Public Health Exam Four

BSL-1

A biosafety level. Agents not known to cause disease. Can work on open lab bench.

BSL-3

A biosafety level. Indigenous or exotic, can cause serious or potentially lethal disease through *respiratory* transmission.

BSL-2

A biosafety level. Indigenous organisms, disease of varying severity.

BSL-4

A biosafety level. No treatment available and infection is frequently fatal.

4 HIGH mortality rate associated with Henipaviruses.

All Henipaviruses are categorized as BSL-_____.

Horses

All human cases of Hendra have been traced back to infected ___________.

There are MANY genotypes for Toxoplasma out there. Most of the sea otters have type X, and type X was found in *mountain lions and bobcats*, as well as a smaller number in domestic cats.

Are the types of Toxoplasma found in domestic and wild felids similar to those infecting sea otters?

R0 (R-naught)

Basic reproduction number. The average number of people infected by one person.

Biosafety Levels

Determinants of levels of containment: -Infectivity: spread rapidly from host to host -Severity of disease -Transmissibility -Nature of the work conducted -Origin of agent -Route of exposure: skin, inhaled, MM, ingestion

Crimean-Congo Hemorrhagic Fever

Disease from a bunyavirus. First recognized in Crimea in 1944, then in Congo in 1969. Reservoir and transmission: *Ixodid ticks* or animal blood. Amplifying hosts are cattle, goats, sheep, hares. Mortality 9%-50%.

Hantavirus

Disease from a bunyavirus. Several types. Transmitted by *mouse* (*deer mouse*, cotton rat, rice rate, white footed mouse) feces, urine, saliva while cleaning old dusty buildings. *WEAR A MASK!* Causes *pulmonary syndrome*. Presents in a very nonspecific fashion. Short *fever* lasting 3-5 days. Others: fever/chills, myalgias, headache, dizziness, non-productive cough, nausea, vomiting, diarrhea, malaise, *tachypnea, tachycardia*. PE usually fairly normal. 50% mortality.

Ebola

Disease from a filovirus. First appeared in Sudan and Congo in 1976. Severe, often fatal, disease with *no known specific treatment or vaccine*. Killed more than 1.5k in parts of Africa. Infected *bats* are thought to transmit the disease to humans, or indirectly through other animals which are hunted. Virus detected in blood/saliva/mucus/feces/sweat/tears/breast milk/urine/semen. *NOT* spread by aerosol other than droplets. Incubation period: *2-21 days*. Signs: fever, sore throat, severe headache, muscle pain, intense weakness, vomiting, diarrhea, impaired liver and kidney function, etc. Death from multiple organ failure. *Easily* killed by disinfectants, survives on surfaces for hours. Survives several days in body fluids at room temp.

Dengue Fever

Disease from a flavivirus. 50-100 million infections yearly. 22k deaths, mostly children. Severe form: shock, hemorrhages, *enlarged liver*, ALT > 1000. Transmitted by the *aedes aegypti and Aedes albopictus* mosquitoes.

Yellow Fever

Disease from a flavivirus. Transmitted by *Aedes or Haemagogus mosquitoes*. Brought to the Americas via *slave trade*. Reservoir: non-human primates (NhP), humans. Three transmission cycles: 1. Sylvatic - Mosq --> NhP --> human 2. Intermediate (Savannah) - similar to sylvatic only in Africa 3. Urban - Aedes aegypti, introduced by infected human from sylvatic or intermediate settings Signs: *yellow* from icterus (hemolysis). 200k cases causing 30k deaths worldwide each year. *90%* in Africa. Vaccine is effective! Acute phase 3-6 days and recover. Longer phase 24 hours after initial remission.

Lassa Fever

Disease from an arenavirus. Infections per year in west Africa: 100k - 300k. 5,000 deaths. Reservoir-rodent known as *"multimammate rat"*. Once it is infected, it is able to excrete virus in urine for a long time. Transmission: eating rodents, inhaled, person to person fluids. 20% morbidity, 1% motality.

Lymphocytic Choriomeningitis (LCM)

Disease from an arenavirus. Transmitted from *Mus musculus* (rodent). Other rodents can be infected from mice and transmit to humans (pets, research). Exposure to fresh urine, droppings, saliva, or nesting materials to open wounds, skin, eyes, mouth, *inhaled*. NO horizontal, but *vertical and organ transplant* transmission can occur. Mice clinically normal and can remain infected for entire lifetime. Humans in the US and Europe are *1-5%* seropositive. 10-20% progress to neurologic DZ. <1% case fatality.

