Sunday, March 18, 2018

Arch. Virology: Co-circulation Of Multiple Genotypes of H7N9 in Eastern China, 2016-2017


While day-to-day reporting on H7N9 (and H5N6) avian flu activity from mainland China has suffered in recent years (at least compared to 2013-14), we continue to get a remarkable flow of quality studies published by Chinese scientists in international journals. 
One of the most remarkable findings we've seen, again and again, is just how much diversity there is in the H7N9 virus. 
Last year a new LPAI Yangtze River Delta lineage became dominant, and a mutated HPAI H7N9 virus emerged in Guangdong Province and began to spread (see MMWR: Increase in Human Infections with Avian Influenza A(H7N9).

H7N9 viruses have also proven themselves to be very promiscuous, reassorting easily with other avian flu viruses, producing numerous new hybrid viruses (genotypes).

Add in a myriad of smaller (although often significant) amino acid changes and the reality is we really don't know how many genetically distinct H7N9 threats there really are in the wild  - we only know that number is large - and getting larger over time.
While most of these variants carry no real evolutionary advantage over the others - and some are likely less biologically fit and doomed to failure - the more variants in circulation, the greater the chances that one will eventually hit the genetic lottery and become a pandemic strain. 
We've a new study (alas, behind a pay wall) published this week in the Archives of Virology that illustrates just how diverse H7N9 has become in Eastern China, with 18 different genotypes identified out of just 41 samples taken in Jiangsu Province.

Equally important, all 41 samples carried the HA G186V and Q226L/I amino acid substitutions, which are linked to switching the virus from binding preferentially to avian (a2,3) receptor cells to mammalian (a2,6) receptor cells.  Some past blogs on these changes include:
PLoS Pathogens: Three Mutations Switch H7N9 To Human-type Receptor Specificity

Sci. Repts: Adaptation of H7N9 in Primary Human Airway Epithelial cells

Eurosurveillance: Genetic Tuning Of Avian H7N9 During Interspecies Transmission
Last year, in Eurosurveillance: Preliminary Epidemiology & Analysis Of Jiangsu's 5th H7N9 Wave, we looked at the study referenced in the opening paragraph of the abstract below. 

Co-circulation of multiple genotypes of influenza A (H7N9) viruses in eastern China, 2016-2017

Xian Qi Email author, Xiaofei An, Yongjun Jiao, Huiyan Yu, Ke Xu, Lunbiao Cui, Shenjiao Wang, Fei Deng, Xiang Huo, Haodi Huang, Qigang Dai, Changjun Bao Email author

First Online: 14 March 2018


Five epidemic waves of human infection with influenza A (H7N9) virus have emerged in China since spring 2013. We previously described the epidemiological characterization of the fifth wave in Jiangsu province.
In this study, 41 H7N9 viruses from patients and live-poultry markets were isolated and sequenced to further elucidate the genetic features of viruses of the fifth wave in Jiangsu province.
Phylogenetic analysis revealed substantial genetic diversity in the internal genes, and 18 genotypes were identified from the 41 H7N9 virus strains. Furthermore, our data revealed that 41 isolates from Jiangsu contained the G186V and Q226L/I mutations in their haemagglutinin (HA) protein, which may increase the ability of these viruses to bind the human receptor. 

Four basic amino acid insertions were not observed in the HA cleavage sites of 167 H7N9 viruses from Jiangsu, which revealed that highly pathogenic avian influenza (HPAI) H7N9 viruses did not spread to Jiangsu province in the fifth wave. 

These findings revealed that multiple genotypes of H7N9 viruses co-circulated in the fifth wave in Jiangsu province, which indicated that the viruses have undergone ongoing evolution with genetic mutation and reassortment. Our study highlights the need to constantly monitor the evolution of H7N9 viruses and reinforce systematic influenza surveillance of humans, birds, and pigs in China.

Despite the surprising lull in H7N9 activity this winter in China, it (or more accurately, `they') remain atop the CDC's Influenza Risk Assessment Tool (IRAT) ranking list of 14 novel flu subtypes/strains that circulate in non-human hosts and are believed to possess some degree of pandemic potential.

H5 Avian Flu Resurfaces At 3 Poultry Farms In South Korea


Avian flu activity this winter has been remarkably subdued in places - like China and South Korea - where in recent years it has flourished.  Remarkably China has only reported three H7N9 cases, and 1 H5N6 case since October. 
Some of this is likely due to China's massive H7+H5 vaccination campaign launched last summer, and the extremely strict bio-security measures taken in South Korea prior to their hosting the Winter Olympics in February.
But part of it is likely due to a newly reassorted H5N6 virus arriving in South Korea this winter - similar to the one now in Europe - which, so far at least - hasn't proven to be as virulent as last year's strain.

