Pakistan - BF Suspected Human Cases December 18, 2007 to Feb 2, 2008

[HenryN]

Re: Pakistan: December 18+, WHO Begins Investigations

AVIAN INFLUENZA, HUMAN (172): CHINA, PAKISTAN
*********************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>

[1]
Date: Fri 21 Dec 2007
Source: EARTHtimes.org, DPA report [edited]
<http://www.earthtimes.org/articles/show/162668.html>


The World Health Organization (WHO) said on Friday [21 Dec 2007] that it
was impossible to say whether a case of bird flu in China in a 52 year old
man was due to human-to-human transmission, but, even if it was, it was
down to very close contact between the victims. The assistant
director-general for health security at WHO, Dr David Heymann, said the
only proven transmission of this nature so far, in Indonesia and Thailand,
had been as a result of very "close contact" in a "very circumscribed area".

WHO was still awaiting final tests results for a recent cluster of cases in
the north west region of Pakistan. The team of WHO experts, who traveled to
the area earlier this week, believed though that the 1st ever human cases
in the country were again a result of intimate contact. Heymann said the
virus could, on "occasional instances, be transmitted" between humans but
that it was not transmittable like influenza with a sneeze. "It's not that
kind of transmission".

In China, both the man and his 24 year old son, who died on 2 Dec 2007, had
been exposed to the same common source. Infection had also occurred during
the incubation period. There had also been close contact with another 600
people, but blood tests had confirmed they were free from the virus.
Heymann said: "Even if there had been human-to-human transmission, it was
limited and did not continue. It was not sustained, and it's that which is
very important."

However, though the H5N1 strain of bird flu has not jumped the species
barrier in a way that would cause a major outbreak so far, the scientific
community remains convinced there is a real possibility of an influenza
pandemic in the future, but it cannot say whether H5N1 will be the source
or another flu variant.

--
communicated by:
ProMED-mail rapporteur Mary Marshall

******
[2]
Date: Fri 21 Dec 2007
Source: Associated Press report [edited]
<http://malaysia.news.yahoo.com/ap/20071221/tap-as-gen-pakistan-bird-flu-1st-
ld-writ-d3b07b8.html>


Limited human-to-human bird flu transmission may have occurred in Pakistan,
but no new infections have been reported for 2 weeks, and there appears to
be no threat of further spread, a top World Health Organization official
said on Fri 21 Dec 2007. A WHO team has finished its initial investigation
in Pakistan after up to 9 patients, including several family members, were
suspected of being infected with the H5N1 bird flu virus in areas north of
Islamabad. They were the country's 1st reported human cases.

The experts were expected back in Geneva to begin piecing together how the
virus may have spread, but they found no evidence of anyone currently
sickened by the virus, Dr David Heymann, WHO's top flu official in Geneva,
told The Associated Press by telephone. "I think the team right now feels
on initial analysis that this might be a small chain of human-to-human,
non-sustained transmission," he said, stressing that there was no cause for
alarm. He said the last reported case was on 6 Dec 2007. Pakistani health
officials have conducted initial testing on the samples and found them to
be positive, but WHO has sent the specimens to one of its collaborating
laboratories for confirmation.

At least 209 people have died worldwide from the virus, which began
plaguing Asian poultry stocks in late 2003. It remains hard for people to
catch, but scientists worry it could mutate into a form that spreads easily
among people, potentially sparking a pandemic. Most cases have been linked
to contact with infected birds, but scientists believe limited
human-to-human transmission has occurred a few times before among blood
relatives who had close contact.

Five brothers were sickened last month [November 2007] in the small city of
Abbotabad, about 50 km (30 miles) north of Islamabad. One was a
veterinarian who was involved in slaughtering sick poultry infected with
bird flu. Two of his brothers fell ill and died, one of whom was buried
before tests were conducted. The veterinarian and his other 2 brothers
recovered. Up to 5 other people in the same area also tested positive for
the virus in preliminary tests.

