Showing posts with label PLoS. Show all posts
Showing posts with label PLoS. Show all posts

The Risks Of Chikungunya Outbreaks In The United States

 

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Credit Wikipedia


# 6855

 

 

Chikungunya, up until about a decade ago, was a little known mosquito-borne disease first described in Tanganyika in the early 1950s. For the next five decades it was sporadically seen across eastern and central Africa.

 

That is, until 2005, when Chikungunya made a surprise jump to the Indian Ocean island of Réunion. There, it infected nearly 1/3rd of the island’s 770,000 residents (see 2006 EID article Chikungunya Disease Outbreak, Reunion Island) in just a matter of months.

 

Chikungunya typically produces a fever, severe muscle and joint pain, and headaches. The symptoms usually go away after a few weeks, but some patients can sustain permanent disability, and some deaths have been reported.

 

In the eight years since that  jump, `Chik’ has spread further across the Indian Ocean, Southeast Asia, and even briefly into northern Italy.

 

While the virus isn't normally found in Europe, the vector, the Aedes mosquito, is.  All it took was one infected traveler to arrive infected with the virus to start the chain of transmission.

 

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I told the story several years ago in It's A Smaller World After All, but the short version is that a traveler, returning from India, brought the virus to Italy in 2007 which led to more than 290 cases reported in the province of Ravenna, which is in northeast Italy.

 

The concern is that the same sort of introduction could happen elsewhere in Europe, or here in the United States, just as we saw with West Nile Virus in 1999 (see DVBID: Final West Nile Report For 2012) and with Dengue Fever in 2010 (see MMWR: Dengue Fever In Key West)

 

The two primary mosquito vectors of Chikungunya are the Aedes aegypti and Aedes albopictus (cite WHO FAQ) both of which can be found across many regions of the Americas.

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Aedes albopictus (Asian Tiger) Mosquito - Wikipedia

Dark blue: Native range
Dark green: introduced (as of December 2007)

 

The risk is considered great enough that early last year, the CDC and PAHO (Pan American Health Organization) put together a 161-page guide on preparing for the arrival of Chikungunya to the Americas (see Preparedness and Response for Chikungunya Virus Introduction in the Americas).

 

All of which serves as prelude to a report that appeared last month in PloS Neglected Tropical Diseases called:

 

Modeling Dynamic Introduction of Chikungunya Virus in the United States

Abstract (reparagraphed for readability)

Chikungunya is a mosquito-borne viral infection of humans that previously was confined to regions in central Africa. However, during this century, the virus has shown surprising potential for geographic expansion as it invaded other countries including more temperate regions.

 

With no vaccine and no specific treatment, the main control strategy for Chikungunya remains preventive control of mosquito populations. In consideration for the risk of Chikungunya introduction to the US, we developed a model for disease introduction based on virus introduction by one individual. Our study combines a climate-based mosquito population dynamics stochastic model with an epidemiological model to identify temporal windows that have epidemic risk. We ran this model with temperature data from different locations to study the geographic sensitivity of epidemic potential.

 

We found that in locations with marked seasonal variation in temperature there also was a season of epidemic risk matching the period of the year in which mosquito populations survive and grow. In these locations controlling mosquito population sizes might be an efficient strategy.

 

But, in other locations where the temperature supports mosquito development all year the epidemic risk is high and (practically) constant. In these locations, mosquito population control alone might not be an efficient disease control strategy and other approaches should be implemented to complement it.

 

Our results strongly suggest that, in the event of an introduction and establishment of Chikungunya in the US, endemic and epidemic regions would emerge initially, primarily defined by environmental factors controlling annual mosquito population cycles. These regions should be identified to plan different intervention measures.

In addition, reducing vector: human ratios can lower the probability and magnitude of outbreaks for regions with strong seasonal temperature patterns. This is the first model to consider Chikungunya risk in the US and can be applied to other vector borne diseases.

(Continue . . . )

 


More background on this modeling study is available from the Cornell University Press Office.

 

 

Chances seen rising for chikungunya outbreaks in NYC, Atlanta, Miami

ITHACA, N.Y. – Global travel and climate warming could be creating the right conditions for outbreaks of a new virus in this country, according to a new Cornell University computer model.

 

The model predicts that outbreaks of chikungunya, a painful virus transported by travelers and spread by the invasive Asian tiger mosquito, could occur in 2013 in New York City during August and September, in Atlanta from June through September, and year-round in Miami. The probability of a disease outbreak is correlated with temperature, as warmer weather allows the Asian tiger mosquito to breed faster and grow in numbers, according to the study published in the November issue of PLOS Neglected Tropical Diseases.

 

According to the simulation, there is a high probability of a chikungunya outbreak if a single infected person arrives in New York in July or August and is bitten by an Asian tiger mosquito. The risks are the same, but with wider time frames, for transmission in Atlanta and Miami, according to the paper.

 

Asian tiger mosquitoes were introduced to the United States in Texas in the 1980s; they are established up the East Coast into New Jersey and are rising in numbers in New York City. The aggressive mosquito outcompetes local varieties and transmits more than 20 pathogens, including chikungunya and dengue, said Laura Harrington, associate professor of entomology and the study’s senior author.

 

“The virus is moving in people, and resident mosquito populations are picking it up,” Harrington said.

 

The model estimates that with typical regional temperatures, a chikungunya outbreak in New York would infect about one in 5,000 people, said Diego Ruiz-Moreno, a postdoctoral associate and the paper’s lead author

 

“However, this number would increase drastically as temperatures rise due to climate change,” Ruiz-Moreno said.

(Continue . . . )

 

While this study focused on Chikungunya, much the same could be said about the potential for seeing Dengue, Malaria, or even Yellow Fever making inroads in the United States and Europe. 

 

In March of 2010 the journal  Eurosurveillance carried a series of articles on vector borne diseases and their potential to impact those living in Europe. One of the articles, Yellow fever and dengue: a threat to Europe? by P. Reiter, had these sobering comments about the future of vector-borne illnesses in Europe.

 

The history of dengue and yellow fever in Europe is evidence that conditions are already suitable for transmission. The establishment of Ae. albopictus has made this possible, and the possibility will increase as the species expands northwards, or if Ae. aegypti is re-established.

 

The epidemic of chikungunya in northern Italy in 2007 [8,49] confirms that Ae. albopictus is capable of supporting epidemic transmission, although laboratory studies indicate that the strain of virus involved was particularly adapted to this species [50,51].

 

Nevertheless, it is not unreasonable to assume that climatic conditions that permit malaria transmission will also support transmission of yellow fever and dengue, in which case transmission could extend into northern Europe [52].

