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Archive Number 20090703.2391
Published Date 03-JUL-2009
Subject PRO/AH/EDR> Influenza A (H1N1) - worldwide (81): epidemic analysis

INFLUENZA A (H1N1) - WORLDWIDE (81): EPIDEMIC ANALYSIS
******************************************************
A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>

In this update:
[1] Epidemic pneumonia
[2] Origins
[3] CFR estimations
[4] Tamiflu resistance - Japan

******
[1] Epidemic pneumonia
Date: Tue 29 Jun 2009
Source: The New England Journal of Medicine [edited]
<http://content.nejm.org/cgi/content/full/NEJMoa0904023>


[The following paper appeared in the 29 June issue of the New England 
Journal of Medicine. - Mod.CP]
G Chowell, SM Bertozzi, MA Colchero, H Lopez-Gatell, C Alpuche-Aranda, M 
Hernandez, et al. Severe respiratory disease concurrent with the 
circulation of H1N1 influenza. N Engl J Med 2009 (10.1056/NEJMoa0904023)

Abstract
--------
Background: In the spring of 2009, an outbreak of severe pneumonia was 
reported in conjunction with the concurrent isolation of a novel 
swine-origin influenza A (H1N1) virus (S-OIV), widely known as swine flu, 
in Mexico. Influenza A (H1N1) subtype viruses have rarely predominated 
since the 1957 pandemic. The analysis of epidemic pneumonia in the absence 
of routine diagnostic tests can provide information about risk factors for 
severe disease from this virus and prospects for its control.

Methods: From 24 Mar to 29 Apr 2009, a total of 2155 cases of severe 
pneumonia, involving 821 hospitalizations and 100 deaths, were reported to 
the Mexican Ministry of Health. During this period, of the 8817 
nasopharyngeal specimens that were submitted to the National 
Epidemiological Reference Laboratory, 2582 were positive for S-OIV. We 
compared the age distribution of patients who were reported to have severe 
pneumonia with that during recent influenza epidemics to document an age 
shift in rates of death and illness.

Results: During the study period, 87 per cent of deaths and 71 per cent of 
cases of severe pneumonia involved patients between the ages of 5 and 59 
years, as compared with average rates of 17 per cent and 32 per cent, 
respectively, in that age group during the referent periods. Features of 
this epidemic were similar to those of past influenza pandemics in that 
circulation of the new influenza virus was associated with an off-season 
wave of disease affecting a younger population.

Conclusions: During the early phase of this influenza pandemic, there was a 
sudden increase in the rate of severe pneumonia and a shift in the age 
distribution of patients with such illness, which was reminiscent of past 
pandemics and suggested relative protection for persons who were exposed to 
H1N1 strains during childhood before the 1957 pandemic. If resources or 
vaccine supplies are limited, these findings suggest a rationale for 
focusing prevention efforts on younger populations.

-- 
communicated by:
ProMED-mail rapporteur Mary Marshall

[The authors add the following in their Discussion. "Of note, during the 
study period, there was proportionately lower morbidity among persons who 
were 60 years of age or older, the age group in which all persons were born 
before the 1957 pandemic. With an annual influenza incidence of 15 to 20 
per cent, most of these persons would have been 1st exposed to influenza A 
(H1N1) strains, which disappeared from circulation after the 1957 A (H2N2) 
influenza pandemic. Francis described the concept of "original antigenic 
sin," in which the immune response is greatest to antigens to which 1st 
exposure occurred in childhood. According to this concept, persons born 
before 1957 who were exposed in childhood to influenza A (H1N1) viruses 
might be better protected against this viral subtype than those who were 
1st exposed to other influenza A subtypes, H2N2 and H3N2, at a later date. 
Age shifts in mortality to younger populations during pandemics have been 
described from the reemergence of a subtype. Although persons who were born 
after 1977 may have been 1st exposed to an influenza A (H1N1) subtype 
virus, such strains rarely predominate. In this data series, persons who 
were 60 years of age or older were proportionately less likely to have 
severe pneumonia, a consideration for future strategies for vaccine allocation.

