WER: Reviewing The 2011-2012 Northern Hemisphere Flu Season

 

 

 

Distribution of 2011-2012  Flu Strains – Source W.E.R.

 

# 6389

 

This week the World Health Organization’s Weekly Epidemiological Record (WER) is devoted to a review of the flu season just completed in the Northern Hemisphere. As you’ll see - while it was unusually mild in the United States - the experiences in other regions of the world varied.

 

 

I’ve excerpted portions of the report below, but you’ll probably want to read the entire article at this link:

 

 

15 June 2012, vol. 87, 24 (pp 233–240)

Contents
232 Review of the 2011–2012 winter influenza season, northern hemisphere

Download full text pdf, 1.76Mb

(Excerpts)

Review of the 2011–2012 winter influenza season, northern hemisphere

This report summarizes the chronology, epidemiology and virology of the winter influenza season in the temperate regions of the northern hemisphere. The review covers influenza activity data collected from October 2011 until the end of April 2012. The data presented have been derived primarily from reports published by national ministries of health or other official bodies reporting on their behalf, or reported to WHO through FluNet and FluID.

 

 

The report describes the mild flu season in the United States:

 

Illness and mortality

In the USA, influenza activity was considerably less in tense than in previous years; clinical consultations for ILI, reported hospitalizations, pneumonia and influenza mortality, and reported influenza-associated paediatric deaths were all lower than in recent years. The percentage of outpatient visits to sentinel physicians for ILI reached the national baseline of 2.4% but never exceeded it, a pattern which has not been observed in at least the last 15 years.

 

Laboratory confirmed influenza associated hospitalizations reported through the Emerging Infections Program, covering 80 counties in 10 of
the 50 states of the USA were lower than the previous year (8.6 per 100 000 population as of 30 April versus 21 per 100 000 population in 2010–2011) and mortality attributed to pneumonia and influenza (P&I) in the 122 Cities Mortality Reporting System slightly exceeded the epidemic threshold (1.645 standard deviations above the weekly mean) only once this season and was below the weekly historical 5-year average for much of the
season.

 

The flu season in Europe was less consistent, with some countries seeing low activity, while others saw an average flu season.

 

Overall, influenza severity indicators were not consistent across Europe. In western Europe, numbers of ILI cases seen in primary care settings were more variable than usual with some countries experiencing relatively few cases scarcely reaching the epidemic baseline (e.g. the United Kingdom and Ireland) while others had more typical seasons (e.g. France and Spain).

 

The number of severe acute respiratory infections reported by 7  participating countries that were positive for influenza was slightly lower than last season (1282 as of 11 May 2012 versus 1548 at the end of the 2010–2011 season). The European Mortality Monitoring Project (EUROMOMO), which pools all-cause mortality data from 15 countries of Europe, reported excess mortality among persons ≥65 years of age in some countries,peaking in February 2012.

This was most notable in countries that experienced more community transmission, around the same time as the peak in influenza transmission. Mortality in the 15 to 64 year old age group was notably lower compared to the 2010–2011 season when A(H1N1)pdm09 was the predominant virus circulating in the area.

 

Meanwhile, Asia saw a very typical flu season, with the exception of Japan, which reported unusually heavy flu activity.

 

Illness and mortality

Reporting rates for ILI visits in northern China, Mongolia and Republic of Korea were all similar to those in previous seasons; however, Japan experienced the highest number of influenza-confirmed cases since 2002, except for the 2009 pandemic period. In Mongolia, the proportion of hospitalizations for pneumonia and the reported number of pneumonia deaths were lower
than during the 2010–2011 season.

 

As is often seen, the influenza strains varied in different regions around the world. While H3N2 virus was the most common strain reported, in Mexico it was the A(H1N1)pdm09 strain that dominated.

 

The season was predominantly associated with A(H3N2) in Europe and North Africa, though influenza B did increase slightly late in the season. Temperate countries of Asia had both influenza B peaks and A(H3N2) peaks, with influenza B appearing first in China and Mongolia followed by A(H3N2) and the reverse sequence in the Republic of Korea and Japan.

 

 

As far as antiviral resistance is concerned, while there were some instances reported, the numbers remain very low.

 

The great majority of the viruses tested this season were sensitive to oseltamivir. However, the late-season appearance of a number of cases with oseltamivir   resistant A(H1N1)pdm09 viruses in Texas, most of which had no direct or indirect exposure to the drug, raises some concern. A cluster of 29 oseltamivir resistant viruses was reported in New South Wales, Australia in the 2011 southern hemisphere winter season but did not result in onward persistence of the resistant virus.