Burbon Virus

Disease from the orthomyxovirus family. *One* fatality in Burbon County, KS. Transmission: ticks, mosquitoes? Intermediate hosts may play a factor.

Yes, *managed domestic cats* have the *lowest* rate of infection of T. gondii. *Unmanaged feral cats have the highest*, and bobcats and mountain lions are close to unmanaged feral cats but not as high. *Odds of T. gondii-like oocyst shedding were over 7 times higher for unmanaged feral cats and bobcats than managed feral domestic cats.* Theory to why: Unmanaged feral cats and bobcats are eating smaller rodents and birds. Mountain lions eat larger livestock like deer and get less exposure to multiple animals. Managed cats eat processed cat food.

Do T. gondii infection and oocyst shedding differ among feral domestic and wild felids? Why?

YES, odds of type X infection is *14x higher in wild felids*, but there are domestic cats infected with and likely shedding type X.

Do both domestic and wild felids contribute to environmental transmission of type X Toxoplasma and other atypical types?

Filoviruses

Family of virus. Transmission possibly from fruit bats --> monkeys --> humans, and humans --> humans. Ex. Ebola

Bunyaviruses

Family of virus. Transmitted by *mosquitoes, ticks, sand flies, mice*. Ex. Rift Valley Fever virus, Crimean-Congo Hemorrhagic Fever virus, Hantavirus.

Flaviviruses

Family of virus. Transmitted by mosquitoes, ticks, and sand flies. Ex. Yellow Fever, Dengue Fever, West Nile, etc.

Arenaviruses

Family of virus. Virus transmitted between *rodents* by fighting, to humans via *contact with excretions*. Ex. Lymphocytic choriomeningitis virus (LCMV), Junin virus, Machupo virus, Lass virus, etc.

Asia

Hantavirus has several types that have been discovered over the years. The original type was dubbed the Hantaan virus found in what continent?

5-16

Hendra virus has a _____-_____ day incubation period in horses.

72

Horses infected with Hendra virus are considered infectious ______ hours PRIOR to signs and until death from disease or euthanasia.

Japanese Encephalitis Virus: -Occurs in children -Mosquito borne -Vaccinations Nipah Virus: -Occurs in adult males in contact with pigs -Very few cases in children -Clustering cases of families -NOT mosquito borne

How are Japanese Encephalitis Virus and Nipah Virus different? (Many thought they were the same thing.)

-Biting and scratching -Fecal/Oral

How are cat zoonoses primarily transmitted to humans?

Water runoff from a watershed. Rains can push oocysts into the ocean.

How could Toxoplasma make it from a wild or domestic felid to a sea otter?

-Ended importation of pigs with Malaysia -1 million pigs were culled

How did Singapore handle the Nipah virus outbreaks in Malaysia?

-Direct contact with pig secretions and fresh pig products -Human to human: secretions, clustering in homes, raw date palm sap

How is Nipah virus transmitted to humans?

Four

How many biosafety levels are there?

Slave trade.

How was Yellow Fever brought to the US?

Viral Hemorrhagic Fevers

Most are BSL-4 agents. Term used to describe multisystemic syndrome. All are RNA viruses. Dependent on *natural reservoir* and sometimes transmitted from human to human after infection from natural reservoir. Location generally limited to location of reservoir.

4

Most viral hemorrhagic fevers are BSL-_____ agents.

Endothelial

Nipah virus has a tropism for ____________ cells. Causes systemic vasculitis leading to CNS, lung, heart, kidney etc. problems. Binding via G protein of the virus to *Ephrin-B2* on neurons, smooth muscle, and __________ cells. Fusion via F protein.

4 Requires long-sleeve overalls, double puncture-resistant gloves taped to overalls, and respirators.

Nipah virus is a BSL-_____ pathogen.

Sylvatic

Occurring in or affecting wild animals.

Toxoplasma gondii

One of the most successful parasites in the world. Related to other coccidia. "Tiny, mysterious, and tough." Global distribution. *Zoonotic*. Can infect almost all birds and mammals. Only shed by *domestic and wild felids*. Diverse transmission routes. Emerging new hosts and environments. Clinical signs of disease not common in animals with healthy immune systems. Abortion in sheep and goats. Wildlife species sensitivity. Disease in immunosuppressed wildlife co-infected with other pathogens (i.e. Grey foxes with distemper).