 

Reason enough that if you live in - or are visiting  - a mosquito prone area, to remember to follow the `5 D’s’  (courtesy Florida Department of Health).

 

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Study: Statins & Cerebral Malaria

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Photo Credit CDC

 

# 6808

 

 

Increasingly, statins – common cholesterol lowering drugs – are being looked at for their inflammation-reducing properties in the treatment of other diseases.

 

Long time readers of this blog will recall that Dr. David Fedson - former Professor of Medicine at the University of Virginia School of Medicine and formerly Director of Medical Affairs, Aventis Pasteur MSD – has advocated research into the potential role of low-cost statins during an influenza pandemic (see Lancet: David Fedson On Statins For Pandemic Influenza).

 

For more on statins, and how they might be used against pandemic influenza, you may wish to revisit:

 

Study: Statins, Influenza, & Mortality

Another Study On Statins And Pneumonia

Dr. David Fedson: The Case For Using Statins In A Pandemic

Statins Revisited

 

A couple of years ago we saw a video presentation at the 2010 ICAAC Conference called A Role for Statins in Infectious Disease? #ICAAC) (excerpt below).

 

Statins are well-known as a class of drugs that are used to help lower cholesterol but recent evidence suggests they might be good for more than your heart. They may play a role in preventing and treating certain bacterial infections including pneumonia and sepsis. Presenters at ICAAC discuss the latest research on the potential of these drugs.

  • Reimar Thomsen, Aarhus University Hospital, Aalborg, Denmark
  • Matthew Falagas, Alfa Institute of Biomedical Sciences, Athens, Greece
  • Nasia Safdar, University of Wisconsin, Madison, WI, United States

 

These presenters suggest that statins may directly affect viruses and fungi, as well as help dampen the body’s inflammatory response. One study discussed found a 30% reduction in 30-day pneumonia mortality among patients already on statins.

 

The caveat being that much of the evidence for statins efficacy comes from in vitro studies, or observational studies that can sometimes be influenced by what is known as the `healthy user bias’.  

 

Simply put, patients who are already on statins when they develop pneumonia, sepsis, or influenza may be more likely to have a healthy lifestyle than those not on statins, potentially skewing the results.

 

Still, the results to date have been intriguing, if not totally convincing.

 

Which brings us to a a new study, appearing in PloS Pathogens, that looks at the potential role of statins in the treatment of cerebral Malaria.

 

According to the WHO:

There were about 219 million cases of malaria in 2010 and an estimated 660 000 deaths. Africa is the most affected continent: about 90% of all malaria deaths occur there.

 

Between 2000 and 2010, malaria mortality rates fell by 26% around the world. In the WHO African Region the decrease was 33%. During this period, an estimated 1.1 million malaria deaths were averted globally, primarily as a result of a scale-up of interventions.

 


Rarely mentioned in all of these figures are the (often life-long) neurological sequelae that cerebral malaria may produce, particularly among children.

 

These may include blindness, epilepsy, decreased motor skills, hearing impairment, aphasia (loss of speech), and behavioral problems, as noted in the following BMC Research Note.

 

 

Severe neurological sequelae and behaviour problems after cerebral malaria in Ugandan children

Richard Idro, Angelina Kakooza-Mwesige, Stephen Balyejjussa, Grace Mirembe, Christine Mugasha, Joshua Tugumisirize and Justus Byarugaba

Conclusions

In addition to previously described neurological and cognitive sequelae, severe behaviour problems may follow cerebral malaria in children. The observed differences in patterns of sequelae may be due to different pathogenic mechanisms, brain regions affected or extent of injury. Cerebral malaria may be used as a new model to study the pathogenesis of ADHD.

 

The PloS Pathogens study, which looks at the potential use of statins for cerebral malaria in a murine (mouse) model, involved infecting lab mice with the malaria parasite, and then treating half of them with just chloroquine, and the other half with chloroquine and Lovastatin. 

 

Mice that received the combination treatment saw a significantly reduced rate of post-infection cognitive dysfunction.

 

Statins Decrease Neuroinflammation and Prevent Cognitive Impairment after Cerebral Malaria

Patricia A. Reis mail, Vanessa Estato, Tathiany I. da Silva, Joana C. d'Avila, Luciana D. Siqueira, Edson F. Assis, Patricia T. Bozza, Fernando A. Bozza, Eduardo V. Tibiriça, Guy A. Zimmerman, Hugo C. Castro-Faria-Neto

Author Summary

Cerebral malaria (CM) is the direst consequence of Plasmodium falciparum infection. Cognitive impairment is a common sequela in children surviving CM. Identification of adjunctive therapies that reduce the complications of CM in survivors is a priority. Statins have been suggested for the treatment of neuroinflammatory disorders due to their pleiotropic effects.

 

Here, we examined the effects of lovastatin on neuroinflammation in experimental CM, and its effect on the prevention of cognitive impairment. Lovastatin reduced adhesion and rolling of leukocytes in brain vessels, inhibited blood-brain barrier disruption, and reversed decreases in cerebral capillary density. Lovastatin also inhibited ICAM-1 and CD11b mRNA expression while increasing HMOX-1 mRNA levels. Proinflammatory cytokines and markers of oxidative stress were lower in the brains of infected mice treated with lovastatin.

 

Lovastatin administered together with antimalarial drugs during the acute phase of the disease-protected survivors from impairment in both contextual and aversive memory 15 days after infection. Similar results were observed in a model of bacterial sepsis.

 

Our findings support the possibility that statins may be valuable pharmacologic tools in treatment of patients with neuroinflammation associated with severe systemic inflammatory syndromes. Clinical trials with statins in CM and sepsis should be speedily considered to examine this point.



Of course, what works in mice isn’t guaranteed to work in humans.  The authors caution:

 

These models may provide important insights into the pathogenesis of cognitive dysfunction associated with cerebral malaria and related disorders that may be relevant to human conditions [7]. While differences between murine models of CM and the human syndrome are often emphasized [10], [11], there are also important similarities [3], [7], [12][14]. Nevertheless, caution must be exerted when translating experimental findings to the clinical scenario.

 

 

The VOA has a nice write up of this study (see Mice Study Indicates Cholesterol Drug Might Help Treat Serious Malaria Cases), including an interview with one of the authors, who recommends that:

 

Zimmerman recommends lovastatin be added to treatments for malaria as well as for sepsis, a systemic blood infection commonly known as blood poisoning that sickens and threatens the lives of more people worldwide than cerebral malaria.

 


The problem with statins is that these are are cheap, generic drugs.  They provide little financial incentive for their manufacturers to mount expensive human trials in order to prove their effectiveness against malaria, pneumonia, sepsis, or influenza.