 

And finally, as you’ve probably already heard, a new flu vaccine formulation will be introduced this fall that will include two new flu strains (see WHO: Northern Hemisphere 2012-2013 Flu Vaccine Composition).

 

The rationale for this change (the first in 3 years) is provided in this report:

 

antigenic testing

The seasonal trivalent vaccine for 2011–2012 contained the same 3 viruses as the 2010–2011 northern hemisphere vaccine: A/California/7/2009 (H1N1)-like virus, A/Perth/16/2009 (H3N2)-like virus and B/Brisbane/60/2008-like virus (B Victoria lineage). Early in the season, nearly all of the influenza A viruses detected globally were antigenically similar to the vaccine viruses.

However, increasing antigenic diversity was noted in A(H3N2) viruses in the latter part of the season. These viruses had reduced titre cross-reactivity with antiserum produced against the/Perth/16/2009 virus but higher titres against A/Victoria/361/2011-like reference viruses. In Europe this was associated with lower vaccine effectiveness than in previous seasons in well controlled field observational studies.

Because of antigenic heterogeneity within influenza A(H3N2) viruses irculating during this influenza season, the updated trivalent influenza vaccine for the northern hemisphere will contain an A/Victoria/361/2011-like virus.

 

Influenza B viruses of both the B/Victoria and the  B/Yamagata lineages circulated during this influenza
season in nearly equal proportions in some areas. The increasing proportion of viruses of the  /Yamagata  lineage prompted a change in the next season  vaccine composition to include a Yamagata virus  (B/Wisconsin/1/2010-like virus).

 

 

Now that the flu season in the Northern Hemisphere is essentially over (there are still a couple areas of activity, including Hong Kong and Bermuda), all eyes turn to the southern hemisphere where their flu season is just about to get started.

 

This year’s flu shot for the southern hemisphere is the same as was used in Europe and the Americas last fall, and so we shall be interested to see if the trend in lower vaccine effectiveness reported in Europe persists south of the equator.

 

As far as what this last flu season tells us about the next flu season to come?  Well, the old adage is that if you’ve seen one flu season, you’ve seen one flu season.

 

Influenza viruses are notoriously unpredictable, and flu seasons that span the globe, even more so.  We won’t know what kind of flu season we are going to have until we’ve had it.

 

A good enough reason to get that flu shot every year, and to practice good flu hygiene (covering coughs, washing hands, staying home when sick) all year round.

»» Read More

WER: Update On Anti-Viral Resistant Influenza

 

 

 

# 5940

 

During the 18 months prior to the emergence of the 2009 H1N1 pandemic virus, the old seasonal H1N1 virus developed nearly complete resistance to the antiviral drug oseltamivir (Tamiflu ®).  

 

The novel swine H1N1 virus – while resistant to the older amantadines – has fortunately remained sensitive to oseltamivir. The concern is, that over time, this newer strain might one day develop resistance as well.

 

So testing influenza samples for resistance-producing mutations, and epidemiological tracking of resistant isolates, is a big part of global influenza surveillance.

 

During the first two years, only 1%-2% of samples tested have shown the most common mutation known to convey oseltamivir resistance; H275Y, where a single amino acid substitution (histidine (H) to tyrosine (Y)) occurs at the neuraminidase position 275.

 

(Note: some scientists use 'N2 numbering' (H274Y) and some use 'N1 numbering' (H275Y))

 

Most of the cases we’ve seen reported are isolated and sporadic, with no apparent epidemiological links. 

 

Most occurred in patients under therapeutic or prophylactic treatment with oseltamivir, or were among immunocompromised patients; factors commonly associated with the development of spontaneous resistance.

In a few instances, we’ve see small clusters of resistant influenza, suggestive of person-to-person transmission of a resistant virus.

 

• In August of this year, in Australia Reports Cluster Of Antiviral Resistant H1N1, I wrote of a large clustering of oseltamivir (Tamiflu) resistant H1N1 cases in New South Wales. More than 2 dozen patients – roughly 14% of the isolates tested from that region since May – have shown a genetic mutation that confers resistance.
• In December of 2009, in  NEJM: Community Cluster Of Tamiflu Resistant H1N1, we saw a report on 7 healthy people who contracted a resistant H1N1 flu while on a train ride from Ho Chi Minh City to Hanoi. 
• Also in December of 2009 we saw a report on a small cluster of resistant H1N1 influenza among cancer patients (see Duke Hospital Reports No Further Spread Of Resistant Strain).