Birthing

Outbreaks of Hendra virus occurred during ______________ season of fruit bats.

-Higher survival rates following Myocardial Infarction -Reduced risk of asthma if children are exposed in the first year of life (mostly dogs) -Cardiovascular health -Psychological well-being *Pets provide social facilitation, social support, and is an affectionate relationship in a person's life.* Pets rock. :)

Pets have been shown to have *positive* health effects on owners. What are some of these effects?

Lipocalins

Small transporters for hydrophobic molecules. Induction of *Th2* immune responses --> production of IgE. Allergic and non-allergic individuals *differ in Th2*. Are "sticky" and can stick to surfaces like carpet, pet hair, clothing, draperies. Are stable and can persist for long periods of time. Disperse efficiently, especially through direct vented HVAC systems.

Hypoallergenic Dogs

Some breeds have continual hair growth (poodle, bichon). These breeds are also likely to be routinely groomed. People get these dogs for their "anti-allergen" properties.

True

T/F: All horses that are infected with Hendra virus are required by law to be euthanized, even if the horse survives the infection.

True

T/F: Both domestic and wild felids contribute Toxoplasma oocysts to terrestrial coastal environments.

True

T/F: Coastal landscape change can influence Toxoplasma transmission cycles and accelerate pathogen flow from land to sea.

False. *Strep pyogenes is NOT host adapted to dogs!* Many physicians target dogs as reservoirs for strep throat. Usually Strep canis in dogs. May pick up transiently from infected children. Don't lick pets.

T/F: Dogs are a common source of "strep throat" in humans.

True

T/F: Emerging infectious diseases can affect animals, plants, and people and are caused by diverse types of pathogens like viruses, bacteria, parasites, fungi, and prions.

True

T/F: Hemorrhagic fevers can often spread from one person to another, once an initial person has become infected.

False. There is NO bat to human transmission or human to human transmission. Modes of transmission: -Bat --> horse -Horse --> human -Horse --> horse

T/F: Hendra virus can be transmitted from bat to horse, from horse to human, from bat to human, from horse to horse, and from human to human.

False. Dogs with less dander and that are more routinely groomed (poodle, bichon) are considered hypo-allergenic, but there is no true allergy-free dog. No difference was found in allergen levels found in homes with or without hypoallergenic dogs.

T/F: Hypoallergenic dogs exist and will not cause allergies in humans.

True :(

T/F: Nebraska is last in inclusion of dogs for Halloween.

True. Nipah infected cells reacted strongly with Hendra virus antiserum. They are related, not identical.

T/F: Nipah virus is related to Hendra virus.

True. Many vets have allergies to pets!

T/F: Pet allergies can be effectively managed.

True

T/F: Reluctance to part with a pet may lead to non-compliance (delay euthanasia or not seek medical care due to fear of hospitalization).

True. Think about the One Health implications of this: forcing animals into urban areas and possibly creating more disease is a huge problem.

T/F: The Earth is currently more urban than rural.

False. They are of *animal* origin (zoonoses). Ex's of animals that are sources of disease: bats, birds, arthropods, skunks, armadillos, etc.

T/F: The majority of emerging infectious diseases in people are of human origin.

True

T/F: The vaccine for Yellow Fever is effective.

True

T/F: There is no "no-risk" pet when it comes to allergies.

False. More wild felids may be infected, but *domestic felids* carry a much higher oocyst load. All felids are contributing to the infected sea otters, but domestic cats are something we can control (keep indoors more, don't flush cat feces, etc.).

T/F: Wild felids have a higher T. gondii oocyst load than domestic felids.

One Health

The collaborative effort of multiple disciplines - working locally, nationally and globally - to attain optimal health for people, animals and the environment. Takes EVERY factor into consideration: climate change, food security, energy, health, water security, land use change, livelihoods, global trade and transport. Ex. Flight transportation is at an all-time high. How does this affect the climate? Disease transmission? Etc.

