This document provides information on various microbial diseases that affect the cardiovascular and lymphatic systems. It discusses topics like sepsis, bacterial infections of the heart, rheumatic fever, tularemia, brucellosis, anthrax, biological weapons, gangrene, animal bites and scratches, plague, relapsing fever, Lyme disease, ehrlichiosis, typhus, spotted fevers, herpes virus infections, viral hemorrhagic fevers, Chagas disease, toxoplasmosis, malaria, and other protozoan infections. Detailed information is provided on the causative agents, symptoms, transmission, and microscopic images of pathogens for many of these diseases.

1. 23
Microbial Diseases of the Cardiovascular
and Lymphatic Systems

3. The Cardiovascular System
and Lymphatics System
 Blood: Transports nutrients to and wastes from
cells.
 WBCs: Defend against infection.
 Lymphatics: Transport interstitial fluid to blood.
 Lymph nodes: Contain fixed macrophages.

5. The Lymphatic System
Figure 23.2

6. Sepsis and Septic Shock
 Sepsis: Bacteria
growing in the blood
 Severe sepsis:
Decrease in blood
pressure
 Septic shock: Low
blood pressure cannot
be controlled
Figure 23.3

7. Sepsis
 Gram-negative sepsis
 Endotoxins caused blood pressure decrease.
 Antibiotics can worsen condition by killing bacteria.
 Gram-positive sepsis
 Nosocomial infections
 Staphylococcus aureus
 Streptococcus pyogenes
 Group B streptococcus
 Enterococcus faecium and E. faecalis

8. Sepsis
 Puerperal sepsis (childbirth fever)
 Streptococcus pyogenes
 Transmitted to mother during childbirth by attending
physicians and midwives.

9. Bacterial Infections of the
Heart
 Endocarditis: Inflammation of the endocardium
 Subacute bacterial endocarditis: Alpha-hemolytic
streptococci from mouth
 Acute bacterial endocarditis: Staphylococcus aureus
from mouth
 Pericarditis: Streptococci

10. Bacterial Infections of the
Heart
Figure 23.4

11. Rheumatic Fever
 Inflammation of heart valves
 Autoimmune complication of Streptococcus
pyogenes infections
Figure 23.5

13. RF
 RF is characterized by a constellation of findings
 major manifestations
 (1) migratory polyarthritis of the large joints
 (2) carditis,
 (3) subcutaneous nodules
 (4) erythema marginatum of the skin
 (5) Sydenham chorea, a neurologic disorder with
involuntary purposeless, rapid movements.

14. RF
 minor manifestations (nonspecific signs and
symptoms)
 fever, arthralgia
 elevated blood levels of acute phase reactants
CRP, ESR, ASO
 The diagnosis is established by the so-called Jones
criteria:
 evidence of a preceding group A streptococcal infection,
with the presence of two of the major manifestations
listed above or one major and two minor manifestations

15. RF
 After an initial attack, there is increased vulnerability to
reactivation of the disease with subsequent pharyngeal
infections, and the same manifestations are likely to
appear with each recurrent attack.
 Carditis is likely to worsen with each recurrence, and
damage is cumulative.
 valvular disease
 cardiac murmurs, cardiac hypertrophy and dilation, and heart
failure, arrhythmias (particularly atrial fibrillation in the
setting of mitral stenosis), thromboembolic complications,
and infective endocarditis.

16. Tularemia
 Francisella tularensis,
gram-negative rod
 Transmitted from
rabbits and deer by
deer flies.
 Bacteria reproduce in
phagocytes.
Figure 23.6

17. Brucellosis (Undulant Fever)
 Brucella, gram-negative rods that grow in
phagocytes.
 B. abortus (elk, bison, cows)
 B. suis (swine)
 B. melitensis (goats, sheep, camels)
 Undulating fever that spikes to 40°C each evening.
 Transmitted via milk from infected animals or
contact with infected animals.