 

But these have really been the exception, not the rule.

 

For the most part, the 2009 H1N1 virus, seasonal H3N2, and influenza B remain overwhelmingly sensitive to oseltamivir.

 

 

 

Today, the World Health Organization’s WER (Weekly Epidemiological Record) updates us on the detection of antiviral resistance in currently circulating influenza viruses.

 

Global monitoring  of antiviral resistance in currently circulating human influenza viruses, November 2011

4 November 2011, No. 45, 2011, 86, 497–508

Introduction

Antiviral treatment is an important tool in the clinical management of severe or complicated influenza, and treatment recommendations need to take account of information on the prevalence of resistance to antiviral medicines among the circulating viruses.

 

This article provides a brief update on global incidence of resistance in currently circulating human influenza viruses since the last published report on oseltamivir resistance in influenza A(H1N1) 2009 viruses, now termed influenza A(H1N1) pdm09 viruses.

 

It also highlights the need to monitor and report resistance during the post-pandemic period.

 

All influenza viruses currently circulating in the community are resistant to adamantanes (amantadine and rimantadine), but most are sensitive to neuraminidase inhibitors, although a limited number of sporadic cases involving resistant viruses have been reported.

 

However, a recently reported cluster of cases involving oseltamivir-resistant influenza A(H1N1)pdm09 virus suggests that such viruses may have been transmitted locally, and reinforces the need for continual surveillance.

(Continue . . . )

 

 

This report notes that a variant of the H1N1 virus I wrote about earlier this summer (see Eurosurveillance: A `Mildly’ Resistant Strain of H1N1 Emerges) has appeared in a small percentage of flu cases in Singapore and Northern Australia, but that no new cases have been reported since April of 2011.

 

 

This variant carries a S247N neuraminidase mutation, instead of the H275Y mutation mentioned above.  At least one case of a patient with both (S247N & H275Y) mutations has been detected, and that patient exhibited high levels of oseltamivir resistance.

 

This report concludes by stating:

 

The prevalence of resistance to neuraminidase inhibitors in circulating human influenza viruses remains low, and WHO guidelines for treatment of patients and use of antiviral medicines remain as previously published.

 

Recommendations For Post-pandemic Surveillance

WHO has collated and reported data on all known cases of infection with influenza A(H1N1)pdm09 virus since the start of the 2009 pandemic.Such data support the conclusion that resistance to neuraminidase inhibitors does not currently constitute a significant risk to public health.

 

However recent characterization of case clusters, and an increased prevalence of resistant viruses in community-based cases, are causes for concern, and suggest that continued vigilance is required.

 

 

While surveillance for antiviral resistance continues to be reassuring, scientists remember the remarkable speed by which seasonal influenza went from being almost 100% sensitive to being nearly 100% resistant.

 

So, as the report says, continued vigilance is required. 

»» Read More

WER: Cholera, 2010

 

 

 

# 5724

 

Today’s World Health Organization’s  WER (Weekly Epidemiological Record) has an extensive overview of the global spread of cholera between the years 2000 and 2010. 

 

Last year, the WHO listed 317,534 cases worldwide, including 7,543  deaths, an increase of 43% over 2009 and up 130% compared to 2000.

 

A good deal of this increase is due to the epidemic which began last October in Haiti.

 

Globally, these numbers are widely assumed to be an undercount, and specifically do not include the 500,000-700,000 cases of ‘acute watery diarrhea’ in southeastern and central Asia.

 

In truth, many countries do not report cholera due to a lack of surveillance and testing capacity or out of fears of negative economic impact. 

 

Under the International Health Regulations adopted in 2005, mandatory notification of all cases of cholera is no longer required.

 

So the true burden of cholera around the world can only be estimated.

 

Last May, the World Health Organization recognized the re-emergence of cholera as a significant global public health problem during their World Health Assembly, and adopted resolution WHA 64.15 (Cholera: mechanism for control and prevention), calling for an integrated and comprehensive global approach to cholera control.

 

A few excerpts from the report follow, but the entire 15-page article is highly informative and very much worth worth reviewing.

 

 

Cholera, 2010

 

 

Cholera control

  Current responses to cholera outbreaks tend to be
reactive, taking the form of ad hoc emergency responses. This approach may prevent deaths but it
fails to prevent cases of cholera.

