Winter Micro 3 Exam

Causes Infectious Mononucleosis

Burkitt's Lymphoma
Nasopharyngeal Carcinoma in China

polyclonal B cell proliferation and activation

Abnormal T cells that appear in Mono.

Mono causes an increase in both B and T cells

The T cell response causes the sx

False - needs to be spread by kissing - droplet.

Really need to work it

Heterophile antibodies are present in IM and aid in diagnosis

due to polyclonal acgtivation of B cells

Accumulation of horse RBC's in Monospot test

*Heterophile antibodies are transient during disease - may fade away*

Permanent, unlike the heterophile antibodies

CMV

Transplants, Fetus (torCh), HIV

Primary Disease in an Immunocompromised Host

CMV

= Owl's Eye = CMV

CMV is heterophile monospot NEGATIVE - presents like EBV though

Greatest risk to fetus is a primary infection in the mother

sublinical

CMV

CMV

Mumps

Mumps - can result in sterility (unlikely)

False: 30-40% are asymptomatic

travel, highly

F: as many as 10% of MMR vaccinated pts remain unprotected after 2 administrations

MMR vaccine has the lowest efficacy against mumps

Thus great mumps outbreak in 2006 in the USA

EBV, CMV, Mumps

Infectious Hepatitis

naked ssRNA - highly resistant capsule

Tx: Post exposure prophylaxis with immunge globulin

Prevention: Vaccination

Shedding of viral particles in stool several weeks before symptomatic

Associated with Restaurants, Daycares, foods irrigated with contaminated water

Endemic in crowded/low hygeine countries

Causes Acute Hepatitis - typically resolves

Replication occurs in Cytoplasm

Enteric Hepatitis - Clinically Identical to HAV

NO VACCINE - unlike A

*Pregnant Women*/Newborns Greater risk

Mainly symptomatic tx

*Travel to Endemic Areas* -India, Mexico, China

Acute Disease with similar sx

A and E "vowels in the bowels"

B, C, D, G

Serum Hepatitis

Enveloped DNA virus (partial stranded) --> Dane Particle

Blood-Borne Transmission - including *SEX* contact and IVD use

Vertical Transmission results in high number of chronic carriers

Longer incubation - up to 3 months

Causes Acute and Chronic Hepatitis

Promotes carcinogenesis via mutations

**Vaccination Exists**
pharm agents and immune globulin as well

Type III Hypersensitivity reacions - Immune Complexes
Serum Sickness: Rash/Arthralgia

Hep B - therefore it needs Reverse Transcriptase

dsDNA completion occurs in the cytoplasm

Transcription occurs in the nucleus using host RNA pol

Surface Antigen - first to be detected

Antibodies indicate immunity

Chronic infection will NOT have anti-HBsAg**

Incorporated into HDV - necessary of HDV infection*

Correlates to infectivity

core antigen - its presence indicates you were definitely infected by virus if you have antibodies to it

the vaccine does not contain HBcAg

Both Dane Particles (HepB virus) and empty envelope (surface antigen0 are released

This results in a large excess of surface antigen HBsAg - may produce NEGATIVE surface antibodies in lab because our immune response is being flooded - Decoys*

They have a less mature immune system -

remember most of the sx are due to the cytotoxic immune response

8

Ineffective Immune Response
Chronic Inflammation results in Immune Complex Deposition
Cirrhosis
Cancer

Space between disappearance of HBsAG and antiHBsAG

Delta Agent

*HBV infection is NECESSARY for infection with HDV*
it needs HBsAg - incorporated into evelope

Clinically similar to HBV

*Delta agent causes direct cytopathologic effects CPE, unlike immune mediated damage of HBV*
=Visual changes to hepatocyte architecture

No real tx - prevent with HBV vaccine

Infected with both HBV and HDV at the SAME TIME

more severe acute sx

most pts recover with immunity

HDV infection superimposed upon chroinc HBV infection

Increased risk of fulminant hepatitis or cirrhosis

Transfusion-Associated Hepatits

Flavivirus - ssRNA

Genotype 1 is the most common in US

Most transmission via infected blood
*IVD use and intranasal Cocaine* also transplant/transfusions

low risk for sexual transmission

Much higher percentage develop to Chronic

Hepatitis C - subsequently require liver transplant

CD81 on hepatocytes

Secreted by activated lymphocytes (including NK cells) to activate Macrophages to release