"Our outline of the age-stratification profile of risk provides a possible 
foundation for control strategies on the basis of the biologic plausibility 
of partial protection from earlier exposure. Further studies are under way 
in Mexico to elucidate other potential risk factors for severity of S-OIV 
infection to guide targeted control efforts." - Mod.CP]

******
[2] Origins
Date: Mon 29 Jun 2009
Source: ScienceDaily, News [edited]
<http://www.sciencedaily.com/releases/2009/06/090629200641.htm>


The current H1N1 swine flu strain has genetic roots in an illness that 
sickened pigs at the 1918 Cedar Rapids Swine Show in Iowa, report 
infectious disease experts at the University of Pittsburgh Graduate School 
of Public Health in the New England Journal of Medicine. Their paper, 
published online 29 Jun 2009 and slated for the 16 Jul 2009 print issue, 
describes H1N1's nearly century-long and often convoluted journey, which 
may include the accidental resurrection of an extinct strain.

"At the same time the 1918 flu pandemic was rapidly spreading among humans, 
pigs were hit with a respiratory illness that closely resembled symptoms 
seen in people," said senior author Donald S Burke, MD, dean, University of 
Pittsburgh Graduate School of Public Health. "Early experiments confirmed 
that this 1918 swine virus and a human strain emerged about the same time. 
Since then, this ancestor virus has re-assorted genetically with other 
influenza strains at least 4 times, leading to the emergence of the new 
2009 strain, which has retained some similarities to the original virus."

In the paper, Dr Burke and lead author Shanta M Zimmer, MD, assistant 
professor, University of Pittsburgh School of Medicine, describe the 
temporary "extinction" of the H1N1 virus from humans in 1957 and its 
subsequent re-emergence 20 years later. They note a small 230 person 
outbreak of H1N1 in 1976 among soldiers in Fort Dix, New Jersey that did 
not extend outside the military base. Then, H1N1 influenza re-emerged in 
1977 among people in the former Soviet Union, Hong Kong and north eastern 
China. Careful study of the genetic origin of the 1977 strain showed that 
it was not the Fort Dix strain, but, surprisingly, was related closely to a 
1950 human strain. Given the genetic similarity of these strains, 
re-emergence was likely due to an accidental release during laboratory 
studies of the 1950 strain that had been preserved as a "freezer" virus, 
they said.

The authors hypothesize that concerns about the Fort Dix outbreak 
stimulated a flurry of research on H1N1 viruses in 1976, which led to an 
accidental release and re-emergence of the previously extinct virus a year 
later. The re-emerged 1977 H1N1 strain has continued to circulate among 
humans as seasonal flu for the past 32 years.

Although originally traced to Mexico, the exact physical origins of the 
2009 H1N1 pandemic virus are unknown. Because the current strain shares 
common ancestry with older flu strains, it is possible that portions of the 
population may have partial immunity to the new pandemic virus.

The authors also go on to explain that the danger posed by a virus isn't 
based solely on its lethality but also on its transmissibility, which is 
the ability to jump from animals to humans and to survive by mutating to 
adapt to its new human host. H1N1 influenza viruses have demonstrated this 
ability throughout their history.

"Studying the history of emergence and evolution of flu viruses doesn't 
provide us with a blueprint for the future, but it does reveal general 
patterns, and this kind of information is critical if we are to be as 
prepared as possible," said Dr Burke.

