Friday, March 16, 2018

FluView Week 10: Influenza Activity Continues To Decline


It's been 12 weeks since the CDC's ILI map (above) has had this little red on it, and while flu remains elevated in some parts of the country, the overall trend continues to decline.
Outpatient visits for influenza-like-illness (ILI) continues above the national baseline (below), but has dropped precipitously over the past 4 weeks. 

While there are likely still a few more weeks of flu activity ahead, at least the worst now appears behind us.  Some highlights from today's FluView Report follow:

2017-2018 Influenza Season Week 10 ending March 10, 2018

All data are preliminary and may change as more reports are received.


During week 10 (March 4-10, 2018), influenza activity decreased in the United States.
  • Viral Surveillance: Overall, influenza A(H3) viruses have predominated this season. However, in recent weeks the proportion of influenza A viruses has declined, and during week 10, the numbers of influenza A and influenza B viruses reported were similar. The percentage of respiratory specimens testing positive for influenza in clinical laboratories decreased.
  • Pneumonia and Influenza Mortality: The proportion of deaths attributed to pneumonia and influenza (P&I) was above the system-specific epidemic threshold in the National Center for Health Statistics (NCHS) Mortality Surveillance System.
  • Influenza-associated Pediatric Deaths: Nine influenza-associated pediatric deaths were reported.
  • Influenza-associated Hospitalizations: A cumulative rate of 89.9 laboratory-confirmed influenza-associated hospitalizations per 100,000 population was reported.
  • Outpatient Illness Surveillance: The proportion of outpatient visits for influenza-like illness (ILI) was 3.3%, which is above the national baseline of 2.2%. All 10 regions reported ILI at or above region-specific baseline levels. Twelve states experienced high ILI activity; 13 states experienced moderate ILI activity; New York City and 14 states experienced low ILI activity; 11 states experienced minimal ILI activity; and Puerto Rico and the District of Columbia had insufficient data.
  • Geographic Spread of Influenza: The geographic spread of influenza in Puerto Rico and 26 states was reported as widespread; Guam and 18 states reported regional activity; the District of Columbia and five states reported local activity; one state reported sporadic activity; and the U.S. Virgin Islands reported no activity.

Sweden: HPAI H5N6 Detected In Backyard Flock

Uppsala County


Just two days after Sweden reported their second detection of HPAI H5N6 in wild terrestrial birds (see March 14th OIE report), the Swedish Board of Agriculture (Jordbruksverket) today announced their first outbreak in poultry by this recently reassorted virus.


New case of bird flu in backyard holding

Bird flu has been found in a small backyard holding Östhammar Uppsala County. After analysis of the National Veterinary Institute (SVA) was found to have the type of bird flu H5N6. It is the first time the virus of the type discovered in poultry in Sweden. This virus circulating in Europe and in Sweden, has never infected humans.

- To avoid spreading to poultry, it is important to poultry producers and hobby bird owners have good infection control procedures, and in the extent possible, preventing contact between domesticated and wild birds, says Karin Ahl, deputy head of the unit for the horse, poultry and game. We recommend that you avoid feeding wild birds near their tamfjäderfän.
Found naturally in wild birds

Bird flu comes in many varieties and is very contagious among birds. Milder variants of the virus occurs naturally among wild birds, especially of seabirds. Level 1 applies in Sweden, which means that poultry must go out, but to feed and water should be under a roof
or under a shelter outdoors.

- Although H5N6 has not been associated with the same mortality rate as last year's virus, H5N8, it is clear that it is circulating among wild birds. Avoid special contact with waterfowl, says statsepizootolog Ann
Lindberg, SVA.

It is important to have good management practices and to the extent possible, preventing direct and indirect contact with wild birds.
Pet owners should be alert and to contact a veterinarian if the poultry show increased mortality, changes in food and water consumption, drop in  egg production or debilitated.
General hygiene rules
  • Make sure that only those who care tamfåglarna have access
  • to animal areas.
  • Keep the area around the house and corrals.
  • Be careful hygiene practices at borders.
  • Wash hands after contact with birds.
  • After a stay abroad should not have contact with
  • domestic birds until after 48 hours.
So far this reassorted (from HPAI H5N8) H5N6 virus hasn't produced anything near the impact of last year's record HPAI H5N8 epizootic across Europe.   In many ways, it is acting like H5N8 did the first time it briefly arrive in Europe, during the spring of 2015.  
It wasn't until 18 months later, after H5N8 had undergone further evolution changes (see EID Journal: Reassorted HPAI H5N8 Clade - Germany 2016) that it gained enough virulence and transmissibility to spark a record-setting avian epizootic across all of Europe. 
While past performance is no guarantee of future results, this is a reminder that if you've seen one H5N6 avian flu season . . . you've seen just that . . .  one H5N6 avian flu season.