IL-1 and TNF-a

*HCV inhibits NK cells and thus a lack of IFN-gamma - delays immune response-

Chronic disease

Flaviviridae
Bunyaviridae
Arenaviridae
Filoviridae

all are enveloped
True reservoir is animal/insect
-human accidental

Geographically Restricted**

Arthropod Vectors are main transmission

Most have no cure or drug tx

Prevention is focused on Control

Fever
hemorrhagic manifestations
thrombocytopenia
shock
neuro disturbances

virus initially infects tissue macrophages and dendritic cells

leads to release of cytokines --> inflammation and clotting pathways
-see clinical manifestations

Infected dendritic cells reduce expression of costimulatory molecules
this results in decreased immune response

Ranges from mild-death

damage to endothelium from cytokines and immune response

small + enveloped RNA virus

Internalized via receptor-mediated endocytosis

If coated by antibodies - can be internalized by macrophages and INCREASE INFECTIVITY

Flaviviridae - VHF

into phagocytes where they can replicate

Flavivirus

Children more affected with DHF more than adults

4 serotypes - NO cross-immunity

Primates are natural reservoirs

Transmission occurs by Aedes aeypti mosquito = arthralgia

Acute infection
Fever, HA, anorexia, myalgia.
Rash develops and fades within a few days

A few days later a secondary maculopapular rash develops

**Disease resolves within 2 weeks due to immune clearance of the virus - neutralizing antibodies**

Typically occurs when patient is infected to a SECOND strain-->

Previous antibodies to first Dengue virus bind, but increase uptake and virility
-remember no cross immunity-

Non-neutralizing Igs promote uptake of virus by macrophages

activates Tm cells that release *inflammatory cytokines*

**Initiates Hypersensitivity Reaction**

Type III - circulating antibodies from the first strain bind the second strain

These do not neutralize the virus, but make it worse

There must be sufficient viremia for mosquito to pick up/transmit

A secondary viremia can develop causing dissemination to other organs

Flavivirus - arbovirus transmitted by mosquitoes

Primate is Jungle Host

*Endemic to Africa and Central/South America*

Biphasic Disease**
acute form has nonspecific sx
sx fade in 3-4 days
15% of pts will progress to Toxic Phase =

Return of fever, GI hemorrhaging (black vomit)
Hepatomegaly and Jaundice

Yellow Fever is trophic for Hepatocytes and Kupffer Cells
(yellow fever) - produces Councilman bodies =
Apoptotic Hepatocytes

Yellow Fever
acute and toxic (hemorrhagic) phases

Yes - live attenuated

negatively stranded enveloped RNA virus

Segmented Genome:
L, M, S, Large, Medium, Small

Budd from the Golgi apparatus and released by exocytosis or cell lysis

Phlebovirus: Rift Valley Fever Virus

Nairovirus: Crimian-Congo Hemorrhagic Virus

Hantavirus: Hantaan Virus

Most are arboviruses except for Hantavirus (rodents)

Bunyavirus: Phlebovirus

Endemic to Eastern/Southern Africa
Rift Valley of Kenya

*Livestock is main reservoir**

Very mild, but can progress to VHF in some pts

Blindness has occurred

Arthropod Vector - can also be transmitted via contact

Path similar to Flaviviruses
Influenza-Like
Some may have hepatitis-like

Vaccine for Livestock

Yes, but for LIVESTOCK - not human

Adult Males

VHF - Hantavirus (Bunyaviridae) - a ROBOVIRUS
rodent-borne virus - field mouse

Primarily in *Asia and Europe*

Hemorrhagic fever with RENAL SYNDROME (HFRS)