-- 
communicated by:
ProMED-mail rapporteur Susan Baekeland

*****
[3] CFR estimations
Date: Thu 2 Jul 2009
Source: Eurosurveillance, Volume 14, Issue 26, 2009 [edited]
<http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19255>


The emerging influenza pandemic: estimating the case fatality ratio
-------------------------------------------------------------------
By: N Wilson, M G Baker (Department of Public Health, University of Otago, 
Wellington, New Zealand)

To determine appropriate influenza pandemic containment and mitigation 
measures, health authorities need to know the approximate case fatality 
ratio (CFR) for this new infection. We present 4 different methods for very 
provisionally estimating the plausible range of the CFR for symptomatic 
infection by this pandemic strain in developed countries. All of the 
methods produce substantially lower values (range 0.06 percent to 0.0004 
percent) than a previously published estimate for Mexico (0.4 percent). As 
these results have many limitations, improved surveillance and serological 
surveys are needed in both developed and developing countries to produce 
more accurate estimates.

Introduction
------------
The 1st published estimate of the case fatality ratio (CFR) for those 
infected by the influenza A(H1N1)v pandemic strain was based on data from 
Mexico [1]. This work estimated the CFR to be 0.4 per cent (range 0.3 per 
cent to 1.5 per cent) based on confirmed and suspected influenza 
A(H1N1)v-related deaths reported up to late April 2009. Since that date, 
the new pandemic strain has spread globally, and new impact data are 
available, but we were unable to identify new estimates of the CFR in the 
literature. Yet this figure is critical if health authorities are to 
produce reasonable estimates of the likely impact of the pandemic in their 
particular countries. The estimated mortality burden is particularly useful 
for calibrating appropriate containment and mitigation measures that 
balance the likely health gains from interventions against their social and 
economic costs.

Methods
-------
We considered 4 different ways to provide provisional estimates for 
plausible ranges of CFRs in developed countries for this pandemic.

1. Multiplier method: This method used confirmed deaths and cases reported 
to the World Health Organization (WHO), but with a range of multipliers for 
the latter to adjust for under-ascertainment. These multipliers were based 
on expert judgment that most symptomatic cases of the new pandemic involve 
relatively mild symptoms and that the great majority of cases were not 
being identified and reported. For example, spokespeople from the United 
States (US) Centers for Disease Control and Prevention (CDC) have announced 
"hundreds of thousands of cases that have occurred in the US" in late May 
and mid-June 2009 [2,3]. Similarly, one estimate for the United Kingdom was 
30 000 cases in the community in May 2009 [4]. Regarding the choice of a 
multiplier to adjust data on laboratory-confirmed cases of pandemic 
influenza, we considered the above assessments, which are specific to the 
current pandemic, to be more informative than past experience with seasonal 
influenza, which only provides very broad estimates of a potential 
multiplier. For example, it has been estimated for seasonal influenza in 
the US that there are 2.3 influenza cases in the community for every 
outpatient consultation, and 84.1 for every case that is hospitalised 
(derived from Molinari et al. [5]). But during a pandemic, patients are 
encouraged to remain at home unless they have "severe illness" or are "at 
high risk for influenza complications." In addition, laboratory testing 
capacity can be quickly saturated in a pandemic, and priority is given to 
those who require hospitalisation or are at high risk for severe disease 
[6]. These processes will tend to push the ratio of community cases to 
laboratory-confirmed cases upwards to the multiplier in the range of 10-30 
that we judged reasonable for this analysis.

In the calculations, we used WHO data for cumulative cases and deaths as of 
26 Jun 2009 [7] for all member countries of the Organisation for Economic 
Cooperation and Development (OECD), but excluding data from Mexico. The 
reason for this exclusion was that the epidemic appeared to have started in 
Mexico, and we were concerned about the quality and sensitivity of 
numerator data in the early stages of the epidemic there -- that is, when 
it was not recognised that the new pandemic strain was spreading.