 

So, while the evidence continues to suggest benefits to using statins for `off label’ purposes,  real proof of their effectiveness may be a long time in coming.

»» Read More

PLoS One: Influenza Viral Shedding & Asymptomatic Infections

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Photo Credit PHIL (Public Health Image Library)

 


# 6776

 

 

Despite major advances in the study of influenza viruses, there remain significant gaps in our understanding of just how they work once they infect a human (or any other animal) host. 

 

Basic questions, such as `How long are we infectious?, or `How common are asymptomatic infections?  remain only partially answered.

 

Complicating matters, variations in individual host’s immune responses, and different strains of flu may produce varying results. Meaning that most studies can only add incrementally to our knowledge, rather than completely answering these questions.

 

Previously, we’ve seen evidence of asymptomatic and `presymptomatic’ shedding of influenza viruses.

 

In 2011, in EID Journal: Pre-Symptomatic Influenza Transmission we looked at three clusters of suspected pre-symptomatic transmission of the 2009 H1N1 virus in Japan.

 

And in Pre-Symptomatic Transmission Of H1N1 Influenza In the Ferret Model, researchers inoculated ferrets with the 2009 H1N1 flu, and then placed them near uninfected ferrets (some in direct contact, others in adjacent cages) at different stages after infection.

 

They then tested the exposed ferrets to see when, and under what circumstances, they became infected. They found that ferrets became infectious just 24 hours after becoming infected, and nearly 24 hours before showing the earliest outward signs of infection (fever).

 

 

The importance of all of this is, if presymptomatic and asymptomatic carriers of a flu virus are able to efficiently transmit the illness on to others, then strategies that seek to identify and isolate flu cases would have only limited success in containing a pandemic.

 

Similarly, understanding how long a person sheds the virus after becoming infected is crucial, so we can know when it is (relatively) safe for flu victims to return to work or school without endangering others.

 

The CDC’s general take on this topic is:

 

The Flu Is Contagious

Most healthy adults may be able to infect others beginning 1 day before symptoms develop and up to 5 to 7 days after becoming sick. Children may pass the virus for longer than 7 days. Symptoms start 1 to 4 days after the virus enters the body. That means that you may be able to pass on the flu to someone else before you know you are sick, as well as while you are sick. Some persons can be infected with the flu virus but have no symptoms. During this time, those persons may still spread the virus to others.

 

 

Yesterday, a new study appeared in PloS One, conducted in Germany over 4 flu seasons (2007-2011) and involving 4 flu strains - seasonal (A(H3N2), A(H1N1), influenza B, and pandemic (A(H1N1)pdm09 - that looks at many of these transmission issues. 

 

Comparison of Shedding Characteristics of Seasonal Influenza Virus (Sub)Types and Influenza A(H1N1)pdm09; Germany, 2007–2011

Thorsten Suess, Cornelius Remschmidt, Susanne B. Schink, Brunhilde Schweiger, Alla Heider, Jeanette Milde, Andreas Nitsche, Kati Schroeder, Joerg Doellinger, Christian Braun, Walter Haas, Gérard Krause, Udo Buchholz

Background

Influenza viral shedding studies provide fundamental information for preventive strategies and modelling exercises. We conducted a prospective household study to investigate viral shedding in seasonal and pandemic influenza between 2007 and 2011 in Berlin and Munich, Germany.

Methods

Study physicians recruited index patients and their household members. Serial nasal specimens were obtained from all household members over at least eight days and tested quantitatively by qRT-PCR for the influenza virus (sub)type of the index patient. A subset of samples was also tested by viral culture. Symptoms were recorded daily.

Results

We recruited 122 index patients and 320 household contacts, of which 67 became secondary household cases. Among all 189 influenza cases, 12 were infected with seasonal/prepandemic influenza A(H1N1), 19 with A(H3N2), 60 with influenza B, and 98 with A(H1N1)pdm09. Nine (14%) of 65 non-vaccinated secondary cases were asymptomatic/subclinical (0 (0%) of 21 children, 9 (21%) of 44 adults; p = 0.03).

 

Viral load among patients with influenza-like illness (ILI) peaked on illness days 1, 2 or 3 for all (sub)types and declined steadily until days 7–9. Clinical symptom scores roughly paralleled viral shedding dynamics.

 

On the first day prior to symptom onset 30% (12/40) of specimens were positive. Viral load in 6 asymptomatic/subclinical patients was similar to that in ILI-patients. Duration of infectiousness as measured by viral culture lasted approximately until illness days 4–6. Viral load did not seem to be influenced by antiviral therapy, age or vaccination status.

Conclusion

Asymptomatic/subclinical infections occur infrequently, but may be associated with substantial amounts of viral shedding. Presymptomatic shedding may arise in one third of cases, and shedding characteristics appear to be independent of (seasonal or pandemic) (sub)type, age, antiviral therapy or vaccination; however the power to find moderate differences was limited.

 

 

While this was a relatively small study, and their findings don’t always align perfectly with others we’ve seen (for instance, children didn’t appear contagious any longer than adults), it does provide us with some interesting data.

 

  • First, nearly 1/3rd of cases began shedding virus while pre-symptomatic
  • Second, viral loads in (six studied) asymptomatic cases were similar to that to patients exhibiting ILI (influenza-like-illness) symptoms.
  • Third, viral load among symptomatic patients peaked on illness days 1, 2 or 3 and declined steadily until days 7–9

 

Some other gems (bolding mine) excerpted from this open access article include:

 

  • Overall 63% of non-vaccinated secondary household cases had an ILI-syndrome and the proportion of asymptomatic/subclinical secondary cases was 14%.
  • Frequency distribution of clinical symptoms did not differ between A(H1N1)pdm09 cases and non-pandemic influenza cases.
  • Interestingly, 21% of adult secondary cases were asymptomatic/subclinical, while all children that contracted influenza were symptomatic.
  • Based on the population of ambulatory patients investigated we found no evidence that the amount of shedding is particularly higher in children, nor that duration of viral shedding is significantly longer in children compared to adults.

 

 

The authors conclude by saying:

 

In summary, our study addresses several important questions on clinical manifestation, duration of infectiousness, viral shedding patterns, including shedding before symptom onset and in asymptomatic/subclinical patients, as well as the effect of vaccination and antiviral therapy on viral shedding.

 

Important single results include the finding that children do not seem to be infected asymptomatically, that shedding one day before symptom onset may occur in one third of influenza patients, that asymptomatic/subclinical influenza patients occur rarely, but viral load (and probably infectiousness) may be substantial, and vaccinated influenza patients do not show different shedding patterns compared to non-vaccinated cases with ILI.

 

Overall results do not show marked differences between seasonal influenza (sub)types and influenza A(H1N1)pdm09.