  Controlling cholera requires more than the prompt medical treatment of cases. The interplay of prevention, preparedness and response activities
within an efficient surveillance system is  
paramount to preventing occurrence, mitigating
outbreaks and decreasing case-fatality rates.

  Sustained development is critical to effectively  
containing cholera. However, simple and efficient
measures can curb the incidence of the disease, pro-
vided that there is a concerted multidisciplinary
approach and strong community involvement aimed
at improving access to safe water, and providing
hygiene education and proper sanitation.

  National and subregional action plans that include
cross-border collaboration should be developed to
enhance multidisciplinary prevention, and preparedness and response activities.

  Travel sanctions and trade sanctions serve only to
increase the burden of cholera in countries affected by the disease.

 

 

 

Future challenges

 

Greater financial support and commitment are needed to strengthen and encourage environmental management in developing countries, in particular to improve water supplies, access to hygiene and sanitation, and to support research on new strategies for prevention and control.

 

Cholera and other epidemic-prone diarrhoeal diseases are major public health problems, which should be recognized and addressed. It is critical that commitments be made and financial support provided for recognition of the burden of cholera and for efforts to implement efficient control measures, in view of the emergence of new strains and the ongoing trends in increasing incidence of the disease.

(Continue . . . )

 

»» Read More

The WHO’s Flu Review

 

 

# 5582

 

 

 

With the 2010-2011 northern hemisphere flu season at its end, the World Health Organization has released a summary of global influenza trends over the past six months.

 

This summary appears in the latest Weekly Epidemiological Record 2011, 86, 221–232 and on the WHO’s Global Alert and Response (GAR) page.

 

I’ve excerpted a few passages (and reformatted for readability), but the entire report is worth reading.  I’ll return with some brief comments:

 

 

 

Summary review of the 2010-2011 northern hemisphere winter influenza season

This review summarizes the chronology, epidemiology, and virology of the northern hemisphere temperate regions' winter influenza season encompassing the time period from October 2010 through the end of April 2011.

 

It is an expanded version of the WHO Weekly Epidemiological Record (WER) 27 May 2011, vol. 86 (pp 221-232).

 

Summary points

• The winter influenza season in the temperate countries of the northern hemisphere began in late October in Asia, a month later in Europe and North America, but was largely over by the end of April.

 
• The most commonly detected virus was different in North America, where influenza A(H3N2) and influenza type B co-circulated with influenza A(H1N1)2009, and Europe, where influenza A(H1N1)2009 was by far the most commonly detected virus.

• Although it was no longer the predominant influenza virus circulating in many parts of the world, H1N1 (2009) otherwise behaved much the same way as it had during the pandemic in terms of the age group most affect and the clinical pattern of illness.

• The impact of the influenza season in some areas where H1N1 (2009) was the predominant virus was more than in the previous year, most notably in the United Kingdom (UK) where intensive care units were stressed by large numbers of cases requiring ventilatory support.

• More than 90% of viruses detected around the world were similar antigenically to those found in the seasonal trivalent influenza vaccine.

 
• Antiviral resistance in influenza A(H1N1)2009 remained at a very low level. There were case reports with no history of exposure to antiviral medications, consistent with some community transmission of resistant virus.

<SNIP>

Conclusions

Influenza A(H1N1)2009 continues to circulate widely. However in contrast to the pattern observed during the pandemic, the virus is now co-circulating with other influenza viruses and was not the predominant influenza A virus in many countries.

 

Circulation this season occurred during the expected influenza seasonal time frame with no out-of-season community transmission reported in temperate northern countries. The pattern of association between severe disease and age was similar to that observed previously.

 

Influenza A(H1N1)2009 continues to be more of a problem for young and middle-aged adults, while influenza A(H3N2) causes more severe disease in adults over the age of 65 years. Influenza type B appears to disproportionately affect young children.

 

A few countries appeared to have a higher number of severe cases compared to last year for reasons that are unclear. This was most notable in the UK though this observation may well be a surveillance artefact related to the active surveillance for severe disease that was carried out there.

 

All three circulating viruses demonstrated very little antigenic drift over the last year and were closely related to the three strains contained in the seasonal influenza vaccine. In addition, all but a very small percentage of viruses tested remain sensitive to neuraminidase inhibitors.

 

This reemphasises the need to continue to vaccinate and to treat early patients at high risk for developing severe disease, including those at the extremes of age, those with certain chronic medical illness, and pregnant women.

