ONE HEALTH OKLAHOMA

January 9, 2020

As a background, Comparative Medicine is a discipline composed of basic science researchers and veterinary clinician scientists that experimentally compare the similarities and differences between human and animal diseases. How does one disease “spillover” to humans? What is the difference between animal and human physiologic response to a pathogen? From that basic science bench, the results are then studied to see if they translate to improving health outcomes (Translational Medicine). 

Some examples include:
1. Genetic variation in glioblastoma, breast, and prostate cancers
2. Reduction of Bovine tuberculosis and brucellosis transmission to humans 
3. Type 2 diabetes in cats and humans
4. Obesity related complications in animals and humans
5. Improvement of adenoviral vectors for canine melanoma
6. Viroimmunotherapy for malignant melanoma
7. Immunotherapy with HER2-expressing L. monocytogenes for pediatric osteosarcoma
8. Regulatory requirements regarding clinical use of human cells, tissues, and tissue-based products
9. One medicine: a development model for cellular therapy of diabetes
10. Novel filovirus risk in New World bats

Reference:
Stroud C, Dmitriev I, Kashentseva E, Bryan JN, Curiel DT, Rindt H, Reinero C, Henry CJ, Bergman PJ, Mason NJ, Gnanandarajah JS, Engiles JB, Gray F, Laughlin D,
Gaurnier-Hausser A, Wallecha A, Huebner M, Paterson Y, O'Connor D, Treml LS,Stannard JP, Cook JL, Jacobs M, Wyckoff GJ, Likins L, Sabbagh U, Skaff A, GulAS, Hays HD, LeBlanc AK, Coates JR, Katz ML, Lyons LA, Johnson GC, Johnson GS,O'Brien DP, Duan D, Calvet JP, Gandolfi B, Baron DA, Weiss ML, Webster DA, Karanu FN, Robb EJ, Harman RJ. A One Health overview, facilitating advances in
comparative medicine and translational research. Clin Transl Med. 2016 Aug;5(Suppl 1):26. doi: 10.1186/s40169-016-0107-4. PubMed PMID: 27558513; PubMed Central PMCID: PMC4996801.

ONE HEALTH AWARENESS DAY 13: ONE HEALTH NON-COMMUNICABLE DISEASE

January 13, 2020

One Health Awareness Day 13: One Health Non-communicable Disease
Where does the One Health Environment-Animals-Humans triad concept begin with the discussion of non-communicable/chronic disease fit? We have discussed infectious disease and transmission in the One Health approach. Chronic diseases such as respiratory, cardiovascular, neurological, and metabolic diseases, obesity, diabetes, and cancer are linked to toxins i our environment. Multifactorial diseases often emerge in organisms whose defense capacities have been reduced by changes in nutrition, temperature, salinity, pH, exposure to pollutants, toxins, sanitation, and radiation have cumulative long-term effects (Destoumieux-Garzon, et al 2018). Environmental stress/pollution is a global concern.

ONE HEALTH AWARENESS DAY 14: FOOD SAFETY

January 14, 2020

“In the modern world, bacteria and viruses travel almost as fast as money. With globalization, a single microbial sea washes all of humankind. There are no health sanctuaries.”-WHO
Food-borne illnesses are significant, costly, and a global problem. The global human population in 2019 exceeds 7.7 billion and by 2050, the world population is estimated to be over 9.7 billion. An estimated 30 billion food animals were produced to help feed this population and meet its growing demand for protein from animal sources King et al 2008). “Ensuring safe, accessible, affordable, and nutritious food is increasingly difficult, especially in a global context. Central to this challenge is the development of a One Health strategy and a new level of thinking and acting”.
It is estimated 48 million people suffer from food-borne illness, 128,000 are hospitalized, and 3,000 die each year (CDC). Of than more than 250 pathogens, 58% are caused by norovirus, Salmonella (11%( Clostridia perfringens (10%), Campylobacter jejuni (15% hospitalizations), Toxoplasma gondii (24% hospitalizations), and others. Potential pathogens include adenoviruses, sapoviruses, saffoldviruses, and picobirnaviruses (REF: FoodNet). Antimicrobial resistance adds to this problem.

New challenges to food safety will continue to emerge, largely because of:
* Changes in our food production and supply, including more imported foods.
* Changes in the environment leading to food contamination.
* Better detection of multistate outbreaks.
* New and emerging bacteria, toxins, and antibiotic resistance.
* Changes in consumer preferences and habits.
* Changes in the tests that diagnose food-borne illness.