18. Anthrax
 Bacillus anthracis, gram-positive, endospore-
forming aerobic rod
 Is found in soil.
 Cattle are routinely vaccinated.
 Treated with ciprofloxacin or doxycycline.
 Cutaneous anthrax
 Endospores enter through minor cut
 20% mortality

19. Anthrax
 Gastrointestinal
anthrax
 Ingestion of
undercooked food
contaminated food
 50% mortality.
 Inhalational anthrax
 Inhalation of
endospores.
 100% mortality.
Figure 23.7

20. Biological Weapons
 1346: Plague-ridden bodies used by Tartar army against Kaffa.
 1925: Plaque-carrying flea bombs used in the Sino-Japanese War.
 1950s: U.S. Army spraying of S. marcescens to test weapons dispersal.
 1972: International agreement to not possess biological weapons.
 1979: B. anthracis weapons plant explosion in the Soviet Union.
 1984: S. enterica used against the people of The Dalles.
 2001: B. anthracis distributed in the United States

21. Biological Weapons
Bacteria Viruses
Bacillus anthracis “Eradicated” polio and measles
Brucella spp. Encephalitis viruses
Chlamydophila psittaci Hermorrhagic fever viruses
Clostridium botulinum toxin Influenza A (1918 strain)
Coxiella burnetti Monkeypox
Francisella tularensis Nipah virus
Rickettsia prowazekii Smallpox
Shigella spp. Yellow fever
Vibrio cholerae
Yersinia pestis

22. Gangrene
 Ischemia: Loss of blood supply to tissue.
 Necrosis: Death of tissue.
 Gangrene : Death of soft tissue.
 Gas gangrene
 Clostridium perfringens, gram-positive, endospore-
forming anaerobic rod, grows in necrotic tissue
 Treatment includes surgical removal of necrotic tissue
and/or hyperbaric chamber.

23. Animal Bites and Scratches
 Pasteurella multocida
 Clostridium
 Bacteroides
 Fusobacterium
 Bartonella hensellae: Cat-scratch disease

24. Plague
 Yersinia pestis, gram-negative rod
 Reservoir: Rats, ground squirrels, and prairie dogs
 Vector: Xenopsylla cheopsis
 Bubonic plague: Bacterial growth in blood and
lymph
 Septicemia plague: Septic shock
 Pneumonic plague: Bacteria in the lungs

25. Plague
Figures 23.10, 23.11

26. Relapsing Fever
 Borrelia spp., spirochete
 Reservoir: Rodents
 Vector: Ticks
 Successive relapses are less severe

27. Lyme Disease
 Borrelia burgdorferi
 Reservoir: Deer
 Vector: Ticks
Figures 23.13b–c

28. Lyme Disease
Figure 23.13a

29. Lyme Disease
 First symptom:
Bull's eye rash
 Second phase:
Irregular
heartbeat,
encephalitis
 Third phase:
Arthritis
Figure 23.14

30. Figure 23.12

31. Ehrlichiosis
 Ehrlichia, gram-negative, obligately intracellular
(in white blood cells)
 Reservoir: Deer,
rodents
 Vector: Ticks
Figure 23.15

32. Typhus
 Epidemic typhus
 Rickettsia prowazekii
 Reservoir: Rodents
 Vector: Pediculus humanus corporis
 Transmitted when louse feces rubbed into bite wound

33. Typhus
 Epidemic murine typhus:
 Rickettsia typhi
 Reservoir: Rodents
 Vector: Xenopsylla cheopsis

34. Spotted Fevers (Rocky Mountain
Spotted Fever)
 Rickettsia rickettsii
 Measles-like rash
except that the rash
appears on palms and
soles too.
Figure 23.18

35. Spotted Fevers (Rocky Mountain
Spotted Fever)
Figure 23.16

36. Tick Life Cycle
Figure 23.17

37. Human Herpes Virus 4 Infections
Ebstein Barr Virus EBV
Infectious Mononucleosis
 Childhood infections are asymptomatic.
 Transmitted via saliva
 Characterized by proliferation of monocytes
Burkitt’s lymphoma
 Nasopharyngeal carcinoma
 Cancer in immunosuppressed individuals, and malaria
and AIDS patients

39. Infectious Mononucleosis
Figure 23.20

40. Cytomegalovirus Infections
 Cytomegalovirus (Human herpesvirus 5)
 Infected cells swell (cyto-, mega-)
 Latent in white blood cells
 May be asymptomatic or mild
 Transmitted across the placenta; may cause mental
retardation
 Transmitted sexually, by blood, or by transplanted
tissue

41. Viral Hemorrhagic Fevers
Pathogen Portal of Reservoir Method of
entry transmission
Yellow fever Arbovirus Skin Monkeys Aedes
aegypti
Dengue Arbovirus Skin Humans Aedes
aegypti;
A. Albopictus
Marburg, Filovirus, Mucous Probably Contact with
Ebola, arenavirus membranes fruit bats; blood
Lassa other
mammals
Hantavirus Bunyavirus Respiratory Field mice Inhalation
pulmonary tract
syndrome

