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Sustained H2H?...

Brilliant Dr. Niman. Absolutely brilliant.

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Sustained Human to Human H5N1 Transmission in Pakistan?

Recombinomics Commentary
December 19, 2007

"Right now it doesn't look like pure human to human transmission. It looks like the veterinarian, who was the index case, and a number of other suspect cases had poultry exposure," Fukuda told Reuters in an interview.

"It is definitely possible that we have a mixed scenario where we have poultry to human infection and possible human to human transmission within a family, which is not yet verified." But human to human transmission "would not be particularly surprising or unprecedented," he added.

In Thailand, a mother was killed by the virus in 2004 after cradling her dying infected daughter all night. The largest known cluster of human bird flu cases worldwide occurred in May 2006 in Indonesia's North Sumatra province, where as many as seven people in an extended family died.

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The above comments on the human to human (H2H) transmission in Pakistan, and two examples of such infections in the past are accurate, but the extensive H2H transmission in Pakistan is likely to cause confusion, because media reports and the public believe that H2H of H5N1 is rare, when it is very common.  The more extended transmission chains, as noted above, are rarer, and the transmission in Pakistan may be the most sustained H2H reported to date, but H2H among family members is quite common, and most first reports of H5N1 in patients are H2H clusters.

The H5N1 H2H usually involves only two people, which are the index case and a family member caring for the index case. These small clusters have the diagnostic time gap between onset dates, but the linkage of the index case to a poultry source extends to a family member, so the proof of H2H is not absolute.

When there are two time gaps, suggesting H2H2H, then the likelihood of H2H increases markedly, especially when there is epidemiological data linking the cases.

However, the number of cited H2H examples is also reduced because samples are frequently not collected from the index case, and testing of contacts may use samples collected after the start of prophylactic oseltamivir (Tamiflu) treatment.

In the first example above. The lack of a poultry connection added to the likelihood that H2H was involved, and the number in the cluster was three and there were two time gaps.  Therefore, it has been cited as the first example of H2H.  The index case was a child staying with her aunt in rural Thailand.  Her mother was an office worker in Bangkok.  The index case was likely infected by a pet chicken, which died and was buried by the child.  However, she was mis-diagnosed as having dengue fever.  Consequently, there was no protective equipment given to her visiting mother, who was probably infected while holding her daughter in the hospital.  The daughter died and was never tested for H5N1, but the mother developed symptoms after returning to Bangkok, and the aunt of the index case also developed symptoms several days after the mother left.  Initially the mother was not tested either, but after she died, a nurse notified investigators of the bird flu symptoms, and samples were collected just prior to cremation.  The mother was H5N1 positive and the aunt was also H5N1 positive, although initial tests on the aunt were inconclusive.  Thus, if there wasn’t a cluster, it is likely hat none of the cases would have been official confirmed cases.  However, because of the lab confirmation in the mother and aunt, the cluster is a strong example of H2H or H2H2H.

The cluster in Indonesia is also considered to be a cluster because there were two time gaps, and there was epidemiological evidence for H2H2H.  However, the index case died prior to collection of a sample.  Seven family members tested positive for H5N1 and the onset of symptoms was several days after the index case, most of whom slept in the same room as the index case while she was very sick and coughing extensively.  The son of one of the infected brothers also developed symptoms several days after his father, so the Indonesia clusters was H2H2H, although the index case was not lab confirmed.

Most clusters however only involve two family members.  The first cases in Cambodia were a cluster.  The index case collected dead chickens.   He developed bird flu symptoms and died prior to sample collection.  When his sister developed symptoms, she went to Vietnam for treatment and was H5N1 confirmed after she died, so although the brother likely infected his sister, the cluster was not considered H2H because no sample was collected from the brother.  The first cases in Hunan China were also a cluster with a time gap, but were not considered a cluster until a rising antibody titer was detected in the index case after he died.  The first cases in Indonesia were also a cluster, but there were no early samples from the index case, no sample was collected from her sister, and H5N1 was confirmed in the father after his two daughters had died.  This cluster had two time gaps, but one sister was not an official case because she was not tested.

There are dozens of similar examples.  Some of the earlier clusters from Vietnam and Thailand were published, but there have been many examples since the earlier clusters were reported, and these clusters include the first case from Turkey, Iraq, Azerbaijan, and Nigeria.  All of these cases involve the Qinghai strain of H5N1, which is almost certainly the case fro the cluster from Pakistan.

However, this cluster is likely to the most sustained to date.  The index case was a veterinarian who developed symptoms on October 25.  Two brothers developed symptoms after visiting the index case in the hospital, and the dates of death on November 19 and 29 suggest this transmission chain was H2H2H.  However, at least two more brothers were infected, and one or two health care workers had symptoms or were H5N1 confirmed, so they represent H2H2H2H, if confirmed, and since one is still hospitalized, the transmission has been sustained for two months.  Moreover, samples of contacts are being collected after the start of Tamiflu treatment, so additional transmissions may not be lab confirmed.

The detail of this cluster will be clearer when disease onset dates are released, but the current cluster appears to be the most sustained H5N1 cluster reported to date, and also representing the largest number of links on the chain.

http://www.recombinomics.com/News/12200701/H5N1_Pakistan_Sustained.html

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