More cases have been reported in 2 outbreaks, one linked to Del Monte veggie trays and the other to McDonald’s salads.
The good, the bad and the ugly.
While we may not be getting all of the data out of China, the remarkable drop in reported outbreaks of H7N9 avian influenza since last fall (see chart below) – which closely follows last summer’s nationwide deployment of a newly developed H7+H5 poultry vaccine – has to be viewed as a very encouraging sign.
How long this lull will last remains to be seen, as antigenic changes in the circulating viruses – or the emergence of a new subtype – may eventually derail the vaccine’s success.
But for now, China’s MOA appears to have hit a home run.
The use of AI vaccines is not without controversy, and while China, Egypt, Indonesia, Vietnam and Hong Kong have embraced them, most countries around the world eschew their use.
Aside from complicated international trade issues, the biggest concern is that most AI poultry vaccines are only able to suppress avian flu viruses to reduce morbidity and mortality in poultry, but they don’t necessarily eliminate them.
And as avian viruses evolve, over time existing poultry vaccines become increasingly less effective. Poor vaccine matches can then allow AI viruses to spread silently among flocks, to continue to reassort and evolve, and potentially lead to the emergence new subtypes of avian flu.
A few earlier blogs on those concerns include:
There are, however, some strong advocates for using AI poultry vaccines, who see their proper use as being the only reasonable course of action for countries where these viruses are firmly entrenched.
Admittedly, the apparent success with China’s recent vaccination program suggests that modern vaccines, when properly and consistently applied, can have a positive effect.
But far too often, we’ve seen badly outdated, illegally obtained, and sometimes even home brewed vaccines used in the field (see Taiwan’s Counterfeit AI Vaccine Trade). Vaccination coverage in many places has been spotty and intermittent, and the results have been less than satisfactory.
In 2012’s Egypt: A Paltry Poultry Vaccine, we saw a study conducted by the Virology department at St. Jude Children’s Research Hospital that looked at the effectiveness of six commercially available H5 poultry vaccines then deployed in Egypt, and found only one (based on a locally acquired H5N1 seed virus) actually appeared to offer protection.
Five months ago, in PLoS One: Effectiveness of HPAI H5N1 Vaccination in Poultry – Indonesia, we saw another study that painted a less than impressive picture of poultry vaccination effectiveness in Indonesia.
The authors cited frequent low HI titres in poultry even after three rounds of vaccines, vaccination failures, and warned of silent infections and the generation of new H5N1 antigenic variants.
Fast forward to today, and we have a new study published in Nature’s Scientific Reports on the efficacy of Egyptian poultry vaccines in light of the arrival (in late 2016) of the clade 220.127.116.11. HPAI H5N8 virus.
Many of the authors contributed to the 2012 paper mentioned above, and the results are eerily similar to what was reported nearly 6 years ago.
Efficacy of commercial vaccines against newly emerging avian influenza H5N8 virus in Egypt
Ahmed Kandeil, Jamal S. M. Sabir, Ahmed Abdelaal, Ehab H. Mattar, Ahmed N. El-Taweel, Mumdooh J. Sabir, Ahmed Aly Khalil, Richard Webby, Ghazi Kayali & Mohamed A. Ali
Scientific Reports volume 8, Article number: 9697 (2018 )
The newly emerging, highly pathogenic avian influenza (HPAI) H5N8 virus of clade 18.104.22.168 was recently detected in wild birds and domestic poultry in Egypt in the 2016/2017 winter season. Vaccination based on commercial H5 vaccines is used as an essential control strategy in Egyptian poultry.
Here, we studied the efficacy of the eight most common commercial H5 poultry vaccines in the Egyptian market and compared them with an experimental vaccine based on the Egyptian LPAI H5N8 virus that was prepared by using reverse genetics.
The experimental vaccine and Re-5 commercial vaccine were able to completely protect chickens and significantly reduce virus shedding.
Our results indicate that most of the commercial poultry H5 vaccines used in the present study were ineffective because the seed viruses in these vaccines are genetically distinct from the H5N8 viruses currently circulating in Egypt.
