KSA Announces Start To Long-Awaited MERS Case Control Study

Saudi Arabia

 

 

 

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One of the first critical steps in understanding any outbreak of a novel infectious disease  is to conduct a `case-control’ study,  where a number of known infected individuals are compared to a much larger number of controls, matched for age, sex, and neighborhood.  

 

A couple of weeks ago, in CDC: Risk Factors Involved With H7N9 Infection, we looked at a case control study that was begun in China literally just weeks after the first cases of H7N9 infection were identified in the spring of 2013.

 

For well over a year the World Health Organization, and many other scientists, have been urging the Saudi’s to conduct this sort of epidemiological investigation, with the WHO publishing  framework for just such a project a year ago (see case-control study protocol Jul 2013).

 

Today, more than two years into the emergence of the MERS virus, Reuters is reporting that Saudi Arabia has begun the process of conducting a case-control study.

 

Saudi Arabia recruits patients for vital MERS virus studies

By Reuters

Saudi Arabia says it has recruited patients for a crucial study on the source of the deadly MERS virus, acknowledging it is late but pledging more work on the epidemic after international criticism of its slow response.

Scientists and global public health experts have faulted Saudi Arabia's response for allowing the spread of the Middle East Respiratory Syndrome (MERS) virus, which has now killed nearly 300 people inside the kingdom.

Among Riyadh's failings has been the lack of a type of research known as a "case-control" study, which compares the histories of people with a disease to a "control group" of people who do not have it, to try to determine what causes it.

The kingdom's chief scientist, Tariq Madani, said the study was now under way, having so far enrolled the first 10 "cases" - people who had the disease and either died or recovered - alongside 40 "controls" to compare them with. Ideally, the study would look at 20 cases and 80 controls, he said.

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The sample size mentioned - 20 cases & 80 controls - is considerably smaller than the Chinese H7N9 case-control study mentioned above which used 89 laboratory-confirmed A(H7N9) cases matched to 339 controls. 

 

I’ll leave it to those better versed in these sorts of studies to weigh in on the `ideal’ size of such a study.

EID Journal: Seroprevalence Of B. Miyamotoi In N.E. United States

(Photo Credit- CDC)

 

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Although they’ve undoubtedly been around and infecting mankind for a long time, in recent years we’ve seen a surge in the number of `new’ tickborne illnesses identified in the United States and around the world.  And as new tests are being developed and deployed, we are finding out that the number of tick borne infections reported previously have only represented  `the tip of the iceberg’.

 

Last year, the CDC revised their Estimate Of Yearly Lyme Disease Diagnoses In The United States, indicating that the number of Lyme Disease diagnoses in the country is probably closer to 300,000 than the 30,000 that are officially reported each year to the CDC.

 

In 2012, the CDC announced the identification of the The Heartland Virus in two farmers from the Midwest (see a New Phlebovirus Discovered In Missouri). Last March (see MMWR: Heartland Virus Disease — United States, 2012–2013) we saw an update from the CDC indicating that 6 more cases had been identified (5 in Missouri, 1 in Tennessee), and last month we saw the  Oklahoma DOH Reports 1st Heartland Virus Fatality.

 

Like many vector-transmitted diseases, the Heartland Virus is likely under-reported.

 

A couple of weeks ago, in The Tick Borne Identity, we looked at a study out of the University of North Florida, that claims to have found a new strain of Borellia (aka Lyme Disease), that is prevalent in ticks in the Southeastern states. In 2011 we saw the NEJM: Emergence Of A New Bacterial Cause Of Ehrlichiosis, while in recent years Babesia microti infection (see Maryn McKenna On Babesia And The Blood Supply) is increasingly viewed as a serious public health concern.

 

One of the more recent discoveries involves a tickborne bacteria called Borrelia miyamotoi, which was first described in ticks Japan in the mid-1990s, .  We’ll let the CDC carry the narrative for a spell:

 

What you need to know about Borrelia miyamotoi, a newly described human pathogen

What is Borrelia miyamotoi?

Borrelia miyamotoi are spiral-shaped bacteria that are closely related to bacteria that cause tick-borne relapsing fever (TBRF). They are more distantly related to the bacteria that cause Lyme disease. First identified in 1995 in ticks from Japan, the bacteria have since been detected in two species of North American ticks, the black-legged or “deer” tick (Ixodes scapularis) and the western black-legged tick (Ixodes pacificus). These ticks are already known to transmit several diseases, including Lyme disease, anaplasmosis, and babesiosis.

What type of illness does B. miyamotoi cause?

Human infections with B. miyamotoi were first described in 2011 in a report from Russia. Most of the patients had fever, headache, and muscle aches--symptoms typical of TBRF. Symptoms similar to those of Lyme disease, such as the erythema migrans rash (bull’s-eye rash), arthritis, or facial palsy, were uncommon.

Recently, three cases of human infection with B. miyamotoi were identified in the United States. One patient was an elderly, immunocompromised woman with confusion and an unsteady gait. The bacteria were seen in samples of the patient’s spinal fluid, and she recovered when treated with antibiotics. The two other patients had fever, chills, and muscle aches, similar to the symptoms of the patients in Russia.

 

While the number of  B. miyamotoi cases reported in the United States remains small, surveillance and testing is just in its infancy.  To that end we have research, published in the July edition of the EID Journal, that looks at the seroprevalence of  B. miyamotoi  infection in archived blood samples (collected 1991–2012) from residents of the Northeastern United States.

 

Volume 20, Number 7—July 2014

Research

Borrelia miyamotoi sensu lato Seroreactivity and Seroprevalence in the Northeastern United States

Peter J. Krause , Sukanya Narasimhan, Gary P. Wormser, Alan G. Barbour, Alexander E. Platonov, Janna Brancato, Timothy Lepore, Kenneth Dardick, Mark Mamula, Lindsay Rollend, Tanner K. Steeves, Maria Diuk-Wasser, Sahar Usmani-Brown, Phillip Williamson, Denis S. Sarksyan, Erol Fikrig, Durland Fish, and the Tick Borne Diseases Group

Abstract

Borrelia miyamotoi sensu lato, a relapsing fever Borrelia sp., is transmitted by the same ticks that transmit B. burgdorferi (the Lyme disease pathogen) and occurs in all Lyme disease–endemic areas of the United States. To determine the seroprevalence of IgG against B. miyamotoi sensu lato in the northeastern United States and assess whether serum from B. miyamotoi sensu lato–infected persons is reactive to B. burgdorferi antigens, we tested archived serum samples from area residents during 1991–2012.