In recent weeks - possibly due to the spring northbound bird migration -  we've started to see renewed activity across Europe (see here, here, and here), in Japan (here), and today we learn that at least three large farms in South Korea have been hit in South Korea.
According to the Korean Times (see Bird Flu confirmed at farms in Gyeonggi and South Chungcheong) more than 1.2 million birds have been culled this weekend in affected and surrounding farms and a nationwide 48 hour transport ban on all domestic poultry was ordered on Saturday.
A couple of admittedly syntax-challenged (translated) press releases from South Korea's Ministry of Agriculture (MAFRA) follow:

Pyeongtaek game hens (chickens) AI issued a global economic decision-temporarily move the stop command of the shaft occurs (3.16, deployment)

2018.03.16 23:55:37

Pyeongtaek game hens ( chickens ) AI of the shaft occurs doctor

Match triggered a global temporary stop command to move

- 3 Mon 17 days 00 am to 24 stops moving for a time in Japan and disinfection carried out -

Agriculture, Forestry, Animal Husbandry and Food is 3.16 ( Fri ) Match Pyeongtaek material laying hens ( chickens ) farms in AI inspection results according to the physician shaft occurs H5 antigen , in the same farm minute yangdoen economic Yangzhou material laying hens ( chickens ) Simple inspection of the farms results confirm the positive as , before the game stations temporarily for the stop moving the command was issued .

❍ The date and time that the move 3 0.16 ( Fri ) held Livestock Defense Council ( written hearing ) Based on the results 3.17 ( Sat ) 00 am to 3.17 ( Sat ) 24 pm 24 hours during the being carried out ,

❍ temporarily move to stop Applies the national animal quarantine when integrated system (KAHIS) to about registered 10 thousand places - a .

     * Poultry farms 3,960 points , it slaughterhouses 11 positions , feed mills 102 positions , vehicle 6725 Lighthouse

(Continue . . . )

Gyeonggi, Chungnam, etc., and a nationwide (excluding Jeju), and the National Association for the Protection of hygiene and the suspension of the temporary move command
    2018.03.17 19:32:41

The Ministry of Agriculture and Livestock farming (the lower farming food) is the ' 18.3.16 ', according to a series of four AI pseudo-axes in the Yangzhou, the province and the 18.3.17, the Asan spawning farm in Chungcheongnam-do, has issued an AI blocking hygiene enhancement action and a pause command to stop nationwide (excluding Jeju).

Anyway is a major preventive measures to prevent the removal of the national spawning system in ① (however, it is taken out upon approval in the admission of livestock Hygiene), ② of the Emergency video conference held by the Ministry of Agriculture, the Deputy Secretary of state (', ③ held the national and Municipalities video conference on the adjustment of the Secretary (' 18.3.18 09:00), ④ nationwide (excluding Jeju-do), and a temporary move to stop command.

The Ministry of Agriculture, the whole country (excluding Jeju), the reason for the suspension of the move, the four-axis doctor on a recent spawning farm, and the mechanics of the vehicle visited by the farmers ․, the facility is distributed nationwide, 

(Continue . . . )

Saturday, March 17, 2018

The Long Road To An H7N9 (or Any Other Pandemic) Vaccine


There is a comforting but unlikely trope in most pandemic fiction which has scientists devising a safe and effective vaccine at the last minute - and even more miraculously - somehow manufacturing and deploying the vaccine around the globe in short order.
The reality is far more complicated, and far less comforting.
The oft heard mantra that `It will likely take at least 6 months before the first doses of an emergency pandemic vaccine will be available' envisions a `best case scenario'; one where the vaccine involves a simple strain change (like in 2009), or where an emergency vaccine has already been developed and tested.
And it carefully ignores the questions of how much vaccine will be available six (or 12 or 18) months into the pandemic, how effective it will be, and who will be prioritized to receive it. 
All of which underscores the need for a `universal' flu vaccine; one that protects not only against seasonal strains, but against novel flu viruses as well (see J.I.D.: NIAID's Strategic Plan To Develop A Universal Flu Vaccine).