 

 

 

While admittedly a convoluted flu season, with four flu strains (five if you count the few remnants of seasonal H1N1) in circulation, and widely varying impacts around the world – some `good news’ stands out.

 

First, the feared rise in antiviral resistance for the 2009 H1N1 virus has not yet happened, with 98% of the samples testing still sensitive to oseltamivir.

 

However, since there were a few cases of oseltamivir resistance with no known exposure to the drug, concerns over possible limited community transmission of a resistant virus remain.

 

 

Second, while scattered mutations in the 2009 H1N1 virus have been detected, the vast majority of viruses tested remain antigenically similar to the current tri-valent influenza vaccine.

 

 

The chart below illustrates 99% of the H1N1 (2009) and 96% of the  H3N2 viruses tested were antigenically similar to the current vaccine.

 

 

With two main lineages of B viruses that co-circulate each year, scientists must decide which strain to include in the vaccine. Some years they guess wrong, but this year nearly 91% of B viruses tested were a match (B Victoria) for vaccine strain.

 

 

While no guarantees can be made for what these influenza viruses will do in the next 6 to 12 months, for now they are behaving pretty much as scientists predicted.

 

The best news is that the vaccine being produced for the 2011-2012 flu season (Southern & Northern Hemisphere) appears to be an excellent match for 90% of the flu viruses currently circulating.

 

Of course, the only constant with influenza viruses is change.  

 

And so we will watch the progress of the upcoming flu season south of the equator with great interest. What happens in Australia, New Zealand, South American, and South Africa can often tell us a lot about the kind of flu season we may see in the fall.

 

Stay tuned.

»» Read More

Measles: Forgotten, But Not Gone

 

 

# 5530

 

 

Measles, which was once almost a youth’s `rite of passage’ in the United States, has been all but eliminated in recent years after the introduction of the first measles vaccine in 1963.

 

The chart below (source: CDC) shows the remarkable effectiveness of the vaccination campaign.

 

 

While many parents today think of measles as a relatively benign childhood illness, it actually produced significant morbidity and mortality with respiratory, ocular, and neurological complications - sometimes resulting in death.

 

During the 1950s – before the introduction of the measles vaccine – in the United States the disease infected roughly 4 million, hospitalized nearly 50,000,  and contributed to the deaths of several hundred every year.  

 

Admittedly, a vast improvement over the mortality rates from earlier in the century, when the disease was far deadlier (for reasons that quite frankly, remain hard to explain – Ian York explored this fascinating mystery in Measles week, part I: Introduction ).

 

But in recent years lower uptake of the vaccine – its reputation tainted by (disproven) claims of a possible link to autism (popularized by Dr. Andrew Wakefield and promoted by various anti-vaccination groups) – and the continual importation of the disease from countries where it remains endemic - have allowed the virus to keep a toehold in developed nations.

 

In developing countries, the incidence – and mortality rate – of measles remains high.   These statistics from the World Health Organization:

 

 

Measles

Fact sheet N°286

Key facts

• Measles is one of the leading causes of death among young children even though a safe and cost-effective vaccine is available.
• In 2008, there were 164 000 measles deaths globally – nearly 450 deaths every day or 18 deaths every hour.
• More than 95% of measles deaths occur in low-income countries with weak health infrastructures.
• Measles vaccination resulted in a 78% drop in measles deaths between 2000 and 2008 worldwide.
• In 2008, about 83% of the world's children received one dose of measles vaccine by their first birthday through routine health services – up from 72% in 2000.

 

Today news on measles from several fronts. 

 

First, the WHO’s  WER (Weekly Epidemiological Record) brings us details on an ongoing measles outbreak in Europe, that has infected more than 6,500 people in 33 nations.

 

Measles outbreaks in Europe

As of 18 April 2011, 33 countries in Europe had reported  6500 measles cases. Epidemiological investigations and genotyping have confirmed transmission of measles virus among several countries in the Region and in the Americas.

<SNIP>

In all these outbreaks, except for the second out-
break in Spain and the outbreak in Turkey, the D4
genotype of measles virus has been confirmed.
The B3 genotype of measles virus was isolated
from cases in the second measles outbreak in
Spain, while the D9 genotype, originating from
and common in south-east Asia (e.g. Malaysia and
Indonesia) was confirmed to have caused the out-
break in Istanbul (Turkey) in January 2011.

(Continue . . . )

 

 

As you can see, there are a number of different strains or genotypes of measles.  New ones emerge, or are detected, every so often.  As of mid-2010, the World Health Organization (WHO) maintained reference strains representing 23 recognized genotypes.

