Tuesday, February 09, 2016

Upcoming COCA Call: Influenza Activity and Clinical Recommendations


Despite an unusually mild flu American season so far (see map above), there are subtle hints that this quiet winter may yet yield some surprises, as heavy flu activity is just now starting to spread into Western Europe.

For several weeks we've been watching reports of unusually severe H1N1pdm09 flu in Russia and Ukraine (see An Update On The Russian Influenza Epi Report), including reports of thousands of schools closed.

Russian epidemiological reports for the past few weeks have included information on a new subgroup of clade 6B of H1N1pdm09, and yesterday the ECDC issued a statement saying it was `unclear if the emergence of a new genetic subgroup of A(H1N1) virus might compromise vaccine effectiveness.' 

We should get a new update from the  WHO National Influenza Centre Of Russia in the next couple of days.

Meanwhile, although flu activity remains generally low in the United States, the CDC has received word of a few sporadic, severe flu cases which they announced last week in a  HAN Advisory: Severe Influenza Illness Reported.

Although a late season surge in North American influenza is by no means assured, it can't be discounted either.

Next week the CDC has scheduled a COCA call to bring clinicians up to date on the current flu season, and the latest recommendations for treatment and management of severe influenza.

Date:Tuesday, February 16, 2016
Time:2:00 - 3:00 pm (Eastern Time)
Participate by Phone:

  • 800-857-9697 (U.S. Callers)
  • 212-287-1833 (International Callers)
Participate by Webinar: https://www.mymeetings.com/nc/join.php?i=PW6927485&p=4396514&t=c


Fiona Havers, MD, MHS
Medical Officer
Influenza Division
National Center for Immunization and Respiratory Diseases
Centers for Disease Control and Prevention


Influenza activity is increasing across the United States and CDC has received several reports of severe influenza illness. Since October 2015, CDC has detected co-circulation of multiple seasonal influenza virus types and sub-types, with recent reports of severe respiratory illness among young- to middle-aged adults with H1N1pdm09 virus infection. During this COCA Webinar, clinicians will learn about 2015-2016 influenza activity, hear an overview of CDC’s current recommendations for vaccination and antiviral medications, and gain insight into data supporting the recommendations.


  • Describe the current status of influenza activity in the United States
  • Discuss the circulating influenza strains seen this season and the implications for clinicians
  • Discuss the use of influenza diagnostic tests and their role in clinical care
  • Discuss antiviral treatment and implications for patient evaluation, treatment and testing

ECDC Zika/Microcephaly/GBS Rapid Risk Assessment - 2nd Update


Three weeks after the first ECDC Rapid Risk Assessment On Zika Virus Epidemic we have a second update, and as we've come to expect from the ECDC, this 16 page document is both up to date, and feature-rich.

I've only included some small excerpts, so you'll want to download and reviewe the entire PDF. 

Rapid risk assessment: Zika virus disease epidemic: potential association with microcephaly and Guillain–Barré syndrome, Second update

08 Feb 2016
Available as PDF 


​This document assesses the risks associated with the Zika virus epidemic currently affecting countries in the Americas. It assesses the association between Zika virus infection and congenital central nervous system malformations, including microcephaly, as well as the association between Zika virus infection and the Guillain–Barré syndrome (GBS).

Main conclusions and options for response 
Considering the continued rapid spread of Zika virus in the Americas and Caribbean, the growing evidence of an association between Zika virus infection during pregnancy and adverse pregnancy outcomes, the association between Zika virus infection and post-infectious Guillain–Barré syndrome (GBS), and the risk of establishment of local vector-borne transmission in Europe during the 2016 summer season, EU/EEA Member States are recommended to consider the following mitigation measures.

• Travellers visiting countries where Zika virus is currently being transmitted should be made aware of the ongoing outbreak of Zika virus infection. A list of countries and territories with documented autochthonous transmission during the past two months is maintained on the ECDC website (see also Table 1).
• Travellers visiting these countries should use personal preventive measures based on protection against mosquito bites indoors and outdoors, especially from sunrise to sunset when mosquitoes are most active in biting. Such measures include:
− using mosquito repellent in accordance with the instructions indicated on the product label. DEET-based repellent is not recommended for children under three months of age but pregnant women can use it.
− wearing long-sleeved shirts and long trousers, especially during the hours when the type of mosquito that carries the Zika virus (Aedes) is most active.
− sleeping or resting in screened or air-conditioned rooms, otherwise use mosquito nets, even during the day.