#Onehealth

ONE HEALTH AWARENESS DAY 15: HUMAN ENCROACHMENT ON WILDLIFE: LOSS OF BIODIVERSITY

January 15, 2020

Biodiversity has had several definitions since 1916, but in general, that term reflects the variability of life and the density of it. 90% of the worlds species are located in the tropics. From the equator to the poles exist a latitudinal gradient of biodiversity. In the history of the world there have been 5 mass extinctions, the last one 65 mya. Following each mass extinction, there has been an increase in biodiversity (loss of natural selection) and many feel we are on the fringe of the sixth mass extinction: The Holocene Extinction.
Over the last 200-300,000 years humans as we know them have been in existence, our population has grown. Humans have only one natural predator: Humans. As such our population growth has created multiple biodiversity hotspots where an endemic species has experienced habitat loss. The majority of these biodiversity hotspots are in the forested regions in the tropics (e.g. Amazonia).
What is the impact of biodiversity loss have on human health?
Climate change are associated with change in biodiversity (changes in populations and distribution of disease vectors, scarcity of fresh water, impacts on agricultural biodiversity and food resources etc.). 
-Increased demand for, and lack of, drinkable water
-Food safety
-With infectious disease, the vectors that survive are the ones that transmit the disease. With endemic species loss, the spread of infectious disease is greater leading to further loss of biodiversity.
-80% of the world’s population depends upon medicine derived from nature. With the loss of biodiversity, options are limited (antibiotic resistance).

ONE HEALTH AWARENESS MONTH DAY 20: OCCUPATIONAL HEALTH RISKS FOR AGRICULTURAL AND ANIMAL WORKERS

January 20, 2020

The current standards here in the US to protect agricultural workers from injury and health risks are within General Industry (29 CFR 1910)  and Agriculture (29 CFR 1928) in  OSHA. Topics included are Grain Bins and Silos, Heat protection, protections from hazardous pesticides and the chemicals, respiratory diseases, unsanitary conditions, and general physical injury protection from falls, vehicle accidents, misuse/use of hazardous equipment and machinery.

As for Animal Workers, these General Industry Standards (29 CFR 1910) also apply, with special emphasis on protection from zoonotic diseases, safe handing standards, etc. The State regulation for importing animals is covered under 9 CFR 93, Chapter 1, Subchapter D and specifically in the Compendium of Veterinary Standard Precautions for Zoonotic Disease Prevention in Veterinary Personnel (Veterinary Infection Control Committee 2015). Since emerging viruses and spillover events are zoonotic in origin, strict adherence to these regulations and safety guidelines not only protects the health care worker but also protect the general public should an animal worker become infected and capable of transmitting disease to the general public. Examples include Material Safety Data Sheets (MSDS) are readily accessible to all workers, safe cleaning with potentially toxic chemicals, noise reduction, proper handling and disposal of objects that come in contact with an animal’s bodily fluid, bit protection, and wash station.

Understanding animal behavior is a major aspect  to the prevention of transmission of disease. We don’t act as we usually do, and animals don’t either.

ONE HEALTH AWARENESS DAY 21: PLASTICS IN THE ENVIRONMENT

January 21, 2020

We seem to embrace plastic versions of Mount Trashmore globally-even as high up as Mount Everest-since 1907. During World War II plastic production increased by 300% since natural resources were diminished, leading to a greater demand for synthetics. As time passed plastic (cheaper) versions of paper, glass, packaging, and even wood in furniture appeared. 

By the sixties, the enthusiasm was was in this quote, “Ben…one word…Plastics” (The Graduate; 1968).

The problem is getting rid of the trash. It might take at least 1,000 years to  decompose in landfills (we won’t know for another 900 years, of course), those rapidly accumulating plastic bags in stores take at least 10-20 years to decompose, and 450 years for those water bottles we regularly use. Factors affecting degradation include chemical structure of the polymer, molecular weight, surface area, hydrophilicity/phobicity, and crystallinity [Ref:  S Kubowicz , A Booth. Biodegradability of Plastics: Challenges and Misconceptions. Environmental Science & Technology 2017 51 (21), 12058-12060 DOI: 10.1021/acs.est.7b04051].

There are an estimated 79 million families in the US that probably can fill one of those 50 gallon recycle trashcans/month with plastic materials. So our annual volume of plastic recycle just might be as high as 5 x 10^10 gallons/year (50 gallons X 12 months X 79,000,000,000 families in the US). Then there is the accumulating mass of unconscious throw aways that end up as runoff in the ocean. 

The scope of the problem includes:

-90% of seabirds and 50% of sea turtles have been found to have non digestible plastic in their gut. These nondigestible plastic chunks cause intestinal obstruction and perforations leading to death

-Wildlife become entangled in plastic debris

- Microplastics are associated with reproductive organ, liver damage, and thyroid dysfunction. For example, Bisphenol A, a compound used in plastics production, has been detected in 95% of adult human urine (National Report on Human Exposure to Environmental Chemicals). Detectable amount do not imply an adverse effect. It just means 95% of us have been exposed.