While not a panacea for a pandemic, an effective universal vaccine (particularly if it's been in use for a few years) would provide a huge leg up against an emerging influenza pandemic. Manufacturing and deploying on a global scale would remain a logistical challenge, but it would beat starting from scratch.
The reality is - assuming that one can be created - we are probably still at least 5 years away from seeing a universal flu jab, and there are a lot of questions over just how effective it might be against novel (non-H1, H2, H3) flu strains. 
Which leaves us - for the foreseeable future - dependent upon current vaccine technology, and desperately in need of effective vaccines against the most obvious novel flu threats. And right now, despite its recent lull in China, that means H7N9.
But it isn't alone.  
The CDC's IRAT (Influenza Risk Assessment Tool) currently tracks 12 additional novel flu subtypes/strains that circulate in non-human hosts and are thought to possess some degree of pandemic potential.  And we could always be blindsided by something not yet on our radar.

Work began on an H7N9 vaccine almost immediately after it appeared 5 years ago in China (see 2013's NIH Begins Phase II Clinical Trials On H7N9 Vaccine Candidates), with results expected in late 2014.
Given the difficulties encountered in the middle of the last decade developing an effective H5N1 vaccine (see 2007's Sanofi Vaccine Hits A Snag), problems were not unexpected.
In October of 2014, in NIH: H7N9 Vaccine Candidate Works Much Better With An Adjuvant, we learned that the H7N9 candidate vaccine only produced an acceptable immune response when administered with an adjuvant.
According to their study: Without adjuvant, immune responses produced by the investigational vaccine were minimal regardless of vaccine dosage.
The following summer, in JAMA: Immune Response Of H7N9 Vaccine With & Without Adjuvant, a new study confirmed the earlier finding – that without an adjuvant – the H7N9 vaccine’s effectiveness was abysmal.
The bottom line, without an adjuvant, only 2% of vaccine recipients saw an acceptable immune response (HAI Titer > 40). Two 15 µg shots were still required, but those who received ASO3-adjuvanted vaccines were more likely to mount an acceptable immune response (84%) compared to those who received the MF59 adjuvanted formula (57%).
Last year, we learned the H7N9 virus had split into two major lineages - Pearl River Delta and Yangtze River Delta - (see MMWR:Increase in Human Infections with Avian Influenza A(H7N9) In China's 5th Wave).  
This new (Yangtze River Delta) lineage had changed enough antigenically that it requires a new vaccine - and that means a new round of vaccine development and testing must begin.
On Thursday the NIH announced the start of two new Phase II clinical trials. First some brief excerpts from their announcement, then I'll return with more:

Thursday, March 15, 2018

H7N9 influenza vaccine clinical trials begin

Two new clinical trials testing an experimental vaccine to prevent influenza caused by an H7N9 influenza virus are now enrolling volunteers at sites across the United States. The Phase 2 studies, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), will test different dosages of the inactivated influenza vaccine candidate (called 2017 H7N9 IIV) as well as different vaccination schedules. The studies also will evaluate whether an adjuvant boosts the immune responses of people receiving the vaccine.

H7N9 is an avian (bird) influenza virus first reported in humans in 2013 in China. Since then, six waves of H7N9 infection have occurred in China, resulting in more than 1,500 cumulative human infections, according to the World Health Organization. No human cases of H7N9 influenza have been detected to date in the United States. 

Currently, the virus does not spread easily from person to person; rather, people typically become infected through direct exposure to infected poultry or contaminated environments. However, if the virus mutates and becomes easily transmissible between humans, it could result in an influenza pandemic because most people have little to no immunity to it. H7N9 has a high mortality rate, resulting in death in 39 percent of those who became infected. 

“As we experience one of the worst seasonal influenza epidemics in recent years here in the United States, we also must maintain a scientific focus on novel influenza viruses, such as H7N9, that have the potential to cause a pandemic,” said NIAID Director Anthony S. Fauci, M.D. “These new clinical trials will build upon initial studies of earlier versions of an H7N9 vaccine candidate to provide a more detailed picture of its safety and ability to generate a protective immune response to current H7N9 strains.”
(Continue . . . .)

The two clinical trials are detailed at:
Sanofi 2017 H7N9 With/Without AS03 in Adults/Elderly

Co-Administration of AS03 Adjuvanted A/H7N9 IIV With IIV4

Despite the many challenges, influenza vaccines are generally easier to create than for some of the other pandemic contenders out there. Five years after MERS-CoV emerged on the Arabian Peninsula, we still don't have a vaccine for humans, or for camels.

In 2003, a close cousin to MERS called SARS emerged in China, and infected 8,000 people around the globe. After 15 years of research, a safe and effective SARS vaccine remains elusive.