• Pregnant women and women who are planning to become pregnant, and who are intending travel to affected areas, should discuss their travel plans and evaluate the risk with their healthcare providers and consider postponing their travel.
• Travellers with immune disorders or severe chronic illnesses should consult their doctor or seek advice from a travel clinic before travelling, and be given advice on effective prevention measures.
• There is evidence that Zika virus can be transmitted sexually through semen, and there are indications that Zika virus can be present in semen for several weeks after a man has recovered from a Zika virus infection. Travellers to Zika-affected areas should be advised that the risk of sexual transmission from an infected man to another person can be reduced by using condoms.
• Travellers showing symptoms compatible with Zika virus disease within three weeks of return from an affected area are advised to contact their healthcare provider and mention their recent travel.
• Pregnant women that have travelled in areas with Zika virus transmission should mention their travel during antenatal visits in order to be assessed and monitored appropriate
• Male travellers returning from areas with local transmission of Zika virus should consider using a condom with a female partner at risk of getting pregnant or already pregnant:
− for 28 days after their return from an active Zika transmission area if they have not had any symptoms compatible with Zika virus infection;
− for 6 months following recovery from a laboratory-confirmed Zika virus infection.
This precautionary advice is based on limited evidence and will be revised as more information becomes available.
Information to healthcare providers
• Ensure that Zika virus-infected patients in areas with Aedes mosquitoes take measures to avoid getting bitten during the first week of illness (insecticide-treated bed nets, screened doors and windows as recommended by PAHO/WHO).
• Increase awareness among health professionals who provide prenatal care of the possible association between Zika virus and microcephaly and adapt prenatal monitoring in accordance with the exposure to the vector.
In addition, due to the unprecedented size of the Zika virus epidemic, health services and practitioners should be alert to the possible occurrence of neurological syndromes (GBS and other neurological syndromes such as meningitis, meningoencephalitis and myelitis according to WHO/PAHO) and potential disease complications not yet described in the scientific literature and atypical clinical presentation among specific populations (i.e. children, the elderly, immunocompromised individuals and those with sickle cell disease).
This document also includes more specific options for substances of human origin, surveillance and preparedness

WHO Update: Guillain-Barré Syndrome (GBS) In Brazil and Martinique


Yesterday, in Guillain-Barre syndrome: The Other Zika Concern, we looked at the suspected - but as yet unproven - link between the recent arrival of Zika to the Americas and French Polynesia and reports of a concurrent rise in cases of Guillain-Barré Syndrome.  

Along the way we also looked at previous outbreaks and individual cases of GBS that have been attributed to a variety of causes, including some linked to arboviral infections like Dengue and Chikungunya.

In early 2014 in Zika, Dengue & Unusual Rates Of Guillain Barre Syndrome In French Polynesia we got our first clue that something unexpected was going on with Zika, and over the past couple of months we've seen reports of increased GBS in Brazil, Colombia, El Salvador, Suriname, and Venezuela - all countries where Zika has recently arrived.

Complicating matters, Zika isn't the only arbovirus circulating in these countries. Dengue has been around for decades, but Chikungunya only began to spread widely in the Americas in early 2014.
Many of those who are now falling victim to Zika have previously had CHKV and/or  Dengue (I-4), raising questions over the potential impact of concurrent or sequential infection.

And trying to compare the rates of GBS from previous years - when surveillance and reporting may not have been particularly thorough - to today, when doctors are actively looking for cases, can produce misleading numbers.

Still - just as with microcephaly in Brazil - something seems to be driving the rates of GBS substantially higher these seven countries.  And right now Zika - or perhaps Zika combined another factor - is at the top of the suspect list.

The World Health Organization published two GBS updates overnight, with the first - from Martinique - of particular interest because it describes two recent Guillain-Barré cases, both of whom have tested positive for the Zika virus

The update from Brazil describes major increases in GBS in some states, but stable rates (or even declines) in others, leaving us with an incomplete, and muddled picture.  As with the apparent increases in microcephalic births, there are still more questions than answers.