Of 639 samples from healthy persons, 25 were positive for B. miyamotoi sensu lato and 60 for B. burgdorferi. Samples from ≈10% of B. miyamotoi sensu lato–seropositive persons without a recent history of Lyme disease were seropositive for B. burgdorferi.

Our results suggest that human B. miyamotoi sensu lato infection may be common in southern New England and that B. burgdorferi antibody testing is not an effective surrogate for detecting B. miyamotoi sensu lato infection.

In the same EID journal edition, in -  Human Exposure to Tickborne Relapsing Fever Spirochete Borrelia miyamotoi, the Netherlands by Fonville M, Friesema IHM, Hengeveld PD, Docters van Leeuwen A, Jahfari S, Harms MG, et al. - we see a case described as:

 

Conditions reported to be associated with B. miyamotoi infection were systemic, including malaise and fever, meningoencephalitis, and neurologic symptoms. Because of the nature of these manifestations and because regular diagnostic tests for B. burgdorferi will most probably not detect B. miyamotoi infections (3,5), B. miyamotoi infections may remain undiagnosed.

Nevertheless, the relationship between B. miyamotoi infection and illness is not very well established; the case-patients reported, including the patient in the Netherlands, were usually hospitalized, severely ill, and often immunocompromised (3–5). The extent to which B. miyamotoi causes infection and disease in immunocompetent persons is unknown.

 

The authors of the first EID report (both of which are worth reading in their entirety), conclude by writing:

 

The determination of B. miyamotoi sensu lato seroprevalence in our population is important because it indicates that this pathogen may infect persons at a rate that is similar to that of B. microti in the northeastern United States (16,23,24). Our data suggest that acute B. miyamotoi sensu lato infection in some persons may be misdiagnosed as Lyme disease because of the presence of antibody to B. burgdorferi from a previous B. burgdorferi infection, a false-positive test reaction, and/or cross-reactivity.

Antibody testing for B. burgdorferi, however, is not adequate to detect infection with B. miyamotoi sensu lato in the United States. The potential for misdiagnosis may be greater in locations like northern California, were the prevalence of B. miyamotoi sensu lato in ticks equals or exceeds the prevalence of B. burgdorferi in ticks (32). Further studies are needed to better characterize the epidemiology and improve the serodiagnosis of human B. miyamotoi sensu lato infection.

The Debate Over Gain Of Function Studies Continues

BSL-4 Lab Worker - Photo Credit –USAMRIID

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`Gain of Function’ research (aka GOF) seeks to enhance the virulence, transmissibility, or host range of potentially deadly microorganisms. Proponents believe this could give us an early warning system for the next pandemic, and could aid in the timely creation of a vaccine.  

 

Opponents say those benefits are likely overstated, and there is a small - but genuine - risk that one of these `engineered’ pathogens could escape the lab, and actually cause the pandemic it was supposed to mitigate.

 

While GOF research isn’t new, the bioengineering tools we have today make possible tasks that would have been considered literally impossible a couple of decades ago.

 

All of this really came to a head about three years ago, when Dutch Virologist and flu researcher Dr. Ron Fouchier announced, at the 2011 ESWI Influenza Conference in Malta, that he’d created a `more transmissible’ form of the H5N1 virus (see Debra MacKenzie’s New Scientist: Five Easy Mutations).

 

At roughly the same time we saw a similar announcement from Yoshihiro Kawaoka, a highly respected virologist at the University of Wisconsin-Madison School of Veterinary Medicine, that together set alarm bells ringing in the world of biosecurity.

 

The early reaction outside of academia was fairly negative, with scathing editorials like An Engineered Doomsday  appearing in the New York Times. There was a year-long self imposed moratorium by a group of major researchers, to allow time for `public discussion and scientific debate’ of the issue, but in the end, very little of that actually took place. 

 

Instead, the moratorium was quietly lifted in early 2013, and research resumed, often in Biosafety level 3+ (Ag) facilities – not – as some have recommended, restricted to the highest containment Biosafety level 4 facilities. 

The revelation two weeks ago of a major breach in biosafety at a CDC lab in Atlanta (see CDC Statement On Possible Lab Exposure To Anthrax), along with the announcement earlier this month that Dr. Kawaoka had recreated viruses similar to the 1918 pandemic strain in his lab (see Cell Host & Microbe: 1918-like Avian Viruses Circulating In Birds Have Pandemic Potential) has helped to reignite the debate.

 

Today the Wisconsin State Journal carries a long article on concerns raised by University of Wisconsin biosafety expert.

 

UW-Madison flu studies raise risk more than prevent it, biosafety panelist says

By David Wahlberg | Wisconsin State Journal

UW-Madison scientist Yoshihiro Kawaoka says he’s creating potentially deadly flu viruses to help prevent a pandemic, but a campus biosafety panel member says the research could cause more harm than good because the viruses could escape from the lab.

“You’re increasing the probability of having a pandemic rather than decreasing the probability,” said Tom Jeffries, a member of the university’s Institutional Biosafety Committee, which reviews sensitive research.

Jeffries said the flu viruses Kawaoka creates in his lab at University Research Park on Madison’s West Side should be genetically modified to minimize the risk to humans. Kawaoka said doing that would undermine his studies, aimed at identifying troublesome flu viruses that could arise in nature.

(Continue . . .)

 

Late last week, the Journal Nature – which published Dr. Kawaoka’s H5N1 study in 2012 – published a cautionary opinion piece on the risks of doing this type of research.  Follow the link to read it in its entirety.

Nature | Editorial

Biosafety in the balance

An accident with anthrax demonstrates that pathogen research always carries a risk of release — and highlights the need for rigorous scrutiny of gain-of-function flu studies.