»» Read More

An Unwanted Lagniappe From The Kitchen

 

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Norovirus – Credit CDC PHIL 


LagniappeA little something extra given to a customer. 


# 6766

 

 

The CDC estimates that norovirus (aka the `Winter Vomiting Bug’ or less accurately, `Stomach Flu’) causes more than 20 million cases of gastroenteritis each year in the United States. Anyone who has endured it can attest that a bout with norovirus is misery incarnate.

 

The CDC maintains an extensive Norovirus webpage where they describe the illness, how it is spread, and how to avoid infection. Among known causes of foodborne illness, norovirus is the largest culprit.

 

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The CDC’s NOROVIRUS: FOR FOOD HANDLERS page warns:

 

The virus can easily contaminate food because it is very tiny and infective. It only takes a very small amount of virus particles (fewer than 100) to make someone sick.

 

Food can get contaminated with norovirus when:

  • infected people who have stool or vomit on their hands touch the food,
  • it is placed on counters or surfaces that have infectious stool or vomit on them, or
  • tiny drops of vomit from an infected person spray through the air and land on the food.

 

All of which makes the thorough cleaning of plates and utensils used in restaurants a priority. 


According to a PLoS One  study, published yesterday, the prescribed methods of cleaning these items in restaurants does a good job against common bacteria – like Escherichia coli K-12 and Listeria innocua – but not so well in sanitizing against norovirus.

 

The open access study is called:

 

Efficacies of Sodium Hypochlorite and Quaternary Ammonium Sanitizers for Reduction of Norovirus and Selected Bacteria during Ware-Washing Operations

Lizanel Feliciano, Jianrong Li*, Jaesung Lee, Melvin A. Pascall*

 

Abstract

Cross-contamination of ready-to-eat (RTE) foods with pathogens on contaminated tableware and food preparation utensils is an important factor associated with foodborne illnesses. To prevent this, restaurants and food service establishments are required to achieve a minimum microbial reduction of 5 logs from these surfaces.

 

This study evaluated the sanitization efficacies of ware-washing protocols (manual and mechanical) used in restaurants to clean tableware items. Ceramic plates, drinking glasses and stainless steel forks were used as the food contact surfaces. These were contaminated with cream cheese and reduced-fat milk inoculated with murine norovirus (MNV-1), Escherichia coli K-12 and Listeria innocua.

 

The sanitizing solutions tested were sodium hypochlorite (chlorine), quaternary ammonium (QAC) and tap water (control). During the study, the survivability and response to the experimental conditions of the bacterial species was compared with that of MNV-1.

 

The results showed that current ware-washing protocols used to remove bacteria from tableware items were not sufficient to achieve a 5 log reduction in MNV-1 titer. After washing, a maximum of 3 log reduction in the virus were obtained. It was concluded that MNV-1 appeared to be more resistant to both the washing process and the sanitizers when compared with E. coli K-12 and L. innocua.


(Continue . . . )

 

Essentially, these researchers took silverware, ceramic plates, and glassware – inoculated them with norovirus, E. coli, and Listeria – and ran them through standard dishwasher or hand washing protocols with either a bleach solution or quaternary ammonium compound (QAC) solution.

 

After that, they tested them for residual pathogens.

 

Although commercial dishwashers did a better job than did handwashing, with both, significant contamination from the norovirus remained behind.

 

The authors write:

 

Conclusions

From the results of our study, it could be concluded that QAC and sodium hypochlorite sanitizers normally used to inactivate bacteria in manual and mechanical ware-washing operations were unable to produce the same level of virus inactivation under similar conditions, irrespective of the nature of the tableware item tested.

Further studies are needed to develop more effective ware-washing protocols for the removal of viruses from food contact surfaces/tableware items. Also, the combination of different detergents and sanitizing solutions (especially those containing surfactant agents) should be evaluated since they may help to enhance the removal and inactivation of non-enveloped viruses.

 

 

Obviously, people who are sick should not be handling food, but people can shed the virus even after they stop showing symptoms.

 

So one of the keys to prevention is good hand hygiene.

Unfortunately, unlike with many other bacteria and viruses, alcohol gel doesn’t do a particularly good job of killing the virus, something we discussed last year in  CMAJ: Hand Sanitizers May Be `Suboptimal’ For Preventing Norovirus.

 

Which makes a good old fashion hand scrubbing with soap and water the best preventative.

 

The CDC recommends the following steps to protect yourself from the virus.

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And of course, the obvious question is . . .if norovirus escapes routine dishwashing protocols, what about other viruses like Hepatitis A and influenza?


Reportedly, these researchers will be looking at those viruses next.

»» Read More

NIH: News From The Human Microbiome Project

 

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Photo Credit HMP

 

# 6385

 

Last year in The Other Reason Not To Abuse Antibiotics I touched briefly on beneficial intestinal bacteria (gut flora or microbiota), and how the use of antibiotics can adversely disrupt their balance.

 

The study of these ubiquitous micro-organisms that reside not only in our intestines, but on our skin, in our nasal passages, oral cavities, gastrointestinal tract, and urogenital tract has gained momentum over the past several years.

 

One of the big reasons is the NIH sponsored Human Microbiome Project, which defines their goal as:

 

 

The Common Fund's Human Microbiome Project (HMP) aims to characterize the microbial communities found at several different sites on the human body, including nasal passages, oral cavities, skin, gastrointestinal tract, and urogenital tract, and to analyze the role of these microbes in human health and disease. HMP includes the following initiatives.

 

 

Today, in advance of the publication today and tomorrow of a number of research articles in PLoS and in the journal Nature, we’ve a couple of lengthy press releases describing this international project’s recent accomplishments, along with an announcement on the PLoS Blog of the availability of this collection.

 

 

First, from the NIH – news that researchers have defined the normal bacterial makeup of the human body.

 

 

NIH Human Microbiome Project defines normal bacterial makeup of the body

Genome sequencing creates first reference data for microbes living with healthy adults

Microbes inhabit just about every part of the human body, living on the skin, in the gut, and up the nose. Sometimes they cause sickness, but most of the time, microorganisms live in harmony with their human hosts, providing vital functions essential for human survival. For the first time, a consortium of researchers organized by the National Institutes of Health has mapped the normal microbial makeup of healthy humans, producing numerous insights and even a few surprises.

 

Researchers found, for example, that nearly everyone routinely carries pathogens, microorganisms known to cause illnesses. In healthy individuals, however, pathogens cause no disease; they simply coexist with their host and the rest of the human microbiome, the collection of all microorganisms living in the human body. Researchers must now figure out why some pathogens turn deadly and under what conditions, likely revising current concepts of how microorganisms cause disease.

