  Like the two surviving cases, the Aswan cases did not have M230I.  Earlier this season all cases with M230I were fatal.  After seven fatalities, the most recent seven cases, including the two above, have survived.  However, the recent isolates from Aswan also had evidence of recombination and reassortment.  The NA, which was identical in both Aswan patients, matched two fatal cases from central Egypt, while the HA was unique.  Those sequences had a novel HA cleavage site, previously found in whooper swans in Mongolia.  Several new polymorphisms in H5N1 isolates from Egypt, including the V223I change in the receptor binding domain have been found in H5N1 Qinghai isolates from Mongolia.  These changes were found this season in Egypt, and were appended onto an Egyptian genetic background defined by the H5N1 isolates in Egypt last season.

These acquisitions are most easily explained via recombination.  However, the isolates from Aswan are also reassortants, because the HA sequences from Aswan are significantly different than the HA sequences from central Egypt, which have a 3 nucleotide deletion, as well as several additional sub-regional polymorphisms.

Both recombination and reassortment require a dual infection of a host, and Egypt�s location in overlapping flyways, as well as widespread H5N1 infections in poultry, facilitates such exchanges of gene segments in reassortment, and portions of gene segments in recombination.

Media reports indicate the first two Aswan cases have recovered and have been discharged after a brief hospital stay.  The WHO description of the three most recent cases suggests that they are also mild cases.  Media reports also indicated these patients had high fevers and cold or flu-like symptoms, raising concerns that other patients with H5N1 mild symptoms would not be tested, which would create problems in monitoring or detecting such cases.

These concerns could extend to patients who travel outside of Egypt. Yesterday, passengers on a Hong Kong flight to Montreal were detained because of passengers with flu-like symptoms.  The passengers were released, based on the mild symptoms of the ill passengers, and lack of exposure to wet markets or dying poultry.  However, the mild symptoms in the H5N1 infected patients in Aswan may have been discounted in current screening protocols.

The above confirmed cases in Egypt raise the total of confirmed cases in the past two weeks to five.  All were children between the ages of 2-10 and all appear to have mild infections, raising concerns that the number of recent mild H5N1 infections in Egypt is markedly higher than the five confirmed cases.

I really hope that this is not being efficiently transmitted.  Do not let the mildness of the flu fool you.  It could and probably will get very much stronger as the efficiency of transmission increases.  This is not merely cause for concern but cause for alarm.  As the efficiency increases, the virulence of the virus will possibly of increase as well.   No, this is truly worrying.
Roidy

It would be useful to have a more precise definition of "mild".

Would these cases have been fatal without Tamiflu ?

This really isn't too difficult to figure out.  There have been many people tested from all over the world who have shown flu symptoms and there  have been no reported cases of a mild h5n1.  From culling workers who showed symptoms of the flu, to residents of those regions flooding into the hospitals because of false alarms, through all of those tests, h5n1 has never been detected.   If there was a mild form floating around, they would have detected it a long time ago.  And no, this isn't because of faulty testing.  

On Mild flu.......


Is Exposure to Sick or Dead Poultry Associated With Flulike Illness?
A Population-Based Study From a Rural Area in Vietnam With Outbreaks of Highly Pathogenic Avian Influenza

Anna Thorson, MD, PhD; Max Petzold, PhD; Nguyen Thi Kim Chuc, PhD; Karl Ekdahl, MD, PhD


Arch Intern Med. 2006;166:119-123.

Background The verified human cases of highly pathogenic avian influenza in Vietnam may represent only a selection of the most severely ill patients. The study objective was to analyze the association between flulike illness, defined as cough and fever, and exposure to sick or dead poultry.

Methods A population-based study was performed from April 1 to June 30, 2004, in FilaBavi, a rural Vietnamese demographic surveillance site with confirmed outbreaks of highly pathogenic avian influenza among poultry. We included 45 478 randomly selected (cluster sampling) inhabitants. Household representatives were asked screening questions about exposure to poultry and flulike illness during the preceding months; individuals with a history of disease and/or exposure were interviewed in person.

Results A total of 8149 individuals (17.9%) reported flulike illness, 38 373 persons (84.4%) lived in households keeping poultry, and 11 755 (25.9%) resided in households reporting sick or dead poultry. A dose-response relationship between poultry exposure and flulike illness was noted: poultry in the household (odds ratio, 1.04; 95% confidence interval, 0.96-1.12), sick or dead poultry in the household but with no direct contact (odds ratio, 1.14; 95% confidence interval, 1.06-1.23), and direct contact with sick poultry (odds ratio, 1.73; 95% confidence interval, 1.58-1.89). The flulike illness attributed to direct contact with sick or dead poultry was estimated to be 650 to 750 cases.