Hendra Virus

Type of Henipavirus. Discovered in 1994 in *Australia* in horse stables. One person was in the hospital for flu-like symptoms; he was readmitted to the hospital with worsening signs like seizures and high fever, died 25 days after admission. Initially named *equine morbillivirus*. Reservoir: *fruit bats* (flying foxes). Nocturnal forages. Roost diurnally in colonies. Located mainly of the Eastern Coast of Australia. Transmission: -*Bats --> horses --> humans* -Can have *horse-horse transmission* in stables -NO bat to human transmission -NO human-human transmission

Nipah Virus

Type of Henipavirus. Discovered in Malaysia on a pig farm. Thought to be Japanese encephalitis, pigs had "barking cough". Pig workers/farmers contracted encephalitis. Risk factors determined by a *case-control study*. Main risk factor was any exposure to *pigs*. Tropism for endothelial cells. Binding via G protein of the virus to *Ephrin-2* on neurons, smooth muscle, and endothelial cells. Dx: Viral RNA by *RT-PCR* of urine and throat swabs.

Case-Control Study

Type of study. Study population is grouped by outcome. Cases are persons who have the outcome. Controls are persons who do NOT have the outcome. Past exposure status is then determined. Done with Nipah virus to identify risk factors for human illness with Nipah.

Henipaviruses

Viruses from the family Paramyxoviridae (negative-ss RNA virus). Others in this family include measles, distemper, and Newcastle. *NOT* in the US. Includes Hendra virus, Nipah virus, and Cedar virus.

-Keep pets out of the bedroom -Use HEPA or other air filtration systems -*Change and wash clothing that is heavily contaminated* -Bathe pet regularly -Minimize carpeting or other dust prone furnishings -Immunotherapy/Immunomodulation -Antihistamines

What allergy recommendations can you make for owners that are allergic to dogs/cats?

-Land use change and human population growth -Increased contact between humans, livestock, and wildlife -Enhanced flow of pathogens -Health risks to humans, livestock, and wildlife -Livelihood impacts and economic pressures

What are some considerations to take when changing the environment? How does this contribute to zoonotic disease?

-Initially: headache, high fever, back pain, joint pain, stomach pain, vomiting -Red eyes, a flushed face, red throat, petechiae on palate, icterus -Changes in mood and sensory perception -Large areas of severe bruising, severe nosebleeds, uncontrolled bleeding at injection sites beginning on the 4th day of illness and lasting for about 2 weeks -Death due to DIC -Spontaneous abortion followed by death of the mother

What are some signs and symptoms of hemorrhagic fevers?

-Arenaviruses -Bunyaviruses -Filoviruses -Flaviviruses

What are the four major virus families that cause viral hemorrhagic fevers?

*-Eating an infected warm-blooded animal with T. gondii cysts in its tissues -Ingesting oocysts in contaminated soil, water, or food -Congenital transmission (mother to offspring)* Others: -Raw goat milk -Eating transport hosts like raw mussels and oysters -Organ transplant -Blood transfusion

What are the most common transmission routes to Toxoplasma?

1. Lipocalins: found in *saliva*, licking of fur can translocate allergens 2. Albumin Can be found in saliva, fur, serum, urine, dead cells.

What are the two canine allergens?

-Methicillin resistant Staph pseudintermedius: pyoderma and otitis, common in dogs -Methicillin resistant Staph aureus: picked up from carrier in household

What are the two most common Staph species transmitted from dogs to humans?

-Loss of fear in rodents (great for the cat and the parasite, parasite spreads to new host and cat gets a new meal) -Links to aggression, schizophrenia, and mental illness in people

What behavioral changes can you see in animals and people with Toxoplasma?

-Severe respiratory distress -Neurologic signs: ataxia -*Nasal discharge that is frothy or bloody (TERMINAL sign)* -Colic-like symptoms -Fever -Inappetence -Depression

What clinical signs would you expect to see in a horse with Hendra virus?

-Acute respiratory distress -Encephalitis (82% fatality rate) -Fever -Vomiting -Headache *Supportive care* for treatment.

What clinical signs would you expect to see in a human with Hendra virus? What is the treatment?

-Fever -Headache -Dizziness -Vomiting -Seizures -Reduced level of consciousness -Profound tachycardia and hypertension -Myoclonus -Focal rhythmic jerking of muscles -Hypotonia and areflexia *Incubation from 6 days to 2 weeks*.

What clinical signs would you expect to see in humans with Nipah virus?

-Febrile respiratory disease -Severe cough: *barking pig syndrome*, "one mile cough" -Encephalitis: sows and boars

What clinical signs would you expect to see in pigs with Nipah virus?