 

In a series of coordinated scientific reports published on June 14, 2012, in Nature and several journals in the Public Library of Science (PLoS), some 200 members of the Human Microbiome Project (HMP) Consortium from nearly 80 universities and scientific institutions report on five years of research. HMP has received $153 million since its launch in fiscal year 2007 from the NIH Common Fund, which invests in high-impact, innovative, trans-NIH research. Individual NIH institutes and centers have provided an additional $20 million in co-funding for HMP consortium research.

 

“Like 15th century explorers describing the outline of a new continent, HMP researchers employed a new technological strategy to define, for the first time, the normal microbial makeup of the human body,” said NIH Director Francis S. Collins, M.D., Ph.D. “HMP created a remarkable reference database by using genome sequencing techniques to detect microbes in healthy volunteers. This lays the foundation for accelerating infectious disease research previously impossible without this community resource.”

(Continue . . . )

 

 

In another press release from the University of North Carolina at Charlotte, we get details on how this research was conducted, and the surprising individuality and diversity among health human biomes.

 

 

Human Microbiome Project finds vast individuality in healthy human bacterial populations

(EXCERPT)

To define the normal human microbiome, HMP researchers sampled 242 healthy U.S. volunteers (129 male, 113 female), collecting tissues from 15 body sites in men and 18 body sites in women (including three vaginal sites). Researchers collected up to three samples from each volunteer at sites such as the mouth, nose, skin (two behind each ear and each inner elbow),and lower intestine (stool).

Where doctors had previously isolated only a few hundred bacterial species from the body, HMP researchers now calculate that more than 10,000 species occupy the human ecosystem. Moreover, researchers calculate that they have found between 81 and 99 percent of all the genuses of microorganisms in healthy adults.

Defining "a" human biome, however, can be difficult, as HMP researchers found immense variation in bacterial communities, both in bacterial diversity and in bacterial group abundances -- variation that includes population differences both between areas in each body and between similar areas in different bodies.

Each body site can be inhabited by organisms as different as those in the Amazon Rainforest and the Sahara Desert. Further, these sites on different individuals are populated with different assemblages of bacteria, or with some of the same bacteria, but in markedly different proportions.

(Continue . . . )


From the Public Library of Science Blog we get details on this expanding collection of research.

 

Announcing the Human Microbiome Project Collection

For the first time, a consortium of researchers has mapped the full community of microbes that inhabit various parts of the healthy human body. Many of these findings will be published today in a new PLoS collection. The PLoS Human Microbiome Project Collection consists of articles from the project’s consortium members, who generate, leverage, and explore microbiome analytical techniques. The articles have been culled from PLoS ONE, PLoS Genetics, and PLoS Computational Biology with more being added to the collection as they are published.

(Continue . . .)

 

The PLoS Microbiome collection features 13 new research papers published today. To access these papers, please visit:

 

PLoS Collections: The Human Microbiome Project Collection (2012) www.ploscollections.org/hmp

»» Read More

PLoS One: Seroprevalence Of H9N2 In Poultry Workers – Pune, India

 

 

# 6337

 


While H5N1 gets the lion’s share of the media’s attention, there are other influenza viruses in the wild believed capable of sparking the next flu pandemic.  Over the past dozen years we’ve seen a number of avian flu strains that have made limited jumps to human hosts.

 

  • In 2003, an outbreak of H7N7 at a poultry farm in the Netherlands went on to infect at least 89 people (mostly mildly, but 1 death), and many more may have been infected subclinically.
  • In Egypt - in 2004 -  2 infants were shown to be infected by the H10N7 avian flu virus.
  • In 2006 1 person in the UK was confirmed to have contracted H7N3, and the following year, 4 people tested positive for H7N2 – both following local outbreaks in poultry.

 

But in terms of greatest concern, the closest runner up to H5N1 is probably H9N2 – which is known to have infected a handful of humans, mostly in Asia.

 

To date, most of these cases have produced relatively mild illness.  

 

Nevertheless, the World Health Organization  has announced that work has begun on the creation of an H9N2 candidate vaccine (see WHO Report : Antigenic & Genetic Characteristics of H5N1 & H9N2 Viruses).

 

Last year, in PNAS: Reassortment Potential Of Avian H9N2 , researchers looked at the reassortment potential of the avian H9N2 virus and H1N1, generating four reassortant viruses, three of which showed efficient respiratory droplet transmission in the ferret model.

 

These authors had previously successfully created laboratory reassortments between seasonal H3N2 and H9N2

 

Experiments that are, in many ways, similar to the H5N1 experiments of Fouchier and Kawaoka that have caused such a stir these past few months, albeit on a (thus far) much-less-pathogenic flu virus.

 

These successes (and others, see PNAS: Reassortment Of H1N1 And H9N2 Avian viruses), along with the wide geographic distribution of the H9 avian virus in poultry across Asia and the Middle East, have led many researchers to call for better research and surveillance on this avian strain.

 

Which brings us to a new study, published late last week in the journal Plos One, that looks at the prevalence of antibodies to the H9N2 strain among poultry workers – and the general population – in Pune, India.

 

Avian Influenza H9N2 Seroprevalence among Poultry Workers in Pune, India, 2010

Shailesh D. Pawar, Babasaheb V. Tandale, Chandrashekhar G. Raut, Saurabh S. Parkhi, Tanaji D. Barde, Yogesh K. Gurav, Sadhana S. Kode, Akhilesh C. Mishra

PLoS ONE 7(5): e36374. doi:10.1371/journal.pone.0036374

Abstract

Avian influenza (AI) H9N2 has been reported from poultry in India. A seroepidemiological study was undertaken among poultry workers to understand the prevalence of antibodies against AI H9N2 in Pune, Maharashtra, India.

 

A total of 338 poultry workers were sampled. Serum samples were tested for presence of antibodies against AI H9N2 virus by hemagglutination inhibition (HI) and microneutralization (MN) assays.

 

A total of 249 baseline sera from general population from Pune were tested for antibodies against AI H9N2 and were negative by HI assay using ≥40 cut-off antibody titre.

 

Overall 21 subjects (21/338 = 6.2%) were positive for antibodies against AI H9N2 by either HI or MN assays using ≥40 cut-off antibody titre. A total of 4.7% and 3.8% poultry workers were positive for antibodies against AI H9N2 by HI and MN assay respectively using 40 as cut-off antibody titre.

 

This is the first report of seroprevalence of antibodies against AI H9N2 among poultry workers in India.

 

 

Although a bit of a gray area, an antibody titer level of ≥40 is generally assumed to be suggestive of a previous (possibly sub-clinical) infection by a specific virus.