Although some of the commercial vaccines protected chickens from mortality, they failed to prevent chickens from shedding the virus. Accordingly, we recommend updating and reinforcing the H5N8 prevention and control strategies in Egypt. The vaccination strategy should be reconsidered based on currently circulating viruses.
The experimental homologous H5N8 vaccine provided the best protection against a challenge with the clade 22.214.171.124 virus. The sera of chickens vaccinated with the Re-5 Merial, Zoetis, EgyFlu, CEVac Flukem and Volvac (B.E.S.T.) vaccines showed reduced cross-reactivity against the Egyptian H5N8 virus and provided ≥ 80% protection, while the Nobilis, ME Flu VAC, and SERA-VAC vaccines did not reach the protection limit recommended by the OIE.
The Re-5 Merial (based on a clade 2.3.4 H5N1 virus) vaccine protected the chickens from mortality and reduced virus shedding. Most of the commercial vaccines protected chickens from mortality but did not reduce or prevent virus shedding. This suggests that the circulating H5N8 viruses may evade vaccine protection.
The genetic dissimilarity and poor reactivity between the H5 commercial vaccines used in Egypt and the currently circulating H5N8 viruses proves that the vaccines might not be effective in the field or may introduce only partial protection and thus could lead to vaccine-induced escape mutant strains.
In many developing countries, poultry and eggs are not only prime sources of badly needed and relatively inexpensive protein, they are often a measure of an individual’s wealth. The wholesale culling of poultry, whether commercial or backyard , can have dramatic economic and societal effects (see Iran: Bird Flu, Food Insecurity & Civil Unrest).
No government is more aware of this fact than China, and so when HPAI H7N9 emerged in early 2017, the decision to go on the offensive with an experimental H5+H7 vaccine was viewed as a matter of national security.
While modern AI poultry vaccines hold a lot of promise – and would likely better the lives of millions of people in low resource countries dealing with endemic avian flu – they have to be frequently updated and correctly applied, if they are to be effective.
But all too often we see exactly the opposite in the field.
Until that changes, and we see more success stories like what we’ve seen this past year out of China, the global reluctance to embrace AI vaccines will likely remain unchanged.
As the Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo (DRC) looks to be under control, how much the vaccine has helped remains an unanswered question. But will it be answered with hardly any new cases being confirmed? Let’s have a closer look at the timing of things.
Vaccine versus care, tracing and supportive treatments
The finals days of the EVD epidemic in West Africa which spanned from 2013 to 2016. https://virologydownunder.blogspot.com/2014/07/ebola-virus-disease-evd-2014-west.html-evd-2014-west.html
Don’t get me wrong – having this vaccine is a fabulous and beneficial addition to the struggle to contain EVD outbreaks. What happened from 2013 to 2016 in Guinea, Sierra Leone and Liberia  should never happen again.
But a question surrounding the use of the vaccine is whether it actually prevented cases of EVD this time around, or were the central pillars of containment sufficient?[8,11] These pillars were recently described by Médecins Sans Frontières  as…
- Early care and isolation of people who present with symptoms
- Tracing and follow-up of patient contacts
- Informing people about the disease, how to prevent it and where to seek help
- Supporting existing healthcare structures
- Temporarily adapting cultural behaviour to make funerals safe
- Outreach activities (pro-active case finding)
#UPDATE: These are the ‘six pillars’ of intervention to contain an Ebola outbreak:
1.Early care and isolation of people who present with symptoms
2.Tracing and following up patient contacts
3.Informing people about the disease, how to prevent it and where to seek pic.twitter.com/G0dDckY3pa
— MSF West Africa (@MSF_WestAfrica) June 8, 2018
These responses were certainly rolled out more quickly in the current outbreak.
What does the timing look like?