MMWR: Emergence of Monkeypox — West and Central Africa, 1970–2017


Over the past few years we've looked at a growing number of Monkeypox outbreaks in Africa, with the most recent beginning last October in Nigeria - a country that had gone nearly 40 years without a case - and which continues today (see chart below).

Human monkeypox was first identified in 1970 in the DRC, and since then has sparked small, sporadic outbreaks in the Congo Basin and Western Africa. It produces a remarkably `smallpox looking' illness in humans, albeit not as deadly. The CDC's Monkeypox website states:
The illness typically lasts for 2−4 weeks. In Africa, monkeypox has been shown to cause death in as many as 1 in 10 persons who contract the disease.
The name `monkeypox’ is a bit of a misnomer. It was first detected (in 1958) in laboratory monkeys, but further research has revealed its host to be rodents or possibly squirrels.

Humans can contract it in the wild from an animal bite or direct contact with the infected animal’s blood, body fluids, or lesions, but consumption of under cooked bushmeat is also suspected as an infection risk.

Human-to-human transmission is also possible.  This from the CDC’s Factsheet on Monkeypox:

The disease also can be spread from person to person, but it is much less infectious than smallpox. The virus is thought to be transmitted by large respiratory droplets during direct and prolonged face-to-face contact. In addition, monkeypox can be spread by direct contact with body fluids of an infected person or with virus-contaminated objects, such as bedding or clothing.
According to the CDC there are two distinct genetic groups (clades) of monkeypox virus—Central African and West African. West African monkeypox - such as hs been spreading recently in Nigeria - is associated with milder disease, fewer deaths, and limited human-to-human transmission.
The more severe form of Monkeypox is most commonly found in the Central Africa countries of the DRC and the CAR - where outbreaks have been on the rise for years - presumably because smallpox vaccinations (which provided up to 85% protection) were halted in the late 1970s.
As the percentage of vaccinated members of the community dwindles, the risks of outbreaks are only expected to increase (see 2010 PNAS study Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo).

In 2013, the DRC reported a 600% increase in cases over both 2011, and 2012 (see EID Journal:Extended H-2-H Transmission during a Monkeypox Outbreak) . The authors also cite a higher attack rate, longer chains of infection, and more pronounced community spread than have earlier reports.

Like all viruses, Monkeypox continues to evolve and diversify, as discussed in the 2014 EID Journal article Genomic Variability of Monkeypox Virus among Humans, Democratic Republic of the Congo, where the authors cautioned:
Small genetic changes could favor adaptation to a human host, and this potential is greatest for pathogens with moderate transmission rates (such as MPXV) (40). The ability to spread rapidly and efficiently from human to human could enhance spread by travelers to new regions.
Although monkeypox is normally restricted to small outbreaks in Africa, in 2003 we saw a rare outbreak in the United States when a Texas animal distributor imported hundreds of small animals from Ghana, which in turn infected prairie dogs that were subsequently sold to the public (see MMWR Update On Monkeypox 2003).
By the time that outbreak was quashed, the U.S. saw 37 confirmed, 12 probable, and 22 suspected human cases. Among the confirmed cases 5 were categorized as being severely ill, while 9 were hospitalized for > 48 hrs; although no patients died (cite).
Routine vaccination against smallpox ended in the United States in 1972, and worldwide by the end of that decade. Today more than half of the world's population is unvaccinated, and the level of protection remaining among those vaccinated 50+ years ago is highly suspect.
All of which makes the potential evolution and spread of monkeypox of growing international concern.
In yesterday's MMWR, the CDC published a detailed overview of the emergence of monkeypox in Africa over the past 6 decades. They cite growing concerns over its zoonotic potential, and describe recent informal consultations with the WHO and other global public health partners on ways to better contain this rising threat.

I've only included some excerpts, follow the link to read it in its entirety.