25 June 2014

The news last week of an accident involving live anthrax bacteria at the US Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, is troubling. Some 84 workers were potentially exposed to the deadly Ames strain at three CDC labs. But the incident will cause much wider ripples: it highlights the risks of the current proliferation of biocontainment labs and work on dangerous pathogens. If an accident can happen at the CDC, then it can happen anywhere.

(Continue . . . )

 

As you might imagine, speaking out against this sort of research isn’t exactly popular in academia, as these research projects can bring in large government grants, along with substantial publicity and prestige to Universities.

 

Suggestions that this sort of research be confined to biosafety level 4 facilities are often met with stiff resistance, since that would exclude most of the University based labs in this country.

 

Last November, in BMC Medicine: Containing Laboratory Escape Of Pandemic Viruses, we looked at a report that found the risks of seeing an accidental release from one of these labs is far from zero.

 

They calculated a .3% chance of release from any given lab each year, which works out to be roughly one every 100 years of lab operation.  With hundreds of of BSL-3 and BSL-4 labs around the world, the odds of seeing an accident in any given year somewhere in the world go up substantially.

While one can certainly argue with the methodologies used to come up with estimates for future events, we do know that between 2003 and 2009, US government laboratories had 395 incidents that involved the potential release of select agents  (see CIDRAP News  report Report: 395 mishaps at US labs risked releasing select agents).

 

While only 7 related infections were reported, this does add weight to the concerns being expressed by GOF research critics.   As does the most recent breach at the CDC lab in Atlanta.

 

For more background on all of this, you may wish to revisit a presentation by Dr. Marc Lipsitch on the the risks of these types of experiments from last September, while last December (see The Call For Urgent Talks On `GOF’ Research Projects), we saw  a letter – signed by 56 scientists – and published both in SciAm and the journal Nature - calling for `urgent talks’ over the future course of GOF research on influenza viruses, and other pathogens.

 

And more recently, we’ve seen the debate renewed, first in the pages of PLoS Medicine last month:

 

Lipsitch & Galvani: GOF Research Concerns

 

The debate then moved to CIDRAP News, where Kawaoka & Fouchier responded to this paper:

Experts call for alternatives to 'gain-of-function' flu studies

 

And most recently, a response back by Lipsitch & Galvani, again at CIDRAP.

 

COMMENTARY: The case against 'gain-of-function' experiments: A reply to Fouchier & Kawaoka

Marc Lipsitch, DPhil, and Alison P. Galvani, PhD

 

Unfortunately, despite the ongoing debate, this issue doesn’t seem to be any closer to resolution than it was two and half years ago when the fate of the Fouchier & Kawaoka H5N1 papers was still in doubt.

Keeping Our Eyes On The Prize Pig

Credit Wikipedia

 

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To give you an idea of how rapidly things change in the world of emerging infectious diseases, two summers ago (June 2012), no one had ever heard of the MERS coronavirus, the H7N9 avian flu virus was still 8 months away from breaking out in China, and avian H5N8, H10N8, H6N1 and H5N6 weren’t on anyone’s radar screen.

 

Aside from the perennial concerns over change in transmissibility of H5N1 virus, our primary emerging disease concerns that summer lay in a major outbreak of West Nile Virus (see DVBID: 2012 Record Number Of West Nile Fatalities), and an outbreak of human infection with variant influenza  contracted from show pigs displayed at county and state fairs. 

 

The CDC describes Swine Variant viruses in their Key Facts FAQ.

What is a variant influenza virus?

When an influenza virus that normally circulates in swine (but not people) is detected in a person, it is called a “variant influenza virus.” For example, if a swine origin influenza A H3N2 virus is detected in a person, that virus will be called an “H3N2 variant” virus or “H3N2v” virus.

Although the actual number of human variant flu infections that occur each year is unknown, the CDC has reported 1 or 2 cases each year since 2005. In 2010, that number jumped to 8, and in 2011, to 12. During the summer of 2012 more than 300 cases were recorded across the United States, and nearly all were linked to contract with pigs displayed at county and state fairs that summer.

 

Last year we only saw a handful of cases, but with state and county fair season once again upon us (it runs June-November around the nation) the potential exists for seeing cases again this summer and fall. 

 

While fairs have instituted inspections for any signs of illness in livestock – as we’ve discussed previously (see Asymptomatic Pigs: Revisited) - pigs can carry this virus without showing any outward signs of infection.

 

Swine are highly susceptible to a variety of flu viruses (human, swine, avian) - and can serve as `mixing vessels’, allowing viruses to reassort into new hybrid strains, a topic well covered by Helen Branswell a few years ago in a SciAm article called called Flu Factories.

 

.

Some of my earlier blogs on swine variant influenza include: H3N2v: When Pigs Flu , You Say You Want An Evolution? & The (Swine) Influenza Reassortment Puzzle.

 

These swine variant strains are – like the 2009 H1N1 pandemic virus – reassortants, that continue to circulate (and evolve) in swine herds.  Starting in 2011, the H1N1v virus was found to have acquired the M (matrix) gene from the 2009 H1N1 pandemic virus. Since then, this M gene has been showing up regularly in all three swine variant viruses (H1N1v, H1N2v, H3N2v).

 

The CDC has speculated that `This M gene may confer increased transmissibility to and among humans, compared to other variant influenza viruses.’

 

The concern with these variant swine flu infections, as it is with any animal flu that jumps to humans, is that it gives the virus another opportunity to better adapt to human physiology. While humans have a long history of exposure to seasonal H3N2 flu viruses, research has shown only limited community immunity to these variant strains (see CIDRAP: Children & Middle-Aged Most Susceptible To H3N2v).

 

The good news is that while some limited community transmission of these variant flu strains appears to have occurred during the summer of 2101, sustained and efficient human-to-human transmission did not, and for the most part, the virus only caused mild to moderate illness.

 

But as we’ve seen so often in the past, things can change quickly in the world of infectious diseases.

 

So while Chikungunya, West Nile Virus and MERS will be getting the bulk of the headlines this summer,  public health officials will also be on the lookout for any new swine variant infections - and more importantly - for any signs that the behavior of the virus has changed.

 

In the meantime, the CDC offers this advice for those planning to visit the fair this year:

 

Exhibitors of swine, and those in charge of the venue, will want to consult  Guidance Associated with Fairs.