Conclusions Our epidemiological data are consistent with transmission of mild, highly pathogenic avian influenza to humans and suggest that transmission could be more common than anticipated, though close contact seems required. Further microbiological studies are needed to validate these findings.


Author Affiliations: Division of International Health, Departments of Public Health Sciences (Drs Thorson, Petzold, and Chuc) and Medical Epidemiology and Biostatistics, (Dr Ekdahl), Karolinska Institutet, and Clinic of Infectious Diseases, Karolinska University Hospital (Dr Thorson), Stockholm, Sweden; Nordic School of Public Health, G�teborg, Sweden (Dr Petzold); Hanoi Medical University, Hanoi, Vietnam (Dr Chuc); European Centre for Disease Prevention and Control, Solna, Sweden (Dr Ekdahl); and Stockholm Group of Epidemic Modeling, Stockholm (Dr Ekdahl).







THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES


Avian influenza: A review
Thomas and Noppenberger
Am J Health Syst Pharm 2007;64:149-165.
ABSTRACT | FULL TEXT   

Flulike Illness and Exposure to Sick or Dead Poultry--Reply
Thorson et al.
Arch Intern Med 2006;166:1421-1421.
FULL TEXT   

Flulike illness and exposure to sick or dead poultry.
Groome and Richardson
Arch Intern Med 2006;166:1420-1421.
FULL TEXT   
http://archinte.ama-assn.org/cgi/content/abstract/166/1/119

   

Men at work ...... and why we can sleep at night ...

In a triangular, 1.2-hectare compound in eastern Cairo, in the shadow of the 1,500-bed Abbassia Fever Hospital – the Middle East’s oldest and largest – a team of Navy and Army scientists, U.S. civilian employees, Egyptian scientists and technicians, and contractors staffs the 60-year-old U.S. Naval Medical Research Unit No. 3 (NAMRU-3).


25 January 2007

U.S. Navy, Egyptian Scientists Fight Global Illness, Infection
Mild resistance to anti-viral drug found in Egyptian avian flu victims

By Cheryl Pellerin
USINFO Staff Writer


Naval Medical Research Unit No.3 researchers train Libyan collaborators in Cairo, Egypt, in virus identification and isolation. (NAMRU)

Naval Medical Research Unit No. 3 researchers train Libyan collaborators in Cairo, Egypt, in virus identification and isolation.(NAMRU)This is the first in a series of articles on U.S. Naval Medical Research Unit No. 3, Cairo, Egypt

Washington – As pathogens, both ancient and emerging, move from country to country, carried by and shared among insects, animals and people to spread illness and death, a small group of U.S. and Egyptian scientists is building a medical line of defense throughout the Middle East, North Africa and Southwest Asia, against diseases that range from malaria and fevers to HIV/AIDS and avian influenza.

In a triangular, 1.2-hectare compound in eastern Cairo, in the shadow of the 1,500-bed Abbassia Fever Hospital – the Middle East’s oldest and largest – a team of Navy and Army scientists, U.S. civilian employees, Egyptian scientists and technicians, and contractors staffs the 60-year-old U.S. Naval Medical Research Unit No. 3 (NAMRU-3).

Their direct mission is to support U.S. military personnel in that region by studying viruses, enteric (intestinal) diseases and disease vectors (carriers) like ticks and mosquitoes, and through disease surveillance, which means monitoring the most important infectious disease threats in the region.

The scientist also engage in an activity not in the official NAMRU mission statement: they make sure they are good neighbors, passing along the benefits of science and medical research to the citizens of nearby countries.

“The idea is that public health work is good diplomacy,” said NAMRU-3 Commanding Officer Captain Bruce Boynton, a doctor, in a recent USINFO interview in Cairo, “and not just in the sense that we represent the United States. [Diseases studied at NAMRU-3] are of interest to public health leaders, and doing good things for people brings countries and people together.”

NAMRU-3 is part of the Naval Medical Research and Development Command in Maryland, whose other overseas research laboratories include NAMRU-2 in Jakarta, Indonesia; a detachment in Manila, Philippines; and the Naval Medical Research Institute Detachment in Lima, Peru.

GOOD NEIGHBORS

The scientists at NAMRU-3 work closely with the Egyptian Ministry of Health and Population (MOHP), the World Health Organization (WHO), the U.S. Agency for International Development, the U.S. National Institutes of Health, the Centers for Disease Control and Prevention (CDC) and many nongovernmental organizations.

At NAMRU-3, the Virology Research Department is a regional influenza reference laboratory for WHO’s Eastern Mediterranean Regional Office, where NAMRU-3 scientists confirm the identity of flu viruses isolated by national laboratories, develop and distribute virus reference reagents (substances used in a chemical reaction to detect and measure other substances), prepare training materials, organize workshops, offer extended laboratory training, collaborate on special surveillance studies and conduct research to improve methods of flu virus surveillance.