Guillain-Barré syndrome – France - Martinique

Disease Outbreak News
8 February 2016
On 25 January 2016, the National IHR Focal Point of France notified PAHO/WHO of 2 cases of Guillain-Barré Syndrome (GBS) in Martinique.

Details of the cases

  • The first case is a 19-year-old with onset of symptoms (paraesthesia of hands and feet) on 26 December. Urine samples, which were taken on 7 January, tested positive for Zika virus by reverse transcription polymerase chain reaction (RT-PCR) at the University Hospital of Martinique. Currently, the patient is being intubated and ventilated in an intensive care unit.
  • The second case is a 55-year-old who was admitted to an intensive care unit on 21 January. On the same day, urine samples were collected from the patient. The samples tested positive for Zika virus by RT-PCR at the University Hospital of Martinique. Currently, the patient is being ventilated because of his respiratory failure.

WHO risk assessment

At present, available information is insufficient to interpret the observed differences in GBS incidence globally and among Brazilian states. The potential cause of the reported increase of GBS incidence in certain Brazilian states remains unknown. Case-control studies are ongoing to determine the cause of the increase. These studies may provide evidence that corroborates or disproves a causal relationship between Zika virus, GBS and other congenital malformations. WHO continues to monitor the epidemiological situation and conduct risk assessment based on the latest available information.

WHO recommends Member States affected or susceptible to Zika virus outbreaks to:
  • monitor the incidence and trends of neurological disorders, especially GBS, to identify variations against their expected baseline values;
  • develop and implement sufficient patient management protocols to manage the additional burden on health care facilities generated by a sudden increase in patients with Guillain-Barre Syndrome;
  • raise awareness among health care workers and establish and/or strengthen links between public health services and clinicians in the public and private sectors.

WHO advice

The proximity of mosquito vector breeding sites to human habitation is a significant risk factor for Zika virus infection. Prevention and control relies on reducing the breeding of mosquitoes through source reduction (removal and modification of breeding sites) and reducing contact between mosquitoes and people. This can be achieved by reducing the number of natural and artificial water-filled habitats that support mosquito larvae, reducing the adult mosquito populations around at-risk communities and by using barriers such as insect screens, closed doors and windows, long clothing and repellents. Since the Aedes mosquitoes (the primary vector for transmission) are day-biting mosquitoes, it is recommended that those who sleep during the daytime, particularly young children, the sick or elderly, should rest under mosquito nets (bed nets), treated with or without insecticide to provide protection. 

During outbreaks, space spraying of insecticides may be carried out following the technical orientation provided by WHO to kill flying mosquitoes. Suitable insecticides (recommended by the WHO Pesticide Evaluation Scheme) may also be used as larvicides to treat relatively large water containers, when this is technically indicated.

Basic precautions for protection from mosquito bites should be taken by people traveling to high risk areas, especially pregnant women. These include use of repellents, wearing light colored, long sleeved shirts and pants and ensuring rooms are fitted with screens to prevent mosquitoes from entering. 

WHO does not recommend any travel or trade restriction to France and the overseas departments of France based on the current information available.

Guillain-Barré syndrome – Brazil

Disease Outbreak News
8 February 2016 

On 22 January 2016, the National IHR Focal Point of Brazil notified PAHO/WHO of an increase of Guillain-Barre Syndrome (GBS) recorded at the national level. 

Data from the hospital-based surveillance system reveal that, between January and November 2015, 1,708 cases of GBS were registered nationwide. While a number of states reported significant increases in reported cases – especially, Alagoas (516.7%), Bahia (196.1%), Rio Grande do Norte (108.7%), Piauí (108.3%), Espirito Santo (78.6%), and Rio de Janeiro (60.9%) – other states reported stable or even diminishing number of GBS cases as compared to 2014. Most of the states in Brazil are experiencing the circulation of Zika, chikungunya, and dengue virus.

WHO risk assessment

At present, available information is insufficient to interpret the observed differences in GBS incidence globally and among Brazilian states. The potential cause of the reported increase of GBS incidence in certain Brazilian states remains unknown. Case-control studies are ongoing to determine the cause of the increase. These studies may provide evidence that corroborates or disproves a causal relationship between Zika virus, GBS and other congenital malformations. WHO continues to monitor the epidemiological situation and conduct risk assessment based on the latest available information.