Inflammation of the *Retina* occurs in 10%

Pathogenesis similar to Rift Valley Fever

C5a - also causes mast cell degranulation

major component of inflammation/pathogenesis of Bunyaviruses

Activated with Immune Complex Deposition

a Nairovirus (Bunyaveridae) -VHF

SE Asia, Europe, Africa

**Bioterrorism Threat**

Arbovirus - with TICK vector

Similar Clinical to other VHFs

Lassa virus --> VHF

enveloped ssRNA

Sandy appearance due to ribosomes within envelope

Nigeria and W. Africa

Robovirus - Rodent Born - Rat
can also be spread by P2P or contamination of water/food

Pharyngitis and Deafness are notable associations

ANTIinflammatory cytokines**

Marburg virus and Ebola virus

Both cause VHF - both endemic to Africa

Both have similar path

Filovirus - VHF

Endemic to Africa

Fruit Bat is most likely reservoir

Filovirus - VHF
mortality rates vary, but high

Endemic to Africa

Mode of transmission unknown
likely fruit bat/primate

Can cause severe hemorrhagic fever - Marburg has similar path..
Severe thrombocytopenia
Extensive Tissue Necrosis

Macrophages release cytokines that mimic shock

Virus replicates VERY RAPIDLY
constant viremia

Death is rapid

Control of vectors/reservoirs

enveloped ssRNA

reverse transcriptase and integrase

RNA is copied to DNA by reverse transcriptase

Release via budding from pm of host

Lentivirus Retrovirus

Reverse Transcriptase

Integrase -RANDOM integration of virus into host genome

Protease - cleaves precursor polypeptides into functional proteins

gag - encodes precursor that is cleaved into 4 functional NUCLEOCAPSID proteins:
p7,9,17,24

pol encodes a precursor that is cleaved into VIRAL ENZYMES - protease, RT, integrase

env - encodes precursor that is cleaved into evelope glycoproteins gp41 and gp120 - attachment

HIV gp120/41 attaches to CD4 (Th cells, also monocytes, macrophages)

Association with a co-receptor (chemokine receptor is also required)

gp41 is the transmembrane glycoprotein that aids in fusion
gp120 is extracellular

1.Acute HIV infection
-may be asymptomatic/flu-like
sx are from cytokine release

2. Clinical Latency
-persistent infection and replication of HIV
-decrease in CD4 Th cells
-asymptomatic period - variable length

3. Early symptomatic HIV infection
-chronic sx - lymphatdenopathy, wt loss nt sweats
-certain opportunistic infections appear

4. AIDS - CD4 count below 200/ul or below 14%
specific AIDS defining opportunistic functions
-AIDS related dementia

True: the "O" in TORCHeS

crosses placenta

HIV

It is a Category C - AIDS defining disease

detection of HIV antibodies using indirect ELISA and Western Blotting.

Must have 2 bands

Retrovirus - Human T-Lymphotropic Virus

Retrovirus similar to HIV, but
NOT CYTOLYTIC - infects CD4 cells

Associated with acute T-cell lymphocytic luekemia (ATLL)
after 30+ yrs of latency

Has additional gene - tax gene
-activates genes for IL-2, IL-2R
-these cause T cell proliferation

IL-2 and IL-2R w/o antigen stimulation results in uncontrolled clonal proliferation

specific antigens/antibodies by ELISA

*Atypical Lymphs on smear*

**Elevated WBC count - 100,000**

Plasmodium vivax

Plasmodium falciparum

transmitted by female anopheles mosquito - night time**

Infective stage of malaria injected into human by female anopheles during bloodmeal

Duffy antigen is a receptor for P vivax merozoites as well as IL-8

Many blacks lack this - confers advantage to P vivax malaria

transmits malaria

night feeder

low flier

aka Benign Tertian Malaria

48 hour life cycle - Fever paroxysms occur every 48hrs

Seldom Fatal

Reactivation occurs, but not after 3-5 years - due to hypnozoites in liver

Tendency to effect young RBCs

stage in Vivax malaria

Exists in Liver - responsible for relapse

Does NOT exist in falciparum - no relapse

Sporozoites injected by mosquito

Migrates to liver and undergoes schizogony - asexual division producing schizonts

