Medical News Blog Information

Flu bad, MERS a diversion?

In an "Infection hot topic" article in Clinical Microbiology and Infection, the Editor, Prof. Didier Raoult writes of the importance of not letting our excessive pride or self-confidence drive our desire to understand a rare and poorly transmissible (slowly-growing epidemic?) virus like the Middle East respiratory syndrome coronavirus (MERS-CoV) and distract us from "real infectious disease epidemics that are well known" at times of mass gatherings like the Hajj.

Because why not?

He notes that the recommendation for influenza vaccination during the recent Hajj probably prevented thousands of influenza cases and that 9% of returning French pilgrims returned an influenza virus positive throat sample. An example of some good communication then.

I wasn't aware that the scientific press, World Health Organization or governments had dropped any other balls in order to give MERS the attention any potentially new human pathogen, with or without pandemic potential, well and truly deserves.

I guess in hindsight, it might look like a lot of wasted effort went into MERS-related reporting. Readers of this blog would be aware of my own opinion on that matter - not nearly enough effort has gone into solving a number of questions about the MERS-CoV and certainly not enough data has been described and reported to make it easy to track and present new cases.

Far from being distracted, the developed nations have continued their fight against flu (so long as their governments aren't shut down), reporting heavily on it and other vaccine preventable diseases that are reappearing in the population (measles and polio for example). Many science communicators of all types in many locations around the world have also been discussing and describing in detail the oncoming wave of antibiotic resistant bacteria and many other viral and bacterial pathogens that can be considered rare depending, on the denominator you choose at the time. SARS-CoV infections were pretty rare (~8,200 confirmed cases) but the social, economic and healthcare impact of that little outbreak was incredibly disproportionate. Or perhaps it was perfectly proportionate? Remembering the SARS outbreak began in the dark without suitable coverage and communication to illuminate the early stages. 

What is the evidence that reporting on MERS has displaced any other efforts to monitor, debate or describe more endemic human infectious diseases?

Thankfully Prof. Raoult didn't call out the scientific community who are working hard to add new knowledge about "rare" human infections; work that will hopefully ensure they stay as rare as possible, for as long as possible if they are not halted at the source forever. 

I'm personally in no rush to read the bazillion Editorials that will follow in the wake of a pandemic due to infection by MERS-CoV, H7N9 or any other viruses with "little known effect on the human population".

Hindsight can be a harsh mistress but communication fosters preparedness.

New MERS-CoV genome sequence on GenBank...

I'm a little bogged down in my day-job for lots of posts just now (and too busy at nights hanging Christmas lights at home!) but just thought I'd post about the latest Middle East respiratory syndrome coronavirus complete genome sequence that's dropped onto GenBank.

It was submitted in October but came online 7-Dec.

I've added in the likely FluTracker's case number - this is the nearest match to the collection date but it may be from the index case (FT#31); both detected in France, the former form the United Arab Emirates.

Key features...

  • Name: Middle East respiratory syndrome coronavirus isolate FRA/UAE, complete genome 
  • Date of sample collection: 7-May-2013, France
  • Sequence length: 29,901nt
  • MERS-CoV case: FT#34; 
  • GenBank accession number: KF745068
  • Link: http://www.ncbi.nlm.nih.gov/nuccore/KF745068.1
  • Authors: Enouf,V., Briand,D. and van der Werf,S.
  • Virus sample source: Vero cell culture isolate
  • Sequencing type: Sanger

Zuni IHS Community Experiences

Despite the small size of the population and the Zuni Health Center, I believe they are doing very progressive work through community outreach, population health and the group practice of medicine.  I have shared just short tidbits of some of the amazing opportunities I had the privilege of being part of during my short time in Zuni.




My last morning in Zuni, I had a chance to work with Dr. Chris Piromalli in the group diabetes clinic.  A program truly on the cutting edge of community medicine; what I believe will be the wave of the future.  Moving towards a model of true individual empowerment accomplished through education and the synergy of empathy and understanding that you are not alone in your struggle with chronic disease by engaging with fellow community members facing similar struggles in facilitated group sessions.  For me it was an absolute honor to be welcomed by all involved with open arms and I�ll certainly be a better physician for having had this exposure to this model of care and a chance to hear the stories of struggle and triumphant with a chronic disease that easily becomes routine in the lives of a primary care physician.  I had the opportunity to witness the transformation of a patient taking ownership and responsibility to begin Insulin through the sharing of struggles with his Diabetic peers, a daunting task for this gentleman that had been refused multiple times in the past.  This experience was a wonderful end to an amazing month here in Zuni.  In a similar vein, I had the opportunity to participate in the joyous class of a group of families undergoing group prenatal session.

