Exam 1

leishmania as a vet

Reportable animal disease •Awareness •Educate

factors driving pathogen emergence

1. Ecological Changes 2. Human Demographic Changes and Behavior 3. Travel and Commerce 4. Technology and Industry 5. Microbial Adaptation and Change 6. Breakdown of Public Health Measures

lyme vaccine

1. Killed Bacterin Vaccine 2. OspA Recombinant Vaccine 3. Bivalent Vaccine (OspA and OspC) *none for humans

leishmania in humans

1.Cutaneous Leishmaniosis •0.7 to 1.2 million cases per year (incidence) 2.Visceral Leishmaniosis •0.2 million to 0.4 million cases per year (incidence) •Most of the ~70,000 deaths per year •Considered a neglected tropical disease •12 million infected (prevalence)

where emerging human pathogens come from

1.Pathogens that are already present (most) •21/25 (84%) 'historically and evolutionarily' significant human diseases had a high likelihood of coming from animals •73% of emerging/re emerging pathogens are zoonotic 2.Agents that have evolved to become new pathogens *risk elevated in tropics due to high biodiversity

coccidiodomycosis valley fever

Agent: Coccidioides immitis/posadasii Maintenance Cycle: Soil saprophyte -Environment Hosts: Multiple, including mammals and reptiles Transmission: Inhalation of arthroconidia, Spherule found in the host (Not infectious to other animals)

lyme disease

An emerging disease •Juvenile Rheumatoid Arthritis (JRA) cluster near Old Lyme, Connecticut -1972 •Many cases had history of erythema migrans •Distribution overlapped with Ixodesscapularis •Suspected a rickettsial organism. Why? tick transmitted and rash •B. burgdorferi identified as the causative agent of Lyme Disease in 1982 *agent = spirochete

Lyme Dx

CBC/Chem/UA •For 'typical' cases: •Nonspecific or unremarkable For Lyme Nephropathy: •Proteinuria •Glomerular disease: Hypoalbuminemia, azotemia, hyperphosphatemia, hyperkalemia •Seropositive for Bb •No other cause for nephropathy identified Serology: •(+) = Exposure •Disease typically occurs after seroconversion-rising titer unhelpful •Cross-reactivity with other spirochetes/vaccine may be problematic. •SNAP-3Dx and 4Dx point-of-care tests use C6 peptide antigen. •C6 test sensitive and specific •Caution* -Subject to over interpretation

leishmania infantum control

Control/Prevention •Euthanasia of sick or seropositive dogs •Vector control •Topical insecticides/repellants •Vaccine licensed for use in Brazil

risks working with valley fever

Culture *Danger* •Coccidioides will grow on all common media •Arthroconidia highly infectious in culture •90% of lab-associated infections result in disease •With other diagnostics, you do not need culture to confirm! Direct Transmission: •Extremely Rare Environmental: •Endemic Areas •Risk may be elevated in dry, dusty areas

emerging pathogen

Definitions: -Incidence is increasing following its appearance in a new host population -Incidence is increasing in an existing host population as a result of long term changes in the pathogen's underlying epidemiology OR: •A newly evolved strain of pathogen •Pathogens that have recently entered the human population for the first time • Pathogens that have probably been present in humans historically, but which have recently increased in incidence

leishmania Dx

Diagnosis •Antibody testing •Microscopy/Culture •Impression smear •Aspirate •Biopsy (IHC) •PCR *located in macros

RMSF DX

Diagnosis •Serology •Confirmed Case •IgM Titer increase or single titer >1:1024 •Paired Titer IgG(2-3 weeks, X4) •PCR •Direct Fluorescent Antibody Treatment •Tetracycline/Doxycycline *if suspected begin immediately

valley fever dx and tx

Diagnosis: •Histopath •Cytology •Serology Treatment: •"Azole" group of Antifungals

domestication --> ecological changes

Domestication of animals and intensification of agriculture coincided with the 'emergence' of many human diseases •Dams/Changes in water systems •Mycobacterium avium complex (MAC ) •Legionella (Legionnaires' disease) •Habitat fragmentation •Climate change

travel emergence examples

Historical Examples: •Asia (Silk Road): Bubonic Plague to Europe •Slave Trade from West Africa: Yellow Fever to the New World Modern Examples: •Asia: Cholera in South America (Bilge Tanks) •Asia: Aedes albopictus in tires and live bamboo plants (shipments) •EEE and Dengue •Africa: Zika to Americas •"Airport" Cases of Malaria •WNV •HIV •SARS •Ebola