PAHO Chikungunya Update & Videos

Aedes Albopictus – Asian Tiger Mosquito

 

 

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Up until about a decade ago, Chikungunya was a rarely seen mosquito-borne virus pretty much limited to central and eastern Africa.  All of that changed in 2005 when it jumped to Reunion Island in the Indian Ocean, where it reportedly infected about 1/3rd of that island’s population (266,000 case out of  pop.770,000) in a matter of a few months.

 

From there, apparently aided and abetted by a recent mutation that allowed it to be carried by the Aedes Albopictus `Asian tiger’ mosquito (see A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential), it quickly cut a swath across the Indian ocean and into the Pacific. 

 

That is, until about six months ago, when one (or more) infected travelers apparently arrived on the French Part of St. Martins, introducing the virus into the local mosquito population.  On December 10th there were 2 confirmed, 4 probable and 20 suspected cases of chikungunya on the island. 

 

A short six months later, and the virus has spread across nearly the entire Caribbean basin, and has infected at least 260,000 people. 

Further expansion into North, South, and Central America seems but a matter of time.

 

A textbook example of what happens when a emerging infectious disease enters an immunologically naive population under favorable environmental conditions.  And the reason why we talk so much about the global spread of disease in this age of globalization and increased international travel  (see The Global Reach Of Infectious Disease).

Yesterday’s update from PAHO has already made headlines, as it shows an increase of roughly 93,000 cases over the previous week (a 40% increase), although not all of those cases emerged over the past 7 days. 

 

As you’ll see by the chart below, some countries are still several weeks behind in their reporting, and surveillance and reporting in some regions is `sub-optimal’, so these numbers are still likely a significant undercount.

 

 

This week the WHO/PAHO Youtube Channel released several short videos showing the effects of the illness. The first one is more of a slide show, but shows the symptoms of the disease.  The second video on Clinical Management is in Spanish, but has English sub-titles. 

 

 

There are currently at total of five videos in their CHIKUNGUNYA Playlist.

 

For more on how the State of Florida and the CDC are working to meet the challenges of chikungunya, you may wish to revisit:

 

Florida Prepares For Chikungunya 

Chikungunya Update & CDC Webinar Online

CDC HAN Advisory On Recognizing & Treating Chikungunya Infection

 

 

California DPH: Whooping Cough Epidemic Continues

Credit CDC

 

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California’s Whooping cough (Pertussis) outbreak – which officials declared as an epidemic two weeks ago -  continues to grow at a rate comparable to what we saw in 2010 – when the last major epidemic broke out. 

 

Over the past two weeks, 1100 new cases have been identified, including one fatality.

Pertussis report 2014-6-24

Almost eliminated in this country by the mid-1970s, Whooping cough has made a worrisome comeback over the past decade, with roughly 50,000 cases reported in 2012. The reasons behind these increases are complex, and not entirely understood, but some factors are believed to be:

 

• lower vaccination uptakes in children and adults
• the move away from whole cell pertussis vaccines to safer (but somewhat less protective) acellular vaccines in the 1990s
• evolutionary changes in the Bordetella pertussis bacteria.

Whooping cough outbreaks are cyclical, and we see localized outbreaks increase every three to five years.  The last `big’ year for Whooping cough in California was 2010, but  2014 is shaping up to be another bad year.   This from the California Department of Public Health.

 

California Whooping Cough Epidemic Continues

Date: 6/27/2014

Number: 14-060

Contact: Anita Gore, (916) 440-7259

SACRAMENTO

1,100 new cases have been reported in the last two weeks

The number of pertussis (whooping cough) cases in the state continues to climb, Dr. Ron Chapman, director of the California Department of Public Health (CDPH) and state health officer reported today.

In the past two weeks, 1,100 new cases of pertussis have been reported to CDPH. This brings the total number of cases to 4,558 (as of June 24). This far surpasses the total number of reported cases in 2013, which was 2,532. One additional infant has died, bringing the total number of infant deaths to three. Children four-months-old or younger account for nearly 2/3 of all pertussis hospitalizations.

“Infants are at the greatest risk of illness and death from pertussis,” said Dr. Chapman. “Vaccination is the best form of protection. We’re encouraging all parents to vaccinate their children, and for pregnant women to be vaccinated to protect their babies. This will ensure maximum protection against this potentially fatal disease.”

The Tdap vaccination for pregnant women is the best way to protect infants who are too young to be vaccinated. All pregnant women should be vaccinated with Tdap in the third trimester of each pregnancy, regardless of previous Tdap vaccination. Inoculated women pass immunity to their unborn babies that protect them until they can be vaccinated. Infants should be vaccinated as soon as possible. The first dose of pertussis vaccine can be given as early as 6 weeks of age.

Older children, pre-adolescents and adults should also be vaccinated against pertussis according to current recommendations.

“It’s particularly important that people who will be around newborns also be vaccinated,” added Dr. Chapman. “This includes babysitters, older siblings, parents and grandparents. When those people are vaccinated they will help protect infants who are too young for immunization.”

The symptoms of pertussis vary by age. For children, pertussis typically starts with a cough and runny nose that can last up to two weeks. The cough then worsens and turns into rapid coughing spells that end with a tell-tale “whooping” sound. Young infants may not have typical pertussis symptoms and may have no apparent cough. Parents describe episodes in which the infant’s face turns red or purple. For adults, pertussis may simply be a cough that lasts for several weeks.

CDPH is working closely with local health departments, schools, media outlets and other partners to inform the general public about the importance of vaccination against pertussis.

WHO To Convene Emergency Meeting On Ebola Next Week

Credit @UNMILNews

 

 

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Although their intent to hold an emergency meeting on the Ebola crisis in Western Africa was telegraphed yesterday (see Ebola In West Africa Now `a sub-regional crisis’ – WHO), we now have details on when, and where it will be held.

 

The following media advisory was emailed to journalists earlier today.