The opportunity to go with Fred, U.S. Public Health Service Nurse, to the Zuni Prison to meet with patients that were down and out was enlightening and an honor.  This is certainly one of the most disadvantaged patient populations out there and to have Fred seek them out to try to help them in times of need was a powerful demonstration of the need for reaching out to this community to make a difference in a very challenging time in their lives.  Educational and thought provoking�.

I had a chance to spend time with the program leaders of DIPS (Diabetes in Preventive Strategy) a program for pre-diabetics that includes exercise, counseling and personalized guidance to try to prevent people to progressing to diabetes and Healthy Living a program for those with diabetes to help support them with exercise and nutritional support in the community.  Zuni, New Mexico is a trial site for the well-known and published research trial the Diabetes Prevention Program (DPP) - http://diabetes.niddk.nih.gov/dm/pubs/preventionprogram/
I especially appreciated this opportunity as it is a goal of mine to one day to work with and perform outcomes research with similar initiatives.

Of all the experiences, perhaps the most poignant was an experience I had during a home visit with the Zuni Home Health Nurse.  She is a truly loving person who cares deeply about her patients.  She and her patients were so amazingly welcoming and friendly; they truly made me feel like an honored guest in their home.  One of her regular patients was a middle-aged woman with depression and advanced diabetes, our major service to her was filling insulin syringes and arranging her medications in a pill box for the week.  As we struggled to fill her pill box with a variety of medications, some weekly, some once a day, some BID/TID, etc. with some obvious confusion about her actual prescribed doses it hit me just how real the threat of poly-pharmacy is for so many of our patients.  It was powerful reinforcement of the need to do a better job of being clear and simplifying prescriptions as much as possible for my patients.  The patient�s functional status and depression was also a major impediment to her ability to care for herself, really a lesson in treating the whole person when formulating a treatment plan for a patient.  This experience made a lasting impact on me and will change my future practice of medicine for the better.


The experiences and opportunity to interact with the community and the variety of healthcare professionals in Zuni have undoubtedly made me a better physician.

Zuni, New Mexico � A Special Place

I had heard a lot of good things, but really didn�t know what to expect upon arriving to work at the Zuni Comprehensive Community Health Center  � a 2 � hour drive from Albuquerque on the Zuni Indian Reservation in Western New Mexico, near the Arizona border.  I was welcomed with open arms to a beautiful community that is visually stunning, culturally unique and home to proud and amazing people.  The health center and its healthcare professionals were inspirational practitioners of healing.  They had found their calling working in Zuni and it came through in their approach to medicine and living life.  I could not have been made to feel more welcome to be part of a community and a practice of medicine.

Zuni Comprehensive Community Health Center serves approximately 10,000 Zunis and 4,000 Navajo who live on surrounding Navajo Nation reservations lands. The majority of Zunis are bilingual, with Zuni being their first language. Many Navajo over 45 years may not speak English. There are Zuni and Navajo employees who can assist with translation.  Silver-smithing is the main source of cash income and Zunis are renowned for their intricate jewelry work and fetish carving. Employment for others is through government or tribal organizations, the school system or our facility. The median Zuni family income (1999 data) is  approximately $21,000/year and approximately 50% of the population falls below the poverty level. Traditional ceremonies are the center of nearly all social activities and Zunis follow a calendar of night dances and rain dances which take place in the plaza at the center of the old village. Zuni society is divided into six fraternal kiva religious organizations, 10 medicine societies, and 12 matrilineal clans. Traditional medicine is also an important part of Zuni culture and many Zunis incorporate visits to medicine men, bone pressors, or traditional midwives along with seeking care at our facility.  


Dowa Yalanne (DY) A Sacred Mesa, a shelter to the Zuni People during their resistance to the Spanish (my wife and son)







Government Housing across from the hospital provided by the IHS
Looking out from housing to back of Zuni Comprehensive Community Health Center
Each day started with checking on any of my inpatients that I had ad
mitted on previous days and then attending morning rounds with the entire team of physicians, pharmacist, nursing, support staff, etc. to discuss admissions, transfers and a variety of patient updates.  That was followed by a variety of 2 day clinical sessions including an opportunity to participate in a variety of community/public health outreach programs.  The model of care was one in the model of family medicine where the majority of practitioners practiced the full spectrum of care including Pediatrics, Obstetrics/Women�s Health and adult medicine.  There are no ED docs and the catchment area for the Health Center is quite large so when you were the on-call physician you are expected to stabilize, evaluate and treat whatever may come through the door � a very different feeling and expectation than being in a large academic medical center such as MGH.  There is no ICU at Zuni Health Center; on average during my time there they flew out 2 patients a week to Albuquerque for a higher level of care.  In some respects the practice of medicine feels like rural medicine, but the major difference being you are part of a group practice of physicians that provide their support and expertise.  Given the close quarters of colleagues� offices, the health center clinics and the group practice done at the hospital you always feel very supported and it fosters a sense of communication and learning between colleagues.  It certainly doesn�t feel rural or isolated to practice medicine in this environment.  There was a wide breadth of expertise and backgrounds at practicing medicine at the facility including pediatricians, family medicine and internal medicine physicians that had trained all over the country. 