RMSF hosts

Hosts: •Wild Rodents, Lagomorphs, Dogs, Opossums, Humans •Dogs and humans are not involved in the maintenance cycle. •Why? ticks are biologic vectors/reservoirs •What kind of hosts are they? incidental/mechanical

RMSF disease

In Dogs: •2-14 day incubation period •Fever •Anorexia •Edema •Mucosal petechiae •Neurologic manifestations •*Thrombocytopenia* •In Humans: •Fever •Rash •Neurologic manifestations •Edema •Acute Renal Failure

Rocky Mountain Spotted Fever

Obligate intracellular bacterium

leishmania reservoirs

Reservoir •Dependent on Leishmaniaspecies •L. infantum, dogs •Prevalence in dogs •Poorly understood •Parts of Spain, France, Italy and Portugal = •>70% (PCR), 2.5 million dogs, serology •Brazil and Venezuela = "In the millions" •US-Foxhound Kennels

basic reproductive number

The expected number of secondary cases produced by a single (typical) infection in a completely susceptible population R0<1 = the disease will die out as low transmissability Ro = 1 = stays at the same level --> called endemic disease Ro >1 = epidemic R0 = the number of individuals one infected host will pass the disease to

RMSF lifeclycle

Transmission/Entry: Tick Bite Rarely: Direct

leishmania treatment

Treatment •Canine disease more resistant to therapy than human disease •Relapses/retreatment are common

lyme transmission cycles

Two independent transmission cycles in the United States •East: Ixodesscapularis, white footed mouse, white-tailed deer (1 tick 2 mammals) •West: I. neotomae/spinipalpis Ixodes pacificus (2 ticks 1 mammal)

gene transfer

major driver of antibiotic resistance through plasmid transfer

east life cycle

no transovarial transmission Egg --> larvae --> blood meal of mouse --> infected nymph/larvae --> adult --> transmit disease to Dogs/humans/horses/deer* --> lay eggs

ecological changes

• For All Emerging Human Pathogens Woolhouse , et al • Changing land use and agriculture are more important for the emergence of zoonoses than for non zoonoses • Changing land use and agriculture are more important for the emergence of viruses than bacteria (or any of the other pathogens)

valley fever in washington

•"Valley Fever fungus found in Washington soil samples" •2010 and 2011: 3 unrelated cases of Valley Fever in WA without travel history •2011-2015: 5 more cases from Yakima areas •16 cases (1/16/20) •3 canine cases and 2 horses diagnosed with Coccidioides *4/5 -extrapulmonaryabscesses (subcutaneous/cutaneous lesions) What are we doing about it? •DOH/CDC enrolled 15 veterinary clinics for passive surveillance •Several hundred samples submitted to CDC •Problems with test (AGID) validity •Unique strain •Prevalence? •Human seroprevalence studies needed •Intradermal coccidioidin skin test •Implications for Epidemiology

lyme prognosis

•'Typical' Cases: Good •Self limiting, rapid response to antibiotics (1-2 days) •Lyme Nephrophathy: Guarded to Poor •Depends on severity of renal disease •Renal disease usually progressive *common to have a co-infection such as rickettsia, anaplasma

RMSF outbreak in AZ

•1981-2001 : 3 cases reported •2002-2004 : 16 cases from NE Arizona (+3) •7 from one community, 9 from another •13 were <12 years old •2 died •All had contact with tick-infested dog •Environmental analysis identified R. sanguineous ticks, no Dermacentor ticks •Rhipicephalus sanguineus (Brown Dog Tick) •3 host tick, feeds on dogs all three stages •3% were positive for RMSF

leishmania

•20 of 30 species in the genus Leishmaniacause human disease •Protozoan •L. donovani •Anthroponotic •Visceral form •L. mexicana (& others) •Zoonotic •Cutaneous and mucocutaneous forms •L. infantum (aka L. chagas) •Zoonotic •Visceral form

valley fever prevalence

•20,000 human cases per year diagnosed in U.S. •150,000 infected each year •2/3 from Arizona •Seroprevalence in animals unknown •28% in Arizona study of puppies to one year old •8% in a cross-sectional study (Pima county)

