Tropical, Vector-borne and Zoonotic Infectious Disease Pathology – Froberg---4.8.10
PURPOSE
•To learn the etiological agents and life cycles of the major
tropical, vector-borne and zoonotic parasites.
•To learn the major pathology associated with the important
tropical, vector-borne and zoonotic pathogens.
CHAGAS’ DISEASE (AMERICAN TRYPANOSOMIASIS)
TRYPANOSOMA CRUZI
•Organism: hemoflagellate (motile)
•Vector: Triatoma infestans (reduviid, kissing or assassin bug)
•Transmission: Vector lives in thatched or mud houses, biting
sleeping victim at night, depositing infected feces in wounds.
•Zoonosis: between mammals and vector
•Dx: finding trypomastigotes in blood
- -Epidemiology: Chagas Disease is most common in Central
America and northern South America.
-Chagas is also a transfusion risk in the United States from
infected blood donors who have immigrated from Latin America
-mirco: Charac “U” or “C” shape of T. cruzi in peripheral blood
-Nuclei (green) and kinetoplasts(black) are stained blue
with Geimsa
Life Cycle:
1
- Dliated cardiomyopathy with destruction of the ventricular
wall and an apical aneurysm 2 to Chagas Diseases
Virulence Factors
•Produces homolog of decay-accelerating factor (DAF) that
inhibits formation of C3 convertase & blocks alternate pathway of
complement
•Produces neuraminidase that cleaves sialic acids from host
proteins lining lysosomes - destabilizes organelle
•Produces hemolysins that form pores in lysosomal membranes
•Burst host cells in going from amastigote to trypomastigote
forms (huge inflam response)
Amastigotes of T. cruzi within
cardiac myocyte
Apical aneurysm from T. cruzi
infection
AFRICAN TRYPANOSOMIASIS SLEEPING SICKNESS
•Trypanosoma brucei rhodesiense
(East Africa). Acute, virulent.
•T. b. gambiense (West Africa), Chronic
•Transmission: Tsetse fly
•Within host, parasite undergoes successive changes of surface
antigens, VSG (variable surface glycoprotein)  waves of
parasitemia (unique!)
•Zoonotic: wild mammals  man
•Disease:
–Waves of antibody-induced parasite deaths 
recurrent fever.
–Invasion  heart, liver, spleen, nodes  (lymphocytes,
macrophages)  brain  often fatal lethargy  coma
 death
•Brain: Leptomeningitis  demyelinating panencephalitis 
plasma cells containing glycoprotein globules (flame cells)
-Chancre at site of Tsetse fly bite with transmission of
Trypanosomes
Life Cycle:
•Clinical:
–Stage 1: Chagoma (local, transient inflammatory lump) at site of
bite
–Stage 2: Dissemination: Myocarditis; enlarged spleen, liver, &
lymph nodes
–Stage 3: Years later (10-30% infected persons): cardiac
inflammation and fibrosis, dilated cardiomyopathy, apical
aneurysm
•Myenteric plexus damage  aperistalsis  mega-esophagus +
mega-colon
•Prevalence:
–Only in western hemisphere.
–Most common cause of heart failure in Latin America
–Up to 1/2 million in USA  transfusion hazard
-Romana’s sign from acute conjunctival T. cruzi infection
ONCHOCERCA VOLVULUS (FALARIAL NEMATODE)
•Transmission: Black flies: genus Simulium (tropical Africa)
•Cycle: Adult worms mate in skin  local infl. Nodule 
microfilariae  eye  keratitis and retinitis  blindness
•Rickettsia-like bacteria of genus Wolbachia live within
nematode-probably cause pathology
-S/Sx: Dermatitis from Onchocerca adults in skin
Tropical, Vector-borne and Zoonotic Infectious Disease Pathology – Froberg---4.8.10
-Keratitis (clouding of cornea) & blindness associated with
microfilarial infection of eye
•Pathology: Parasite-laden macrophages in granulomatous
inflammation
Filariasis WUCHERERIA BANCROFTI
Brugia malayi (less common)
•Mosquito is vector. Tropics.