In 2012, a PLoS One  research article found that mice vaccinated with four different experimental SARS candidate vaccines developed the expected antibodies, but experienced lung damage when challenged with the virus.
Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus
Chien-Te Tseng, Elena Sbrana, Naoko Iwata-Yoshikawa, Patrick C. Newman, Tania Garron, Robert L. Atmar, Clarence J. Peters, Robert B. Couch

These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.
With a growing list of SARS-like coronaviruses being discovered in the wild (see PNAS: SARS-like WIV1-CoV Poised For Human Emergence), we may need a safe and effective SARS vaccine sooner rather than later. 
The recent debacle over Sanofi's Dengue vaccine in the Philippines (see WHO Unveils Interim Dengue Vaccine Recommendations) illustrates just how difficult, time consuming, and unpredictable vaccine development and testing can be.
Vaccines are wonderful tools and may be invaluable during the second wave or in stamping out the remnants of a pandemic - but given the amount of time they take to create, test, manufacture and deploy - are unlikely to have much impact during the opening months (or longer).

Unless we are exceedingly lucky, we'll have to make do with a wide range of Non-pharmaceutical Interventions (NPIs) - which, while not ideal - can be surprisingly effective if properly pursued.

The CDC’s Nonpharmaceutical Interventions (NPIs) web page defines NPIs as:
Nonpharmaceutical interventions (NPIs) are actions, apart from getting vaccinated and taking medicine, that people and communities can take to help slow the spread of illnesses like influenza (flu). NPIs are also known as community mitigation strategies. Measures like social distancing, hand hygiene, staying home when sick, avoiding crowds, wearing a mask if you are sick, even the closure of schools or other public venues are all potential NPIs.
Although there may be other pharmaceutical options - like antivirals - available at the start of an epidemic, those will be in finite supply and are not a panacea for infection. Prevention is always better than treatment, but never more so than during an epidemic or pandemic, when treatment options may quickly become limited.

In last year's Community Pandemic Mitigation's Primary Goal : Flattening The Curve we looked at the primary goal of the HHS/CDC's 2017 revised Community Mitigation Guidelines to Prevent Pandemic Influenza - which is to slow the spread of any severe outbreak, in hopes of limiting its impact on hospitals, essential workers, infrastructure, and ultimately reducing the death toll.

Hospital beds, ventilators, even hospital staff - may all be in short supply during a pandemic (doctors and nurses get sick, too) - which makes it all the more imperative we flatten the curve - even if it means extending the duration of a pandemic wave.
While telling people to wash their hands, cover their coughs, avoid crowds, and stay home while sick may seem like a weak response to a pandemic - in truth, they (and other more disruptive measures like school closures, cancellation of public events, etc.) may be our most powerful weapons in any pandemic.
Hopefully the unexpected lull in H7N9 outbreaks in China this winter will provide enough of a window for these new clinical trials to complete (results expected in the fall of 2019), but having this one vaccine only helps if H7N9 is the cause of the next pandemic. 
As we discussed a week ago in WHO List Of Blueprint Priority Diseases, there are plenty of other contenders.
Last May, in World Bank: World Ill-Prepared For A Pandemic, we looked at a 131-page working paper from The World Bank, that warned that far too many nations have let pandemic preparedness slide, and that the world remains unprepared to face even a moderately severe pandemic.

A conclusion not unlike that reached in 2015 by a World Bank Poll: Majority Believe World Is Not Ready For A Pandemic, and by a 2011 WHO Panel: World Ill-Prepared To Deal With A Pandemic.

In 2015, we looked at an 84-page Bipartisan Report of The Blue Ribbon Study Panel On Biodefense that looked at our nation’s vulnerability to the triple threat of a biological attack, an accidental release, or naturally occurring pandemic with a highly pathogenic biological agent.  
Their conclusion?  We aren't anywhere near ready.
I can't tell you what will spark the next severe pandemic, or how soon it will arrive. Only that each day that passes brings us closer to that day, and that when it does happen, we will find ourselves with precious little time to prepare.

A little over a decade ago, in Quotable Quotes, we looked at some statements by government officials on what an H5N1 pandemic might look like. While many were excellent, the one that best exemplifies the problem with pandemic preparedness is:
“Everything you say in advance of a pandemic seems alarmist.  Anything you’ve done after it starts is inadequate."- Michael Leavitt,  Former Secretary of HHS
Despite those challenges, we need to make pandemic preparedness a national priority. For more, you may wish to revisit:
The Challenge Of Promoting Pandemic Preparedness

WHO: Candidate Vaccines For Pandemic Preparedness - Sept 2017
#NatlPrep : Pandemic Planning Considerations

Upcoming Webinar: The Strategic National Stockpile Are We Prepared
to Help Low-Resource Populations Mitigate a Severe Pandemic?

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.