Emergence of Monkeypox — West and Central Africa, 1970–2017

Weekly / March 16, 2018 / 67(10);306–310

Kara N. Durski, MPH1; Andrea M. McCollum, PhD2; Yoshinori Nakazawa, PhD2; Brett W. Petersen, MD2; Mary G. Reynolds, PhD2; Sylvie Briand, MD, PhD1; Mamoudou Harouna Djingarey, MD3; Victoria Olson, PhD2; Inger K. Damon, MD, PhD2; Asheena Khalakdina, PhD1 (View author affiliations)

The recent apparent increase in human monkeypox cases across a wide geographic area, the potential for further spread, and the lack of reliable surveillance have raised the level of concern for this emerging zoonosis.
In November 2017, the World Health Organization (WHO), in collaboration with CDC, hosted an informal consultation on monkeypox with researchers, global health partners, ministries of health, and orthopoxvirus experts to review and discuss human monkeypox in African countries where cases have been recently detected and also identify components of surveillance and response that need improvement. 

Endemic human monkeypox has been reported from more countries in the past decade than during the previous 40 years. Since 2016, confirmed cases of monkeypox have occurred in Central African Republic, Democratic Republic of the Congo, Liberia, Nigeria, Republic of the Congo, and Sierra Leone and in captive chimpanzees in Cameroon. Many countries with endemic monkeypox lack recent experience and specific knowledge about the disease to detect cases, treat patients, and prevent further spread of the virus. 

Specific improvements in surveillance capacity, laboratory diagnostics, and infection control measures are needed to launch an efficient response. Further, gaps in knowledge about the epidemiology and ecology of the virus need to be addressed to design, recommend, and implement needed prevention and control measures.

What is already known about this topic

Human monkeypox is a viral zoonosis that occurs in West Africa and Central Africa. Most cases are reported from Democratic Republic of the Congo. The disease causes significant morbidity and mortality, and no specific treatment exists.

What is added by this report?

Nigeria is currently experiencing the largest documented outbreak of human monkeypox in West Africa. During the past decade, more human monkeypox cases have been reported in countries that have not reported disease in several decades. Since 2016, cases have been confirmed in Central African Republic (19 cases), Democratic Republic of the Congo (>1,000 reported per year), Liberia (two), Nigeria (>80), Republic of the Congo (88), and Sierra Leone (one). The reemergence of monkeypox is a global health security concern.

What are the implications for public health practice?

A recent meeting of experts and representatives from affected countries identified challenges and proposed actions to improve response actions and surveillance. The World Health Organization and CDC are developing updated guidance and regional trainings to improve capacity for laboratory-based surveillance, detection, and prevention of monkeypox, improved patient care, and outbreak response.

WHO Update - MERS-CoV Case In Oman


Last week there were vague rumors of a MERS-CoV case in Oman - rumors which were confirmed (albeit, without details) in yesterday's blog (see WHO EMRO MERS-CoV Report - Feb 2018) - which cited `one case reported in Oman'.
Late yesterday the WHO published a DON (Disease Outbreak News) report on the Omani case.  This is their first case for 2018 - in 2017 Oman reported just two cases (see Nov report  & Sept Report).
As in Saudi Arabia - and the rest of the Middle East - mild or asymptomatic cases are unlikely to be picked up by surveillance, and some of the more severe cases may go undiagnosed, making it difficult to know just how prevalent the virus really is in the region (see EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016).

Some excerpts from the WHO update follow:

Middle East respiratory syndrome coronavirus (MERS-CoV) – Oman

Disease outbreak news
15 March 2018

On 4 March 2018, the National IRH focal point of Oman reported one additional case of Middle East respiratory syndrome coronavirus (MERS-CoV).

The patient was a 74-year-old male Omani national, living in Batinah, who had symptom onset on 23 February 2018. The patient had neither recently travelled nor had any contact with any person with respiratory symptoms or with a known MERS-CoV case. The patient took care of camels that were reportedly ill.

The investigation of the patient’s exposure in the 14 days prior to the onset of symptoms is still ongoing.

Prior to this patient, the last laboratory-confirmed case of MERS-CoV from Oman was reported in November 2017.

Globally, 2144 laboratory-confirmed cases of MERS-CoV, including at least 750 related deaths, have been reported to WHO.
Details of the case

Detailed information concerning the patient reported can be found in a separate document (see link below).