Researchers discovered there was viral shedding in monkeys and bats that inhabit the edges of the forest. Some people use the edge of forest for tourism, farming, etc., so these people are in contact with the primates and bats. Located four prime areas where people were in contact with these animals: two in the mountains and two at the base of the mountains. Tested sick people with fevers from these areas (most viral diseases cause fevers). Tested poop samples from primates and bats, and other samples from bats by trapping and tracking them. Found that bats were partially eating mangoes in a certain area, which opens up a new way for transmission via saliva. Our speaker found overlapping viral families in these four areas, she's trying to see if they are the same virus and if there are certain risk factors (Can the people eat fruit here? Are water sources safe?). *Takeaway: a ONE HEALTH approach allowed for more discovery and a more holistic approach to solve this problem of people interacting with certain animals and their environments.*

What did our One Health lecture about Tanzania teach us?

Self-limiting in immunocompetent people. *Immunocompromised and pregnant women/fetuses* are at a greater risk. Will see fever, confusion, headache, nausea, coma, miscarriage, stillbirth, birth defects (hydrocephaly), and death in these patients. Waterborne outbreaks where people ingest oocysts in contaminated water have led to ocular disease or more systemic disease in people with healthy immune systems.

What human populations does Toxoplasma infect? How does it present in humans?

Rabies

What is the #1 biological hazard in dogs that can be transmitted to humans?

Dermatophytes

What is the #1 condition in dogs that gets exposed to humans?

Campylobacter

What is the #1 human health risk due to dog zoonoses?

Deer Mouse

What is the most common reservoir for Hantavirus in the US?

*Fleas*. Flea control on cats is critical to reduce spread of zoonoses. Also reduction of exposure to feral cats.

What is the most common way zoonoses are transmitted from cat to cat?

B. Allergies

What is the most frequent topic that physicians are likely to deal with involving vet public health with their patients? A. Rabies B. Allergies C. Bite wounds D. Zoonotic diseases E. All of the above

*Fruit bats*. These bats eat halves of fruits that are fed to hogs. Tests confirm virus in fruit. Also urine secretion in pig lots can contribute.

What is the primary reservoir of Nipah virus?

Skin-eating dust mites. Second: dogs and cats.

What is the top indoor allergen in people?

-Mainly supportive with mechanical ventilatory support -Anticonvulsants -Ribavirin, a broad spectrum antiviral (reduced mortality of patients)

What is the treatment for Nipah virus in humans?

Fruit bats (flying foxes). These are nocturnal foragers and roost diurnally in colonies.

What is the wildlife reservoir of Hendra virus?

-Wash hands -Clean equipment after use on horses -Wear PPE -Refrain from kissing horses on the muzzle -Be cautious doing post-mortem exams, one vet got encephalitis doing a necropsy on a horse with Hendra

What precautions can you take to not get infected with Hendra virus?

-Type of pet: no young farm animals, no reptiles/poultry/amphibians, no exotics/monkeys -Keeping animals healthy: avoid young, sick, or chronically ill pets, spay/neuter, feed only commercial diets -Practice good hygiene: wash hands, avoid contact with stool, prevent licking, reduce bites and scratches, keep environment clean

What recommendations can you make for immunocompromised owners with pets?

Hendra, a suburb of Brisbane, Australia

Where does Hendra virus originate from?

Water runs quickest on the coasts. This is also where people hang out. Greater risk for Toxoplasma infection being carried onto the beaches and into the oceans!

Where in California does water run the fastest? How does this impact Toxoplasma transmission?

From a villager's CSF in *Malaysia*. Has spread to Indonesia and Bangladesh.

Where was Nipah virus first isolated?

C. Sleeping with dogs (longer contact time)

Which of the following would pose the highest risk for interspecies transmission of Staph? A. Petting dogs B. Grooming/bathing dogs C. Sleeping with dogs D. Exposure to dog feces

We need sea otters to eat sea urchins to keep the kelp healthy. Healthy kelp leads to a healthy oxygenated water system. (Would ya look at that One Health in action!!)

Why do we need sea otters for ocean health?

DIC

With viral hemorrhagic fevers, death is usually due to _______.

90

_____% of pet owners regard the pet as a valued family member.

15 1 billion/year on health care costs. Increases the risk for *new-onset asthma*.

_____% of the population is allergic to either dogs or cats.

70

______% of pet owners would disregard medical advice to get rid of a pet due to allergies.