 

From Eurosurveillance this week, a report on a novel strain of (an existing genotype:G3) of measles which has spread across Europe over a 2 month period.

 

Eurosurveillance, Volume 16, Issue 17, 28 April 2011

Rapid communications

Appearance of a novel measles G3 strain in multiple European countries within a two month period, 2010

K E Brown, M N Mulders, F Freymuth, S Santibanez, M M Mosquera, S Cordey, J Beirnes, S Shulga, R Myers, D Featherstone

During late 2010, a previously unrecognised strain of measles genotype G3 virus was identified in five different European countries by the World Health Organization Measles and Rubella Laboratory Network. Apart from one, none had a travel history to south-east Asia, the usual source of G3 viruses, although epidemiological links could be established between some of the cases. This case series illustrates the value of genotyping and sequencing in tracking measles infections, and identifying otherwise unrecognised chains of transmission.

(Continue . . . )

 

And next, from the Journal of Infectious Diseases a report on the impact of an outbreak of measles in Tucson, Arizona in 2008 that affected two healthcare facilities. 

 

 

Health Care–Associated Measles Outbreak in the United States After an Importation: Challenges and Economic Impact

 

J Infect Dis. (2011) jir115 first published online April 28, 2011 doi:10.1093/infdis/jir115

Sanny Y. Chen,

Shoana Anderson, Preeta K. Kutty, Francelli Lugo, Michelle McDonald, Paul A. Rota, Ismael R. Ortega-Sanchez, Ken Komatsu, Gregory L. Armstrong, Rebecca Sunenshine, and Jane F. Seward

 

You can follow the above link to read the entire article, or for the short version, you can read the press release from the IDSA.

 

Infectious Diseases Society of America

Measles outbreak underscores need for continued vigilance in health care settings

[EMBARGOED FOR APRIL 29, 2011] The U.S. measles vaccination program has been successful in eliminating endemic measles in the United States; yet this success has provided challenges that require ongoing vigilance for the rapid identification and response to measles cases in health care settings. In 2008, the largest reported health care-associated measles outbreak in the United States since 1989 occurred in Tucson, Arizona, costing approximately $800,000 in response and containment efforts. In a report published in The Journal of Infectious Diseases and available online, researchers identify preventive measures hospitals and health care facilities can implement to reduce the likelihood and decrease the economic impact of a future measles outbreak in these settings.

 

Due to a highly effective vaccine and high vaccine coverage, measles was declared eliminated in the United States in 2000; however, the potential for measles infection still exists in this country. Non-adherence to U.S. vaccination recommendations and infection among unvaccinated travelers coming into the United States continue to pose potential threats to the public and to health care personnel. In the 2008 Tucson outbreak, an unvaccinated, infected Swiss traveler visited a hospital emergency department on February 12. The traveler was admitted to the hospital the next day, but a measles diagnosis was not confirmed until February 20. This ignited an intense and lengthy public health investigation and response to persons with suspected and confirmed measles as well as contacts of those persons.

(Continue . . . )

 

And again from the Journal of Infectious diseases, an editorial comment on the above study by Stephen M. Ostroff.  

The full text of both articles is freely available.

 

EDITORIAL COMMENTARY:

Stephen M. Ostroff

Measles: Going, Going, But Not Gone

J Infect Dis. (2011) jir125 first published online April 28, 2011 doi:10.1093/infdis/jir125

 

 

While not the scourge of the early 20th century in the United States, measles remains a serious public health threat in much of the world, and is only held at bay in developed countries by relatively high vaccination rates.

 

There is a lot more to the measles story, and I highly recommend reading the entire Mystery Rays blog series on the disease by Ian York from 2010.

 

Measles week, part I: Introduction

Measles week, part II: Emerging disease

Measles week, Part III: Not the answers

Measles week, part IV: Some of the answers

Measles week, Part V: What about the vaccine?

 

 

»» Read More

WER Review: Oseltamivir Resistance In Pandemic H1N1

 

 

# 4325

 

 

Concerns that the novel H1N1 virus could develop widespread Tamiflu (Oseltamivir) resistance - as did its seasonal cousin in 2008 & 2009 – have been the topic of much discussion in scientific circles since last April. 

 

Thus far, it appears that the overwhelming majority of pandemic flu cases still respond to Tamiflu, although sporadic resistant cases have been seen.    Testing is only done on a miniscule percentage of cases however, and so the actual incidence of resistance is unknown.