I’ve added to my latest graph of totals (cases, suspected cases, probable cases, confirmed cases and fatal cases). Two new vertical dashed lines indicate when vaccination with the recombinant vesicular stomatitis virus carrying an Ebola virus glycoprotein gene (rVSV-ZEBOV) EVD vaccine began in the Mbandaka region (which sits in the Wangata health zone) and in the Iboko and Bikoro health zones. These lines help tell us some things:
- There were 7 confirmed cases of EVD after the Mbandaka vaccinations began and before the Bikoro/Iboko campaign commenced; all within 3-days (23rd to 24th May) after the first shots
- There were 3 confirmed cases of EVD after the Bikoro/Iboko vaccinations began; 2 within 2 days (29th and 30th May), and 1 at 9 days later (6th June)
What does the literature say about how quickly the vaccine protects?
In the discussion of a study of the effectiveness of ring vaccination in Guinea, the authors noted that the time to induce protective immunity using this same vaccine, “might happen quickly, within a few days or a week.” If so, the vaccine may indeed have been responsible for the slowing and stopping of confirmed cases days after it was deployed.[2,12] We know for certain that a good immune response is usually in place 28 days after vaccination.[2,12]
The DRC outbreak has been much smaller than that in West Africa. The rVSV-ZEBOV vaccine remains unlicensed requiring individual consent for each dose. Use of the vaccine in the DRC has been accompanied by ethical approval and oversight from the DRC Ministry of Health and has also been part of studies to better understand its effectiveness. Because it is unlicensed, widespread use of the vaccine has not been on the agenda and so numbers of vaccinated people are also fairly small.
Previous studies in macaques found that, if given within a short time after infection, the rVSV-ZEBOV vaccine could provide a prophylactic effect.[3,4] One of these studies suggested that protection may result from an initial non-specific innate immune response that matures into a more specific response, while the other pointed to natural killer cells and non-neutralizing antibody as essential factors with day 6 after infection being a critical time point in macaque studies.
If we look more closely at each of the health zones, we can see some other interesting things.
The vertical dashed lines show when vaccine rollout began in the health zones. From these graphs, we can see some really interesting differences.
One difference is unrelated to vaccination. There is a very different proportion of fatal cases (PFC) in Iboko (currently at 20%) compared to Bikoro (72%) and Wangata (74%; but low case numbers). Is this low value in the Iboko health zone due to lost fatal cases, cases that could not be tested or to better care? We saw better survival rates in West African treatment units like that in the Hastings Police Training School near Freetown, Sierra Leone where more aggressive support (including intravenous fluids, antibiotics and antimalarials) was provided (h/t @AhmedTejanSie).
In Bikoro, there were no confirmed cases for days before vaccination began, and there have been none since. That means we can’t tell if there was a protective effect. But we will still be able to follow the vaccinated people and determine whether a protective immune response resulted.
In Iboko there were confirmed EVD cases before and a few after. It will be interesting to learn whether those post-vaccination cases were among vaccinated people or in different transmission chains or among known contacts who just hadn’t been vaccinated yet.
In Wangata, like Bikoro, there were no confirmed EVD cases in the days leading up to the vaccination campaign, and none added since. Iboko, which also has had the highest caseload of this outbreak, may be our only hope of answer the question of vaccine effectiveness.
The outbreak slows before treatments get trialled
Graphing the day-by-day doses of vaccine given in the 3 affected DRC health zones. Data from DRC MOH.Click on image to enlarge.
Teasing out the role of the vaccine in the DRC-2018 outbreak will be a challenge and with the way things look, the need for another vaccine  or perhaps even for treatments, is fading quickly. At least, unless there are plans by the Chinese to vaccinate their citizens ahead of the next outbreak.
Another marker of outbreak control is that vaccine administrations have slowed. Today’s data from the DRC MOH included the lowest number of vaccinations (81;) since the roll-out began (averaging around 165 per day). With just over 2,100 vaccinations provided so far, it’s unlikely all of the first batch of 7,500 doses will be needed. And the second batch certainly won’t be unless things take a dramatic turn for the worse.
The decreasing need for preventative and therapeutic drugs is a good thing for the people of the DRC since it means the outbreak is probably controlled. On the other hand, it means we won’t learn more about what could be useful in treating EVD cases before the next outbreak.