Outside of work, there is an array of things to keep you busy.  There seems to always be a unique cultural event going on in the community � I was lucky enough to be in town for the annual Harvest Festival tribal dancing.  There is an array of amazing outdoor opportunities in the area including multiple national parks/monuments and the local scenery on the Zuni Reservation is also quite breathtaking.  It is the classic west with sunny days and bright blue skies where you can see for miles, filled with beautiful mesas.  During my time there I was lucky enough to make it to Sedona, Arizona (famous for its beautiful Red Rock formation and vortexes), Flagstaff, AZ (mid-size college town and base for trips to Grand Canyon) and the Grand Canyon.  I also visited friends on the Navajo Reservation and hiked Canyon de Chellay National Monument, a beautiful, sacred canyon to the Navajo.  I also made a day trip over to El Morro National Monument, a beautiful mesa with quite a history inscribed in its walls � also home to the highly recommended hang-out �Ancient Way Caf�.   I only scratched the surface of outdoor activities as other co-residents made the way to Moab and many other surrounding parks in Colorado and Utah.

I leave you with an essay about the day in the life of a Zuni physician that I think illustrates the experience well.  It was written some time ago by the clinical director of the Zuni Comprehensive Health Center, Dr. Thomas Faber, a former graduate of the Harvard Med-Peds Program:  https://www.dropbox.com/s/wooa7rfc6uxg76q/Tom%20Faber%20Essay.doc
My family in front of a red rock formation in Sedona

My family and I at the Grand Canyon

Canyon de Chelly - Spider Rock; a sacred canyon and rock formation to the Navajo Indians

Editor's note #12

Click on image to enlarge.
Latest H7N9 map.
VDU's Editor-in-Chief (okay it's just me - I also get coffee and sweep up the keyboard at the end of the day) was asked to comment on the recent influenza A (H7N9) virus case in Hong Kong.


See Bloomberg's latest article here.









�Respiratory viruses do their own thing; they don�t respect boundaries,� said Ian Mackay, an associate professor of clinical virology at the University of Queensland in Brisbane, Australia, in a telephone interview. �It does seems that it�s continuing to add to provinces and regions, rather than reappear in all the old places it started in back in February and March.�


References...

  1. http://www.bloomberg.com/news/2013-12-02/hong-kong-confirms-city-s-first-human-case-of-bird-flu.html

Rhinovirus transmission by aerosol and lower respiratory tract disease after inoculation

In the next instalment to answer the question posed in last week's post, we also find that rhinovirus can a lower respiratory tract infection (LRTI), if it is delivered directly to the site; several issues around this topic are contentious in current age of PCR diagnosis of lower respiratory tract disease using specimens from the upper respiratory tract (URT).


From Thomas R. Cate et al, Am J Epidemiol.
Author: Thomas R Cate et al
Journal:  Am J Epidemiol 81(1):95-105
Year: 1965
RV type used: NIH 1734 (RV-A151)
RV receptor type: major group; ICAM-I

This study set out to investigate the impact of RV on the lower respiratory tract.

Key features of the study layout..

  • 16 healthy adult male inmate volunteers
  • Safety-tested preparation of RV-15
    • 6 volunteers given 1ml nasopharyngeal serum-inactivated virus via a hand atomizer (coarse droplets expected to mainly deposit in the upper respiratory tract), and 1ml instilled intransally by pipette with subject lying on back
    • 8, RV-15-antibody-free volunteers were exposed to 10l of air (16, 20 or 66 TCID50 RV15), via a mask, containing 15-second-old 0.2-3.0um particles generated from a Collison atomizer (see Figure)
    • A number of re-inoculations were also performed on each virus-delivery group
    • Aerosols was also sampled using a Shipe impinger (this device contained cell culture medium onto which some aerosol was impacted) for virus isolation, after storage at -70�C. These data determined the dose that had been used
    • Prior (2-days) to inoculation, nasal, pharyngeal and anal swab specimens and 10ml of nasopharyngeal wash (NPW) were collected, frozen at -20�C for testing to identify pre-existing viruses or bacteria (all culture based). The same specimen types were collected after inoculation (minus the anal swab). RV culture was conducted on human embryonic fibroblast cultures, with rotation at 33�C)

Key results included...