 

Resistance is generally caused by a mutation, known as H274Y, where a single amino acid substitution (histidine (H) to tyrosine (Y)) occurs at the neuraminidase position 274.

 

In the The World Health Organization’s latest (No. 6, 2010, 85, 37–48) Weekly Epidemiological Record (WER), we get an update on this mutation.

 

I’ve just reproduced some excerpts below.  Follow the link to read the entire report. A Hat tip to Ironorehopper on FluTrackers for posting this link.

 

 

 

 

Update on oseltamivir resistant pandemic A (H1N1) 2009 influenza virus: January 2010

Since the first report of oseltamivir-resistant pandemic influenza A (H1N1) 2009 virus in June 2009, >200 cases of resistant virus have been reported worldwide. The purpose of this article is to provide a brief global update on cases of oseltamivir resistant pandemic (H1N1) 2009 viruses since the first report published in the Weekly Epidemiological Record2 in October 2009.

With the exception of the 225 cases summarized here, all clinical samples tested for pandemic (H1N1) 2009 virus lack the H275Y mutation and are therefore assumed to be sensitive to the influenza virus neuraminidase inhibitors oseltamivir and zanamivir. While this indicates the absence of wider community circulation of oseltamivir-resistant virus, recently reported clusters of cases suggest that such viruses are being transmitted in local settings.

<SNIP>

Conclusions

The number of reported cases of oseltamivir-resistant pandemic (H1N1) 2009 influenza virus remains low despite the large scale of the pandemic, widespread use of oseltamivir and extensive monitoring of susceptibility. Although there is no evidence of general community circulation of such resistant viruses, there is clear evidence of limited person-to-person transmission in several epidemiological settings. Active surveillance for antiviral resistance in pandemic (H1N1) 2009 virus needs to be maintained by clinicians, laboratories and agencies. All cases of oseltamivir-resistant pandemic A (H1N1) 2009 influenza virus should be investigated and promptly notified to relevant agencies including WHO. 

»» Read More

WER Review: D222G Mutation In H1N1

 

# 4280

 

 

It seems that every month or so we are confronted with a new aspect of the H1N1 (or H5N1) virus that generates a certain amount of consternation in the blogosphere.  

 

In very early November it was the Ukraine story, which had morphed into wild tales of Russian bio-weapons, `pneumonic plague’, and a UN cover up of massive numbers of fatalities.

 

On November 14th, I wrote of this spectacularly unbridled speculation In Ukraine And The Internet Rumor Mill.

 

Scarcely a week later we were hit by two stories, one revolving around an announced mutation in the pandemic H1N1 virus by scientists in Norway, and another concerning a pair of Tamiflu resistant clusters of novel H1N1.

 

Both have launched their fair share of media reports, and no lack of speculation.  Of the two, the `Norway Mutation’ has captured perhaps the most attention.

 

While announced by Norwegian scientists (see Norway Reports An H1N1 Mutation) , this mutation D222G (or D225G in influenza H3 numbering) had actually been detected months earlier, and in many other countries.   

 

Norway was simply the first country to announce a possible connection between that mutation and greater virulence.

 

This mutation involves a single amino acid change in the HA1 gene at position 222 from aspartic acid (D) to glycine (G).

 

 

Over the past couple of months, much has been made over the potential dangers of this mutation – mostly by those in the `new media’.   Little direct evidence of this mutation posing a public health threat has emerged over that time, however.

 

In the The World Health Organization’s latest (No. 4, 2010, 85, 21–28) Weekly Epidemiological Record (WER), we get an update on this mutation. 

 

To my loyal reader in France, who emailed me this link overnight: Merci beaucoup, Anne.

 

While noting that it is worthy of further study (along with other mutations to the virus), for now the WHO’s position is that `Based on currently available virological, epidemiological and clinical information, the D222G substitution does not appear to pose a major public health issue.’

That is not to say that the book has been closed on this mutation. Certainly not.  Only that – at this point in time – WHO scientists find insufficient evidence to link this mutation to greater virulence in the H1N1 virus.

 

Will D222G prove to be a public health concern down the road?

 

Perhaps.

 

But it may well require other mutations in the virus to occur - in lieu of, or in concert with D222G - to produce a `Frankenswine’ virus.

 

And those changes may never happen.  Or we could start seeing them tomorrow . . .

 

Influenza is (quite literally) an evolving story.

 

Stay tuned.