Monday, February 08, 2016

CDC Statement On Level 1 Activation Of Their EOC For Zika

Credit WHO/PAHO week 5 Zika Spread

# 10,987

The CDC posted a link this afternoon to the following statement - which is dated Feb 3rd on their website - announcing their Emergency Operations Center (EOC) is moving to a Level 1 activation status for Zika.

CDC Emergency Operations Center moves to highest level of activation for Zika response

Media Statement

For Immediate Release: Wednesday, February 3, 2016 Contact: Media Relations, (404) 639-3286

To further enhance its response to the Zika virus outbreak, CDC’s Emergency Operations Center is moving to a Level 1 activation—reflecting the agency’s assessment of the need for an accelerated preparedness to bring together experts to focus intently and work efficiently in anticipation of local Zika virus transmission by mosquitoes in the Continental U.S.
Activated for the Zika response since January 22, 2016,  the EOC is the command center for monitoring and coordinating the emergency response to Zika, bringing together CDC scientists with expertise in arboviruses, reproductive health, and birth and developmental defects. Their work includes:
  • Developing laboratory tests to diagnose Zika
  • Conducting studies to learn more about the possible linkages with microcephaly and Guillain Barré syndrome
  • Surveillance for the virus in the United States, including US territories
  • On-the-ground support in Puerto Rico, Brazil and Colombia
The EOC is currently home to more than 300 CDC staff working in collaboration with local, national, and international response partners to analyze, validate, and efficiently exchange information about the outbreak. The EOC has resources to rapidly transport diagnostic kits, samples and specimens, and personnel. The EOC is serving as CDC's command center for monitoring and coordinating the emergency response to Zika, including the deployment of CDC staff and the procurement and management of all equipment and supplies that CDC responders may need during deployment.

B-roll of Zika response in CDC Emergency Operations Center: http://www.cdc.gov/media/b_roll.html.

CDC: New Lyme-Disease-Causing Bacteria Species Discovered

Credit CDC

# 10,986

Having contracted Lyme Disease back in the mid-1990s, I have a particular interest in tick borne diseases (and a deep seated hatred for ticks), and have written about them fairly frequently over the years.

Some of my blogs on recently discovered viruses carried by ticks include:

CDC & EID Journal On The Recently Discovered Bourbon Virus
EID Journal: Novel Bunyavirus In Livestock – Minnesota
MMWR: Heartland Virus Disease — United States, 2012–2013

Far more common is Lyme disease, which the CDC estimates may affect 300,000 Americans every year The CDC maintains a long  (and growing) list of of tick borne pathogens available in North America, including:

Anaplasmosis, Babesiosis, Borrelia miyamotoi, Colorado tick fever, Ehrlichiosis, Heartland virus, Lyme disease, Powassan disease, Rickettsia parkeri rickettsiosis ,Rocky Mountain spotted fever (RMSF), STARI (Southern tick-associated rash illness)Tickborne relapsing fever (TBRF), Tularemia,364D rickettsiosis 

To this growing rogues gallery we can now add Borrelia mayonii, which has recently been discovered to be causing a Lyme-like illness in Minnesota and Wisconsin. Details of this discovery are contained in the following CDC statement.

New Lyme-disease-causing bacteria species discovered

Borrelia mayonii closely related to B. burgdorferi

Press Release

For Immediate Release: Monday, February 8, 2016 Contact: Media Relations (404) 639-3286
The Centers for Disease Control and Prevention, in collaboration with Mayo Clinic and health officials from Minnesota, Wisconsin, and North Dakota, report the discovery of a new species of bacteria (Borrelia mayonii) that causes Lyme disease in people. Until now, Borrelia burgdorferi was the only species believed to cause Lyme disease in North America.
Scientists at the Mayo Clinic in Rochester, Minnesota, first suspected the possibility of new bacteria after lab tests from six people with suspected Lyme disease produced unusual results, according to the findings published today in Lancet Infectious Diseases. Additional genetic testing at the Mayo Clinic and CDC found that the bacteria, provisionally named Borrelia mayonii, is closely related to B. burgdorferi.