Schizont produces merozoites which escape from liver to infect RBCs
-Enters Erythrocytic Stages)
trophozoites in RBCs

become erythrocytic schizonts (segmenters)

RBC ruptures - merozoites escape to invade new cells

Shizogony begins or gametogony

Another mosquito ingests the gametocytes where they are fertilized and result in a gamete

Malaria parasite consumes hemoglobin and converts it to hematin -
malarial pigment

bursts of TNF

repeating pattern of chills and fever

Venous blood process with Giemsa stain

ENLARGED infected RBC with Schuffner's dots (STIPPLING, surface invaginations)

Malignant Tertain Malaria

All stages of the parasite are infective - infects all ages of RBCs

Causes Hyperpyrexia > 106

Can Result in Blackwater Fever
Cerebral malaria: fever > 108

No relapse because NO HYPNOZOITE stage in liver

50% of malaria in the world - most fatal

Erythrocytes with double or multiple ring stages

Cresent-shaped gametocyte

Maurer's clefts

Result of inadequate Quinine therapy for P falciparum (malignant) malaria

high levels of free Hgb in urine (due to immune mediated kidney damage)

50% mortality

Occur in P falciparum (malignant Tertian Malaria)

can result in capillary obstruction

Nantucket Fever - NEW ENGLAND

Deer Tick Vector - Ixodes scapularis

malaria-like parasite - intraerythrocytic

may destroy RBCs, may be asymptomatic

Clindamycin + Quinine

Sporozite
Trophozoite
Schizont
Merozoite

Trophozoite
Schizont
Merozoite
Gametocyte

caused by protozoan T gondii

Common infection
-worst in 1st trimester, immunocomprtomised

Infection by RAW MEAT, cat feces
Chorioretinitis, microcephaly etc in fetus, disseminatino in AIDs

Tachyzoite - active merozoite in ACUTE infection
Bradyzoite - merozoite in zoitocyst = tissue cyst in CHRONIC disease

Affinity for many kinds of tissues -disseminates via RES

1. Ingestion of zoitocyst in undercooked meat (lamb, port)
-MOST COMMON WAY*******
freezing/cooking kills

2. Ingestion of oocyst from cat feces - especially kittens

1st trimester pregnancy

It can travel trans-placentally

TORCHeS

"African trypanosomiasis
T brucei gambiense (W Africa)
T brucei rhodesiense (E Africa)

Glycoprotein Switching**

Transmitted by Tsetse fly - day feeder

**GLYCOPROTEIN SWITCHING**

It avoids recognition by continuously developing new antigenic types

Coat is encoded by a single gene -
more than 1000 building genes that are switched in a predetermined order

Vaccine must cope with "bait and switch"

Bite of tsetse fly - metacyclic trypomastigote is inoculated

riverine tsetse fly = Glossina

Reservoir is humans and pig

Acute - T rhodesiense

Chronic - T gambiense

Causes acute sleeping sickness

Chancre sore at innoculation site

Somnolence and CNS disorders typically absent - pt dies first

Reservoirs: native game animals of Africa

Chloroquine
Quinine
Doxycycline
Primaquine - for liver stages (vivax)

Causative agent of Chagas Disease

Transmitted by Reduviid bug (kissing bug/assassin bug)
-infection via bug droppings
=posterior station

Entrance of metacyclic trypanosomes

Cardiac and GI manifestations
Cardiac aneurysm, megacolon

Acute (children) and chronic (adults) manifestation
Cardiac and Intestinal complications in chronic disease

swelling of the eyelid as a result of rubbing bug feces into eyes

Chagas Disease - 50% of cases

-Chaga's Disease

Makes pseudocysts in heart

Muscle and nerve tissues --> degeneration of nerves

Arboborne * kissing bug
Venereal - STI
Blood transfusion
Transplacental
Transmammary

Acute: Trypomastigot in blood

Chronic: amastigote in pseudocysts

Xenodiagosis with a triatomid bug

Toxoplasma gondii

Leishmaniasis

ulcerative lesions

Ingestion of Raw Pork

Intracellular parasite similar to trypanosomes

Infective stage: promastigote (anterior flagellum) - gut of SAND FLY

Dx stage: amastigote (no flagellum)

Cutaneous manifestations - skin ulcers

L braziliensis causes mucocutaneous lesion (recurrence)

L donovani - viscerotropic form - may be asymptomatic

Post-kala-azar may occur from inadequate tx.