 

 

Preliminary review of D222G amino acid substitution in the haemagglutinin of pandemic influenza A (H1N1) 2009 viruses

Summary

Since the first appearance of pandemic influenza A (H1N1) 2009 viruses, certain mutations, including those leading to the D222G substitution in the haemagglutinin (HA) protein and the K340N substitution in the polymerase basic protein 2 (PB2), have appeared sporadically. These substitutions in HA and/or PB2 have been reported in viruses obtained from cases of mild to severe to fatal illness but such viruses have neither formed distinct phylogenetic clusterings nor been associated with consistent changes in virus antigenicity.

 

Based on currently available virological, epidemiological and clinical information, the D222G substitution does not appear to pose a major public health issue. However, the WHO Global Influenza Surveillance Network (GISN) and its partners will continue to closely monitor pandemic viruses for the D222G and other amino acid substitutions and continually assess  associated risks.

 

Background

Influenza viruses are known for their high evolutionary rate and tendency to acquire point mutations at different positions in their genomes. Some mutations can result in amino acid  substitutions at key locations in proteins, such as antigenic sites or the receptor binding site of the HA, and can alter properties such as those associated with the virus antigenicity or  pathogenecity.

 

Recently, the D222G substitution was observed in the HA of pandemic (H1N1) 2009 viruses isolated from fatal cases in several countries. WHO organized a global  teleconference with experts from GISN laboratories, external research institutions and WHO regional offices to assess the public health significance. This review is based on those data and other information provided by GISN laboratories.

 

Detection of D222G substitution by GISN

The D222G substitution has been detected in virus isolates from around 20 countries, areas and territories in the Americas, Asia, Europe and Oceania. These changes have been  found since April 2009 but have not been associated with temporal or geographical clustering, strongly suggesting the mutation in these viruses has occurred sporadically as  opposed to the emergence and sustained transmission of a variant virus.

Based on currently available data shared with WHO, the prevalence of D222G substitution is <1.8% (52 detections among >2755 HA sequences). Of 364 fatal cases analysed to date, viruses from 26 cases (7.1%) had the D222G substitution.

 

The clinical information about potential underlying medical conditions in these cases is limited. Surveillance and laboratory analysis efforts to study this substitution have given priority to specimens from hospitalized and severely ill patients, leading to potential biases in the data. Additionally, a study done by the WHO Collaborating Centre for Reference and Research on Influenza (WHOCC) in Atlanta – located in the United States Centers for Disease Control and Prevention (CDC) – found the D222G substitution in 14 virus isolates but not in viruses in the original clinical specimens indicating the D222G substitution in these 14 virus isolates occurred after growth in the laboratory.

 

These observations have made determining the clinical relevance of this substitution difficult. Otherwise, the pandemic (H1N1) 2009 viruses with D222G substitution have been antigenically similar to the A/California/7/2009 (H1N1) virus, the WHO-recommended vaccine virus. Three of the D222G variant viruses carry the H275Y substitution in the neuraminidase (NA) associated with oseltamivir resistance.

 

Other substitutions of potential public health significance WHO has been monitoring several other reported substitutions in the HA (D222E and D222N) and K340N substitution in PB2. The clinical significance of these substitutions remains uncertain.

 

Ongoing studies

Preliminary results from in vitro studies suggest that D222G substitution in the HA may increase binding to a2-3 sialic acid (avian-like) cell receptors. Ferret studies have shown that viruses with D222G substitution, whose virulence is similar to wild-type viruses lacking this mutation, can be transmitted efficiently. Studies using mice and guinea-pigs are ongoing to better characterize the receptor-binding specificity, replication fitness, transmissibility and pathogenicity of viruses with this D222G substitution alone or in combination with other substitutions.

 

More detailed information on clinical, epidemiological and viral features is needed to assess the future public health significance of these viruses.

 

 

Since I’m not a scientist, I have no theory in this fight.   All I can do is review the literature and listen to those experts that I have faith in (admittedly, a purely subjective criteria on my part), and report what they currently believe.  

 

Conducting good science takes time. 

 

What scientists believe today may change tomorrow.  In fact, you can almost count on it.

 

We call that progress.

 

This proves somewhat problematic for the media (both new & traditional), however.  They would much prefer that all science be complete, definitive, and wrapped up with a tidy bow instead of riddled with caveats.  

 

Like Harry Truman - who once said what he wanted most as President was a one-armed economist -  I’m sure we all wish for the day when scientists couldn’t follow every statement with:

 

“But . . . on the other hand . . . “

 

I just wouldn’t hold my breath.

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