leishmania importance

•41 since 2007 cases of cutaneous leishmaniosis in US •59% endemically acquired •Cats in Texas •0 domestically acquired visceral leishmaniosis cases

canine lyme experiment

•6 -12 week puppies •2 -5 months after tick exposure •Oligoarthropathyin limbs closest to tick bite •+/-Lymphadenopathy •Self limiting and resolved in 4 days without treatment •No disease in adult dogs •Tissue migration rather than hemotogenous spread suspected in dogs

lyme in canines

•95% seropositive dogs are asymptomatic (10% humans) •Fever •Monoarticular or polyarticular lameness •Joint swelling •Lethargy •Mild lymphadenopathy •Field cases-small number of renal cardiac, neurologic or dermatologic manifestations have been attributed to B.b. They have not been reproduced experimentally. *most prevalent in younger animals

lyme neuropathy

•<2% seropositive dogs •No definitive evidence for isolated condition •Immune-mediated glomerulonephritis, protein-losing nephropathy •30% had history of arthritis, 30% history of vaccination •Breed Predisposition: labs retrievers sheltys

leishmania vector

•<3mm •Feed dusk to dawn

lyme disease agent

•Agent: Borreliaburgdorferi •A spirochete •Spiral-shaped bacteria

microbial adaptation

•Antimicrobial Resistance •Natural Selection •Mutations •Nucleotide Substitution •Gene Capture •Recombination/ Reassortment

public health response

•ArboNET(2000) •Passive Surveillance System •Dead birds, veterinary cases, blood donors, human cases*, mosquitoes*, sentinel animals •What is passive surveillance (versus active surveillance)? •What are the benefits? •What are some limitations? •CDC warns that ArboNETdata is not be comparable over time or space. Why? •What do they use?

lyme syndrome in horse

•Best documented syndromes: •Neuroborreliosis-cranial nerve dysfunction, meningitis, dysphagia, spinous muscle atrophy, facial paresis, ataxia, behavorial changes •Uveitis •Cutaneous pseudo-lymphoma at site of tick bite •Poorly documented syndromes: •Stiffness •Lameness •No evidence that B. burgdorferi causes •Laminitis

Lyme frequently asked questions

•Can I get Lyme Disease from my pet that has it? •No, the bacteria are transmitted through ticks. •Once dogs (or humans) get Lyme Disease and are treated for it, can they get it again? •Yes, reinfection can and does occur. •Can my cat get it? •Cats have been shown to be seropositive, but there are conflicting experimental results regarding clinical illness. •Cases also reported in horses and cattle.

WNV in New york

•Cluster of Encephalitis Reported on 23rd •All index cases were active outdoors and lived in 2 mile radius •Arbovirusidentified with serology •SLE (flavivirus) positive •Earlier that summer -Crows dying •Necropsies: Hemorrhagic encephalitis •3 flamingoes, and a cormorant died at the Bronx Zoo over labor day weekend •NYC DOH, CDC, and Bronx Zoo Veterinarians alerted that human and animal cases may be linked •Increase in horses with neurologic disease •SLE not detected by PCR in animal or human samples •Late-September: Two different researchers identified WNV from human and animal sources (later mosquitoes) •Why was it misdiagnosed? because SLE can cross react with WNV •The largest WNV outbreak in humans and •The largest arboviral encephalitis outbreak in the Western Hemisphere.

travel and commerce

•Complex food systems and international trade •2016 Select USA Livestock Imports/Exports •Beef imports : 2,814,628 x 1,000 lbs •Beef e xports : 2,295,416 x 1,000 lbs •Pork imports : 1,000,813 x 1,000 lbs •Pork exports : 4,739,961 x 1000 lbs •Human migrations •Backyard animal production

cutaneous leishmania

•Cutaneous form •Papules/nodules •Progressing to Ulcers •Crusty or not •Painless to Painful •Localized lymphadenomegaly •Some cases progress to mucocutaneous form •Can be disfiguring

Lyme dx in horse

•Diagnostics: •Difficult! •Cornell; OspA, OspC, OspF •C6 peptide test •Diagnosis based on: •Location and serologic testing •Compatible clinical signs •Ruling out other diseases •PCR difficult-paucity of organisms •Potential for infection with A. phagocytophilumor co-infection

lyme in horses

•Horses are increasingly being diagnosed with Lyme Disease •Seroprevalence 45-62% in endemic areas •Disease not well-defined •Experimental infection: organisms recovered 9 months after infection in skin near tick bite around nerves and blood vessels near synovial membranes •No associated disease

WNV in horses

•Horses: •Incubation period: 7-14 days •>90% Subclinical •~8-9% have mild febrile illness (ADR X 2-3 days) •~1-2% have serious neurologic complications •*Ataxia •Hyperesthesia •Muscle tremors •Fever •Death (1/3 CNS cases) •Long-term sequelae not uncommon •Equine cases are reportable!