 

 

WHO calls emergency sub-regional Ministerial meeting in Accra, Ghana to tackle the on-going Ebola virus in West Africa

In an effort to interrupt further spread of the Ebola virus in the shortest possible time, the World Health Organization is convening a special meeting of Ministers of Health of eleven (11) countries and partners involved in the Ebola outbreak response in Accra, Ghana from 2-3 July 2014 to discuss the best way of tackling the crisis collectively as well as develop a comprehensive inter country operational response plan

WHAT:  Press conference and sub-regional ministerial meeting to address solutions for ending the Ebola virus outbreak that has been spreading in Guinea, Liberia and Sierra Leone since March 2014.    

WHEN: Press Conference will be held on Thursday, 3 July 2014, 1730-1830
In addition, two sessions of the meeting will be open to the media:  Wed, 2 July 2014, 0900-1000 and Thursday, 3 July, 1400-1700.  These sessions will focus on the situation, risk assessment, testimonials from Ebola survivors, a summary of technical discussions and a declaration of the operational plan.  

WHO:  Ministers of Health from: Cote d’Ivoire, DR Congo, Gambia, Ghana, Guinea, Guinea Bissau, Liberia, Mali, Senegal, Sierra Leone and Uganda. Partners  involved in the outbreak, extractive industry from the affected countries, UN Agencies, CDC , DFID, EU, ECHO, Institute Pasteur, IFRC, MSF USAID, and WAHO

WHERE:  La Palm Golden Beach Hotel, Accra, Ghana

WHY:  The emergence of Ebola virus disease outbreak in West Africa threatens regional and global public health security.  The World Health Organization has so far provided technical assistance through the deployment of over 150 multidisciplinary team of experts involved in a range of outbreak response activities such as surveillance, communication and social mobilization, infection control, logistics, data management.

Despite this, there has been significant increase in the number of daily reported cases and deaths of Ebola as well as newly affected districts over the last three weeks.  As of 23 June 2014, the total cumulative number of cases reported was 635 out of which 399 died. This makes the on-going Ebola outbreak, the largest in terms of the number of cases and deaths as well as geographical spread.

Decisions taken at this meeting will be critical in addressing the current and future outbreaks.

WWW.AFRO WHO.INT     
Space is limited. For more information or to RSVP, please contact:

Eurosurveillance: Genetic Tuning Of Avian H7N9 During Interspecies Transmission

 

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This week’s Eurosurveillance bonanza of avian flu transmission & evolution papers has more than enough good stuff to keep us busy reading for hours. All of these papers are of great interest, but one in particularly grabbed my attention, mainly due to the potential impact of its findings.

A study that looks at the continual evolution of the H7N9 virus in Mainland China.

 

To recap: in February of last year a new and dangerous avian influenza virus (H7N9)  jumped to humans in Eastern China, although we did not learn about it until the end of March (see More Details Emerge On Shanghai H7N9 Case). Unlike many of the other avian influenza viruses we’ve seen - this virus produced no visible signs of illness in poultry - making it particularly difficult to detect and control.

Benign in poultry, but not in humans, H7N9 often produces a severe form of pneumonia.  One that has killed roughly 30% of those known to have been infected.

 

The only saving grace has been this virus has not yet achieved the ability to transmit efficiently from one human to another. The vast majority of human cases appear to be the result of direct exposure to infected birds or to their environment.

 

In that first wave about 130 human cases emerged, tapering off only after aggressive controls on live bird markets were imposed in April and May of 2013 (see The Lancet: Poultry Market Closure Effect On H7N9 Transmission). After a quiescent summer, colder fall and winter temperatures brought with it a resurgence in the number of human cases, with the second wave roughly double the size of the first (cite).

Two Waves of H7N9  - Credit Hong Kong’s CHP

 

A month ago, in EID Journal: H7N9 As A Work In Progress, we looked at a study that found the H7N9 avian virus continues to reassort with local H9N2 viruses, making the H7N9 viruses that circulated in wave 2 genetically distinct from those that were seen during the 1st wave.

As we’ve discussed before, the genetic contributions from the avian H9N2 virus appear to be significant. 

 

Of the three avian flu viruses we are currently watching with the most concern – H5N1, H7N9, and H10N8 – all  share several important features (see Study: Sequence & Phylogenetic Analysis Of Emerging H9N2 influenza Viruses In China):

• They all first appeared in  Mainland China
• They all  have come about through viral reassortment in poultry
• And most telling of all, while their HA and NA genes differ - they all carry the internal genes from the avian H9N2 virus

 

It turns out the relatively benign and ubiquitous H9N2 is actually a fairly promiscuous virus, as bits and pieces of it keep turning up in new reassortant viruses.  See PNAS: Reassortment Of H1N1 And H9N2 Avian viruses & PNAS: Reassortment Potential Of Avian H9N2 for some earlier looks at H9N2’s active social life.

 

Today, in research from a group of scientists working for China’s National and Provincial CDCs, we learn that the genetic diversity of the H7N9 virus is even greater than previously described, and that continual reassortment with the H9N2 virus, along with passage through a variety of host species, appears to be influencing its ongoing evolution.

 

A process the authors call `genetic tuning’.

 

Non-scientists will likely find this article tough sledding (parts certainly were for me), as it is more than a little technical.  It is, however, a fascinating paper. 

 

With apologies in advance to any real scientists who may be reading this - come back after the link and abstract - and I’ll do my best to hack through some of the tall grass and go over a few of the highlights.

 

 

          Eurosurveillance, Volume 19, Issue 25, 26 June 2014

Research articles

Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013

D Wang^1,2, L Yang^1,2, R Gao¹, X Zhang³, Y Tan⁴, A Wu⁵, W Zhu¹, J Zhou¹, S Zou¹, Xiyan Li¹, Y Sun⁶, Y Zhang⁷, Y Liu⁸, T Liu⁹, Y Xiong¹⁰, J Xu¹¹, L Chen¹², Y Weng¹³, X Qi¹⁴, J Guo¹, Xiaodan Li¹, J Dong¹, W Huang¹, Y Zhang¹, L Dong¹, X Zhao¹, L Liu¹, J Lu¹, Y Lan¹, H Wei¹, L Xin¹, Y Chen¹, C Xu¹, T Chen¹, Y Zhu¹, T Jiang⁵, Z Feng¹⁵, W Yang¹⁵, Y Wang¹⁵, H Zhu¹⁶, Y Guan¹⁶, G F Gao¹⁵, D Li¹, J Han¹, S Wang¹, G Wu¹, Y Shu ()¹

Date of submission: 28 July 2013

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A novel avian influenza A(H7N9) virus causing human infection emerged in February 2013 in China. To elucidate the mechanism of interspecies transmission, we compared the signature amino acids of avian influenza A(H7N9) viruses from human and non-human hosts and analysed the reassortants of 146 influenza A(H7N9) viruses with full genome sequences.