42. Ebola Virus
Figure 23.21

43. American Trypanosomiasis (Chagas’
Disease)
 Trypanosoma cruzi
 Reservoir: Rodents,
opossums, armadillos
 Vector: Reduviid bug
Figures 23.22, 12.33d

44. Toxoplasmosis
 Toxoplasma
gondii
Figure 23.23

45. Malaria
 Plasmodium vivax, P. ovale, P. malariae, P. falciparum
 Anopheles mosquito
Figure 12.31b

46. Malaria
Figure 23.25

47. Malaria
Figure 23.24

48. Malaria
Figure 12.19

49. OTHER PROTOZOA
BLOOD and TISSUE PROTOZOA
 Plasmodium
 Babesia
 Trypanosoma brucei
 Trypanosoma cruzi
 Toxoplasma gondii
 Leishmania

50. PROTOZOA FROM OTHER BODY SITES
 Free-living Amebae
 Naegleria
 Acanthamoeba
 Trichomonas vaginalis

51. PLASMODIUM
 Disease: Malaria
 P. vivax: Benign tertian malaria
 P. malariae: Quartan malaria
 P. falciparum: Malignant tertian malaria
 P. ovale: Ovale tertian malaria
 Lab Dx: Giemsa stained thick and thin
blood smears; IFA; PCR

52.  Infected RBC:
 P. vivax and P. ovale: reticulocytes
 P. malariae: senescent erythrocytes
 P. falciparum: erythrocytes of all ages
 Cyclic paroxysm of fever:
 P. vivax and P. ovale: every 48 hours
 P. malariae: every 72 hours
 P. falciparum: every 36-48 hours

54. P. falciparum: Blood
Stage Parasites
Thin Blood Smears
Fig. 1: Normal red cell;
Figs. 2-18: Trophozoites
(among these, Figs. 2-10
correspond to ring-stage
trophozoites);
Figs. 19-26: Schizonts (Fig.
26 is a ruptured schizont);
Figs. 27, 28: Mature
macrogametocytes (female);
Figs. 29, 30: Mature
microgametocytes (male).

55. Gametocytes of P. falciparum in thin blood
smears. Note the presence of a “Laveran’s bib”,
which is not always visible.

56. P. falciparum rings have delicate cytoplasm and 1 or 2 small
chromatin dots. Red blood cells (RBCs) that are infected are not
enlarged; multiple infection of RBCs more common in P. falciparum
than in other species. Occasional appliqué forms (rings appearing
on the periphery of the RBC) can be present.

57. P. falciparum schizonts: seldom seen in peripheral
blood. Mature schizonts have 8 to 24 small merozoites;
dark pigment, clumped in one mass.

58. Plasmodium
malariae: Blood
Stage Parasites
Thin Blood Smears
Fig. 1: Normal red cell;
Figs. 2-5: Young
trophozoites (rings);
Figs. 6-13: Trophozoites;
Figs. 14-22: Schizonts;
Fig. 23: Developing
gametocyte;
Fig. 24: Macrogametocyte
(female);
Fig. 25: Microgametocyte
(male).

60. P. malariae rings: have sturdy cytoplasm and a large
chromatin dot. The red blood cells (RBCs) are normal
to smaller than normal (3/4 ×) in size.

61. P. malariae schizonts: have 6 to 12 merozoites with large
nuclei, clustered around a mass of coarse, dark-brown
pigment. Merozoites can occasionally be arranged as a
rosette pattern.

62. P. malariae trophozoites: have compact cytoplasm and a
large chromatin dot. Occasional band forms and/or
"basket" forms with coarse, dark-brown pigment can be
seen.

63. Plasmodium
ovale: Blood Stage
Parasites
Fig. 1: Normal red cell;
Figs. 2-5: Young
trophozoites (Rings);
Figs. 6-
15: Trophozoites;
Figs. 16-23: Schizonts;
Fig. 24:
Macrogametocytes
(female);
Fig. 25: Microgametocyte
(male).

64. P. ovale gametocytes: round to oval, and may almost fill
the red blood cells (RBCs). Pigment is brown and more
coarse than that of P. vivax. RBCs are normal to slightly
enlarged (1 1/4 ×), may be round to oval, and are
sometimes fimbriated. Schüffner's dots are visible
under optimal conditions.

