Observed low case fatality ratio in 2008-9
Information made available to WHO indicates that, on 8 April 2009 the Ministry of Health of Egypt reported 3 new confirmed human cases of infection with avian influenza A(H5N1). The latest report can be accessed here The first case is a 2 year-old boy from Kom Hamada District, El Behira Governorate who developed symptoms on 27 March and was admitted to hospital on the 30 March where he was started on oseltamivir the same day. He is reported to remain in a stable condition. The second case is also a 2 year old male from the same district and was detected through the investigation around the first case. He developed symptoms on 31 March and was admitted to hospital on 1 April where he was also started on oseltamivir the same day. He is also reported to remain in a stable condition. Both boys are reported to have had contact with sick/dead poultry prior to the illness onset. Close contacts of both boys have been identified and none has as yet shown symptoms of the infection. The third case is a 6 year-old boy from Shubra El Khema District, Qaliobia Governorate. He developed symptoms on 22 March and was admitted to hospital on the 28 March where he was again started on oseltamivir (on 3rd April). He was also reported to have been exposed to sick/dead poultry prior to the onset of his illness. He was reported to be in a critical condition. For all of the three cases reported above, infection with H5N1 avian influenza virus was following testing by the Egyptian Central Public Health Laboratory and subsequently confirmed by the United States Naval Medical Research Unit No. 3 (NAMRU-3). Of the 63 cases confirmed to date in Egypt, 23 have been fatal. The last fatal case, had an onset date of December 8th 2008 and died on December 15th see here. Details of all the Egyptian cases can be seen through the general country page on the WHO web-site. It means than since December 2008 there have been 12 new confirmed A(H5N1) infections in humans all in childrenunder age 3 apart from one woman in her 30s and none of the 12 are known to have died as of April 16th .
ECDC Comment (09-04-15): The low Case Fatality Ratio (CFR) for human infections with Highly Pathogenic Avian Influenza (HPAI) H5N1 virus in Egypt is most welcome. However it was noted at a WHO global review two years ago.(2) Therefore, what is being described now is not entirely new, except that there have been a series of 12 cases in 2009 with no deaths.Clinically, mild illness with HPAI H5N1 virus infection has been reported in children in several countries apart from Egypt i.e. Turkey, Indonesia and Bangladesh and it should be noted that Egypt seems to be testing more children with milder illness soon after onset than any other countries. This could be because children are brought to medical care for H5N1 testing early in their illness. Moreover, testing and care (including early commencement of the antivial oseltamivir as recommended by WHO and ECDC (3,4)) seems to be relatively available in Egypt. It is noticeable in the recent reports how soon after onset dates treatment with oseltamivir seems to have started. The occurrence of so many cases late in 2008 and early in 2009 is not in itself unusual. It was also the pattern in the 2007-8 period.(Figure) (5)
Despite the above speculation, it is not yet known how to explain the commendable low CFR being achieved in Egypt with a virus that overall has been observed to have a CFR of around 60-70%.(5) Various hypotheses have to be tested. It could reflect a further adaptation of the virus to humans and a lessening of its virulence but equally it could be the result of good local surveillance, or that the clade 2.2 virus infections in Egypt has a lower CFR, or that its because early oseltamivir and other treatment has a better outcome. There are no reports as yet of a change in the virological sequences and it is commendable that the Egyptian authorities have been sharing viruses with the global community as evidence from the WHO A(H5N1) Tracking Mechanism.(6) The clade hypothesis theory seems unlikely since in nearby Turkey the same clade of H5N1 cases in 2005/6 resulted in a CFR for Turkey of 4 out of 12 in circumstances where it was difficult to achieve early treatment (a rural areas in then middle of a severe winter).(5) Hence the good surveillance / early treatment theory seems the strongest hypothesis. However uncertainty remains and it will be important to investigate further. It is very welcome that the Egyptian authorities have invited WHO to send senior staff to Egypt next week to assess the current epidemiological situation. It is especially reassuring that despite the low CFR and apart from two of the cases in the most recent report there have been no clusters in the cases suggesting more easy human to human transmission. However it would be hoped that this would be investigated in Egypt with serological surveys to look for milder and asymptomatic cases and any suggestion of clustering since even though the seeming lack of significant change in the sequence of the virus is reassuring the changes can be subtle and its how the viruses behave that is most important.(7) A good example of such investigations were recently published in the Weekly Epidemiological Report of joint National / WHO work done in Pakistan in 2007.(8)
Figure (from reference 5 below): ‘Avian Influenza A(H5N1) cases reported in humans in Egypt 2006~2009 by onset date’
Click to see larger graph
WHO Reports Source accessed April 16th 2009
1. Media Report New bird flu cases suggest the danger of pandemic is rising
Independent UK April 12th 2008
2. Writing Committee of the second WHO consultation on clinical aspects of human infection with avian influenza A (H5N1) virus. NEJM 2008; 358: 261-73 .
3.WHO Clinical management of human infection with avian influenza A (H5N1) virus August 2007
4. ECDC Oseltamivir prophylaxis following suspected exposure of humans to Highly Pathogenic Avian Influenza (HPAI) with particular reference to HPAI type A/H5N1, Version 30th April 2006
5. WHO Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO April 8th 2009 (see figure above)
6. WHO Influenza Virus Tracking System (interim)
7. Nicoll A (Yet) another human A/H5N1 influenza case and cluster – when should Europe be concerned? Eurosurveillance 2008; Volume 13, Issue 15, 10 April 2008
8. WHO Human cases of avian influenza A(H5N1) in North- West Frontier Province, Pakistan, October–November 2007 WER 2008 3 October 2008, vol. 83, 40 (pp 357–364)