Medical News Blog Information

H7N9 vaccine progresses through Phase I trials...

Back in August I wrote about Novavax entering Phase I clinical trials with its virus-like particle vaccine (VLP) to prevent influenza A(H7N9) virus disease. It is based on the A/Anhui/1/2013 strain.

Novavax, A United States company, has now reported in the New England Journal of Medicine that 80% of people may be protected by the generation of anti-H7N9 antibodies in response to 2x 5�g injections in the presence of 60 units of CSL's Iscomatrix adjuvant (see more on adjuvants in my August piece). 284 people were enrolled in a trial in Australia to determine these "very preliminary" results. Increased reactions were seen among the immunized at the injection site, but few were severe.

The move away from the egg-based vaccine manufacturing system is likely to allow vaccines to be produced in much shorter periods; 12-weeks after an outbreak starts, with 50,000,000 doses potentially available in 4-months.

You may ask, why then is it precisely 9-months after the 1st H7N9 case was retrospectively identified, and Novavax is still only at Phase I trials? I think, and I'm no expert in this area, that the process will increase in speed once the 'backbone' (the VLPs being used here which are based on a baculovirus, all produced in insect cells) in combination with this adjuvant etc, have been through the entire clinical trial process the first time. A successful backbone can be leveraged for other vaccines too.

You can see a little more of the process of making the VLPs, in this case for respiratory syncytial virus, here.

So, big changes lie not-too-far ahead for influenza vaccines....assuming the course through clicnial trials is smooth sailing of course!


For those hypersensitive to hyperlinks...

EMERGENCY NEEDS ASSESSMENT IN WESTERN KENYA

After the first few weeks performing a needs assessment in and around Kisumu, Kenya, I'm getting the handle on the survey. I've managed to adopt a bit of an accent in order for the practitioners to understand me. And if I speak slowly enough, a true challenge for me, the language barrier is minimal. All the providers have been very helpful. At first, most seem a little skeptical and resistant to sit down with me for a full hour of interviewing. Eventually, they are able to find some time for our team and have a good conversation about their emergency care capabilities. Unfortunately, sometimes the conversation can run over sometimes, but that usually means we were laughing to much trying to get to know each other.


Dave Young, MD

MERS-CoV tally....



Click on image to enlarge.
The global MERS-CoV map as of 18-11-2013.
Kuwait is currently depicted as having imported, 
rather than locally transmitted or acquired cases.
The WHO tally for Middle East respiratory syndrome coronavirus (MERS-CoV) lab-confirmed cases now stands at 157, of which 66 have died. 

The 2 latest cases, with lots of relevant WHO details are from Kuwait but are reportedly not contacts.


  • FT#158. 47-year old male, ill on 30-Oct, hospitalized 7-Nov. He is critically ill. Travel outside of Kuwait, within a time-frame that might suggest MERS-CoV acquisition, has not been noted so far so I am marking this in red on the map to indicate a local acquisition for now.
  • FT#159. 52-year old male, ill on 7-Nov, hospitalized 10-Nov. He recently travelled overseas and there is possible exposure to camels (WHO tweet without specific detail, 16-Nov). Also critically ill.

My tally lists another case, that of the case imported into Spain (61-year old female). However, that case has not yet been confirmed to WHO standards which may require a change to the map if the case, like the 2 from Italy in September, are classified as "probable" rather than confirmed cases. 
Thus the proportion of fatal cases stands at 42%.

RSV retreated, flu fading, parainfluenza picking up: Queensland respiratory virus numbers up to Week 45, 2013

If you like to keep track of influenza cases in Queensland, Australia, then the Queensland Government's Queensland Health (QH) influenza data website is for you.

It's a great place to drop by and check out the comings and goings of influenza viruses and many of the other traditional respiratory viruses including adenoviruses (AdVs), parainfluenzaviruses (PIVs) 1, 2 and 3, human metapneumovirus (MPV) and respiratory syncytial virus (RSV) - the "Big8". Testing is not routinely conducted for the rhinoviruses (RVs).

The snippet below is from data that are publicly reported on the QH website. These images cover to the week beginning 3rd of November (up to Sunday, Nov 10th, 2013).

The charts highlight that
 the 2013 flu season is winding down in Australia, also reflected by the WHO global updates. This year flu followed on from what seemed to have been a large RSV season. Unfortunately I couldn't find data for this same time period last year to compare RSV prevalence.

In the wake of influenzavirus season, the parainfluenzaviruses are now on the rise in the lead up to summer. I expect the RVs (and enteroviruses) are also climbing, but in greater numbers.

Click to enlarge. 
A snippet from the Queensland Health Statewide Weekly Influenza Surveillance Report for 01.01.2013-10.11.2013
My thanks to the team at the Communicable Diseases Unit, Queensland Health.