Heymann said no one knows when a pandemic will occur or what virus will
start it, but countries need to be prepared to take action. "The more it
reproduces, whether it's in humans or chickens, the more likely it is that
there will be an event that will occur that causes it," he said. "We just
have to wait to see what's going to happen."

Meanwhile, Indonesia, which is the world's hardest-hit country with 93
human deaths, also reported on Friday [21 Dec 2007] that 5 people from an
extended family had been hospitalized with flu-like symptoms in an area
where bird flu was earlier reported in poultry. Specimens have been taken
to determine whether any of the relatives were infected with the H5N1
virus. Myanmar reported its 1st human case last week, and a number of other
countries have recently reported poultry outbreaks during the winter
months, when the virus typically flares.

[byline: Margie Mason]

--
communicated by:
ProMED-mail rapporteur Mary Marshall

[These 2 reports indicate that the recent outbreaks in China and Pakistan
have not spread. Limited human-to-human transmission cannot be excluded in
either of these recent incidents, but if it occurs, it appears to be
restricted to blood relatives, suggesting that innate genetic
susceptibility is still the main predisposing factor.

As yet, none of the H5N1-positive cases in Pakistan has been confirmed by
an independent WHO reference laboratory. A significant factor in the
Pakistan outbreak may be that the index case has been identified as a
veterinarian (and one of the group of 5 brothers) employed in the culling
of infected poultry. - Mod.CP]

[see also:
Avian influenza, human (159): China (Jiangsu), WHO 20071211.3987
Avian influenza, human (171): Pakistan 20071220.4089
Avian influenza, human (169): Pakistan 20071218.4072
Avian influenza, human (168): Pakistan 20071217.4059
Avian influenza, human (167): Pakistan 20071216.4049
Avian influenza, human (166): Pakistan, WHO 20071215.4038
Avian influenza, human (165): Pakistan 20071214.4023
Avian influenza, human (163): Pakistan 1st report 20071213.4008]

................cp/msp/sh

[Commonground]

Re: Pakistan: December 18+, WHO Begins Investigations

So this is etched in stone, as the "word" from WHO. Right?
@ 11:44:

Nine people, including five brothers, became infected with the H5N1 bird flu virus in a small town north of Islamabad. One was a veterinarian involved in culling sick poultry. Two of his brothers fell ill and died. The veterinarian and his other two brothers subsequently recovered.

Edit: Sorry didn't see the following post:

WHO was still awaiting final tests results for a recent cluster of cases in
the north west region of Pakistan.

[HenryN]

Re: Pakistan: December 18+, WHO Begins Investigations

ISLAMABAD: World Health Organization (WHO) has said that there was no threat of further spreading of bird flu virus in Pakistan, presently, as no new case came to the fore during the past two weeks. WHO team has completed its initial investigation about the bird flu in Pakistan. This team was dispatched to Pakistan on the information of the existence of nine persons infected by bird flu. This is for the first time in Pakistan that the human bird flu case has come to the fore. WHO high official in Geneva, Dr. David told that the team after the initial investigation was of the view that there might have been few cases of human-to-human bird flu transmission incidents in Pakistan, but no new case during the previous two weeks came to the fore and, therefore, there was no threat of further spreading of bird flu virus in Pakistan, presently. He said that the last bird flu case was reported on December 6. The officials had got the suspected patients laboratory tested, which were found positive, but the WHO has sent the samples for test in its laboratory for certification.

http://www.pakistanlink.com/Headlines/Dec07/22/05.htm

[HenryN]

Re: Pakistan: December 18+, WHO Begins Investigations

Commentary at

http://www.recombinomics.com/News/12220704/H5N1_H2H_Comps.html

[AlaskaDenise]

Re: Pakistan: December 18+, WHO Begins Investigations

Commentary at

http://www.recombinomics.com/News/12...H2H_Comps.html

Commentary

H5N1 Human to Human Transmission Comparison

Recombinomics Commentary
December 22, 2007

Doctor Heymann says an analysis of the information is not yet complete. But preliminary results indicate there was human-to-human transmission of the virus. He says there could have been a common source of the infection.
"The team feels, we have not seen all their evidence yet, but they feel that this could be an instance of close contact of human-to-human transmission in a very circumscribed area and not sustained," he explained. "Just like happened in Indonesia and in Thailand."