RMSF vets role

•Human Cases are Reportable •Canine Cases are NOT Reportable •What is your role? treat the dog and let owner know about risks

RMSF risks

•Humans •Children and Young Adults •Rural> periurban>urban •Chronological association of dogs getting sick before people •Delayed treatment •Dogs •Purebred dogs •German Shepherd •English Springer Spaniel •Delayed treatment

WNV in humans

•Humans •Incubation period: 3-14 days •~80% Asymptomatic •~19-20% have mild febrile illness •<1%have neurologic complications •Meningitis •Encephalitis (30% seizures) •Flaccid Paralysis •10% Fatality Rate •Long-term neurologic defects common Note the common clinical features!

valley fever disease

•Humans and Animals •Incubation 1-3 weeks •~60% Asymptomatic, ~40% mild respiratory disease •Fever, anorexia, weight loss, depression (non-specific) •Disseminated disease affects many body systems (<2% humans) •Dogs: bones, eyes, heart/pericardium, testicles, CNS, visceral organs •Occurs ~4 months after respiratory symptoms, but variable

valley fever emergence

•Increased travel or relocation to endemic areas •Changes in environmental factors such as temperature and rainfall •Changes in the way cases are being detected and reported

WNV public health response

•Integrated Vector Management Programs •Habitat modification •Larval mosquito control •Adult mosquito control •Community Education •Related to risk and intervention •Vector control and avoidance

WNV history

•Isolated in 1937 in Uganda •*1957 Meningoencephalitis outbreak in Israel •1999 marked the first time the virus was isolated in the Western Hemisphere •How did it get here? •Infected mosquitoes? •Infected birds? THIS ONE •Infected humans? *Widely reported to be the first time linked to neuro disease. Sadly, no.

east ticks

•Ixodesticks feed to repletion in ~72 hours. •Why is this important? •*Tick must feed for >48 hours to transmit Lyme disease* •Transplacental transmission? •Reportedly rare but resulted in infant death in 2 cases where it was reported

vets role in emergence

•Maintaining health and welfare of animals (incl. exotics) •Controlling food borne & zoonotic diseases •Conducting research (vaccines, pharmaceuticals, diagnostics) •Outbreak Investigations •Public Education •Policy •Emergence is complex and not easily categorical •Veterinarians, whether in public or private practice, play a pivotal role in identification, surveillance, reporting, and education.

breakdown of public health measures

•Many re emerging diseases •Others •Plague •Leptospirosis •Leishmaniasis •Foodborne illness •Cryptosporidiosis outbreak •Antimicrobial resistant organisms

technology and industry

•Mass food production •Changes in food handling processes •Medical technologies •Nosocomial infections •SARS, Ebola, MRSA, MERS CoV •Transplants/infusions •HIV, Cryptococcus neoformans , Baboon Cytomegalovirus •Iatrogenic •Related to implants or surgical instruments •vCJD , Fungal meningitis in contaminated steroid injections •Contact lens fluid Fusarium •Changes in rendering processes •BSE •Mass food processing technologies (meat comtamination •E. coli O157:H7

leishmania in the US

•Mediterranean strain of L. infantum •14 sandfly species in the United States •Lutzomyia shannoniin SE US •Lutzomyia vexatorin NE US •Transmission remains a puzzle Other vectors? •Iatrogenic? •Direct horizontal/verticaltransmission? •Probable vertical transmission, not published

WNV drivers for emergence

•Microbial Change •WNV not known to cause significant mortality in birds until 1998 •Dead goose in Israel high homology to NY99 •WN02 completely displaced NY99 by 2004 •13 consistent nucleotide changes (different genes), one leading to a single amino acid change •Improved vector transmission •Newer Genotypes? Higher viremia, more neuro-invasive disease? •Human Behavior? •Travel/Commerce? •How did it get here? •Infected mosquitoes? •Infected birds? •Infected humans?

