# 2355
Last December the world learned that there were several confirmed and suspected human cases of H5N1 in the NWFP (North West Frontier Province) of Pakistan.
Early reports were murky, with conflicting data regarding the number of victims, their relationships, and their illness onset dates.
While these cases reportedly began in late October of 2007, it wasn't until December that the WHO was notified, and the first official word was released from the WHO on December 15th.
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.
Up until today, the last update came in April of 2008, with this summation.
Avian influenza – situation in Pakistan - update 2
3 April 2008
Two additional H5N1 cases were confirmed by serological testing, thus providing final H5N1 infection test results on a previously reported family cluster in Peshawar.
These tests were conducted by the WHO H5 Reference Laboratory in Cairo, Egypt and the WHO Collaborating Centre for Reference and Research on Influenza in Atlanta, USA. The table below summarises the testing results of the confirmed/probable cases in the family cluster.
- The preliminary risk assessment found no evidence of sustained or community human to human transmission.
- All identified close contacts including the other members of the affected family and involved health care workers remain asymptomatic and have been removed from close medical observation.
These laboratory test results support the epidemiological findings from the outbreak investigation in December 2007, and the final risk assessment that suggested limited human to human transmission likely occurred among some of the family members which is consistent with some human-to-human transmission events reported previously. This outbreak did not extend into the community, and appropriate steps were taken to reduce future risks of human infections.
Today we get a far more detailed look at the events that transpired in Pakistan late last year, and a much clearer understanding of the chain of transmission of the virus via this review in the WHO's Weekly Epidemiological Record 2008,83, 357-364 for the week of October 3rd, 2008.
A hat tip goes to Ironorehopper on Flutrackers for posting this account.
The WHO's Weekly Epidemiological Record (WER), which is released each Friday, is described by the WHO as follows:
The Weekly Epidemiological Record (WER) serves as an essential instrument for the rapid and accurate dissemination of epidemiological information on cases and outbreaks of diseases under the International Health Regulations and on other communicable diseases of public health importance, including emerging or re-emerging infections.
This is a lengthy report, and so I've only posted some of the more relevant snippets. Interested parties will want to read it in its entirety.
Following a detailed account of each of the 5 brothers involved in this family cluster, including onset dates, testing, and outcomes the following discussion and conclusion are offered:
Discussion
After thorough epidemiological investigation by the international investigation team and confirmatory testing of clinical specimens by WHO influenza A/H5 reference laboratories, 3 cases were confirmed as avian influenza A(H5N1) infection.2 The 3 confirmed cases were brothers aged between 25 and 32 years. One of the cases died within 7 days of onset of illness; the other 2 cases recovered.
In addition, the investigation detected 1 probable case of H5N1 infection and 1 asymptomatic seropositive case within the same family. These are the first human cases of influenza A(H5N1) virus infection documented in Pakistan.
Case 1 is also the first person to have documented influenza A(H5N1) disease following occupational exposure during poultry culling.
With respect to the chain of transmission, evidence gathered during the investigation supports the theory of initial transmission from poultry to humans followed by human-to-human transmission involving a third generation.
Only 1 of the brothers (the first to become ill) had a clear history of contact with sick or dead poultry (the poultry had been laboratory-confi rmed as being infected with H5N1 virus); the other brothers who became ill had not been working in occupations related to the poultry industry or farming.
<snip>
Conclusion
The illnesses of the 4 brothers are consistent with influenza A(H5N1) virus infection. After considering the information gathered during investigation of this cluster of cases, evidence supports a chain of transmission beginning with poultry-to-human transmission followed by human-to-human transmission for 3 generations of transmission.
Despite thorough investigation and active surveillance, there was no evidence of sustained transmission in the community. Contacts in the immediate and extended family and health-care workers received follow-up clinical and laboratory testing, but there was no evidence of further influenza A(H5N1) infection.
Evidence gathered during the investigation supports the hypothesis that this outbreak of influenza A(H5N1) infection was limited to a family cluster and was not sustained in the community.
Human-to-human transmission probably occurred, but only after prolonged and intimate contact among family members.
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Other than filling in the gaps, and strongly suggesting 3 generations of transmission, the biggest news here is the addition of a 5th brother, one who apparently experienced an asymptomatic seroconversion to the H5N1 virus.
* Case 5
Case 5 was a 33-year-old brother of Case 1. He was asymptomatic but clinical specimens were collected from him owing to the close and prolonged contact with his ill brothers. Initial testing at the National Institute of Health yielded positive results for H5 RT–PCR on a throat swab collected on 29 November.
When serum specimens were tested by microneutralization assay, a specimen collected on 8 December yielded an H5 antibody titre of 1:320 and a positive western blot assay.
Asymptomatic seroconversion, where someone can be exposed to the virus and develop antibodies against it - without getting ill- is something we've seen on rare occasions in the past with the H5N1 virus. As the report notes:
Case 5 had had frequent close contact with all 4 of his brothers when they were ill, and infection may have occurred after exposure to any of them. Case 5 had no known contact with sick or dead poultry.
Asymptomatic seroconversion in household contacts has been documented previously in a study in Hong Kong SAR conducted after the 1997 outbreak of influenza A(H5N1)
The identity of the fifth brother isn't readily apparent from this report, but it may be the brother who returned to the United States in December, and who was declared `not infected' by local health officials upon his arrival.
There is, however, a discrepancy in the ages given the news accounts of the returning brother (38) and the 5th brother in this report (33). (Hat tip Laidback Al on FluTrackers)
A person can seroconvert, carry the antibodies to a virus, without being infected or contagious. The presence of such antibodies only indicate an exposure in the past.
We are still left with a few unanswered questions here. Early reports had as many as 8 people supposedly testing positive for the virus, and here we have only 5 accounted for.
Early reports are often confused, and that may explain the discrepancy.
The WHO is also only counting 3 of the 5 brothers as definitely infected with the H5N1 virus, even though 4 tested positive for antibodies to the virus. Perhaps a semantical difference, as the fifth victim never showed clinical signs of the illness - only antibodies.
The 2nd brother (who died) was never tested for the virus, although he remains a highly probable infection.
In any event, we have a good deal more detail today than we've seen before regarding this cluster, and the evidence is pretty strong that there was human-to-human-to-human transmission of the virus.
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