We propose a genetic tuning procedure with continuous amino acid substitutions and reassorting that mediates host adaptation and interspecies transmission.

When the early influenza A(H7N9) virus, containing ancestor haemagglutinin (HA) and neuraminidase (NA) genes similar to A/Shanghai/05 virus, circulated in waterfowl and transmitted to terrestrial poultry, it acquired an NA stalk deletion at amino acid positions 69 to 73. Then, receptor binding preference was tuned to increase the affinity to human-like receptors through HA G186V and Q226L mutations in terrestrial poultry. Additional mammalian adaptations such as PB2 E627K were selected in humans.

The continual reassortation between H7N9 and H9N2 viruses resulted in multiple genotypes for further host adaptation. When we analysed a potential association of mutations and reassortants with clinical outcome, only the PB2 E627K mutation slightly increased the case fatality rate. Genetic tuning may create opportunities for further adaptation of influenza A(H7N9) and its potential to cause a pandemic.

 

 

What these researchers did was to collect specimens (as well as clinical and epidemiological information) from human H7N9 cases, along with avian and environmental samples from areas where human cases were identified. 

 

From this they assembled 173 influenza A(H7N9) viruses (103 human and 70 non-human) and analyzed them to try to determine how (and from where) they had evolved.

 

Remarkably, out of 146 H7N9 viruses with full genome sequences, they detected at least 26 seperate genotypes, mostly from the first wave in 2013. Of those 26, twenty were only detected once or twice, suggesting they were transient, and perhaps not as `biologically fit’ as some of the other genotypes.

 

Based on their observations, the authors propose that `a genetic tuning procedure with continuous amino acid substitutions and reassortations, mediates the host adaptation and interspecies transmission of H7N9 viruses (Figure 4)’.

 

Essentially, they describe two processes that they believe  facilitate the evolution and adaptation of the virus.  Processes that may be `tuning’ the virus in the direction of  a `human-adapted’ pathogen.

 

The first is ongoing reassortment with H9N2 viruses.  

 

Reassortment occurs when two different influenza viruses infect the same host simultaneously.  In `close quarters’ they can swap out gene segments, and if they hit the right combination, generate a successful hybrid virus. 

 

Reassortment also produces the biggest, and most abrupt changes in the virus, and is believed the mechanism behind the emergence of many pandemic viruses.  You can view a short (3 minute) video from NIAID on reassortment here.

 

Based on 26 distinct genotypes described in this paper, the reassortment of H7N9 appears to be a vigorous, and ongoing, process. The greatest concentration of genotypes was found in the Yangtze river delta (see map below), suggesting this may be the region where the virus first emerged.

 

The second evolutionary path occurs as these reassortant viruses passage through different species and pick up specific amino acid changes.

 

When a virus infects a cell, it immediately sets upon making thousands of copies of itself in order to spread the infection throughout the host. Single-stranded RNA influenza viruses are notoriously sloppy replicators, so invariably, some of these viral copies will carry small transcription errors (in the form of amino acid substitutions).

 

Most of these `variants’  will prove either neutral or perhaps even detrimental to the survival and propagation of the virus, but occasionally a helpful change occurs (positive selection) that increases the `biological fitness’ of the virus  – at least for the current host species. 

 

Viral progeny that are the best suited for their host usually win the replication wars, and soon outnumber and overrun less `fit’ variants. As a result, a better `adapted’ virus can emerge.  And if those adaptations help it jump to another host species, it is a viral win-win.

 

The authors point out that the `mixed bird’ environment of live markets may have helped H7N9’s evolution along, as it was able to spread stealthily, and without interruption, among a variety of species – picking up useful adaptations along the way.

 

As an example, avian flu viruses bind preferentially to the α2-3 receptor cells found in the gastrointestinal tract of birds.  But the H7N9 virus also binds (albeit, not as robustly) to human α2-6 human receptor cells, which are found in mammalian tracheas and upper airways (see Nature: Receptor Binding Of H7N9).

. 

 

The authors speculate H7N9’s partial affinity to α2-6 receptor cells may have been picked up when it passaged through quail or pigeons, which are known to carry both types of cells.

 

And even once it infects man, the H7N9 virus continues to adapt and evolve, with the PB2 E627K mutation detected in a large number of human isolates.  E627K and/or D701N mutations in the PB2 protein are considered critical for mammalian adaptation of avian influenza viruses, as they allow the virus to replicate efficiently in the lower temperatures found in the upper airway.

 

As H7N9 reassorts and passages through different species – a process the authors call `genetic tuning’ - it continues to evolve, and reinvent itself.  Meaning that the virus we get next fall , winter, or spring may not act like the virus we saw during the first two waves. 

 

Obviously, I’ve just covered some of the highlights, and then, only with the broadest of strokes.  I’m certain many of my readers will want to read the entire paper.  But to close, I’ll let the authors speak to the significance of their findings.

 

Genetic tuning not only mediated species switching, but may also allow the virus to adapt so that it infects humans more easily and transmits among people more efficiently. Recently, Malaysia reported its first human case of influenza A(H7N9), imported from Guangdong province, China [28]. Rapid transportation and frequent travelling have made it possible to transfer the virus from China to other regions.

Overall, due to the genetic tuning procedure, the potential pandemic risk posed by the novel avian influenza A(H7N9) viruses is greater than that of any other known avian influenza viruses. A response to this threat requires the combined effort of different sectors related to human health, poultry and wild birds, as well as vigilance and co-operation of the world.

Eurosurveillance: Papers on potential transmissibility and evolution of avian influenza A viruses

 

 

# 8787

 

 

While I’ll probably return later today or tomorrow with a deeper look at some of these papers (after I’ve had a chance to actually read them), but for now I’ll just post the links to what looks like an interesting bunch of avian flu centric research.