MERS_CoV details xls, 229kb
Public health response

Identification, tracing and follow up of family and health care workers contacts is ongoing, including MERS-CoV screening. All identified contacts will be monitored for 14 days from the last possible date of exposure.
WHO risk assessment

Infection with MERS-CoV can cause severe disease and subsequently, results in a high mortality rate. Humans are infected with MERS-CoV from direct or indirect contact with dromedary camels. MERS-CoV has demonstrated the ability to transmit between humans. So far, the observed unsustained human-to-human transmission has occurred mainly in health care settings.

The notification of additional cases does not change the overall risk assessment. WHO expects that additional cases of MERS-CoV infection will be reported from the Middle East, and that cases will continue to be exported to other countries by individuals who might acquire the infection after exposure to animals or animal products (for example, following contact with dromedaries) or human sources (for example, in a health care setting). WHO continues to monitor the epidemiological situation and conducts risk assessment based on the latest available information.

(Continue . . . )

Thursday, March 15, 2018

WHO EMRO MERS-CoV Report - Feb 2018



With the Saudi MOH only issuing (usually belatedly) daily MERS reports for 16 of February's 28 days (see recap here), and disparities between their English and Arabic case lists (see Saudi MOH: Mismatching MERS Reports), we've been waiting for an update from the World Health Organization to try to sort out last month's numbers.
Amid incomplete data and rumors of more cases, the Saudi MOH reported either 14 MERS cases in February (English page total) or 16 cases (Arabic page total).
The last detailed WHO report was released on January 26th, and covered cases reported to them by the National IHR Focal Point of KSA between December 9th, 2017 and January 17th of this year.

But we also get a brief MERS-CoV summary (lacking individual case details) once each month from WHO's EMRO (Eastern Mediterranean Office), generally published around the 15th, covering the previous month.

We've EMRO's report for February, and not unexpectedly, the number of Saudi MERS Cases reported here are higher (n=23) than what was originally announced.  Additionally, we learn of a single (previously unannounced) case in Oman.

MERS situation update, February 2018

At the end of February 2018, a total of 2182 laboratory-confirmed cases of Middle East respiratory syndrome (MERS), including 779 associated deaths (case–fatality rate: 35.7%) were reported globally; the majority of these cases were reported from Saudi Arabia (1807 laboratory-confirmed cases, including 705 related deaths with a case–fatality rate of 39%).
During the month of February, 24 laboratory-confirmed cases of MERS were reported globally: 23 cases in Saudi Arabia including 5 associated deaths and one case reported in Oman. A cluster of nosocomial infection was detected on 5 March 2018 in a health-facility in Riyadh region. At least 3 secondary cases were reported in this cluster; investigation is ongoing to identify the index case as well as testing of all close contacts for identifying additional secondary cases.
The demographic and epidemiological characteristics of the cases reported in February 2018 do not show any significant difference compared with cases reported during the same period from 2012 to 2017. Owing to improved infection prevention and control practices in the hospitals, the number of hospital-acquired cases of MERS has dropped significantly in 2015, 2016 and 2017.
The age group of those aged 50–59 years continues to be the group at highest risk for acquiring infection as primary cases. For secondary cases, it is the age group of 30–39 years who are mostly at risk. The number of deaths is higher in the age group of 50–59 years for primary cases and 70–79 years for secondary cases.

As the epi curve chart at the top of this blog shows, even with these revised numbers, the level of MERS activity in Saudi Arabia if far below what we were seeing in 2014-2015.
A trend which has been attributed to better infection control in hospitals, resulting in fewer - and smaller - nosocomial outbreaks. 
While the spotty reporting of cases from KSA in recent weeks is disappointing - even at its best - surveillance can only be expected to pick up a fraction of the cases in the population (see EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016).
Although MERS-CoV remains a serious public health concern - and we've seen recent studies (see Study: A Pandemic Risk Assessment Of MERS-CoV In Saudi Arabia) suggesting the virus may have gotten a little better at transmitting in the community - so far we've seen no signs of any sustained or efficient transmission of the MERS virus outside of health care facilities.
That said, MERS continues to evolve, and as long as it continues to enter the human population via infected camels, will continue to pose a serious public health threat.