  • Only 1 other virus, apart form RV-15, was found in the subjects. Culture may have missed fastidious or unculturable respiratory viruses (like the RV-Cs) however.
  • During the 1st week after inoculation, usually starting from day-2..
    • NPWs contained culturable virus in at least 1 specimen from 8/8 subjects
  • During the 2nd week after inoculation..
    • 7/8 subjects gave virus-positive NPWs
  • During the 3rd week after inoculation..
    • 5/8 subjects gave intermittent virus-positive NPWs
  • Maximal virus titre aligned in time with most severe illness
  • Nasal and pharyngeal swabs specimens did not yield virus as often as NPWs
  • All subjects had a rise in antibody titre of 4-fold or greater, indicating infection, by 3-weeks with a further bump after 4-5-weeks
  • Tracheobronchitis was diagnosed in 6/8 antibody-free aerosol-inoculated volunteers. This is a lower respiratory tract disease.
    • Signs and symptoms included cough (sometimes in fits), substernal chest pain,, wheezing, tender trachea.
    • 3 had a primary diagnosis of tracheobronchitis , the other 3 also had a prominent coryzal illness (nasal obstruction/discharge, sneezing, sore throat, swollen neck lymph nodes). 
    • Fever was determined in 5/8, within the 1st 1-2-days.
    • Signs and symptoms lasted for 1-4 days, a little longer for a rhinitis-alone
  • No tracheobronchitis developed among 31 antibody-free volunteers inoculated through a course spray/drop method into the nasopharynx
  • No infection (no suitable rise in antibody) or illness was detected among 6 volunteers inoculated with a preparation of virus that had first been inactivated by incubation with an antibody-positive serum. This identified that there were no other viruses/bacteria in the preparation that could have caused the disease. This had been, infrequently, found in other preparations by the authors so this step was important part of their comprehensive approach.
  • 4-weeks later, 2 volunteers from the aerosol infection group, 2 from the inactivated virus group, and 2 new volunteers, were (re-)inoculated
    • No infection, illness or virus shedding resulted in the aerosol pair
    • No illness but infection and shedding occurred in the pair previously inoculated with inactivated virus
    • Infection, illness and shedding were apparent in the new volunteer pair
  • Neutrophil counts were significantly raised in aerosol-inoculated volunteers at illness onset and also, but to a lesser extent, in the 6 volunteers given inactivated virus. This explains to me why in those with a predisposition to severe RV outcomes, including those with asthma, a symptomatic RV infection is not necessary to trigger an attack.
The authors concluded...
  • The aerosols generated here, which carried relatively small amounts of virus, would likely travel beyond the nasopharynx and tracheobronchial tree and be carried into the lungs, probably with <50% deposited and the remainder exhaled
  • No evidence of pneumonia was found
  • If RV is suitably aerosolized in sufficiently small particles, inhalation can result in lower respiratory tract disease while site-specific installation into the upper respiratory tract usually results a typical URTI or "common cold"

How do these findings translate to everyday exposures to RV coughs and sneezes and in children? In the general community we are constantly exposed to virus and have a complex, person-specific panoply of antibodies resulting from different infections beginning in childhood. This is probably why we are incapacitated by bad colds and LRTIs all the time! An addendum in the discussion of Cate's paper highlights how symptoms resulting from RV infection are best considered as part of the entire spectrum of possible outcomes. 

Previous symptomatic infection, as shown above, protects from lower respiratory tract disease hence adults are less likely to have LRTIs than children who see these viruses for the first time. Also, there is literature showing that the antibody to some RVs can protect against, or moderate, disease due to infection by other RVs. If you are antibody-free, then disease can potentially be more severe.

Cate's studies are all conducted without knowledge of the 50+ RV-Cs because they could not be grown (detected) using the cells employed by the culture methods of the day. Why is that relevant? Because some consider RV-Cs to be more asthmagenic/pathogenic and because we don't know the receptor or natural tissue tropism/distribution of the RV-Cs in humans. How the RV-Cs perform in human volunteer infections is unknown.

Certainly room remains for some new research building upon excellent studies like this one by Cate et al and highlighting (a) that RV can infect the lungs and cause disease if an aerosol is encountered and (b), that one outcome from RV infection does not fit all.

Further reading and references...

  1. First HRV nomenclature assignment publication
    http://www.nature.com/nature/journal/v213/n5078/pdf/213761a0.pdf

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