“This discovery adds another important piece of information to the complex picture of tickborne diseases in the United States,” said Dr. Jeannine Petersen, microbiologist at the Centers for Disease Control and Prevention.

So far, new Lyme species found only in upper Midwest

Limited information from the first six patients suggests that illness caused by B. mayonii is similar to that caused by B. burgdorferi, but with a few possible differences. Like B. burgdorferi, B. mayonii causes fever, headache, rash, and neck pain in the early stages of infection (days after exposure) and arthritis in later stages of infection (weeks after exposure). Unlike B. burgdorferi, however, B. mayonii is associated with nausea and vomiting, diffuse rashes (rather than a single so-called “bull’s-eye” rash), and a higher concentration of bacteria in the blood.

The researchers believe that, like B. burgdorferi, B. mayonii is transmitted to humans by the bite of an infected blacklegged (or “deer”) tick. B. mayonii has been identified in blacklegged ticks collected in at least two counties in northwestern Wisconsin. The likely exposure sites for the patients described in Lancet Infectious Diseases are in north central Minnesota and western Wisconsin. It is highly likely, however, that infected ticks are found throughout both states.

The newly recognized species was discovered when six of approximately 9,000 samples drawn from residents of Minnesota, Wisconsin, and North Dakota with suspected Lyme disease between 2012 and 2014 were found to contain bacteria that were genetically distinct from B. burgdorferi. Scientists analyzed the DNA sequences of these bacteria and found that they belonged to a previously unrecognized Borrelia species. Blood from two of the patients was also tested by culture at CDC, whereby the organism is grown in the laboratory.
To date, the evidence suggests that the distribution of B. mayonii is limited to the upper midwestern United States. The new species was not identified in any of the approximately 25,000 blood samples from residents of 43 other states with suspected tickborne disease taken during the same period, including states in the Northeast and Mid-Atlantic region where Lyme disease is common.

Current tests, treatments should work for new Lyme strain

Results from the cases described in this report suggest that patients infected with B. mayonii will test positive for Lyme disease with currently available Food and Drug Administration-cleared Lyme disease tests. Specific identification of the organism can be made by using polymerase chain reaction assays (PCR.), which detects the DNA of the Lyme disease bacteria. In some instances, B. mayonii bacteria may also be seen on a blood smear.
The patients described in this report were treated successfully with antibiotics commonly used to treat Lyme disease caused by B. burgdorferi. CDC recommends that health care providers who treat people infected with B. mayonii follow the antibiotic regimen described by the Infectious Diseases Society of America.

CDC is working closely with state health departments in Minnesota, North Dakota, and Wisconsin to better understand B. mayonii and to plan future investigations, including better descriptions about the clinical aspects of the illness and the geographic extent of the infected ticks.

To further support advances in the detection and discovery of tickborne diseases, CDC in 2015 funded a partnership with the Minnesota Department of Health, Mayo Clinic, Tennessee Department of Health, and Vanderbilt University to collect over a 3-year period up to 30,000 clinical specimens from patients with suspected tickborne illness. CDC will use advanced molecular detection methods, including metagenomics screening and whole genome sequencing, to test the specimens for other bacteria that cause tickborne illness.
"CDC is investing in advanced technology to bring study of tickborne infections into a new era," said Ben Beard, Ph.D., chief of CDC’s Bacterial Diseases Branch. "Coupling technology with teamwork between federal, state, and private entities will help improve early and accurate diagnosis of tickborne diseases.”
To reduce the risk of tick bites and tickborne diseases, CDC recommends that people:

  • Avoid wooded and brushy areas with high grass and leaf litter;
  • Use insect repellent when outdoors;
  • Use products that contain permethrin on clothing;
  • Bathe or shower as soon as possible after coming indoors to wash off and more easily find ticks;
  • Conduct a full-body tick check after spending time outdoors; and
  • Examine gear and pets, as ticks can come into the home on these and later attach to people.
To view the article online: http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(15)00483-1/fulltext

For more information, please visit www.cdc.gov/ticks.

ECDC Risk Assessment : Reports Of Severe A(H1N1)pdm09 In Europe


Although influenza has been late in arriving this year in North America (and Western Europe) for the past couple of weeks we've been watching reports of unusually severe influenza in Russia and Eastern Europe, with Russian epidemiological reports indicating a new subgroup of A(H1N1) has recently emerged.