Perhaps some of these treatments will prove useful in clearing our persistent Ebola virus infections. That would certainly be a good thing. If not, then we’ll just go through this whole process again next time; hopefully, more quickly. But at least we’ll have more ducks in a row because we will have learned and planned ahead for all of the necessary steps.
- Democratic Republic of Congo: Fighting Ebola on the ground, a race against time
- Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial
- Efficacy of Vesicular Stomatitis Virus–Ebola Virus Postexposure Treatment in Rhesus Macaques Infected With Ebola Virus Makona
- Effective Post-Exposure Treatment of Ebola Infection
- post-Ebola syndrome or just chronic Ebola virus disease…?
- China may compete with the West for limited opportunities to test Ebola vaccine
- Ebola treatments approved for compassionate use in current outbreak
- Excitement over use of Ebola vaccine in outbreak tempered by real-world challenges
- Vaccines Alone Won’t Beat Ebola
- Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Sufft!)
- Ebola in Freetown Area, Sierra Leone — A Case Study of 581 Patients
While influenza activity has dropped back to inter-seasonal levels in the Northern Hemisphere – the yearly flu season runs from October 1st to September 30th – and low level activity and delayed reporting means that the numbers in today’s FluView report may continue to rise in the weeks and months ahead.
Nevertheless, the 2017-18 flu season has been one for the record books, with an overall hospitalization rate in excess of 106.6 per 100,000 population. Comparisons with years prior 2010 are difficult because the method for collecting data has changed, but this is a modern record.
This flu season has also taken a heavy toll among pediatric patients, with a record matching (for a non-pandemic season) 171 flu-related fatalities, equaling the 2012-2013 season, which had set the record for the highest number of pediatric flu related deaths since record keeping began in 2004.
Since reporting became mandatory in 2004 yearly pediatric influenza deaths have ranged from a low of 35 during the 2011-2012 flu season to a high of 282 during the 2009—2010 H1N1 pandemic.
As tragic as the 2009 pandemic tally was, the CDC estimated that the number of pediatric deaths in the United States probably ranged from 910 to 1880, or anywhere from 3 to 6 times higher than reported.
Even during non-pandemic seasons, the CDC believes the officially reported numbers likely understate the true number of pediatric deaths due to influenza by half.
In 2013, in Pediatrics: Influenza-Associated Pediatric Deaths, we looked at a study by Karen K. Wong et al. called Influenza-Associated Pediatric Deaths in the United States, 2004–2012 that analyzed the first 8 years of data on pediatric flu-related deaths.
They reported the median age was 7 years, that 35% of children died before hospital admission, and of 794 children with a known medical history, 43% had no high-risk medical conditions.
A few months ago we looked at a new study (see Influenza-Associated Pediatric Deaths in the United States, 2010–2016), published in the journal Pediatrics, that looked at pediatric flu-related deaths during the next 6 post-pandemic flu seasons (2010–2016) and found the median age has dropped to 6 years, and the percentage of kids with no high-risk medical conditions had jumped to 50%.
While the flu shot isn’t always as effective as we’d like – particularly in recent years against H3N2 – it often works better in children, and the (quadrivalent) vaccine is usually far more effective against both H1N1 and Influenza B.
Less than a year ago, in Pediatrics: Study Shows Flu Shot Reduces Flu Related Pediatric Deaths By Half, we looked at another CDC study which found:
`. . . . flu vaccination reduced the risk of flu-associated death by half (51 percent) among children with underlying high-risk medical conditions and by nearly two-thirds (65 percent) among healthy children.’
Yesterday the CDC released the following statement on the record-matching pediatric flu-related death toll, which warns that due to delays in reporting, this year’s number could climb higher.
June 1, 2018 – In CDC’s FluView report for the week ending June 1, 2018, two additional flu-related deaths in children were reported, bringing the total number this season to 171. This number matches the 2012-2013 season, which previously set the record for the highest number of flu-related deaths in children reported during a single flu season (excluding pandemics). Approximately 80% of these deaths occurred in children who had not received a flu vaccination this season. CDC recommends an annual flu vaccine for everyone 6 months and older. These deaths are a somber reminder of the importance of flu vaccination and the potential seriousness of flu. CDC experts have described the 2017-2018 season as a high severity season, with influenza-like-illness (ILI) remaining at or above baseline for 19 consecutive weeks, record-breaking flu hospitalization rates, and elevated pneumonia and influenza mortality for 16 weeks.