 

Interestingly, none of the 249 sera samples from the general population showed elevated antibody titers to the H9N2 virus (using the ≥40 cut-off standard), but among poultry workers, 21 of the 338 sera samples (6.2%) tested positive for H9N2 antibodies.


A fairly low number given the amount of exposure,  but indicative that some transmission of the virus to humans appears to be taking place.


The authors warn that:

 

The evidence of AI (H9N2) in poultry market may provide the opportunity for human infections and the possibility of reassortment with the existing poultry AI viruses including HPAI H5N1 virus.

 

Warnings over the pandemic potential of the H9N2 virus are not new. A few notable stories from the past include:

 

  • In December 2008 I ran a blog featuring an interview in which world famous Hong Kong virologist Malik Peiris cautioned that the H9N2 virus may be circulating far more commonly than we believe. Revisiting A Malik Peiris Interview On H9N2.
  • In January of 2010, in H9N2: The Other Bird Flu Threat, I wrote about the World Health Organization  recommending the creation of a candidate vaccine virus for H9N2.

 

 

Unlike the H7 and H5 avian flu strains, poultry (and swine) infections by the H9N2 virus are not required to be reported to the OIE.  

 

Admittedly, the next influenza virus to successfully jump species could come out of left field, as we saw in 2009 with the H1N1 swine flu.

 

image

 

Which is why the global monitoring of influenza viruses - in humans, on the farm, and in the wild - remains crucial if we hope to detect, and prepare for, the next pandemic at the earliest possible moment.

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Branswell: PLoS One Study On Adverse Reactions To MMR Vaccine

 

 

# 6006

 

I was in the process of reading a paper on reactions following the administration of the MMR vaccine that appears this morning in the PloS One  journal (and considering blogging on it), when luckily I saw that Helen Branswell of the Canadian Press has already covered the story.

 

The paper can be read at:

 

Adverse Events following 12 and 18 Month Vaccinations: a Population-Based, Self-Controlled Case Series Analysis

 

Kumanan Wilson, Steven Hawken, Jeffrey C. Kwong, Shelley Deeks, Natasha S. Crowcroft, Carl Van Walraven, Beth K. Potter, Pranesh Chakraborty, Jennifer Keelan, Michael Pluscauskas, Doug Manuel

 

Helen’s article appears this morning on the Global News website, and so I’m going to do the smart thing and quickly step aside and let one of the best science writers in the business explain the findings.

 

 

MMR vaccine reactions fairly common at 12 months, but serious reactions rare

Helen Branswell,  Monday, December 12, 2011 9:28 PM

 

Global News | MMR vaccine reactions fairly common at 12 months, but serious reactions rare

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PLoS One: Viremia In The 2009 H1N1 Pandemic Influenza

 

 

# 5868

 

 

Today, a fascinating study  that associates viremia, and a specific mutation (D222G/N) in the 2009 H1N1 virus, to more severe disease presentation.

 

Viremia simply refers to the presence of viruses in the blood stream.

 

While many viruses cause viremia (ie. Dengue, Chikungunya, WNV) – seasonal influenza, being primarily a respiratory disease, isn’t usually one of them.

 

But as we’ve seen demonstrated over the past several years, the pathogenesis of the 2009 H1N1 virus sometimes deviated from what one normally sees with seasonal flu.

 

Recently, in mBio: Lethal Synergism of H1N1 Pandemic Influenza & Bacterial Pneumonia we saw how novel H1N1 infection exacerbated lung damage due to bacterial co-infection, when seasonal flu did not.

 

In April of 2010, in There’s No Flu Like A New Flu, I listed many of the other differences observed between seasonal flu and the novel H1N1 virus, including:

 

 

  • Research out of Hong Kong that discovered that the novel H1N1 virus – unlike seasonal flu – easily infect and replicate in the conjunctival tissues of the eye  (see I Only Have Eyes For Flu).

 

 

 

 

Although the H1N1 pandemic virus of 2009 proved to be relatively mild for the vast majority of those infected, for a very small percentage, it produced serious and sometimes life-threatening illness.

 

Add to this the fact that this flu, unlike seasonal flu, was also frequently detected in companion animals, and it certainly appears that something was inherently different about the 2009 H1N1 virus.

 

Today, a new study appears in PLoS One that adds more weight to that argument. The open access study is called:

 

 

Clinical and Virological Factors Associated with Viremia in Pandemic Influenza A/H1N1/2009 Virus Infection

 

Herman Tse, Kelvin K. W. To, Xi Wen, Honglin Chen, Kwok-Hung Chan, Hoi-Wah Tsoi, Iris W. S. Li, Kwok-Yung Yuen

Positive detection of viral RNA in blood and other non-respiratory specimens occurs in severe human influenza A/H5N1 viral infection but is not known to occur commonly in seasonal human influenza infection.

Recently, viral RNA was detected in the blood of patients suffering from severe pandemic influenza A/H1N1/2009 viral infection, although the significance of viremia had not been previously studied. Our study aims to explore the clinical and virological factors associated with pandemic influenza A/H1N1/2009 viremia and to determine its clinical significance.

Methodology/Principal Findings

Clinical data of patients admitted to hospitals in Hong Kong between May 2009 and April 2010 and tested positive for pandemic influenza A/H1N1/2009 was collected. Viral RNA was detected by reverse-transcription polymerase chain reactions (RT-PCR) targeting the matrix (M) and HA genes of pandemic influenza A/H1N1/2009 virus from the following specimens: nasopharyngeal aspirate (NPA), endotracheal aspirate (ETA), blood, stool and rectal swab.

Stool and/ or rectal swab was obtained only if the patient complained of any gastrointestinal symptoms. A total of 139 patients were included in the study, with viral RNA being detected in the blood of 14 patients by RT-PCR.

The occurrence of viremia was strongly associated with a severe clinical presentation and a higher mortality rate, although the latter association was not statistically significant. D222G/N quasispecies were observed in 90% of the blood samples.

Conclusion

Presence of pandemic influenza A/H1N1/2009 viremia is an indicator of disease severity and strongly associated with D222G/N mutation in the viral hemagglutinin protein.

 

The authors propose several theories as to why the virus was detected in the bloodstream, and gastrointestinal tract.

 

The detected viral RNA in blood could either reflect extensive pulmonary damage with phagocytic uptake of virus-infected cells or true infection of monocyte-derived dendritic cells and macrophages [26].

On the contrary, viruses in the stool may originate from swallowed respiratory secretions, although viral replication in the epithelial tissue along the gastrointestinal tract cannot be ruled out entirely.

 

 

The significance of the H222G/N mutation in the 2009 H1N1 virus has been vigorously debated for nearly two years.