•Larva circulates in blood  mature worm in lymphatics
•Humans only reservoir
•Nematode worm  intense inflammation, necrosis, destructive
scarring
•Resulting lymphatic obstruction  massive edema
(elephantiasis)
•Wuchereria bancrofti  90% of infections
-Epi: Tropical distribution of filarial nematodes
-Dx: Diagnosis is made by finding microfilaria in blood smear
VISCERAL LEISHMANIASIS (KALA-AZAR: BLACK DISEASE)
•Etiology:
–L. donovani (Old World)
–L. chagasi (New World)
•Clinical: Systemic dissemination  nodes, liver, spleen 
•Pathology: Like mucocutaneous but involving viscera
•Death: Bacterial infection, pancytopenia, progressive wasting
Enlarged liver & spleen in Pt
with visceral leishmaniasis
Cross section of adult filarial
nematode within lymphatic
channel  fibrinous Rx 
obstruction
Massive lymphedema from
filariasis – thickening of skin
from lymphedema and poor
circ
LEISHMANIASIS
•Mucocutaneous Leishmaniasis (Espundia)
-3 types: visceral, cutaneous, and mucocutaneous
•Etiology: Leishmania braziliensis (protozoan)
•Transmission: Sandfly. Only in tropical New World
•Thrive in macrophage phagolysosomes, proton pump raises
pH, lipophosphoglycans inhibit lysosomal enzymes
•Glycolipid gp63 = complement-cleaving proteinase
•Cell-mediated immunity protective, parasite causes Th1 
Th2 switch which inhibits macrophage activation (TQ)
•Dense glycocalyx binds C3b and resists lysis by C5-9.
-Epi: Tropical distribution
-Life Cycle: amastigotes can survive within macrophages
–Disfiguring
–destructive inflammation, nose
–anus
–vulva
Kupffer cell containing
amastigotes in visceral
leishmaniasis
SCHISTOSOMA MANSONI, S. JAPONICUM, S. HEMATOBIUM
•Life cycle: complex: Snail  larvae  human (via skin) 
mature adult worms in portal & pelvic veins  eggs 
granulomas with eosinophils - so Th1 & Th2 responses
•Disease:
–S. mansoni, S. japonicum  liver cirrhosis & portal HTN
–S. hematobium  bladder  hemorrhage & Sq carcinoma
Life Cycle:
-SM & SJ come out in feces; SH in urine
Eosinophilic & granulomatous
inflammation around
Schistosome eggs in bladder
•Clinical:
2
Squamous cell carcinoma of
bladder in pregnant Pt with
Schistosomiasis
ZOONOSES
•Pathogens that are spread to humans from other animals
•Transmission may involve insect/arthropod vectors, direct or
indirect transmission
3
Tropical, Vector-borne and Zoonotic Infectious Disease Pathology – Froberg---4.8.10
Not all of these in the lecture:
•Epidemiology:  prevalence if clothing not changed
–war, poverty
•Brill-Zinsser: recurrent typhus after long latent interval
-decades, probs due to change in host immunity
RICKETTSIA
•Rickettsia: small aerobic gram negative coccobacilli
•Vector-borne obligate intracellular parasites
•Infect endothelial (TQ!)& smooth muscle cells
•Endotoxin
•Abrupt onset fever, chills, headache, myalgia, rash
•Rx: tetracyclines
Q FEVER
•Q fever: Coxiella burnetti, worldwide
•Droplet inhalation or direct contact
•Reservoir: cattle, sheep, goats
•Clinical: subacute, fever, HA, malaise
–lungs: interstitial pneumonitis
–liver:  LFP, hepatomegaly, 1/3 jaundice
•Epidemiology: slaughterhouse & farm animals
•Pathology:
–lung  intersitial pneumonitis
–liver & BM  ring granulomas
–DX: serology
–Rx: tetracycline
–Prognosis: rarely fatal
Ring granuloma in liver (also
in BM)
RG = Central lipid vacuole
surrounded by macros
EPIDEMIC TYPHUS
•Rickettsia prowazekii, ~worldwide
•Vector: body louse (Pediculus corporis)
•Louse lives only on humans or in human clothes
•Clinical: fever, vasculitis  rash, cerebral damage
•Mortality 5-25%
•Pathology:
–skin  necrosis & gangrene
–heart, lungs, etc.  ecchymosis/hemorrhage
–brain  typhus nodule (perivasc cuffing of vessel
w/microglia cells)
ROCKY MOUNTAIN SPOTTED FEVER (misnomer)
•Rickettsia rickettsia: U.S., esp. SE & SC
•Vector: Dermacentor ticks (wood, dog, lone star)
•Reservoir: dogs & wild rodents
•Clinical: rash incl. soles & palms, fever, chills, myalgia, DIC
•Mortality 3% -- mainly from DIC
•Pathology:
–skin  vascular necrosis & thrombosis
–brain  perivascular inflammation (like typhus
nodule)
–lungs  pneumonitis
-bugs in endothelium of bld vessels
•Epidemiology:
–90% April  September
–Most common in children
-Central/SE US
Erythematous
maculopapular rash of
RMSF. Rash often
involves soles and
palms
Denuded endothelium & thrombosis
from RMSF
ANAPLASMOSIS (EHRLICHIOSIS)