The above comments reference the clusters in Indonesia and Thailand, which have been called proven human to human transmission (H2H) in other media reports, but really are only slightly more "proven" than the dozens of other H5N1 H2H clusters.

The cluster in Thailand was somewhat unusual because the mother of the index case was an office worker and did not have exposure to poultry. She had close contact with her daughter after hospitalization, and then developed symptoms after her daughter died. The index case's aunt also was infected, and the cluster might have been H2H2H, but the New England Journal of Medicine report focused on transmissions from the index case, and discounted the scenario where the index case infected her mother and her mother infected her aunt. The index case was never tested for H5N1 because she was misdiagnosed as having dengue fever, but the cluster was characterized as the first proven case of H5N1 H2H transmission.

The cluster in Karo, Indonesia was larger and had two time gaps indicating H2H2H. The source of the infection of the index case was unknown, but her condition deteriorated just the day before a family barbeque and many blood relatives slept in the same small room with the index case. They developed symptoms within a day or two of each other, and the final case was the son of one of the family members infected by the index case. Once again the index case wasn't tested before she died, but the family members were H5N1 positive and all but one died.

However, the differences between these clusters and the dozens of other clusters were minor. Other clusters did not involve an obvious source, had significant time gaps between the disease onset dates, and had contact between the index case and infected family members.

Thus, the evidence for H2H in most of the other clusters was similar to that for the two cited clusters. The cited clusters did not have obvious genetic changes in the H5N1 sequences.

However, many of the clusters associated with the Qinghai strain did have receptor binding domain changes, and the Pakistan cluster almost certainly involves the Qinghai strain. Thus, a comparison with those clusters would be more appropropriate. In Turkey and Azerbaijan there were multiple clusters that developed at the same time, as was seen in media reports of the Pakistan outbreak. These Qinghai outbreaks also had receptor binding domain changes in the H5N1 isolates from the cluster members. Therefore comparison with those clusters would seem to be more appropriate.

In Turkey, the locations of the clusters was concentrated in eastern Turkey, but was not limited to one geographic location. The same pattern was seen in the Azerbaijan clusters. In Iraq, there was only one official cluster, but media reports raised questions about additional clusters. Sample collection in Iraq was less than ideal, and the one cluster may have not have been unique.

Media reports indicate that new infections in Pakistan have not been found since December 6. However, there is no situation update with specifics, and comments have already been made about infections being mild. Detection of mild cases has been difficult because of similarities with other respiratory diseases, coupled with limited testing and application of Tamiflu blankets.

Media reports indicate this outbreak has been sustained for the longest period reported to date, and the delay in release in a situation update following confirmed H5N1 clusters is without precedent.

The first case was reported have been exposed two months ago, lab confirmed almost two months ago, and reconfirmed a week ago.

These extensive delays remain cause for concern.

.

[HenryN]

Re: Pakistan: December 18+, WHO Begins Investigations

Commentary at

http://www.recombinomics.com/News/12230702/H5N1_Genetic_Myth.html

[HenryN]

Re: Pakistan: December 18+, WHO Begins Investigations

Pakistan still probing human transmission in bird flu: ministry <!-- END HEADLINE -->
<!-- BEGIN STORY BODY -->1 hour, 1 minute ago


Pakistan's health ministry said it was still investigating whether there was human transmission in the country's first death from bird flu.
It said initials tests by the World Health Organisation (WHO), which sent a team here last week, had ruled it out but that Pakistan had sent samples to Geneva -- the WHO's headquarters -- for further confirmation.
Scientists fear that if the virus were passed from one person to another, rather than from infected birds, it might indicate a mutation that could lead to a global pandemic with the potential to kill millions.
"In their preliminary tests the WHO team excluded suspected human-to-human transmission, but we have sent the samples to Geneva for further confirmation," health ministry spokesman Oriya Maqbool Jan told AFP.
The WHO team was sent after the ministry announced the death of a man who was one of six people infected with the deadly H5N1 strain of the avian influenza virus in North West Frontier Province along the Afghanistan border.
A brother of the victim also died before being tested for the virus. Both had worked on a cull of infected poultry.
"We have been very closely monitoring the situation," said Rafiqal Hasan Usmani, the animal husbandry commissioner. "There has been no new outbreak."
The H5N1 strain of bird flu has killed more than 200 people worldwide, mostly in Southeast Asia, since late 2003.