2. Community survey method: This method used an estimate for community 
cases from a telephone survey done by the New York City Department of 
Health [8]. It reported that 6.9 per cent of New Yorkers had symptoms of 
influenza-like illness (ILI) between 1 and 20 May 2009. The report on this 
survey did not publish confidence intervals, so we calculated these to be 
5.6 per cent to 8.5 per cent (for the survey of 1005 households). 
Furthermore, at the time of this survey, only 90 per cent of the influenza 
samples tested in the city were of the current pandemic strain [9], and so 
we adjusted the CFR estimate accordingly by this proportion. We 
conservatively used the cumulative death toll for New York City at 3 weeks 
after the time period used in this survey (when it was n=12) to allow for a 
lag in illness progression and then in reporting fatalities to health 
authorities [10]. We identified that there were no pandemic influenza 
deaths prior to May 2009 [11], and the New York City population of 8 274 
500 used in our calculations was that for 2007 [12].

3. Method extrapolating from seasonal influenza mortality: This method was 
based on evidence that the elderly population appear to have a relatively 
low mortality rate compared to other age groups in this pandemic. Data from 
Canada on hospitalisations and deaths [13] and US data indicate a median 
age of hospitalisation at 19 years and of death at 37 years [14]. Hence, we 
assumed that a CFR for seasonal influenza in the age group of under 65 
years could provide a crude approximation for the CFR of the new pandemic 
strain. To obtain this value, we used the full range estimates that could 
be derived from a detailed US study [15] that used 7 models for determining 
excess mortality attributable to influenza. [These data are presented as a 
table in the original text].

4. Method extrapolating from a more "mature" epidemic: This method was 
restricted to data from Canada and assumed that the epidemic there was 
relatively advanced in that the trend data for cases and hospitalisations 
were suggestive of a peak in early June 2009 with a subsequent waning of 
the epidemic in the following 3 weeks [17]. To calculate the CFR, we 
assumed that the epidemic in Canada was half complete in terms of 
cumulative deaths (with n=21 deaths confirmed as of 26 Jun 2009 [17]), 
which is possibly a conservative assumption given the low level of new 
hospitalisations in late June 2009. We also assumed that the cumulative 
total of symptomatic cases would ultimately reach between 5 per cent of the 
total population (which is within the range of seasonal influenza) and 
around 30 per cent (which is about the value predicted by modelling for a 
pandemic with an R0 value of 1.5 [18] as estimated for the current pandemic 
using the Mexican data [1]).

Results
-------
The 4 different methods produced a wide range of estimates for the CFR in 
developed countries, from 0.0004 per cent to 0.06 per cent, a range of 
150-fold (table 2). The ranges for each model overlapped with at least one 
other model. When these CFR estimates were applied to a country with a 
population of 10 million that ultimately experienced a cumulative incidence 
of symptomatic infection with the pandemic strain of 30 per cent, the total 
number of deaths would range from 12 to 1800.

Table: Case fatality ratio for symptomatic infection with influenza 
A(H1N1)v pandemic strain in developed countries, estimated by 4 different 
methods [abbreviated]:
Method / Range of CFR (per cent) / Projected number of deaths in developed 
country of 10 million inhabitants
1 / 0.004 - 0.06 / 120 - 1800
2 / 0.01 - 0.03 / 300 - 900
3 / 0.002 - 0.003 / 60 - 90
4 / 0.0004 - 0.003 / 12 - 90

Discussion
----------
All these estimated CFRs are substantially lower than the previously 
published estimate (0.4 per cent for Mexico). They also differ markedly 
from the simplistic estimate that would be derived from using surveillance 
data available only for confirmed cases reported to WHO (that is, CFR = 
0.29 per cent, based on 110 deaths in 38 409 cases for the 29 OECD 
countries used in this analysis [7]). A low CFR would be consistent with 
the mild 1st wave seen in previous pandemics which caused widespread 
infection but low mortality [19]. It could also be related to the 
relatively young age of the majority of cases and the use of highly 
effective modern treatment for those who are seriously ill.