 

The `Norway’ or D222G/N (D225G/N in influenza H3 Numbering) mutation cited in this study was first linked to more severe disease by Norwegian Scientists in November 2009, although patients carrying these strains can have mild illness as well. 

 

While we’ve covered this territory a number of times over the past year, a brief (and hopefully simple) review is in order. If you are up to speed on receptor binding, and the history of the D222G/N variant, feel free to skip the next section.

 

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

 

The pdmH1N1 virus carrying this mutation appears to bind more readily to receptor cells (α2-3) found deeper in the lungs, whereas unmutated seasonal flu strains bind preferentially to the (α2-6) receptor cells found in the upper airway.

 

A virus’s ability to bind to specific cells is controlled by its RBD or Receptor Binding Domain; an area of its genetic code that allows it to attach to, and infect, specific types of host cells.

image

(A Very Simplified Illustration of RBDs)

Like a key into a padlock, the RBD must `fit’ in order to open the cell to infection.

 

The evidence for the D222G/N  amino acid substitution driving increased virulence has been mixed, with the World Health Organization, the CDC, and the HPA continuing to investigate. 

 

Complicating matters - viruses can have multiple amino acid changes – and it may be the combination of these changes can unpredictably (at least for now) alter the virus’s behavior. 

 

Since the D222G/N mutation has been found in patients showing mild disease, it may be that a second (or third) mutation elsewhere in the virus – in concert with D222G/N – is required to produce greater virulence.

 

There is simply a lot we don’t know yet.

 

During the first week of January, Eurosurveillance  printed a study looking at fatal and non-fatal cases of influenza in the UK (see Eurosurveillance: Analysis Of Fatal H1N1 Cases In The UK). 

 

Ellis et al. reported that almost all of the virus samples tested in fatal and non-fatal cases during the early wave of the 2010/11 influenza season showed aspartic acid (D) at position 222.

 

In other words, no `Norway’ mutation.

Towards the end of January 2011, Eurosurveillance published a letter from an Italian researcher who had found a high percentage of D222G/N mutations in severely ill patients (43%)  – particularly when taking virus samples from the lower respiratory tract (lungs).

 

In a reply, the authors of the original study concede that in many cases, only upper respiratory swabs were available for this analysis, and that when possible, samples from the lower respiratory system would be useful.

 

This scholarly debate wasn’t over, as Ellis et al. state in their reply:

 

The selection and emergence of the D222G mutation as a cause or consequence of more severe lower respiratory tract infection is still to be resolved.

 

Emergence of this mutant is likely to exacerbate severity of disease, but by itself, may be neither necessary nor sufficient to account for a severe disease outcome, which is invariably a balance between virus virulence factors and host immune response capability.

 

And so the debate has continued, with some scientists believing the `Norway’ mutation causes more severe illness, while others are less certain.

 

It will take more samples, more research, and more time to determine the truth in the matter.

 

Still, this study is another step forward in our understanding of the unusual pathogenesis, and genetic evolution, of the pandemic H1N1 virus.

 

And since we’ve seen similar severe lung damage, and scattered reports of viremia, among the small number of H5N1 `bird flu’ cases that have been examined, what we can learn about the 2009 H1N1 virus may provide clues on how to tackle a more severe pandemic in the future.

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PLoS One: H1N1 Seroprevalence Study

 

 

 

#5614

 

 

 

Although relatively mild by pandemic standards, the novel H1N1 virus of 2009 will undoubtedly turn out to be the most studied influenza outbreak in history. Two years after the outbreak began, we continue to see new and sometimes surprising research being published.

 

Today, we’ve a seroprevalence study appearing in PLoS One  that looks at the incidence of infection by the 2009 H1N1 pandemic virus in eastern Scotland during the pandemic.

 

It finds that transmission rates, and number of people infected, was far higher than previously believed; more than 40% of adults tested showed specific antibodies to the pandemic flu.

 

A snippet from the open access study follows, after which I’ll return with more.

 

 

Sero-Prevalence and Incidence of A/H1N1 2009 Influenza Infection in Scotland in Winter 2009–2010

Nigel J. McLeish, Peter Simmonds, Chris Robertson, Ian Handel, Mark McGilchrist, Brajendra K. Singh, Shona Kerr, Margo E. Chase-Topping, Katy Sinka, Mark Bronsvoort, David J. Porteous, William Carman, James McMenamin, Andrew Leigh-Brown, Mark E. J. Woolhouse

(EXCERPTS)

Methods and Findings

We obtained serum samples from a representative sample of 1563 adults resident in Scotland between late October 2009 and April 2010.

 

Based on a microneutralisation assay, we estimate that 44% (95% confidence intervals (CIs): 40–47%) of the adult population of Scotland were sero-positive for A/H1N1 2009 influenza by 1 March 2010.

 

Correcting for background cross-reactivity and for recorded vaccination rates by time and age group, we estimated that 34% (27–42%) were naturally infected with A/H1N1 2009 by 1 March 2010.

 

The central estimate increases to >40% if we allow for imperfect test sensitivity.

<SNIP>

Conclusions

We estimate that almost half the adult population of Scotland were sero-positive for A/H1N1 2009 influenza by early 2010 and that the majority of these individuals (except in the oldest age classes) sero-converted as a result of natural infection with A/H1N1 2009. Public health planning should consider the possibility of higher rates of infection with A/H1N1 2009 influenza in more deprived areas.

 

There is also a press release from the University of Edinburgh, which led this study.

 

Swine flu spread was much wider than first thought, scientists say

The swine flu outbreak of winter 2009-2010 was much more widespread than was previously realized, research suggests

The swine flu outbreak of winter 2009-2010 was much more widespread than was previously realised, research suggests.

 

Blood samples taken from Scottish adults in March last year at the end of the H1N1 flu season showed that almost half were carrying antibodies to the virus.

 

Most of the 44 per cent who tested positive had contracted swine flu, although some had acquired immunity from a previous bout of flu, or had been vaccinated.

 

The research, led by the University of Edinburgh, shows that many cases of swine flu went unreported. Only 100,000 people consulted their GP regarding flu, out of about two million who are believed to have contracted the virus.

 

People living in the most deprived areas were twice as likely to have contracted the virus. Scientists add that it is possible that many people who were vaccinated against the virus were already immune.

(Continue . . . )

 

 

What makes this research particularly interesting is that the attack rate of the H1N1 virus in this study appears to be higher than earlier studies would have suggested. 

 

Last summer, in New Zealand Seroprevalence Study On H1N1, researchers came up with a much lower attack rate (approx. 20%, half asymptomatic).