 

 

Eurosurveillance, Volume 19, Issue 25, 26 June 2014

Table of Contents

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Editorials

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Epidemiological and genetic investigations of human-to-human transmission of zoonotic influenza viruses

by S Herfst, R Fouchier

Surveillance and outbreak reports

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Two clustered cases of confirmed influenza A(H5N1) virus infection, Cambodia, 2011

by N Chea, SD Yi, S Rith, H Seng, V Ieng, C Penh, S Mardy, D Laurent, B Richner, T Sok, S Ly, P Kitsutani, N Asgari, MC Roces, P Buchy, A Tarantola

Transmission of avian influenza A(H7N9) virus from father to child: a report of limited person-to-person transmission, Guangzhou, China, January 2014

by XC Xiao, KB Li, ZQ Chen, B Di, ZC Yang, J Yuan, HB Luo, SL Ye, H Liu, JY Lu, Z Nie, XP Tang, M Wang , BJ Zheng

Research articles

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Limited human-to-human transmission of avian influenza A(H7N9) virus, Shanghai, China, March to April 2013

by J Hu, Y Zhu, B Zhao, J Li, L Liu, K Gu, W Zhang, H Su, Z Teng, S Tang, Z Yuan, Z Feng, F Wu

Genetic tuning of the novel avian influenza A(H7N9) virus during interspecies transmission, China, 2013

by D Wang, L Yang, R Gao, X Zhang, Y Tan, A Wu, W Zhu, J Zhou, S Zou, X Li, Y Sun, Y Zhang, Y Liu, T Liu, Y Xiong, J Xu, L Chen, Y Weng, X Qi, J Guo, X Li, J Dong, W Huang, L Dong, X Zhao, L Liu, J Lu, Y Lan, H Wei, L Xin, Y Chen, C Xu, T Chen, Y Zhu, T Jiang, Z Feng, W Yang, Y Wang, H Zhu, Y Guan, GF Gao, D Li, J Han, S Wang, G Wu, Y Shu

Genesis of the novel human-infecting influenza A(H10N8) virus and potential genetic diversity of the virus in poultry, China

by W Qi, X Zhou, W Shi, L Huang, W Xia, D Liu, H Li, S Chen, F Lei, L Cao, J Wu, F He, W Song, Q Li, M Liao, M Li

Lightning Safety Awareness Week June 22nd - 28th

Credit NOAA 

 

 

# 8786

 

One of the indelible lessons I learned as a young paramedic – working as I did in the lightning capital of North America (Tampa Bay) – was the absolute folly of standing on wet grass, while wearing steel spiked shoes (this was in 1973 or 1974), and then hoisting a metal rod above one’s head on a hot, humid, and overcast summer’s day.

Poor Charlie (or whatever his name was), undoubtedly never saw it coming.  

 

But he probably should have, as every year lightning claims several dozen lives in the United States, and injures hundreds more, often in open spaces like golf courses and beaches. 

 

While Florida leads the nation in Lightning deaths each year, there really isn’t anywhere you can go in North American that is immune.

Credit Vaisala Inc.

 

Fatalists who think that if lightning gets them, they’ll never know it, should understand that only about 10% of those struck by lightning each year die. Among those that survive, many experience serious, and sometimes life long injury or disability.

 

This week NOAA is promoting  Lightning Safety Awareness Week: June 22-28, 2014. Below you’ll find links to some of their information.

 

Summer is the peak season for one of the nation's deadliest weather phenomena--lightning. Though lightning strikes peak in summer, people are struck year round. In the United States, an average of 51 people are killed each year by lightning, and hundreds more are severely injured.

Safety: Learn what you need to do to stay safe when thunderstorms threaten.

Victims: Learn what happens to people who are struck by lightning and look at fatality statistics for the U.S.

Science: Learn how thunderstorms develop and what happens during a lightning discharge.

Myths and Facts: Get answers to many of the questions you have always wondered about

Teachers: find curriculum guides, presentations games, activities, and more. Kids: Download games, videos, coloring pages and other fun stuff.

More Resources: Download toolkits, posters, pamphlets, and other information to help communities, organizations, and families stay safe from the dangers of lightning

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Egypt Reports H5N1 Case

 

 

# 8785

 

Although we saw a couple of media reports over the winter and spring on suspected H5N1 cases in Egypt ( here and here), it has been well over a year since the last official H5N1 case was reported from Egypt. (see correction below).

 

My thanks to Sharon Sanders for correcting my faulty memory by pointing out that two cases were confirmed in March, 2014.  (WHO report)

We have seen ongoing reports of outbreaks in poultry, however, and so we know the virus continues to circulate widely.

Egypt’s Ministry of Health Website is off line (and has been the last few times I’ve tried to access it), but local media is reporting that the MOH has announced the first case since 2013.

This English translation from MENA, the Middle East News Agency of the original Arabic report  from http://www.masrawy.com:

 

Health Ministry: Man catches bird flu in Minya

Thu, 26/06/2014 - 12:42

The Ministry of Health and Population announced that a 34-year-old man in Minya has been inflected with the A/H5N1 virus known as bird fllu.

It added the patient was currently on a ventilator at hospital and his condition was unstable.

The ministry said in a statement on Wednesday evening that it has taken preventive measures once the case was suspected and isolated the patient in Minya Fever Hospital. A sample for the patient was sent to Cairo labs for analysis and his infection with bird flu was confirmed according to results.

A team from the Preventive Medicine Sector was dispatched to the patient's residence in Minya, the statement said. His wife and children  were inspected and they are in good health and have no bird flu symptoms, according to the statement. They will be reinspected after 10 days, it added.

(Continue . . .)

 

 

After peaking in 2011 (39 cases, 15 deaths), the number of H5N1 cases reported out of Egypt has dropped markedly, with only 4 cases (3 deaths) reported in 2013.  

 

When confirmed by the WHO, today’s case should bring that nation’s official total to 176 cases.

Reporting, both by the government and by the media, has been highly constrained since the `Arab Spring’ revolution which began in 2011, and so there are concerns as to just how good the surveillance and reporting coming out of Egypt on H5N1 (and other health issues) really is.