Since flu-related deaths in people younger than 18 years became nationally reportable in 2004, the number of deaths reported to CDC has ranged from 37 during the 2011-2012 season to 171 deaths during the 2012-2013 season. This excludes the 2009 H1N1 pandemic, when 358 pediatric deaths were reported to CDC during April 15, 2009, through October 2, 2010. The 2012-2013 season was similar to the current one in that influenza A(H3N2) viruses predominated overall. The severity of that season was characterized as moderate severity overall among children and adults, but high severity was reported among older adults. H3N2-predominant flu seasons are typically associated with more severe outcomes for both children and older adults.
While flu vaccination is recommended for everyone 6 months and older, certain people are known to be more vulnerable to serious flu-related complications, including children younger than 5 years (and especially those younger than 2 years) and children of any age with certain long-term health problems, such as asthma or other lung disorders, heart disease, or a neurologic or neurodevelopmental disorder.
Reported flu deaths in children this season are evenly split between boys and girls, and about half of these children are reported to have had a medical condition that placed them at high risk of developing serious flu complications. About 60% of these children died after admission to the hospital, while about 40% of children died at home or the emergency department. Most children died within 7 days of symptom onset. More information about reported flu deaths in children this season, and previous seasons, is available on FluView Interactive.
Data this season is similar to what has been previously reported, including in a recent CDC study published in the journal Pediatrics showing that half of flu-related deaths in children from 2010 to 2016 occurred in otherwise healthy children, only 22% of whom were fully vaccinated. The same study also showed antiviral treatment was only given in about half of all pediatric flu deaths. Nearly two-thirds of children died within seven days of developing symptoms. Over one-third died at home or in the emergency department prior to hospital admission.
While flu vaccine can vary in how well it works each season, a CDC study published in Pediatrics in 2017 showed that flu vaccination can be life-saving for children. The study, which looked at data from four flu seasons between 2010 and 2014, found that flu vaccination reduced the risk of flu-associated death by half (51 percent) among children with underlying high-risk medical conditions and by nearly two-thirds (65 percent) among otherwise healthy children.
As reporting of deaths in children can be delayed, it’s possible that additional flu-related deaths in children during the 2017-2018 season will be reported to CDC.
Not quite two years ago (June 2016) the CDC issued a Clinical Alert to U.S. Health care facilities about the Global Emergence of Invasive Infections Caused by the Multidrug-Resistant Yeast Candida auris.
C. auris is an emerging fungal pathogen that was first isolated in Japan in 2009. It was initially found in the discharge from a patient’s external ear (hence the name `auris’). Retrospective analysis has traced this fungal infection back over 20 years.
Since then the CDC and public health entities have been monitoring an increasing number of cases (and hospital clusters) in the United States and abroad, generally involving bloodstream infections, wound infections or otitis.
Adding to the concern:
- C. auris infections have a high fatality rate
- The strain appears to be resistant to multiple classes of anti-fungals
- This strain is unusually persistent on fomites in healthcare environments.
- And it can be difficult for labs to differentiate it from other Candida strains
The CDC has updated their C. Auris surveillance page, where they show – as of April 30th – 279 confirmed cases and 29 probable cases, across 11 states. An increase of more than 10% over the previous month.
Additionally, based on targeted screening in four states reporting clinical cases, the CDC reports an additional 517 patients have been discovered to be asymptomatically colonized with C. auris.
As previously mentioned, this isn’t just a United States’ problem, but a global health threat. This fungal infection, which was first detected in Japan in 2009, has now turned up on multiple continents.
- In last month’s update we looked at a CDC’s MMWR report on C. Auris in South America, illustrating how easily this fungal infection can fly under the surveillance radar (see Notes from the Field: Surveillance for Candida auris — Colombia, September 2016–May 2017).