Although based on the most current data possible, all the methods used 
still have substantial limitations. The multiplier method merely relied on 
the judgment (from other experts as well as ours) of widespread and 
relatively mild disease that is not being reported. Nevertheless, the 
suggestion of widespread community spread in the US is broadly consistent 
with the community survey in New York City and another community survey in 
the US with around 6 per cent cumulative incidence of ILI [14].

The New York City survey was limited by asking only about ILI that occurred 
during a 20 day period in May 2009 and by ignoring illness in April 2009 
even though there were hospitalisations in New York City in that month. 
Therefore, the method using this survey could have overestimated the CFR, 
although the opposite could have occurred if some of the reported ILI 
symptoms were due to other respiratory infections and allergic conditions 
such as hay fever.

The method that extrapolated from seasonal influenza mortality data in 
people under 65 years of age was limited in that it effectively considered 
no aspects of the epidemiology of the new pandemic influenza virus other 
than the age distribution -- that is, that it seems to affect younger age 
groups more than older age groups. Yet there is little information 
comparing the current pandemic strain with seasonal influenza strains in 
terms of mortality risk in this younger age group. Furthermore, the data 
from which the estimated range was derived may be outdated in that modern 
medical care has progressed since the early part of the period used in the 
particular US study [15] that the estimates were based on.

Although the Canadian epidemic appears to be waning, the method using the 
crude extrapolation of the course of this epidemic was very simplistic. 
Indeed, rather than being half complete, this epidemic wave could continue 
throughout the northern hemisphere summer and beyond.

These methods tended to focus on correcting for under-ascertainment of the 
denominator, yet there is also a potential bias from underascertainment of 
the numerator of the CFR. Particularly in the early stages of an epidemic, 
there will be a lag in reported deaths and other severe outcomes. 
Sophisticated statistical methods have been proposed for obtaining adjusted 
CFR estimates using data from the early phase of an epidemic [20], and 
these result in adjustment for various time lags and an upward shift of the 
CFR. However, such adjustments would probably have little effect on the 
estimates presented in this article which are based on data from country 
epidemics which have progressed well beyond their early stages (for 
example, the Canadian data). There is also the potential for 
under-recognition of deaths attributable to influenza in those with serious 
co-morbidities, but this can only be addressed by careful research studies 
and post-epidemic modelling to determine total excess deaths. Nevertheless, 
this bias might be relatively smaller in this pandemic where more deaths 
involve young people. Also, once the new influenza A(H1N1)v strain was 
recognised, there is likely to have been increased sensitivity for 
diagnosing influenza-related deaths (at least in developed countries where 
hospitalisation is likely to precede influenza-related death).

All of the presented methods have limitations and could be refined using 
additional data to provide more robust estimates. Ultimately, such 
estimates require enhanced surveillance, outbreak investigations in a range 
of settings, and carefully designed population studies, ideally with 
serological testing [21]. Additionally, the ranges of CFRs for 
disadvantaged populations in developed countries and for most of the 
population in developing countries are likely to be much higher than those 
estimated here, given likely differences in disease transmission, 
co-morbidity, access to antivirals and standards of medical care.

Conclusion
----------
We present several methods for provisionally estimating the plausible range 
for the CFR of the emerging influenza pandemic in developed countries. All 
methods used have significant limitations, but they collectively suggest 
that infection with this particular pandemic strain is likely to cause 
illness with a relatively low CFR compared to an earlier estimate and also 
to historical standards. A further reason for presenting this range of 
methods is to encourage data collection that can start to reduce the 
uncertainty around this important pandemic parameter.