The source of these data  can be read in full..


Antenatal Ultrasound Training in Resource-Limited Regions of Western Kenya

 

Maternal mortality continues to be a significant public health problem throughout the developing world.  Sub-Saharan Africa accounts for approximately 50% of all maternal deaths globally.  World Health Organization data suggests that the majority of these deaths could be prevented if emergency obstetric care were available at every birth. However, since almost half of all births in developing countries take place at home without a skilled birth attendant, life-saving obstetrical interventions are often delayed.  This results in unnecessary maternal and fetal morbidity and mortality.

 

A new generation of affordable, hand-held ultrasound machines has opened the possibility for antenatal ultrasound screening programs in resource-limited settings, such as rural Kenya.  However, given the general paucity of radiologists in Kenya, the training of non-radiologist clinicians in point-of-care ultrasound is essential.  I had the pleasure of working with the Division of Global Health and Human Rights and Kisumu Medical Education Trust, our in country partner, to train midwives in point-of-care maternal ultrasound in Western Kenya.

 

Working with an ultrasound-trained Emergency Room physician from California and three Kenyan midwives with subspecialty training in ultrasound, we provided one week of refresher training in antenatal ultrasound to 16 nurse midwives from all over Western Kenya.  The midwives participating in the refresher course had received initial antenatal ultrasound training through our program nearly 1 year prior.  In the mean time they had integrated limited antenatal ultrasound services into their rural obstetrical practices.

 

 

It was great to reunite with the midwives whom I had worked with before and to meet and hear the stories of those midwives whom I was meeting for the first time.  These dedicated health care providers shared powerful stories of how ultrasound had impacted their patients in positive ways.  By identifying high-risk conditions early (i.e., placenta previa, twin gestation, and abnormal presentation), providers could arrange hospital delivery for these patients.  In the absence of these ultrasound-based diagnoses, these patients may have delivered at home, potentially resulting in untreated complications of delivery.

 

 

Overall, I feel blessed to have had the opportunity to participate in the amazing ultrasound work happening in Western Kenya.  Recently, the Kenyan Ministry of Health decided to provide free hospital-based labor and delivery care to any woman in Kenya who desired it � effectively eliminating another barrier to safe perinatal care for Kenyan women.  I look forward to continuing my participation in this important mission and thank the Partners Center of Expertise in Global and Humanitarian Health for helping to make it possible.

 

H. Benjamin Harvey, MD, JD

Resident

Department of Radiology

Massachusetts General Hospital

The book of MERS has several chapters yet to write

Epidemic is a big word, and while it generally means "a rise in the number of cases above what you'd expect", you can see from the definitions below that there are many ways to spin the meaning. For the public at large, it generally means "bad scary stuff" and so it's important that we use this word sparingly.

An epidemic is defined by Oxford Dictionaries as:


a widespread occurrence of an infectious disease in a community at a particular time

..or more applicably..



a sudden, widespread occurrence of an undesirable phenomenon

...from Merriam Webster online...


affecting or tending to affect a disproportionately large number of individuals within a population, community, or region at the same time

...from Wikipedia...


In epidemiology, an epidemic (from ep? (epi), meaning "upon or above" and d?�?? (demos), meaning "people") occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience.

The Middle East respiratory syndrome (MERS) was so-named back in May 2013, and prior to March 2012, there had been no known cases of the coronavirus (CoV) named for the disease it was associated with.

Yesterday we saw a detailed publication by Cauchemez and colleagues in the Lancet Infectious Diseases (LID). Accompanying that was an excellent piece in the Canadian press written by Helen Branswell which included some comments from the authors.

Click to enlarge. 
Accumulation of MERS-CoV lab detections by week (blue
mountain, 
left y-axis) and the accumulating deaths
(red line, left y-axis). The proportion of fatal cases is slowly
declining as fewer cases have died recently (ratio; black line,
right y-axis). No data exist for ~3 or so deaths and I include
the unconfirmed 2nd case in Kuwait for now.

Feel free to use, just cite me and here.

The key phrase slowly-growing epidemic, used by both, has been not-so-slowly appearing everywhere since then. Does that phrase accurately represent MERS to the world?