http://news.yahoo.com/s/afp/20071224/wl_sthasia_afp/healthflupakistan_071224084627&printer=1;_ylt=Aj6AeZxSdGbfFp4DUVbLZnnuOrgF

[HenryN]

Re: Pakistan: December 18+, WHO Begins Investigations

Commentary at

http://www.recombinomics.com/News/12240702/H5N1_Pakistan_False.html

[HenryN]

Re: Pakistan: Human H5N1 Cluster December 2007

<TABLE cellSpacing=0 cellPadding=0 width="98%" align=center border=0><TBODY><TR><TD></TD></TR><TR><TD vAlign=top><TABLE cellSpacing=0 cellPadding=1 width="99%" align=center border=0><TBODY><TR><TD>WHO says human-to-human bird-flu transmission unlikely in Pakistan </TD></TR><TR><TD><TABLE cellSpacing=0 cellPadding=0 width="100%" border=0><TBODY><TR><TD width="83%">Posted on : 2007-12-24 | Author : DPA
News Category : Health</TD><TD vAlign=bottom width="17%"></TD></TR></TBODY></TABLE></TD></TR><TR><TD>
<TABLE cellSpacing=2 cellPadding=0 width="100%" border=0><TBODY><TR vAlign=top><TD>Islamabad - The World Health Organization (WHO) has all but ruled out human-to-human transmission of avian influenza among nine Pakistanis who contracted the virus last month, one of whom became the country's first bird-flu fatality, a health official said Monday. While retests of blood samples were still to be conducted at a WHO laboratory in Geneva, investigators who were in Islamabad last week said they did not believe H5N1, the strain of avian influenza that can be deadly in humans, was passed among the nine people in the North-West Frontier Province, six of whom are blood relatives.

"Since there are no symptoms, no new cases or correlation among these people, they say it's not human-to-human bird flu but maybe bird-to-human," said Maqbool Jan Abbasi, a bird-flu spokesman for Pakistan's Health Ministry.

He said 63 people who were in contact with the nine patients tested negative for the virus and that a final report on the findings would be released next week.

The cases began in late November when a man involved in the culling of suspected sick birds outside the city of Peshawar contracted bird flu, followed by one of his brothers who later died from the virus.

http://www.earthtimes.org/articles/show/163757.html#

Human-to-human transmission is extremely rare but has occurred among family members in Indonesia and Thailand. Last week, WHO said it could not confirm a feared human-to-human transmission involving a 52-year-old man in China.

There have been multiple bird-flu outbreaks among Pakistan's poultry population since 2006, but there had never been a human case until last month.

Globally, bird flu has killed at least 210 people worldwide since 2003. Most human cases of H5N1 are linked to contact with infected birds, but experts fear the virus might mutate into a form that spreads easily among humans, potentially sparking a pandemic that could kill millions of people.
</TD></TR></TBODY></TABLE>
</TD></TR></TBODY></TABLE></TD></TR></TBODY></TABLE>

[HenryN]

Re: Pakistan: December 18+, WHO Begins Investigations

Commentary at

http://www.recombinomics.com/News/12240703/H5N1_Pakistan_Overdue.html

[sharon sanders]

Re: Pakistan: December 18+, WHO Begins Investigations

Commentary at

http://www.recombinomics.com/News/12...n_Overdue.html

This is the last situation update by WHO dated Dec. 15th 2007:

Avian influenza ? situation in Pakistan


15 December 2007
The Ministry of Health in Pakistan has informed WHO of 8 suspected human cases of H5N1 avian influenza infection in the Peshawar area of the country. These cases were detected following a series of culling operations in response to outbreaks of H5N1 in poultry. One of the cases has now recovered and a further two suspected cases have since died.
Samples taken from the suspected cases have tested positive for H5N1 in the national laboratory and are being forwarded to a WHO H5 Reference Laboratory for confirmation and further analysis. The MoH is taking steps to investigate and contain this event, including case isolation and contact tracing and monitoring, detailed epidemiological investigations, providing oseltamivir for case management and prophylaxis, reviewing hospital infection control measures and enhancing health care-based and community-based surveillance for acute respiratory infections.
WHO is providing technical support to the MoH in epidemiological investigations, reviewing the surveillance, prevention and control measures that have been implemented and carrying out viral sequencing of avian and human isolates.
Multiple poultry outbreaks of H5N1 influenza have been occurring in Pakistan since 2006. In 2007, there have also been outbreaks in wild birds. A majority of the outbreaks discovered have been in the ?poultry belt? of North-West Frontier Province, particularly in the Abbottabad and Mansehra area and cases of infection in wild birds have been identified in the Islamabad Capital Territory.
<!-- include footer--><!-- include ftr-->

http://www.who.int/csr/don/2007_12_15/en/index.html

[sharon sanders]

Re: Pakistan: December 18+, WHO Begins Investigations

Do we know if they have tested beyond the contacts of the cluster? Fellow poultry workers? Extended family? Neighbors? Those who have not taken tamiflu but were in contact with the cluster individuals? Also, any antibody testing?

[HenryN]

Re: Pakistan: December 18+, WHO Begins Investigations

Do we know if they have tested beyond the contacts of the cluster? Fellow poultry workers? Extended family? Neighbors? Those who have not taken tamiflu but were in contact with the cluster individuals? Also, any antibody testing?

Usually most contacts are health care workers.

[AlaskaDenise]

Re: Pakistan: December 18+, WHO Begins Investigations

Commentary at

http://www.recombinomics.com/News/12...etic_Myth.html

Commentary

H5N1 Genetic Predisposition Media Myth

Recombinomics Commentary
December 23, 2007

Some experts believe that a sick person is more likely to pass the infection on to a blood relative rather than an in law if both are in close and continuous physical contact with him/her.

The above comment is another widely circulated media myth. It shows up in wire service stories, and well as ProMed commentaries. However, the speculation has little scientific basis.

The speculation became more widespread after the Indonesia cluster in Karo. In that cluster, there were 8 family members who died or were H5N1 confirmed. Since all infected were blood relatives, and genetic predisposition was postulated and the lack of clusters involving a husband and wife was cited in support.

However, the Karo cluster is easily explained by close contact with patients who are fatally infected with a high H5N1 viral load Data supporting close contact comes from the WHO update:

The newly confirmed case is a brother of the initial case. Specimens were taken on 21 May and flown the same day to Jakarta. Tests run overnight confirmed his infection. His 10-year-old son died of H5N1 infection on 13 May. The father was closely involved in caring for his son, and this contact is considered a possible source of infection.

Although the investigation is continuing, preliminary findings indicate that three of the confirmed cases spent the night of 29 April in a small room together with the initial case at a time when she was symptomatic and coughing frequently. These cases include the woman?s two sons and a second brother, aged 25 years, who is the sole surviving case among infected members of this family. Other infected family members lived in adjacent homes.

All confirmed cases in the cluster can be directly linked to close and prolonged exposure to a patient during a phase of severe illness. Although human-to-human transmission cannot be ruled out, the search for a possible alternative source of exposure is continuing.

The index case had developed symptoms May 24 from an unknown source. A family gathering was planned for May 30. As noted in the update, four of the eight members of the cluster slept in the same small room on May 29. They developed symptoms a few days later, as did the index case?s daughter, niece, and nephew. The family gathering and the location of their housing allowed for additional close contact on or about May 30, which is the approximate date of exposure based on symptoms a few days later. Another brother developed symptoms after his son (who was the nephew of the index case) died.