References
----------
1. Fraser C, Donnelly CA, Cauchemez S, Hanage WP, Van Kerkhove MD, 
Hollingsworth TD, et al. Pandemic potential of a strain of influenza A 
(H1N1): early findings. Science 2009; 324(5934): 1557-61.
2. CDC. CDC telebriefing on investigation of human cases of novel influenza 
A (H1N1). 18 June 2009. Atlanta: CDC; 2009. Available from: 
<http://www.cdc.gov/media/transcripts/2009/t090618.htm>.
3. CDC. Update on the novel influenza A H1N1 virus and new findings 
published today. 22 May 2009. Atlanta: CDC; 2009. Available from: 
<http://www.cdc.gov/media/transcripts/2009/t090522.htm>.
4. Lean G. UK swine flu toll is really 30 000, says leading scientist. 
London: The Independent; 24 May 2009. Available from: 
<http://www.independent.co.uk/life-style/health-and-families/health-news/uk-swine-flu-toll-is-really-30000-says-leading-scientist-1690130.html>. 

5. Molinari NA, Ortega-Sanchez IR, Messonnier ML, Thompson WW, Wortley PM, 
Weintraub E, et al. The annual impact of seasonal influenza in the US: 
measuring disease burden and costs. Vaccine 2007; 25(27): 5086-96.
6. CDC. Interim guidance for clinicians on identifying and caring for 
patients with swine-origin influenza A (H1N1) virus infection (4 May). 
Atlanta: CDC; 2009. Available from: 
<http://www.cdc.gov/h1n1flu/identifyingpatients.htm>.
7 WHO. Influenza A(H1N1) - update 54. 26 June 2009. Geneva: WHO; 2009. 
Available from: <http://www.who.int/csr/don/2009_06_26/en/index.html>.
8. New York City Department of Health and Mental Hygiene (NYCDHMH). 
Prevalence of flu-like illness in New York City: May 2009. A preliminary 
report from the Health Department. New York: NYCDHMH; 2009. Available from: 
<http://www.nyc.gov/html/doh/downloads/pdf/cd/h1n1_citywide_survey.pdf>.
9. NYCDHMH. Community transmission of H1N1 flu appears to decline in New 
York City (press release 12 Jun 2009). New York: NYCDHMH; 2009. Available 
from: <http://www.nyc.gov/html/doh/html/pr2009/pr042-09.shtml>.
10. NYCDHMH. Health Department survey suggests that 7 per cent of New 
Yorkers had flu-like illness in May (press release 10 June 2009). New York: 
NYCDHMH; 2009. Available from: 
<http://www.nyc.gov/html/doh/html/pr2009/pr041-09.shtml>.
11. NYCDHMH. Health Department updates flu status (press release, 2 May 
2009). New York: NYCDHMH; 2009. Available 
from:<http://www.nyc.gov/html/doh/html/pr2009/pr021-09.shtml>.
12. United States Census Bureau. Population finder. Washington DC: US 
Census Bureau; 2009. Available from: 
<http://factfinder.census.gov/servlet/SAFFPopulation?_submenuId=population_0&_sse=on>. 

13. Public Health Agency of Canada. FluWatch: June 14, 2009 to June 20, 
2009 (Week 24). Public Health Agency of Canada. Ottawa; 2009. Available 
from: <http://www.phac-aspc.gc.ca/fluwatch/08-09/w24_09/index-eng.php>.
14. CDC. CDC telebriefing on investigation of human cases of novel 
influenza A (H1N1). 26 June 2009. Atlanta: CDC; 2009. Available from: 
<http://www.cdc.gov/media/transcripts/2009/t090626.htm>.
15. Thompson WW, Weintraub E, Dhankhar P, Cheng PY, Brammer L, Meltzer MI, 
et al. Estimates of US influenza-associated deaths made using four 
different methods. Influenza Other Respi Viruses 2009; 3(1): 37-49.
16. United States Census Bureau. Quick table (QT-P1A): age and sex for the 
total population: 1990. Washington, D.C.: US Census Bureau; 1990. Available 
from: 
<http://factfinder.census.gov/servlet/QTTable?_bm=y&-state=qt&-qr_name=DEC_1990_STF1_QTP1A&-ds_name=DEC_1990_STF1_&-redoLog=false&-_caller=geoselect&-geo_id=01000US&-format=&-_lang=en>. 