 

And in late 2009, in UK: H1N1 Serology Tests Reveal Significant Asymptomatic Rate a small study revealed that about 1/3rd of children tested – who were believed more susceptible to the virus than adults – showed antibodies to the virus, while only about 1 in 10 reported flu symptoms.  

 

While we were lucky that this virus produced mild (or even asymptomatic) illness in most cases, the next novel virus to erupt may not be nearly so accommodating. 

 

So research such as this is of more than just academic interest. 

 

It helps to increase our understanding of the attack rates and the patterns of community spread of a novel influenza virus, which should help planners better prepare for the next pandemic.

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PLoS: Human-Type H5N1 Receptor Binding In Egypt

 

 

# 5579

 

 

The mantra over the past five years or so on H5N1 bird flu has been that:

 

The H5N1 virus remains poorly adapted to human physiology, and despite ample opportunities in places like Egypt and Indonesia, only causes rare, sporadic infections in humans.

 

 

H5N1 is generally a gastrointestinal malady in birds, and the virus is usually spread via infected feces. The virus binds preferentially to the kind of receptor cells commonly found in avian digestive and respiratory tracts; alpha 2,3 receptor cells.

 

Human influenzas, on the other hand, are adapted to bind to the kind of receptor cells that line the surfaces of the human respiratory system; alpha 2,6 receptor cells.

 

While not an absolute, flu viruses that bind to one type of receptor cell, tend not to bind well to the other.

 

This ability to bind to a specific type of cell has often been described as the host cell being a padlock, and the virus needing a specific key (determined by the genetics of the virus’s Receptor Binding Domain: RBD) to unlock it.

 

image

(A Very Simplified Illustration of RBDs)

 

 

Now humans do have some avian-like alpha 2,3 receptor cells, particularly deep in the lungs.

 

This has been suggested as the reason that - when on rare occasions humans contract H5N1 - it is usually a deep lung infection.

 

It has also been postulated that H5N1’s deeper lung infections may reduce human-to-human transmission, as sneezing is a less common symptom.

 

The concern is that over time, the H5N1 (or some other avian flu) virus might mutate in such a way as to be able to bind to human α2,6 receptor cells of the upper airway.

 

And while that may not be the only obstacle keeping the virus from becoming a pandemic strain, it does appear to be a major one.

 

Although only introduced to the region in 2006, Egypt has rapidly become a hotspot for avian flu (see this list of human cases maintained on FluTrackers). 

 

Unlike some Asian countries, where the virus has proved fatal in 80% of reported cases, the CFR (Case fatality ratio) in Egypt has ranged from 10% (2009) to 34% (2010).

 

This variability in virulence has sparked concerns that important changes were taking place in the virus. 

 

Which brings us to an open access research article (excerpts slightly reformatted for readability) appearing today in PLoS Pathogens called:

 

Acquisition of Human-Type Receptor Binding Specificity by New H5N1 Influenza Virus Sublineages during Their Emergence in Birds in Egypt

Yohei Watanabe, Madiha S. Ibrahim, Hany F. Ellakany, Norihito Kawashita, Rika Mizuike, Hiroaki Hiramatsu, Nogluk Sriwilaijaroen Tatsuya Takagi, Yasuo Suzuki, Kazuyoshi Ikuta

PLoS Pathog 7(5): e1002068.

doi:10.1371/journal.ppat.1002068

AUTHOR SUMMARY

Even though highly pathogenic avian H5N1 influenza viruses lack an efficient mechanism for human-human transmission, these viruses are endemic in birds in China, Indonesia, Viet Nam and Egypt. Hotspots for bird-human transmission are indicated in areas where human cases are more than 80% of total H5N1 influenza cases.

 

Circulation among hosts may allow H5N1 virus to acquire amino acid changes enabling efficient bird-human transmission and eventually human-human transmission. The receptor specificity of viral hemagglutinin (HA) is considered a main factor affecting efficient transmissibility. Several amino acid substitutions in H5 virus HAs that increase their human-type receptor specificity have been described in virus isolates from patients, but their prevalence has been limited.

 

In contrast, we show here that new H5 sublineages in Egypt have acquired a change in receptor specificity during their diversification in birds. We found that viruses in those sublineages exhibited increased attachment and infectivity in the human lower respiratory tract, but not in the larynx.

 

Our findings may not allow a conclusion on the high pandemic potential of H5N1 virus in Egypt, but helps explain why Egypt has recently had the highest number of human H5 cases worldwide.

 

 

Since the entire research article is open access (and quite lengthy), I’ll not go into great detail on how they conducted this research here. 

 

Instead, we’ll focus on what all of this might mean.

 

While we tend to talk about the H5N1 virus as if it were a single, monolithic entity, in truth it is more akin to the mythical Hydra that is continually growing new heads.

 

The virus, as it spread from birds to other species and around the world, has evolved into a number of distinct genetic groupings called clades. As of 2009, the World Health Organization had classified the  H5N1 virus into 10 first order clades (0-9).

 

As  you can see from the chart below, while additional clades have been established over the past 10 years, the greatest diversity has been among the Clade 2 viruses.

 

image

 

 

Within each of these clades, the virus is continually evolving into subclades and sublineages. A few are biologically fit and manage to persist and spread, while others are not, and eventually die off.

 

Essentially H5N1 is a moving target; constantly changing, looking for an evolutionary advantage.

 

What the authors of today’s study found was that among recent human infections in Egypt, examination of viral isolates showed that several new H5 sublineages have emerged with an increased affinity for (human) α2,6 SA receptor cells while still retaining their binding ability to (avian) α2,3 SA receptor cells.

 

Using reverse genetics, they identified the the amino acid mutations that produced this new receptor binding affinity (essentially, a single mutation at HA residue 192 or a double mutation at HA residues 129 and 151).

 

They believe that the emergence of these new sublineages of H5N1 explains the increase in human cases in Egypt over the past three years.

 

Before anyone decides its time to head down to the bunker, it should be noted that this move towards greater `humanization’ of the H5N1 virus is far from complete.

 

The authors found `increased attachment and infectivity in the human lower respiratory tract, but not in the larynx.

 

Many scientists believe the virus must learn to bind to, and replicate in, the upper airway of humans in order to transmit efficiently from human to human.

 

Something that hasn’t happened yet.

 

And there may very well be other – as yet unidentified -genetic changes that must occur before the virus can acquire human pandemic capability.

 

Something that could take years or even decades to evolve. Or admittedly, might never happen.

 

But today’s study is a not-so-gentle reminder that the H5N1 virus has not gone away, that it continues to try out new evolutionary tricks, and that it could still some day pose a pandemic threat to humanity.

 

Which is why the world remains at Pre-pandemic Phase III for the H5N1 virus.

 

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