Viscerotropic: L donovani

Mucocutaneous: L braziliensis

Anterior - infection spread via bite/infectious stage in anterior of vector
-Leishmaniasis, African Sleeping Sickness


Posterior - spread by feces/infectious stage resides in posterior compartment
-Chagas Disease

Chagas Disease

Mucocutaneous form of Leishmaniasis

L braziliensis

L braziliensis, mexicana

Entrapped eggs in host tissue - CHRONIC PHASE

It is a chronic hypersensitivity disease

acute phase may be asymptomatic

-trematodes - blood flukes

trematodes (blood flukes)

separate sexes, unlike other flukes

Uses a SNAIL vector

distribution of specific snail

S haematobium

S mansoni and japonicum migrate to mesenteric veins

cercariae release enzymes that facilitate passage through skin

eggs are passed in feces - picked up by snail

Occurs with any schistosome species in a nonimmune host

Amplified manifestations are seen
-nocturnal fever, cough, myalgia etc

True
S japonicum and mansoni in the hepatic/mesenteric vv

S haematobium to urinary bladder venules

Schistosomiasis

They incorporate host proteins into their tegument

IL-7 stimulates worm growth
TNF stimulates egg production

demonstration of eggs in the stool specimen (S mansoni & S japonicum) or URINE (S. haematobium).

-Less eggs with chronic - more are entrapped causing more serious disease

Schistosoma haematobium

Cause cercarial dermatitis (swimmer's itch)

Waterfowl are the definitive host
humans are accidental

Need suitable waterfowl and snail

Clincal: seldom go further than epidermis
rare systemic manifestations

Itching accompanied by erythema and maculopapular eruptions where cercariae entered the skin

Dx: eruptions and history

Preventative: Swim away from shore/vegetation
treat with molluscicide

Lare nematode - Guinea/Serpent Worm

ENDEMIC TO SUDAN*

Larvae are ovoviviparous

1st stage larva ingested by copepod

We INGEST COPEPOD - 3rd stage larvae is infective
-Female worm causes most of the problems

Affects subQ and skin - can see the worm under the skin

Best tx is slowly winding out on a stick a few inches a day
-may be as long as a meter

staph of Aesculapius?

Wurchereria bancrofti
=
Lymphatic Filariasis
=
Elephantitis

Africa, Asia, Brazil

Filariform juvenile is infective stage

Vector is night-flying mosquito

Inflammation from dead/dying worms --> Lymphadema
--> Elephantoid Tissue (irreversible)

WWII GI Psychological Factors

Diagnostic: Microfilaria

Not Zoonotic - Humans Only

Mosquito Control!

DOC - diethylcarbamazine

Wurchereria bancrofti

*Brazil*

Drinking water that contained infected copepods

Onchocera volvulus

Onchocerciasis = River Blindness
2nd leading cause of blindness

AFRICA and ECUADOR

Infective: filariform larva
Dx: microfilariae

Spread by black fly: Simulian damnosum

Nodules and Elephantoid sx of the groin

***Chorioretinitis***

Tx: Ivermectin

Onchocerciasis - a major cause of blindness

Eye Worm

Endemic to AFRICA

Infective - filariform larvae

Intermediate hosts are deer flies
Definitive host - human - no animal reservoirs

DOC: diethylcarbamazine

Not a documented infection with same organism elsewhere in the body

-bacteria can travel down IV

Secondary developes subsequent to documented infection

Invasive devices

Surgery

Respiratory infections

Underlying disease

Extremes of age!