17. Public Health Agency of Canada. Cases of H1N1 flu virus in Canada. 26 
June 2009; 2009. Available from: 
<http://www.phac-aspc.gc.ca/alert-alerte/swine-porcine/surveillance-archive/20090626-eng.php>. 

18. Milne GJ, Kelso JK, Kelly HA, Huband ST, McVernon J. A small community 
model for the transmission of infectious diseases: comparison of school 
closure as an intervention in individual-based models of an influenza 
pandemic. PLoS One 2008; 3(12): e4005.
19. Miller MA, Viboud C, Balinska M, Simonsen L. The signature features of 
influenza pandemics--implications for policy. N Engl J Med 2009; 360(25): 
2595-8.
20. Ghani AC, Donnelly CA, Cox DR, Griffin JT, Fraser C, Lam TH, et al. 
Methods for estimating the case fatality ratio for a novel, emerging 
infectious disease. Am J Epidemiol 2005; 162(5): 479-86.
21. Lipsitch M, Riley S, Cauchemez S, Ghani AC, Ferguson NM. Managing and 
reducing uncertainty in an emerging influenza pandemic. N Engl J Med 28 May 
2009; [E-pub ahead of print].

-- 
communicated by:
ProMED-mail <promed@promedmail.org>

[The authors have indicated that their methods tended to focus on 
correcting for underascertainment of the denominator. All methods used have 
significant limitations, but they collectively suggest that infection with 
this particular pandemic strain is likely to cause illness with a 
relatively low CFR compared with an earlier estimate and also to historical 
standards. - Mod.CP]

******
[4] Tamiflu resistance - Japan
Date: Thu 2 Jul 2009
Source: Reuters News [edited]
<http://www.reuters.com/article/internal_ReutersNewsRoom_ExclusivesAndWins_MOLT/idUSTRE5614TW20090702>


Japan has confirmed its 1st case of a genetic mutation of the new H1N1 
influenza that shows resistance to Tamiflu [oseltamivir], the main 
antiviral flu drug, a health ministry official said on Thursday [2 Jul 2009].

The World Health Organization has declared a global pandemic is under way 
from the virus, known as swine flu, which has so far been treatable with 
Tamiflu, made by Switzerland's Roche. Takeshi Enami, an official at Japan's 
health ministry, said that the patient's sensitivity to Tamiflu had yet to 
be tested.

The patient, who was confirmed in May 2009 with the H1N1 strain of the flu 
in the Osaka prefecture of western Japan, has since recovered, and no other 
cases of the new flu have been confirmed around the patient, Enami said. He 
could not confirm the age or the sex of the patient.

The 1st case of H1N1 that did not respond to Tamiflu was a patient in Denmark.

Earlier this week, WHO said that the case, revealed by Roche and Danish 
officials on Monday [29 Jun 2009], was an isolated one and did not amplify 
the severity of the virus. Resistance to Tamiflu has been previously 
documented in the deadly bird flu virus H5N1 and seasonal H1N1 flu.

-- 
communicated by:
ProMED-mail <promed@promedmail.org>

[Dr Irene Lai of SOS International has provided the following information 
with regard to the 1st occurrence of Tamiflu-resistance (in Denmark). 
According to the press release from Denmark's State Serum Institute 
(<http://www.ssi.dk/sw174.asp?PAGE=3D1&ArtNo=3D3651423>), the strain 
isolated from the Danish patient remains sensitive to the alternate 
neuraminidase inhibitor, zanamivir. In that case, the resistance arose in a 
person who was on post-exposure prophylaxis with Tamiflu [oseltamivir]. - 
Mod.CP]