Yes, it does. If you have a look at the chart above, its been a steady increase ("blue mountain"), but despite the apparent steep slope of new cases, the steepest part of the mountain, extracted and plotted below, is in fact very linear. A steady but slow growth in cases. No exponential take off. No major deviations. So yes, there is an epidemic. And yes, it is slow. 156 (157 if 2nd Kuwaiti instance is confirmed) cases over 87 weeks in a country of 20,000,000+; a country that just hosted the biggest human gathering of the year (the Hajj) and a country which provides a launch point for around 18,000,000 travelers and a destination for almost as many



Click to enlarge.
A slowly growing outbreak of an emerging  coronavirus.
Cases have been accumulating worldwide but at a
linear rate since the week beginning April 7th.
Why the spike from this week? I'm not sure.
Feel free to use, just cite me and here.
But I think we need to be careful when throwing around the "E" word. An outbreak of an emerging virus may still be the best term to describe this chapter in the book of MERS. When someone asks on Twitter "to panic or not to panic"? (this was in reference to the latest MERS-map I posted) then I wonder if the correct message is being conveyed.
Another central message of the new LID paper was a no-brainer; well it was to me but perhaps I'm just too close to it all - in which case take this with a grain of salt.


I thought it was as obvious as the hump on a camel that where 1 case of a respiratory virus infection was detected, others were there to be found. After all, a virus needs us to survive - no us (which means no us actually harbouring infections, acting as a living incubator) then no more cases of the virus). Perhaps that's not obvious at all. Perhaps there is a lack of general understanding that our pathology laboratory systems do not test everyone with illness for even the "standard" endemic human respiratory viruses; that only those presenting to the right place, with the appropriate signs and symptoms, get a sample collected and get tested. This is apparently also true for MERS-CoV-which is by no means a standard virus. Do you go to your doctor if you feel mildly crook? Of course not - you go to work. What if you just have a fleeting headache, a stiff neck, feel a bit hot? Still going to work? Still going shopping? Still packing the kids off to school? Of course you are because we have these all the time and we have an immune system that does a wonderful job keeping it all mostly under control. Life goes on.
But you may be positive for a virus and you are a key part of the transmission chain. You are an incubator. A host.


So if routine testing is not geared towards finding out this extra information how do we find out what's going on in those who are not presenting with kidney failure or pneumonia; a relative small sliver of the population? Someone has to run a research study in which you enrol or get permission from people who are not very ill and sample them. Then you know something new about how widely the virus you are interested in is spread, for how long a person sheds it (if you sample the same person a few times during a month) and even how many other people get it (because all of a sudden your "contacts" become those of a less ill person and the numbers go up and you capture more of a picture of what's happening). So where are the research studies doing this?

When the illness is just some fleeting thing its no real problem. Especially when it's due to a virus we know all about and don't track for public health reasons (we track influenza virus positives, but the reality is you have to be sick enough to be tested in order to add to that pool of data). 



Click to enlarge.
A very exaggerated example of how failing to test mildly ill or asymptomatic
cases of infection in the community may confound our ability to make a link
between cases of severe illness leaving knowledge gaps. These gaps prevent our ability
to track spread of the pathogen and thus interrupt spread of disease.
Feel free to use, just cite me and here.

But if that virus is not yet in a textbook, not yet understood, not yet weighed and measured against the viruses we are more familiar with, emerges from an unknown place, is not considered endemic and is often notifiable, then not knowing this basic stuff becomes a major hole in our knowledge and our ability to respond appropriately. This is where we (still) are, 87-weeks after the first known MERS-CoV positive. Guessing (however educated) at what's happening by extrapolation and modelling.

I guess not everyone knows that for every time there is a noticeably ill person infected with a "respiratory virus", it's fair to assume that there will be at least 1 or other who gave it to them, got it from them or got it from the one who gave it to them and who are not as sick or even considered sick at all. For MERS-CoV, they are missed and thus we have no idea how the virus is spreading. Just models. But we can make mathematically supported guesses to back up gut instinct, fair assumptions and logic.


The hallmark of, and big problem with, the MERS outbreak (an epidemic mostly for the Kingdom of Saudi Arabia [KSA]), is that testing has been LIMITED to those who have pneumonia, or another severe disease, and their close contacts. Back in August Memish noted that surveillance was focused on those with pneumonia which was again noted by a WHO representative yesterday.


Why, why oh why not test more people? Why?! Is it because "it's too costly to prospectively test people by RT-PCR unless they are (very) ill"? It might be for some nations, but the KSA is not one of those. 


If you don't test others then you see these modelling publications arise. Idle hands and all that. Yes, it is great to have a model to support what many of us think to be true. And as Fisman and Tuite note in their editorial accompanying the LID article..



..inferences based on the best available data, even if those data are imperfect, allow decision makers to follow optimum courses of action based on what is known at a given point in time.

The question is, can decision-makers sign off on any actions if they don't have actual data? If those data are not forthcoming, how can we ever test the validity of the MERS models?

For now at least, I think we can agree that there is just too little testing to know enough to write more than a few chapters of the MERS-CoV textbook. A book for which we do have a table of contents. Many viruses have emerged before this one and they have each taught us what pages to skip ahead to. Unfortunately, we seem to have a recalcitrant author for 1 or 2 chapters. 

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