Systemic Inflammatory Response Syndrome

2+ of the following:
Fever
HR greater than 90bpm
RR >20
High WBC count

NO PRESENCE OF MICROBE**

Caused by a variety of condtitions:
Autoimmune disorders, Pancreatitis, vasculitis, burns, surgery

SIRS + Microbe

Severe Sepsis - Sepsis +1 sign of hypoperfusion or organ dysfunction

Sepsis +1 or more:
-BP <60
maintaining bp requires drugs

Multiple Organ Dysfunction

Primary - direct insult to organ

Secondary - not in direct response to insult, but organ failure due to host response

Resuscitate pt

ID source of infection and treat

Maintain adequate organ system function

results from primary or secondary bacteremia

sx are a result of pathogen dispersal - ie emboli

Always presents with FEVER

Complications develop within 1 week

Possibly Staph aureus

Low grade fever

Nonspecific sx

onset to diagnosis is about 6 weeks

Possibly Viridans Strep

HCIE/NIE - Nosocomial
PVE - Prosthetic valve
IVDA - Intravenous drug abuse
Valvular infections
NVE - Native Valve Endocarditis - COMMON

Strep bovis - group D, gamma hemolytic

1. Nonbacterial thrombotic vegetation -
aggregation of platelets and fibrin due to heart endothelium damage

2. Bacteremia and colonization of fibrin plate

Pathognomonic of IE (acute)

Flat, painless red to bluish red macules/nodules on palms and soles

Red painful intradermal transient nodules

Pads of fingers and toes - small

Characteristic sign of IE

compare to Janeway Lesions

Lymphocytes, edema, and hemorrhage resulting in white spots of the retina

Observed in IE, but other diseases as well
such as DM

Often observed in IE

also Lung Cancer and any hypoxic conditions

Most of the bacteria are in a low metabolic state
Most antibiotic mechanisms disrupt/inhibit microbial metabolism

Surgical Removal - Valve Replacement/Repair

Bacterial Zoonosis -Francisella tularensis

Fastidious, gram (-) coccobacillus
Facultative intracellular pathogen - Macrophage

Many Mammal Reservoirs

Vector: Rabbits, hares, ticks (summer)

Transmission: many - animal contact, vector bite, aerosool, ingestion

**Bio-Warfare Agent = Reportable**

Ulceroglandular Disease is most common form - skin penetration

Lymphatic involvement occurs

Ulceroglandular - rarely fatal

Glandular
Pneumonic - inhalation - higher mortality
Oculoglandular
Others

Ingesting non-pasteurized DAIRY PRODUCTS/MILK
B melitensis (goats and sheep)

arbotus from cattle

Bacterial Zoonosis - Most commonly cause by
Brucella melitensis (from goats and sheep)

Severity of disease dependent on reservoir host/species

Facultative intracellular pathogens - multiply in RES

Causes an UNDULENT FEVER

Ingestion of unpasteruized MILK*

From various animals via
SANDFLY VECTOR - arbo

RBC PENETRATION -->
acute = Oroya fever
Chronic = verruga

SOUTH AMERICA

Causes Trench Fever and Bacillary angiomatosis

Transmission via HUMAN BODY LOUSE

Prominent infection during WW I

Causes Cat Scratch Disease and Bacillary Angiomatosis

Cat Scratch: cat is colonized (no disease) - transmission from scratch/bite

Early red papule becomes purple

Regional lymphadenopathy - may only be 2 node

Bartonella quintana and *henselae*

Caused by Bartonella henselae or B. quintana

In immunocompromised - AIDS

Proliferative disease of small blood vessels of skin/viscera

Rickettsial Triad

Ricketssiaciae

Obligate Intracellular - Arbos

Ricketssia

Caused by R. ricketssii

Triad + Centripetal Rahs (wrist first)

From bite of tick (must feed 24-48 hrs)
Dog Ticks (dermacentor)
Rocky Mountain Wood Tick
-Transovarial passage allows the ticks to be reservoir and vector-

Tx SHOULD NOT BE DELAYED

Most occur in SOUTHEAST US

Rickettsia akari

Mousemite (Vector AND reservoir)
House Mouse serves as reservoir as well

ESCHAR formation - red papule that forms at bite site which progresses to ulceration