•Ehrlichia canis, Anaplasma phagocytophilum,
E. ewingii, E. chaffeensis, U.S.
•Vector: ticks (deer, wood, dog)
•Reservoir: unknown
•Clinical: like RMSF: Fever, HA, rash 20%
•Pathology: like RMSF but less severe, thrombocytopenia
•Dx: “purple blobs” in WBCs
Morulae (bact clumps) in WBCs in Pts with Anaplasmosis:
Tropical, Vector-borne and Zoonotic Infectious Disease Pathology – Froberg---4.8.10
LYME DISEASE
•Borrelia burgdorferi, spirochete, US, Europe & Japan
•Vector: hard-shelled ticks (Ixodes scapularis)
•Reservoirs: deer, deer mice
•Clinical:
–tick bite  erythema migrans
–dissemination  cranial neuritis, meningoencephalitis, heart block, myocarditis
–late chronic  chronic, destructive arthritis,
neuropathy
•Dx: serology, PCR, culture
•Pathology:
–skin  Perivasc lymphocytes & plasma cells
–meninges  hypercellular CSF, IgGs vs. Borrelia
–joints  like Rheumatoid arthritis (usu a large jnt)
¨plasma cell synovitis
¨“onionskin”- like arteries (most commonly seen in SLE)
¨erosion of cartilage
Epi: May- July highest incidences; most in NE and N. Central US
and west coast
LEPTOSPIROSIS
•Spirochetes, multiple serotypes, worldwide
•Spread: contaminated water or occupational exposure
•Reservoirs: wild & domestic animal
•Clinical: most subclinical, fever, myalgia
–meningitis  ~aseptic
–liver  10% jaundice, mortality ~10%
–lungs pneumonitis, hemorrhage
•Pathology: scant inflammation
TULAREMIA
•Francisella tularensis
–small gram-negative coccobacillus
–worldwide
•Spread: contact, ticks, inhalation
•Reservoirs: rabbits, ticks, beaver (many!)
•Clinical: protean, fever, chills, malaise
–ulceroglandular  ulcer, draining nodes 
–systemic  bacteremia, pneumonia
•Pathology:
–early = neutrophilic infl., then granulomatous infl.,
stellate abscess (pale histocytes surrounded by dark
lymphocytes)
•Dx: serology, culture
•Rx: streptomycin
•Mortality < 1% with antibiotics
PLAGUE
•Yersinia pestis
–gram-negative rod, intracellular
–~ worldwide
•Vectors:
–urban plague, rats (Rattus rattus)  rat flea
(Xenopsylla cheopsis)  humans
–sylvatic plague  rodents, rabbits (SW US)
•Clinical: high fever & painful bubo
–bubonic = lymph node abscess
4
–pneumonic = rapidly develop pulmonary signs
(deadliest)
•Pathology: neutrophilic response
–lymph nodes  ulcerating lymphadenitis
–lungs  hemorrhagic, necrotizing bronchopneumonia,
fibrinous pleuritis
•Mortality: without antibiotics
–bubonic ~75%
–pneumonic ~90%
•USA ~30 cases/yr
Practice Questions:
1. What is the vector for Chagas’ disease?
2. Which of the following are virulence factors in Chagas’
disease?
a. Decay-accelerating factor
b. Neuroaminidase
c. Hemolysins
d. Burst host cells
e. All of the above
3. Trypanosoma brucei is responsible for which disease?
How is it transmitted? What is unique about this
parasite?
4. What is transmitted by black flies, mates in human skin,
and causes blindness?
5. WUCHERERIA BANCROFTI is transmitted by what
vector? Causing what disease?
6. What can thrive in macrophages phagolysosomes
proton pump raises pH, lipophosphoglycans inhibit
lysosomal enzymes? What effect does this bug have on
Th2?
7. What group of diseases are caused by an obligate
intracellular parasites that infects endothelia?
8. Q Fever is transmitted by? Describe ring granulomas.
9. Ulcerograndular, stellate abscess, and small gram
negative coccobacilli are characteristic of what disease?
10. Yersinia pestis is transmitted by what vector?
Answers:
1.
2.
3.
reduviid
E
Sleeping sickness, Tsetse fly, parasite undergoes
successive changes of surface antigens, VSG (variable
surface glycoprotein)
4. ONCHOCERCA VOLVULUS
5. Mosquito, elephantiasis
6. Mucocutaneous Leishmaniasis; •Cell-mediated
immunity protective, parasite causes Th1  Th2 switch
which inhibits macrophage activation
7. RICKETTSIA
8. Droplet inhalation; Ring granuloma = Central lipid
vacuole surrounded by macros
9. TULAREMIA
10. rats (Rattus rattus)  rat flea (Xenopsylla cheopsis) 
humans