What is being done now?

We need to better understand the interaction of biotic and abiotic degradation

1. Develop technology towards microbial degradation of polymeric materials

2. Use biodegradable additives to allow increased microbial degradation

ONE HEALTH AWARENESS MONTH DAY 22: THE ZOONOTIC SPILLOVER EFFECT. ONE HEALTH AND WILDLIFE . A COMPARATIVE MEDICINE RESEARCH APPROACH

January 22, 2020

In the wake of the discovery of the Wuhan coronavirus in the news lately, this appears to be another spillover vent. Looking back into its relative, SARS, bats (mainly Rhinolophus; also Pipistrellus) seem to be the primary reservoir; palm civets and raccoon dogs are also known to harbor SARS. 
So now we have yet another spillover event that has ties to a seafood wetmarket in Wuhan, China. Is there a connection with bats? Possibly, just like in Africa, bat bushmeat is not uncommon in Southern China, almost 43 species are hunted (Bats as bushmeat: a global review, Mickleburgh 2009; Exploitation of Bats for Bushmeat and Medicine, Mildenstein 2016).
Transmission does appear to be human-to human. Angiotensin Converting Enzyme 2 (ACE2) is the conserved human receptor for SARS-CoV S glycoprotein [Ren 2008]necessary to infect a human cell. So if we do what we usually do and compare the SARS S protein to the Wuhan coronavirus S protein, they are about 75% similar (using PDB structure sequences).
Inquiry Cover E-value %ID
6ACC_A 95% 0.0 75.12% (used in model)
5WRG_A 95% 0.0 74.04%
5X58_A 93% 0.0 76.01%
6NB6_A 93% 0.0 76.01%
6CRV_A 92% 0.0 75.78%
6CRW_A 92% 0.0 75.78%

In the S protein BD pocket (image shown), mutation at Asn-479 and Thr-487 in palm civet coronavirus seems necessary and sufficient for the virus to acquire the ability to efficiently infect humans.
In Wuhan coronavirus however, Asn-479 is replaced by Gln-493 (nonsynonymous) and Thr-487 is replaced by Thr-500 (synonymous). We don't know if that SARS Asn-479 to Wuhan Gln-493 affects infectivity but it might prove someday to be a monoclonal antibody target.
Then there might be the issue with protein disorder...time will tell.

ONE HEALTH AWARENESS MONTH DAY 23: ECONOMIC BENEFITS OF ONE HEALTH: A CHRONOLOGY OF THOUGHT FROM 2011-2019

January 23, 2020

Ruston et al 2011 [Economic benefits or drivers of a ‘One Health’ approach: Why should anyone invest?”]
-Why is One Health not main stream? Where are extra resource needed and who has control of the resources?
-If One Health is important, how can the case for a major paradigm shift be more persuasively 
presented? Realize the dynamics of human population growth include expansion of livestock product and resurgence of transboundary zoonotic disease such that we recognize costs of disease in terms of losses in production of livestock, , the costs of controlling the disease , the human health impact costs. We need to look at avoidable costs by establishing efficient disease programs.
“In common with all the disease groups there is the need for an understanding of the role of human behavior in terms bringing host and pathogen together“.

2012 
Between animal and human medicine there are no dividing lines—nor should there be. 
-Rudolf Virchow, 1856 
Häsler et al 2012 [The Economic Value of One Health in Relation to the Mitigation of Zoonotic Disease Risks]
The limitations of an economic approach are due to the necessary resources are not instantly available. The time investments and costs for training and to develop human, institutional, and infrastructure capabilities exceed initial fixed capital investment. There increasing demands on disease surveillance with new emerging and reemerging pathogens particularly with the aforementioned increased demand for livestock-derived food products, production intensity, and changes in geographic range of trade volumes. All these increase the risk of disease transmission. To emphasize that, look at the new coronavirus that arose from an unknown food source in a wetmarket in Wuhan, China as well as the use of bushmeat globally. 
Economic assessments in three stages: 1) Strategic planning and outcome prediction; 2)Provide an interim assessment of the probability of a successful outcome and redirect funds towards that goal, and 3) Final analysis of the factors relevant to the success or failure and its economic value.
Narrod et al 2012. [A One Health Framework for Estimating the Economic Costs of Zoonotic Diseases on Society]
A stepwise approach is utilized:
1. Estimate the extent of the disease and potential spread; The impact and burden of disease (DALYs: years of life lost+years of life with a disability)
2. Estimate the cost of zoonotic disease on livelihoods outcomes (income, health, and trade), including environmental impacts; using cross-sectional data and compare cost of disease before and after interventions
3. Assess the cost-effectiveness of risk management strategies currently employed for reduction of human and animal zoonotic disease exposure risk; Direct costs and cost-effectiveness analysis
4. Identify factors affecting adoption of zoonotic risk reduction strategies in poor households, the commercial sector and government bodies. The KAPs: Knowledge; Attitude, and Perception Analysis; Willingness to Pay Analysis