Generalized rash (similar to chickenpox)
Self-Limited

Mediterranean Spotted Fever
Caused by R conorii

Mediteranian See
Brown dog tick is reservoir AND vector

Eschar forms

Characteristic Lesion of Rickettsial Pox
-caused by R anikari

Red papule that ulcerates

takes 9-14 days to form - organism is spreading systemically during this time

R. parkeri via Gulf Coast Tick and Lone Star Tick

Rickettsia prowazekii via Human Body Louse
-requires feces innoculation into bite site

Humans are reservoir (NO Transovarial)

Triad + CentriFugal spread of rash

Poor Sanitation/Urban/Crowding

Recurdescence = Brill-Zinsser disease - milder form

Mild recurdescence of Epidemic Typhus
R prowazekii

=Murine Typhus - R. typhi via Rat Flea feces into bite wound

Rat is vector

Occurs in warm, humid areas

Sx similar to Epidemic Typhus but milder

Orientia tsutsugamushi

Chigger Mite is vector
Rodent is Reservoir

Centrifugal Rash, Often Self-Limited

Eastern Asia/Pacific

DOC is Doxycycline

Gm (-) motile bacillus
Vi antigen
Causes Typhoid FEVER
-rose spots

H2S fermenter (not lactose!) - Black Colonies

Targets CFTR channels (CF heterozygote advantage)

Enters gut via Type 3 secretory system
-Bacterial-Mediated Endocytosis

Peyer's Patches Macrophages

Large innoculum needed

Vaccine Exists

Achlorhydria
(typically a LARGE inoculum is needed to overcome stomach acid)

Cholelithiasis/Gall Bladder DIsease

Begin Epiric antibiotic tx immediately!

PERFORM SUSCEPTIBILITY TESTING*****

ELISA test will confirm a carrier (gallbladder)

recovery of organisms in blood/intestinal secretions/stool
-1 WEEK AFTER INCUBATION-

Salmonella typhi capsule

Yersinia pestis - plague

non-motile - opposite of salmonella
Has temperature tolerance

1 organism - LOW INFECTIOUS DOSE

Cats

Only plague that is P2P transmission

Salmonella typhi
Yersinia pestis

TEMPERATURE RESISTANCE

Fibrinolysin/Phospholipase

Coagulase; Polysaccharaide biofilm
plug the rat gut - regurge

F1 envelope antigen - antiphagocytic capsule

Ca-regulated Endotoxin LPS (not temp regulated)

Yersinia pestis - flea ingests blood meal from infected animal

COAGULASE causes blood clot
-clogs gut of flea

Flea regurgitates 1000s of bacteria onto host

Phagocytosed by host PMNs --> LNs

Lymph node necrosis/dissemination

Lysis of phagocytes causing
Bacteremia/Septicemia

MASSIVE growth of microbes in blood

Invasion of other organs
Spread to lungs = pneumonotic

buboes - bubonic plague

Can be primary or secondary via septicemia of bubonic (most common form) of plague

Highly Contagious**

100% mortality if not treated

Bioterorism

May be primary or secondary

High mortality

NVD with
Large purple/black lesions - black death
NO BUBOES

Immunofluorescence stain positive for Y pestis *F1 antigen*

Looks like "starry night"

culture blood for plague bacilli

Lyme Disease = Lyme Borreliosis

Borrelia burgdorferi infection via Ixodes tick bite

NOTIFIABLE

Spirochete - Borrelia burgdorferi

Borrelia burgdorferi

Juvenile RA

Borrelia burgdorferi
Babesia microti - Nantucket
Anaplasma sp**************

Ixodes deer tick

Bartonella
Mycoplasmas
Chronic viral infections (CMV, EBV)

White-footed mouse - reservoir for B burgdorferi and also important for tick maturation

White-tailed deer
maturation of FEMALE TICK
(B. burgdorferi is killed by serum)