Ebola In West Africa Now `a sub-regional crisis’ – WHO

Ebola Virus - Credit CDC

 

 

#8784

 

Despite local and International attempts to control it over the past three months, the Ebola epidemic in West Africa continues unabated, with scores of new cases being reported each week. With well over 600 cases (suspected & confirmed) reported across three nations, this outbreak is easiest the largest both in numbers and geographic spread.

 

Exact numbers are always hard to ascertain, regardless of where a disease outbreak occurs, but is likely doubly so in Western Africa, where surveillance and medical resources are limited.

 

Yesterday, the World Health Organization Regional Office for Africa released a statement (see Ebola epidemic in West Africa: WHO urges comprehensive inter-country response) calling Ebola `no longer a country specific outbreak but a sub-regional crisis that requires firm action by Governments and partners', and announcing :

`A special meeting of Ministers of Health of eleven (11) countries and partners involved in the Ebola outbreak response in Accra, Ghana from 2-3 July 2014 to discuss the best way of tackling the crisis collectively as well as develop a comprehensive inter country operational response plan.

Today the WHO has released the following statement:

 

Ebola Challenges West African countries as WHO ramps up response

Report from World Health Organization

Published on 26 Jun 2014

Geneva- The emergence of an Ebola virus disease outbreak in West Africa in 2014 has become a challenge to the three countries involved, as the Governments of Guinea, Liberia and Sierra Leone work intensively with WHO and other partners to ramp up a series of measures to control the outbreak. Since March 2014, more than 600 cases of Ebola and over 390 deaths have been reported in Guinea, Liberia and Sierra Leone. While the number of suspected, probable and confirmed cases and deaths changes rapidly, the outbreak is causing concern among health authorities because the deadly disease is being transmitted in communities and in health-care settings, and it has appeared in cities as well as rural and border areas. The disease, which causes severe hemorrhaging and can kill up to 90% of those infected, is spread by direct contact with the blood and body fluids of infected animals or people.

WHO, the Global Alert and Response Network (GOARN), and its partners are providing guidance and support and have deployed teams of experts to West African countries and to WHO’s African Regional Office in Brazzaville, Congo.

These experts include:

• Epidemiologists to work with the countries in surveillance and monitoring of the outbreak.
• Laboratory experts to support mobile field laboratories for early confirmation of Ebola cases.
• Clinical management experts to help health facilities treat affected patients.
• Infection and prevention control experts to help the countries stop community and health-care facility transmission of the virus.
• Logisticians to dispatch needed equipment and materials.
• Social mobilization and risk communications teams to help health officials deliver appropriate messages about how to report, handle, and treat Ebola cases.

Recognizing that a coordinated regional response is essential, WHO is convening the leading health authorities from the affected and nearby countries in Accra, Ghana July 2 to 3, to agree on a comprehensive operational response to control the Ebola outbreak. A wide range of partners have been invited, and Ministries of Health of Guinea, Liberia, and Sierra Leone will report on their preventive and control measures, contact identification and tracing; case management; infection and prevention control; social mobilization; and situation reports.

The countries are working to bring supportive care to the ill, inform affected communities of recommended practices, trace contacts of infected patients, control infections in health care settings, and taking other measures to control the outbreak. Despite their progress in implementing preventive and control measures, health authorities still face challenges in curbing the spread of the outbreak, and will discuss these at the Accra meeting .

The latest numbers, which change as cases are discovered, investigated, or discarded, are:

Guinea has reported some 396 cases and 280 deaths,

Sierra Leone has 176 cases and 46 deaths,

Liberia reports 63 cases and 41 deaths.

 

 

Sharp-eyed readers may notice that the number of deaths reported out of Sierra Leone has dropped from 78 to 46.  This is apparently due to a change in the way that Sierra Leone chooses to report cases, as was explained in an email from the WHO this morning:

 

While there were 78 deaths, only 46 are listed because of a change in the reporting methodology on the part of Sierra Leone. The new method does not include probable or suspect deaths, only deaths of laboratory-confirmed cases.

While this may look better on Liberia’s official tally sheet (and they may well have legitimate reasons for changing their criteria), it is generally preferable when everyone uses the same methodology.   

Referral: Are MERS Cases In Saudi Arabia & UAE Linked To Camel Imports?

Credit VDU Blog 

 

# 8783

 

One of the great advantages (and pleasures) of following scientists on Twitter is you get to hang around – like a fly on the wall – while they discuss and hash out theories, possibilities, and SWAGs on various issues.   On the downside, the 140 character format often leads to cryptic conversations.

 

So I’m very pleased to see that @Influenza_bio (A Biologist) has returned to Dr. Ian Mackay’s VDU blog today with another guest article – one  that fleshes out a running twitter conversation (with graphics) from earlier this week.

 

You may recall that @Influenza_bio previously penned a couple of terrific guest articles at VDU, including Watching zoonoses evolve... and Can we believe every H7N9 seroprevalence study we see? – both of which are absolutely worth taking the time to read.

 

Today’s offering is a lengthy, step-by-step analysis of the potential role that imported camels may play in the spread of MERS in Saudi Arabia and the UAE.   While the author describes it as a `very speculative hypothesis’, it is also both well reasoned, and well presented.

 

Follow the link to read:

 

 

Thursday, 26 June 2014

Are MERS cases in Saudi Arabia and the UAE linked to camel imports?

Special Guest writer: @influenza_bio

Looking at the history of MERS coronavirus infections to date, many puzzling questions come to mind.

Evidence of MERS infection has been detected in dromedary camels from Spain to Egypt to the Arabian Peninsula. Why have we seen human cases arise only in a handful of countries in the Arabian Peninsula?

Why have nearly all MERS cases originated in Saudi Arabia (KSA)?

As of June 22, 2014, 718 cases are thought to have been contracted in KSA. The UAE, a distant second, has had 69 cases. Jordan has had 17; Qatar has had 9 (although 1 had a travel history to KSA), Kuwait 3, Oman 2 and Yemen 1. All of these countries have a lot of camels.

(Continue . . . )

 

 

Given the quality of these first offerings from @Influenza_bio, I look forward to future installments.