Updating Russia's Flu Outbreak
An Update On The Russian Influenza Epi Report
A Russian Influenza Epidemiology Report To Ponder

The most recent (week 5) Russian Epidemiology report states:
Genetic characterization55 investigated influenza A(H1N1)pdm09 virus strains were A/South Africa/3626/2013-like. All viruses bear clade 6B specific mutations in HA (S84N, S162+N and I216T) and formed new genetic group according to phylogenetic analysis. Two A(H1N1)pdm09 sequences obtained directly from autopsy sample showed the presence of additional mutation D222G in HA1.

We've discussed the significance of the D222G mutation a number of times (see here & here), but essentially it promotes lower lung infections, and is linked to increased virulence. The Russian epi report also mentions reduced titers against the current vaccine strain for some viruses sampled.

Despite the lack of North American flu cases so far, last Monday the CDC issued a HAN Advisory: Severe Influenza Illness Reported. 

Today, the ECDC cites - strong indications from some EU/EEA countries that the A(H1N1)pdm09 virus is responsible for the hospitalisation of a large number of severe cases - and published the following mid-season risk assessment.

A(H1N1)pdm09 dominant influenza strain in Europe: mid-season risk  assessment

08 Feb 2016

This year’s seasonal influenza risk assessment identifies type A viruses, in particular A(H1N1)pdm09, as dominant thus far in EU/EEA countries. There are strong indications from some EU/EEA countries that the A(H1N1)pdm09 virus is responsible for the hospitalisation of a large number of severe cases. This includes hospitalisations for severe outcomes for both risk groups and otherwise healthy young adults. A similar pattern of severity is likely to be observed in other countries as the season progresses.

The season started in EU/EEA countries in week 52/2015, with the Netherlands reporting regional spread, while Sweden reported widespread activity. The A(H1N1)pdm09 virus is the most prevalent so far this season overall but B viruses predominated in four countries, and three countries had an even distribution of both A and B viruses. B viruses could emerge later and become dominant by the end of the season. In previous seasons, B viruses have tended to be more prevalent in the second half of the season.

The A(H1N1)pdm09 virus is responsible for the vast majority of patients in intensive care units due to influenza; 61% of those were in the 15–64 years old age group. This contrasts with the 2014–15 season where the predominant A(H3N2) virus affected the elderly more.
Seasonal influenza vaccine effectiveness

The composition of influenza vaccines in the southern hemisphere in 2015 and in the northern hemisphere in 2015–16 were identical and thus provide an indication of how effective vaccination could be in Europe. Estimates of vaccine effectiveness in New Zealand are encouraging, with an overall effectiveness against hospitalisations of 50%.

For Europe, the vaccine effectiveness is expected to be lower than in the 2015 season in New Zealand. Europe is seeing a higher prevalence of B/Victoria virus circulating, which is not included in the widely used trivalent vaccine, and it is unclear if the emergence of a new genetic subgroup of A(H1N1) virus might compromise vaccine effectiveness.
Susceptibility to antiviral drugs

Almost all viruses tested for neuraminidase inhibitor (antiviral) susceptibility, showed no reduction in effectiveness.

ECDC advises:

Simple measures such as self-isolation, good hand hygiene and cough etiquette can reduce transmission and protect others.
Early treatment and post-exposure prophylaxis with neuraminidase inhibitors (antivirals) can assist in protecting the elderly and people in risk groups against serious influenza illness.
EU Member States are encouraged to report ICU-admitted, laboratory-confirmed influenza cases to the European Surveillance System (TESSy) in a timely fashion in order to facilitate the assessment of the severity of the season.
Although influenza season normally peaks by February, every flu season is different, and we may still be on pace to see a late onset flu season.  It isn't too late to get a flu shot, and as always, it is important to practice good flu hygiene.

As for the ultimate impact and significance of the changes being reported in the H1N1 virus, we'll just have to wait and see.  

Last week we looked at similar changes reported in India in 2015, in Eurosurveillance: Emergence of A(H1N1)pdm09 Genogroup 6B In India, 2015. There you will also find further discussion of the H275Y mutation which confers resistance to Oseltamivir.