NAMRU-3 technicians analyze and study the genetic composition of viruses to identify specific types of viruses, a process important to the development of vaccines and therapies. They also examine the genetic material of influenza viruses, including the highly pathogenic H5N1 strain of avian influenza, and share the data with the scientific community so scientists around the world can benefit from the information.

For example, in Egypt on January 18, H5N1 viruses were found to have a genetic mutation that was linked in laboratory testing with moderate resistance to the anti-viral drug oseltamivir (TamiFlu®). These were found in two people with H5N1 infections, according to a WHO statement.

Both patients – a 16-year-old girl and her 26-year-old uncle who lived in the same house in Gharbiyah province north of Cairo – had been treated with oseltamivir for two days before the clinical samples were taken. Despite the efforts of health workers, the girl died December 25, 2006, her uncle December 28, 2006. Of the 267 H5N1 cases reported worldwide since 2003, 18 have occurred in Egypt.

Egypt's monitoring and rapid virological analysis conducted at the Central Public Health Laboratory in Cairo initially allowed the H5N1diagnoses to be made. Confirmatory testing and genetic sequencing were done at NAMRU-3 and two WHO collaborating centers in the United States (at CDC) and the United Kingdom.

According to WHO, there is no indication that oseltamivir resistance is widespread in Egypt or elsewhere.

TRAINING THE TRAINERS

“One of the major things we do as a regional reference laboratory when it comes to influenza or avian influenza,” said U.S. Navy Lieutenant Commander Marshall Monteville, head of the NAMRU-3 Viral and Zoonotic Diseases Research Program, “is give [scientists and technicians] in the region training [in influenza diagnostics] here at NAMRU-3, then we send a field team to train them in their own laboratories ... and we visit them once in a while to make sure they’re doing okay.”

Such thorough training is in the interest of quality assurance, he added.

“We want to make sure they’re doing things correctly in their laboratories. When they send people to us for training, we’re usually training the trainers, so we want to make sure the trainers are going back and teaching their people appropriately,” Monteville said. “Also, they’re collaborators of ours, so it’s good business.”

More information about NAMRU-3 is available at the Naval Medical Research Center Web site.

(USINFO is produced by the Bureau of International Information Programs, U.S. Department of State. Web site: http://usinfo.state.gov)
Avian Influenza Causes More Human Deaths in Indonesia, Egypt
U.S. Navy Scientists Share Research Benefits with the World
More Information on Naval Medical Research Unit 3

http://usinfo.state.gov/xarchives/display.html?p=washfile-english&y=2007&m=January&x=20070125113122lcnirellep0.3603327&chanlid=health

    

I see no evidence of easier transmission in Egypt. The human cases are still low, less than Indonesia last year. And the current death rate has been greater than Indonesia. I just don't think his 'facts' support his theories

Deleted ( By Ross )

Hi Albert ,

           I have never seen H. Niman or heard him speak , all I know of him
is mainly from the posts at his website.  I agree that from time-to-time
he comes across as alarmist ,  but I find it hard to criticize him on those
grounds because I certainly could be accused of the same fault .

I have always interpreted his apparent alarmism as just wanting to be
the first person to discover or note a significant event.

I took his comments about the Flu-laden aircraft to be more of a warning
about the inadequacey of current  screening procedures than a serious
warning that the passengers were infected with Egyptian style flu.


It is hard not to notice that you seem to have a very negative opinion of
him , is there something here that I am missing ?. Because to me he
seems very technically competent and generally ahead of the pack.

Ross,

I just don't think that 3 cases that didn't die without knowing all the facts about type and length of treatment supports the theory that there is now a mild strain of H5N1 in circulation in Eqypt. maybe I am missing some of the facts. It just seems he is making a very large leap on his own assumptions.


The altered cleavage site MAY increase transmission, as evidence by three confirmed cases in nine days. Thus far there are no reports of H5N1 in contacts, but detection MAY BE linked to high fevers, and lower levels of H5N1 MAY produce milder symptoms which MAY limit testing and/or detection. Therefore, increased efficiency of infection MAY NOT be evident.


That's 5 levels of mays and may nots to get to his conclusion. In my opinion it is pure speculation with the only suporting evidence of 3 people in 9 days that tested positive and didn't die. I think there is a better likelyhood that the tests were flawed and those people had seasonal flu.
    
    

From Niman site 2 April 2007



The health ministry said late on Saturday that Mariam Abdel Fatah from the town of Qanater, just north of Cairo, had been diagnosed with the H5N1 virus and taken to a hospital specialising in treating the condition.

Two other cases, both children from the impoverished south of Egypt, were announced the same day: Ibrahim Mahmud Helmi, four, from Qena province and Mahmud Mohammed Shalabi, seven, from Sohag.