ACVIM recommendations for vaccines

•No agreement about use of vaccine •Practice tick control, good efficacy when used correctly •Fipronil, amitraz, etc.. •Tick checks + early tick removal (feed >48 for transmission) •Tick control prevents other tick-borne diseases •Babesia, Anaplasma, Ehrlichia....

post treatment lyme disease syndrome

•Persistent Infection? •Chronic muscle and joint pain •Chronic cognitive defects •Fatigue and sleep disturbance •Controversial!

human demographic changes --> emergence

•Population Growth •Urbanization •War •Famine •Behavior •Reforestation around homes and other conditions favoring tick vector and deer (a secondary reservoir host •Lyme borreliosis Borrelia burgdorferi •Importation of monkeys •Ebola, Marburg •Urbanization favoring rodent host, increasing exposure •Lassa fever •Sexual transmission, IV drug use •HIV

vaccine controversy

•Potential Benefits •Non-compliance with tick control products •Relatively few side-effects •Some efficacy in protection against disease •Potential Problems •Short duration of immunity •Possible exacerbation of immune-mediated nephropathy •Many dogs are seropositive •Clinical cases respond to treatment

Quantatative C6 lyme test

•Quantitative C6 Test •Usually done secondary to qualitative test •No "cutoff" ie: no magnitude of quant C6 ab that predict illness or treatment decisions (monitor treatment) •Many practitioners use to monitor response •Do 6 month repeat test to observe decreasing titers •In humans, a drop in post treatment titers is associated with better prognosis •More confidence in diagnosis •Typically for symptomatic dogs

WNV vets role

•Report •Educate •Be aware of current/projected risks in your area •Advise on-farm regarding vector management •Vaccinate •Effective in preventing neuro-invasive disease in horses

vets role in valley fever

•Report** •Be Aware! •Educate *if their dog is sick they could be sick too!

visceral form

•Subacute, Acute, Chronic •Fever •Weight Loss •Hepatosplenomegaly •Pancytopenia •Highly fatal if untreated

RMSF Px

•Tick Control/Prevention of Exposure •Early Tick Removal •Advise Owners of Zoonotic Potential (not direct) •Acaricides *no vaccine

RMSF ticks

•Ticks: •Dermacentor andersoni (Wood Tick) •Dermacentor variabilis(American Dog Tick) •Dermacentor are 3 host ticks, first two stages are rodent or lagomorph hosts •Novel vectors are increasingly spreading disease •R. sanguineus relatively new vector in the U.S. Trans-ovarial and Trans stadial Passage of RMSF •TO Passage primary means of maintenance in nature

Lyme treamtne in horse

•Treatment: •Little data to inform ideal treatment •Tetracycline class antibiotics •Neuroborreliosis and uveitis respond poorly to antibiotics •Prevention: •Acaricides •Clipping pastures •No approved vaccine in horses

WNV treatmetn

•Treatment: •Supportive •Vaccination: •For horses •2X Killed vaccine (adjuvant) •Recombinant modified-live vaccine (adjuvant) •Live chimera vaccine •For humans •None

west lyme disease life cycle

•Two intersecting cycles are necessary for the transmission of B. burgdorferito humans/domestic animals. 1. Reservoir is dusky-footed woodrat and vector is Ixodes neotomae/spinipalpis ticks 2. Ixodes pacificusis vector to humans/domestic animals from dusky-footed woodrat •Prefers to feed on lizards •< 1-5% of I. pacificusticks are positive for B. burgdorferi

WNV risks

•Urban habitats •Rural irrigated land •Increase temperature •Precipitation patterns •Socioeconomic Factors •Community drainage patterns •Housing Age •Per capita income Rainwater collection & Stagnate water troughs

leishmania infantum risk

•Visceral leishmaniosis •Children •Immunosuppressed adults •Positive association between prevalence in dogs and humans •Lifestyle factors •Socioeconomic factors •In dogs: •Boxer, Cocker Spaniel, Rottweiler, German Shepherd •Young dogs (2-4), Old dogs (>7)

host roles in lyme disease

•What is the role of White-tailed deer in the maintenance cycle of the spirochete? maintain the ticks in the environment •What is the role of humans/animals in the maintenance cycle? spill over