Making One Health Operational (World Bank):
“What am I responsible for? (Classical approach)” or should it be, “What needs to be done? (Integrated Approach)” 

2014
Häsler et al 2014 [A review of the metrics for One Health benefits ]
Benefits include
– protection of the environment and healthier ecosystems – enhanced social and cultural values 
– improvements in human and animal health and well- being, and animal welfare 
– better/improved/more effective/more rapid disease control and/or biosecurity measures 
– a higher quality or quantity of information and data; more knowledge and better skills. 

2016
Baum et al 2016 [Evaluating one health: Are We demonstrating effectiveness?]
“The absence of a standardized framework to capture metrics across disciplines, even in a generic format, may hinder the more widespread adoption of One Health among stakeholders.”

2017
Machalaba et al 2017 [One Health Economics to confront disease threats]
Key recommendations include: 1. systems thinking to identify risks and mitigation options for decision-making under uncertainty (hazard-specific); 2. multisectoral economic impact assessment to identify wider relevance and possible resource-sharing (opportunity costs of resources, financial consequence of zoonotic disease, post-analysis of benefits of prevention) and 3. consistent integration of environmental considerations (valuing ecosystem regulation of disease risk, the impact of mitigation measures on ecosystem
services, and the role of pathogens in regulating other ecosystem processes and services)

2019
Smith et al 2019 [Infectious disease and economics: The case for considering multi-sectoral impacts]
These involve the Health sector (e.g, Zika epidemic estimate costs $7-18 billion dollars), agricultural sector (50% livestock losses are from zoonotic disease); tourism and travel (SARS lost 41% international travel; H1N1 epidemic cost Mexico $2.8 billion dollars in pro and travel), trade and retail (SARS global economic loss=$40 billion dollars; Nipah virus $582 million dollars) 

This is why we need ONE HEALTH.

#onehealth

ONE HEALTH AWARENESS MONTH DAY 24-ONE HEALTH SUCCESSES. A STRANGE CASE OF HUMAN RABIES

January 24, 2020

In the early 1990’s, there were more than 100 cases of human rabies-virtually all were lethal. From 1960 to 2018, only a total of 125 human rabies cases were reported in the United States, with 25% resulting from dog bites during international travel. Of the infections acquired in the United States, 70% were attributed to bats. This decline is most likely due to widespread pet vaccinations, effective post-exposure treatment and the relative rarity of undetected bites by rabid animals.
In Oklahoma in 2018, there were 30 reported cases of animal rabies. As of January 2020, there have been a reported 23 cases of animal rabies, with the majority found in skunks (see image). There seems to be a peak rise in the spring. Every spring skunks, raccoons, foxes, and bats become more active as they transition from winter to spring. This activity leads to interactions with cats, dogs, and humans and with it comes the risk of transmission. 
As for a personal story, back in 1981, I was a full-time microbiology student at OU and worked full-time in the ER at South Community Hospital in Oklahoma City as an ER Tech along with Ben Potter (now DDS) , Marty Lopez (now MD), and Jay Cunningham (now DO).  Pretty good company I’d say. Sandy Gilbreath was the nurse on duty. During that summer, I clearly remember this odd fellow that had the chief complaint of difficulty swallowing. No fever, but I do recall that he was a bit disheveled, anxious, and somewhat sweaty. He also asked for a cup of water but couldn’t swallow.  A barium swallow was negative so it was felt to be just anxiety. He came in every day and progressively had difficulty breathing and was visibly agitated and a bit confused. Aspiration? Possibly. Anyway, he was always discharged from the ER, only to return the next day with worsening symptoms. On the following Saturday, he was brought in in full arrest and expired. The internist on duty, Dr. Fernando (?) reviewed his history and suggested a diagnosis of rabies.
He was right. A brain biopsy was positive for Negri bodies.
Needless to say, with all of us exposed to him over the course of 5 days, the CDC came in and there ere around 100 of us that had “significant” exposure to warrant post-exposure vaccination (HDCV). Luckily, none of us developed rabies.
Lesson learned, “There are more things in Heaven and Earth, Horatio, than are dreamt of in your philosophy.” That concept has always remained prominent in consideration of the differential diagnosis. When you hear hoofbeats, think of horses, not zebras. That said, unicorns don’t exist but zebras do.