The above description of three confirmed H5N1 case in Egypt is in addition to the two cases confirmed earlier this week.  One of the patients confirmed Tuesday (6F) is the sister of the patient (4M) from Qena.  US NAMRU-3 sequenced the HA and NA form the sister.  It is closely related to HA and NA sequences from Beni Suef and Fayyoum.  The HA sequence has a characteristic 3 BP deletion.

The large number of cases in the past two weeks is cause for concern.  H5N1 from the three cases from Aswan as well as the case from Mena form another cluster of patients will similar H5N1 sequences.  Moreover, the proximity of Sohag to Mena and Qina suggests H5N1 us infecting patients along an extensive region of the Nile.

So that makes 7 in a weeks time. Just when i thought I was going to get some sleep tonight. Thanks Ross, now I am concerned. i guess we will know in a week or two how bad it is. i have far less faith in Egypt to contain anything than I do in Indonesia. The Saudi Arab mentality is very much a save face mentality. If they are announcing these cases, it is my opinion that it could be much worse than they are letting on. JMO

PS. The fact that US NAMRU-3 in in country says a lot
    

Just a word grab from another site that has a worrying message about
the Middle East .


In the United States, Dr. Moore, of the Kansas State University, worries particularly about poorly regulated markets in live birds that cater to Muslims and Jews who want poultry slaughtered according to religious custom.

I don't know if this has any bearing on the cases in Egypt of tamiflu resistant and also milder cases, but when I read this article, I sure did think of what is going on in Egypt.....My apologies if this has been posted elsewhere...

Kparcel.
I believe that the more recent cases in Egypt have not developed in to
pneumonia and have been associated with shorter hospital stays .
The symptoms see to be more like that of the common cold.
Thus indicating a milder version of the flu.

Since the flu appears  so mild there is a fair chance that survivors have not
been accurately counted , particularly in adults who may have some
acquired immunity from other flu types.

I also understand that the more recent cases in Egypt do not display
Tamiflu resistance . All the earlier cases that displayed Tamiflu resistance
were associated with a particular gene sequence and were fatal.
They also were associated with lower transmissability .

Medclinician ,
               I have to agree that an uncontrolled  explosion would  be sudden and unmistakable  but  I think most people  come to this website to detect the last half inch of the fuse igniting  .  I know I do . 

And it may happen so quickly that if you blink you will miss it .  Which in my opinion explains the obsession with small detail and events.

Because of the actions of  Governments and the WHO  in both suppressing outbreaks and concealing data we are forced to spend our time scanning through the clues.
                   

Bird flu arrives at the Chicken Farm Capital of Egypt
The Qalublia area North of Cario is home to the biggest poultry
farms in the country.


A Human case was hospitalized from Qanater ( in this area ) on
approx 2 April 2007

The following is an extract from an Egyptian paper .

Digitalizing animal farming is a strategic project that will restructure the industry, help intensify efforts to resist epidemics on a timely basis and create awareness about which sites should need immediate assistance during emergencies. �The reason why we started with Qalubia is known to all chicken farmers: Qalubia houses the biggest poultry farms in the country and specialists know that the chicken stock market hinges on that province, so it was the natural starting point.� The project is the brainchild of Dr Hussein Mansour, an official at the Egyptian Embassy in Washington, who is also a desert expert. �Not only were we welcomed by the farm-owners,� says Azamel, �but in some cases we were called in to receive the data. Some of the farmers guided us to the whereabouts of farms that are tucked away in the remote recesses of the province.� The majority of farmers, he says, have realized that the survey is a way of protecting their interests and safeguarding an industry that has been dealt serious blows ever since the bird flu scare began. He explained that the survey will not only be beneficial in terms of providing statistics, but it has also tipped data collectors on how flaws in the design of these farms could precipitate the spread of the virus. According to Azamel, Qalubia houses 3, 547 farms existing, 1, 555 of which are located in Banha, 621 in Kafr Shukr, 738 in Tukh, 215 in Shebin El Qanater, 99 in Khanka, 110 in Qalub, and 209 in El Qanater El Khairiya. It was shocking to learn that 80 percent of the farms are in the first three divisions of the governorate,  he noted. The new digital map indicated that some 64 farms are crammed within one square kilometer in the northern villages as compared to 10 in every square kilometer in the southern areas, he added. Besides the help of the general-public, the Desert Research Center will join hands with the health, environment and agriculture ministries to form a national committee tasked with monitoring the bird flu situation in Egypt.

 http://www.sis.gov.eg/En/Society/Birdhttp://www.sis.gov.eg/En/Society/BirdFlu/BirdFluinEgypt/091503000000000093.htmFlu/BirdFluinEgypt/091503000000000093.htm

I have been under the impression that Egypt was failing to report
outbreaks in poultry farms , however here is a website that details
such outbreaks .

Unfortunatel the website  is confusing since much of the information
seems to relate to 2006 rather than 2007.