- Since then, we’ve also looked at ECDC: C. Auris Rapid Risk Assessment For Healthcare Settings – Europe, where at least 620 cases of infection or colonization have now been identified in 7 EU nations.
For more on this emerging fungal pathogen, you may wish peruse the CDC’s dedicated web page:
And for some older blogs on the topic, you may wish to revisit:
The Nipah virus – normally carried by fruit bats common to S.E. Asia – was only first identified 20 years ago after an outbreak in Malaysia, which spread from bat to pigs – and then from pigs to humans – eventually infecting at least 265 people, killing 105 (see Lessons from the Nipah virus outbreak in Malaysia).
Similar to Australia’s Hendra virus – Nipah – because of its high mortality and (limited) human-to-human transmissibility – has garnered a reputation among researchers as having at least some pandemic or bio-terrorism potential.
- In Steven Soderbergh’s 2011 pandemic thriller `Contagion’, technical advisor Ian Lipkin – director of Columbia University’s Center for Infection and Immunity in New York – painstakingly created a fictional MEV-1 pandemic virus based on a mutated Nipah virus.
- In 2015’s Blue Ribbon Study Panel Report on Biodefense a bi-partisan panel described a fictional biological attack on Washington D.C. using a genetically engineered Nipah virus as part of their presentation.
- Just last week, in the Johns Hopkins Clade X exercise, a genetically altered Nipah virus (spliced onto a parainfluenza backbone) was the cause of their fictional pandemic.
- And earlier this year, in WHO List Of Blueprint Priority Diseases, we saw Nipah and Henipaviral diseases listed among the 8 viral threats in need of urgent accelerated research and development.
Overnight, India media (and now Western media) have been reporting on an outbreak of Nipah in Kozhikode, in India’s southern Kerala state (see Crof’s blog Kozhikode: 11 die of suspected Nipah virus infection; medical officials say no need to panic).
While the Indian media is known for its hyperbole, and the exact number of cases and/or deaths vary between accounts – other reports – such as the BBC’s Deadly Nipah virus claims victims in India at least confirm the main points of the story.
The only official statement I’ve found (the MOH website remains typically silent) has been the following brief press release from the Press Information bureau.
Ministry of Health and Family Welfare 21-May, 2018 13:51 IST
In view of the rising number of cases and reported deaths due to Nipah Virus in Kozhikode, Kerala, Shri J P Nadda, Union Minister of Health and Family Welfare has assured all support to the Kerala Government and has directed a multi-disciplinary Central team from National Centre for Disease Control to immediately visit the district, and assist the State and closely monitor the situation. The team will reach Kerala today.
“We are closely monitoring the situation. I have spoken to Shri Alphons and Smt K Shailaja, Health Minister, Kerala and assured them all support of the Central government. I have also dispatched a Central team to assist the State government and initiate required steps,” the Union Health Minister said in a statement from Geneva.
On the directions of the Health Minister, Smt. Preeti Sudan, Secretary (HFW) has also spoken to the Principal Health Secretary of Kerala and reviewed the situation.
The Central team includes Dr Sujeet K Singh, Director, National Centre for Disease Control, Dr S K Jain, Head Epidemiology, NCDC, Dr P Ravindran, Director, Emergency Medical Relief (EMR), Dr Naveen Gupta, Head Zoonosis, NCDC along with two clinicians and one expert from Ministry of Animal Husbandry.
Over the past decade nearly all of the reported Nipah outbreaks have come out of Bangladesh, often linked to date palm sap collection (see Bangladesh: Nipah Update).
Fruit bats of the Pteropodidae family have a preference for roosting in the tops of trees rather than caves, which allows them to contaminate date juice collection jars with their virus laden urine and feces
Once infected via a zoonotic exposure, humans can transmit the virus on to others, albeit not terribly efficiently (see EID Journal Person-to-Person Transmission of Nipah Virus in a Bangladeshi Community).
While outbreaks of Nipah have tended to be limited in size, we’ll be following the events in Kozhikode (pop. 550,000) closely, as our knowledge of the virus is limited as well.