Wednesday, March 14, 2018

Infect. Gen. Evol.: Emergence Of Novel Reassortant H6N2 Avian Influenza Viruses In Ducks In India


Five years ago avian H7N9 - at least as being a threat to human health - wasn't on our radar screen.  Neither were H5N8, H5N6, H10N8, or H6N1. Yet all five of those viruses have evolved, emerged - and to varying degrees - have infected humans in recent years.
H7N9 came to light at the end of March 2013, sparking 130+ infections in its first spring outbreak in China. Despite being an LPAI virus in poultry, it was the first consistently severe H7 influenza ever reported in humans.
Like most newly emerging flu viruses, it was formed though reassortment.  The swapping of genetic segments from two or more existing influenza viruses in a shared host (in this case H7N?, H?N9, H9N2). 

The H7N9 Reassortment – Credit Eurosurveillance

Reassortments like this occur frequently, particularly in birds - and while many end up being evolutionary failures - every once in awhile a highly successful new virus is created.
Even after a new hybrid virus emerges, it continues to evolve, and so we often see dozens of genotypes within a single subtype.  With this diversity often comes marked differences in behavior, and robustness.
While we primarily watch for avian H5 and H7 viruses - since they have shown the greatest ability to mutate into HPAI strains - they aren't the only avian subtypes that have jumped to humans.
LPAI H6N1 viruses have been around for decades in Chinese poultry and possesses similar internal genes to H5N1 and H9N2 (cite 2002 J Virol  Molecular evolution of H6 influenza viruses from poultry in Southeastern China by Webster, Webby, Shortridge  et al.). It has been speculated that it may even have been involved in the genesis of H5N1 in Hong Kong in 1997.
While H6 viruses aren't exactly at the top of the list of avian viruses that we watch, they aren't necessarily benign.  All of which lays the foundation for a new report, that describes the emergence of a novel reassorted H6N2 virus in India.
Emergence of novel reassortant H6N2 avian influenza viruses in ducks in India
Manoj Kumara, 1Shanmugasundaram Nagarajana, 1, Harshad V. Murugkara, Barnalee Saikiab, Bharati Singha, Amit Mishraa, Sushil K. Tripathia, Sonam Agarwala, Shweta Shuklaa, Diwakar D. Kulkarnia, rights and content


  • Antigenic and genetic characterization of two H6N2 AIVs isolated in India.
  • The two H6N2 AIVs are antigenically distinct with >4 fold reduction in HI titer.
  • Phylogenetically both are novel ressortants with different gene constellations.
  • Independent introductions probably through wild birds in Central Asian flyway
  • Continued AIV surveillance in poultry and wild birds is essential.

H6 subtype avian influenza viruses (AIV), established in terrestrial poultry, have jumped species barriers and caused human infection indicating pandemic potential of the virus. 

Here, we report isolation, and antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively. 

Hemagglutination inhibition assay revealed antigenic divergence between the two isolates. This result was corroborated by amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA) 1. The sequence analysis of the viruses indicated avian receptor specificity, avian origin, low pathogenicity to poultry and sensitivity to oseltamivir. 

However, Kerala14 had V27I mutation marker for amantadine resistance in M2. The Assam15 virus had an additional N-linked glycosylation on HA2 (position 557) compared to Kerala14 virus. Analysis of the HA gene revealed that both the viruses belonged to distinct lineages (Eurasian and Asia I). 
Analysis of neuraminidase (NA) and internal gene segments revealed distinct gene constellation indicating that both the viruses are novel reassortants and are genetically distinct. The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India.
Therefore, continued AIV surveillance in poultry and wild birds is essential for detection of emergence of novel strains, which may have pandemic potential and control of their spread.

While all of this may end up being nothing more than interesting footnote in the evolution of avian influenza viruses, it is a reminder that Nature's laboratory is open 24/7, and it never stops tinkering with the evolutionary process.

The trend over the past decade has been seeing an increasing number of novel virus threats emerge, with the CDC's  IRAT (Influenza Risk Assessment Tool) currently following 14 novel flu subtypes/strains that circulate in non-human hosts and are believed to possess some degree of pandemic potential. 
That's an increase of 3 new viruses (Canine H3N2, a second lineage of H7N9, and North American H7N8) over the past 2 years.
Given H6's ubiquity in Chinese poultry, it's apparent (albeit, currently limited) ability to infect humans, and its uncertain and diverse evolutionary path going forward, H6Nx can't be ruled out as a future threat.