The development of symptoms close to the date of death of the index case is common. Just prior to death the viral load is usually at a peak. Most H5N1 isolates come from samples collect just prior to or on the date of death. Thus, the infection of family members, including blood relatives who cared for the infected relative, is not unexpected.

The number of large H5N1 clusters is relatively small. The index case frequently is a child or teenager, which is likely due to an increased exposure risk. A requirement of infection of three family members or more is required for infection of husband and wife.

However, a cluster of five in Haiphong did involve a husband, wife, and three daughters. Similarly, there have been clusters that involved a health care worker in Vietnam, and a friend in Azerbaijan. Thus, although the number of larger clusters is limited, they contain clear examples of infections in contacts that are not blood relatives.

Similarly, media reports suggest that one or two health care workers were infected through contact with the larger familial cluster in Pakistan, and health care workers linked to patients infected in 1997 in Hong Kong had antibodies, indicating the were infected with H5N1 by patients who were not blood relatives.

Moreover, many of the outbreaks are multi-focal. In Pakistan in addition to the large familial cluster, there was a smaller familial cluster, as well as at least one additional patient who did not appear to be a blood relative of any of the cluster members. The relationships in the Pakistan outbreak will be clearer when the situation update is released.

However, earlier clusters do not support the genetic predisposition that is cited in media reports.


.

[AlaskaDenise]

Re: Pakistan: December 18+, WHO Begins Investigations

Commentary at

http://www.recombinomics.com/News/12...tan_False.html

Commentary

H5N1 False Negatives in Pakistan?

Recombinomics Commentary
December 24, 2007

?In their preliminary tests the WHO team excluded suspected human-to-human transmission, but we have sent the samples to Geneva for further confirmation,? health ministry spokesman Oriya Maqbool Jan told AFP.

The above comments suggest that the shipment of samples from patients in Pakistan to London was due to false negatives at the NAMRU-3 mobile lab. Media reports had indicated that the positive results obtained in October by labs in Pakistan were confirmed in Pakistan over a week ago. Moreover, the sustained transmission in H5N1 lab confirmed contacts strongly supports human-to-human transmission.

False negatives by the NAMRU-3 mobile lab could be due to a number of factors including sample degradation due to multiple tests, viral RNA depression due to collection of samples after the start of Tamiflu treatment, or primer mismatches due to sequence differences between the H5N1 in Pakistan compared to Egypt, lack of fine tuning in the testing by the mobile lab.

Unfortunately, there is precedent for all of the above. Media quotes from the Pakistan Health Minister indicated samples from patients were collected one to two after the start of Tamiflu treatment. Since Tamiflu inhibits the release of H5N1 from an infected cell, treatment can cause to drop in RNA levels, resulting in a false negative result. Sequence differences between the H5N1 in Pakistan and Egypt are likely because the isolates in Pakistan are likely to be related to the Uva Lake strain, which is currently widespread in Europe and was previously detected in Kuwait in early 2007, but has not been reported in human H5N1 sequences generated by NAMRU-3 in Egypt.

However, there is also evidence of detection failures at the regional centers also. A year ago, 21 patients were H5N1 confirmed by labs in Turkey. However, only 12 of the 21 were confirmed by Weybridge in England. These failures were almost certainly false negatives because the samples in Turkey formed clusters, and the likelihood of pairing up false negatives is remote. These failures extended to the fourth sibling from the index cluster. Moreover, sequences from only four patients have been released, suggesting that there were significant isolation failures at Weybridge. These failures extended to mixtures because the index case from Turkey had S227N, while the isolate from the sister of the index case did not. H5N1 false negatives in Egypt were also seen in the Gharbiya cluster. Although three family members died with bird flu symptoms, sequence data was not obtained for one of the three fatalities.

Some or all of these failures may also be linked to use of a Tamiflu blanket. In addition to failures in detecting clade 2.2 in the above examples, the Tamiflu blanket may have led to the lab confirmation failures for the recent suspect cluster in Indonesia.

Details on collections histories relative to the start of Tamiflu treatment would be useful.


.