Transmit Lyme Disease
Ixodes scapularis
Ixodes pacificus

NO TRANSOVARIAL PASSAGE

Since no transovarial passage and these ticks only feed once per life cycle:

First must become inoculated with bacteria:
Larval Stage is earliest this can happen
From White Tailed Mouse

Then must deliver to human
NYMPH and ADULT are only ones that can do this
-must feed 48 hours to transmit LD

Nymph - smallest, more abundant,
COINCIDES w/ human outdoor activity - May to July

OSP-A binds tick midgut

OSP-C allows mammalian host invasion

Erythema Migrans = Bull's Eye Rash

=Stage 1

occur in 80% of cases

Spirochetes isolated from leading edge

NO GI OR RESPIRATORY manifestations*

Lymphohematogenous spread of Spirochetes

Move to Joints, CSF, Spleen, Liver, Heart

Cause arthralgia, Neuro manifestations,

AV block - Cardiac Disease

First detect anti-Borrelia antibodies by ELISA
-highly sensitive - no false negative

Confirm ELISA with WESTERN BLOT (proteins)
highly specific - no falso positives

Seen with spirochetal infection Treatment (LD, Relapsing Fever, Leptospirosis)

OVERactive Immune Response

Characterized by intesne rigors, profuse sweating and a fever followed by decline in temp and bp

Rapid killing of spirochetes releases toxic products -

-INCREASes circulating CYTOKINES - 5% mortality

Southern Tick Associated Rash Illness

Similar to LD but vector is
Amblyomma americanum = Lonestar Tick

Much more aggressive feeding than Ixodes

Causes ePidemic relapsing fever

Louse vector (LBRF)
-Pediculus humanis

Occurs in Europe Asia and Africa

Borrelia spp (not recurrentis)
B hermsii

Tick vector (vs louse of epidemic)

NORTH AND SOUTH AMERICAS

Ig (humoral > CMI

ANTIGENIC VARIATION**

Variable Outer Membrane Protein VOMP

11 genes that randomly express

Causes eNdemic relapsing fever

Soft body tick - Ornithodoros hermsii is vector AND reservoir

TRANSOVARIAL PASSAGE
-any bite is potentially infective

Brief Feeding Period - 20s
North America

Pediculus humanus (ePi Pediculis)

Epidemic (LBRF) - Africa and Peru

Endemic (TBRF) - The Americas has a low mortality

Doxycycline

Tightly-Coiled spirochete

Microscope is NOT dx like other spirochetes

Aerobic and SLOW GROWING - Hardy organisms

Most common zoonosis in the world

found in RENAL TUBES of many mammals
-URINARY shedding

Seasonal Appearance with warm, wet weather

Vertical AND Horizontal Transmission
Triathelete from infected lake****
or occupational exposure to animals

Targets kidney and liver - may cause JAUNDICE

Aseptic Meningitis and Conjunctival suffusion

Leptospira interrogans

aseptic meningitis is most important immune stage occurrence

during the immune/leptospiuric stage

Weil Syndrome - most SEVERE from of Leptospirosis

Immune system overreaction*

MODS is present

Leptospirosis

Urine, CSF

MAT - microscopic agglutination test

Dip-S-Ticks rapid IgM antibody test

Onchocerca volvulus - River Blindness

Blackfly simnulium damnosum is vector

Intracytoplasmic vesicles that protect Ehrlichia and Anaplasma from lysosome fusion/NADPH oxidase

They are obligate intracellular pathogens

Monocytes/macrophages

Neutrophils

Ixodes tick

Amblyomma americanum

Very similar to RMSF - spotted rash possible

Because it infects macrophages - releases many cytokines

ELEVATED CRP, ESR
also leukopenia, thrombocytopnia
mild elevation in serum transaminases

Anaplasmosis - often requires hospitalization!

DO NOT DELAY Tx*

Doxycycline

Elevated antibodies to *phase I* antigen with decreasing antibodies to phase 2 antigen (associated with acute)

Coxiella burnetii

Transmission is mostly due to inhalation

Subacute endocarcitis

Chronic Q Fever

Coxiella burnetii