[see also:
Influenza A (H1N1) - worldwide (80): Argentina, human to pig 20090701.2376
Influenza A (H1N1) - worldwide (79): case count 20090701.2372
Influenza A (H1N1) - worldwide (78): Tamiflu resistance, DK 20090630.2359
Influenza A (H1N1) - worldwide (77): case count 20090627.2338
Influenza A (H1N1) - worldwide (76): comments on 1918 virus (03) 20090625.2309
Influenza A (H1N1) - worldwide (74): susp. origin 20090624.2303
Influenza A (H1N1) - worldwide (73): case count, epidemiology 20090622.2288
Influenza A (H1N1) - worldwide (72): case count, epidemiology 20090619.2261
Influenza A (H1N1) - worldwide (70): risk factors 20090619.2260
Influenza A (H1N1) - worldwide (69): other viral infections 20090618.2254
Influenza A (H1N1) - worldwide (68): southern hemisphere 20090618.2253
Influenza A (H1N1) - worldwide (65): antivirals in pregnancy 20090616.2224
Influenza A (H1N1) - worldwide (64): case count, pandemic 20090616.2221
Influenza A (H1N1) - worldwide (62): Egypt, Lebanon 20090611.2150
Influenza A (H1N1) - worldwide (62): Egypt, Lebanon 20090611.2150
Influenza A (H1N1) - worldwide (60): Egypt (Cairo) 20090608.2117
Influenza A (H1N1) - worldwide (59): Worldwide 20060608.2117
Influenza A (H1N1) - worldwide (58): USA, Africa 20090607.2109
Influenza A (H1N1) - worldwide (57): Brazil, USA 20090605.2090
Influenza A (H1N1) - worldwide (55) 20090603.2056
Influenza A (H1N1) - worldwide (47): China, epidemiology 20090526.1962
Influenza A (H1N1) - worldwide (45) 20090525.1951
Influenza A (H1N1) - worldwide (42) 20090523.1929
Influenza A (H1N1) - worldwide (39) 20090521.1903
Influenza A (H1N1) - worldwide (37) 20090520.1893
Influenza A (H1N1) - worldwide (34) 20090518.1863
Influenza A (H1N1) - worldwide (31) 20090516.1835
Influenza A (H1N1) - worldwide (29) 20090515.1824
Influenza A (H1N1) - worldwide (26) 20090514.1798
Influenza A (H1N1) - worldwide (23) 20090511.1764
Influenza A (H1N1) - worldwide (21) 20090510.1749
Influenza A (H1N1) - worldwide (19) 20090509.1733
Influenza A (H1N1) - worldwide (17) 20090508.1722
Influenza (H1N1) - worldwide (15) 20090507.1709
Influenza A (H1N1) - worldwide (13) 20090506.1695
Influenza A (H1N1) - worldwide (11): coincident H3N2 variation 20090505.1679
Influenza A (H1N1) - worldwide (09) 20090504.1673
Influenza A (H1N1) - worldwide (07) 20090503.1658
Influenza A (H1N1) - worldwide (05) 20090503.1657
Influenza A (H1N1) - worldwide (03) 20090501.1646
Influenza A (H1N1) - worldwide (02): case counts 20090430.1638
Influenza A (H1N1) - worldwide 20090430.1636
Influenza A (H1N1) "swine flu": worldwide (07), update, pandemic 5 
20090429.1622
Influenza A (H1N1) "swine flu": Worldwide 20090427.1583
Influenza A (H1N1) virus, human: worldwide 20090426.1577
Influenza A (H1N1) virus, human - New Zealand, susp 20090426.1574
Influenza A (H1N1) virus, human - N America (04) 20090426.1569
Influenza A (H1N1) virus, human - N America 20090425.1552
Acute respiratory disease - Mexico, swine virus susp 20090424.1546
Influenza A (H1N1) virus, swine, human - USA (02): (CA, TX) 20090424.1541
Influenza A (H1N1) virus, swine, human - USA: (CA) 20090422.1516
Influenza A (H1N1) virus, swine, human - Spain 20090220.0715]

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


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