65. Plasmodium
vivax: Blood Stage
Parasites
Thin Blood Smears
Fig. 1: Normal red cell;
Figs. 2-6: Young
trophozoites (ring stage
parasites);
Figs. 7-18:
Trophozoites;
Figs. 19-27: Schizonts;
Figs. 28 and
29: Macrogametocytes
(female);
Fig. 30:
Microgametocyte (male).

66. P. vivax gametocytes: round to oval with scattered
brown pigment and may almost fill the red blood cell
(RBC). RBCs are enlarged 1 1/2 to 2 × and may be
distorted. Under optimal conditions, Schüffner's dots
may appear more fine than those seen in P. ovale.

67. P. vivax rings: have large chromatin dots and can show
amoeboid cytoplasm as they develop. RBCs can be normal
to enlarged up to 1 1/2 × and may be distorted. Under
optimal conditions, Schüffner's dots may be seen.

68. P. vivax schizonts: large, have 12 to 24 merozoites,
yellowish-brown, coalesced pigment, and may fill the
red blood cell (RBC).

69. P. vivax trophozoites: show amoeboid cytoplasm, large
chromatin dots, and have fine, yellowish-brown pigment.

70. Positive IFA result with P. malariae schizont antigen.

71. TRYPANOSOMA BRUCEI
 Disease: African trypanosomiasis
 T. b. gambiense: Gambian trypanosomiasis,
West & Mid-African sleeping sickness
 T. b. rhodesiense: Rhodesian
trypanosomiasis, East African sleeping
sickness
 Lab Dx: Giemsa stained thick and thin blood
smears or lymph exudate (early stage); Giemsa
stained smears of CSF (late stage)

72.  Site in host: lymph glands, blood stream, brain
 Portal of entry: skin
 Source of infection: tsetse fly
 Winterbottom’s sign: enlargement of
posterior cervical LNs

74. Trypomastigote: slender to fat and stumpy forms; in
Giemsa stained films – C or U shaped forms NOT seen;
small, oval kinetoplast located posterior to the nucleus; a
centrally located nucleus, an undulating membrane, and an
anterior flagellum. The trypanosomes length range is 14-
33 µm

75. A dividing parasite is seen at the right. Dividing forms
are seen in African trypanosomiasis, but not in American
trypanosomiasis (Chagas' disease)

77. Tsetse fly. The vector of African trypanosomiasis

78. Winterbottoms sign

79. TRYPANOSOMA CRUZI
 Disease: American trypanosomiasis, Chaga’s
disease
 Lab Dx: Giemsa stained thick and thin blood
smears for the trypomastigote; histopath
exam for the amastigote
 Site in host: Tissues – heart; blood
 Portal of entry: skin
 Source of infection: Kissing bug Triatomidae

80. Trypomastigote: shape is short & stubby to long &
slender; in Giemsa stained blood films – C or U shaped;
kinetoplast is large, oval & located posterior to the
nucleus; anterior long free flagellum

81. Trypanosoma cruzi crithidia

82. Trypanosoma cruzi: Leishmanial form

83. Riduviid bug: the vector of American
trypanosomiasis

84. Ramana's sign: unilateral
conjunctivitis and orbital
edema

85. TOXOPLASMA GONDII
 Disease: Toxoplasmosis
 Site in host: All organs
 Portal of entry:
 Ingestion of oocyst contaminated water
 Aerosolization of oocyst contaminated dust or
litter
 Consumption of raw or undercooked cyst
infected meat
 Transplacental passage of the tachyzoite

86. - Definitive host: domestic cats
- Intermediate host: infected rodents
 Accidental intermediate host: humans
 Lab Dx: IFAT and ELISA; Giemsa-stained
smears of exudates, aspirates or tissues

88. T. gondii tachyzoites: crescentic to pyriform
shaped with a prominent, centrally placed nucleus.

89. Toxoplasma gondii cyst in brain tissue stained with
hematoxylin and eosin (100×).

90. T. gondii oocysts in a fecal floatation (100×).

91. A: Positive reaction (tachyzoites + human antibodies to
Toxoplasma + FITC-labelled antihuman IgG = fluorescence.)
B: Negative IFA for antibodies to T. gondii.

92. LEISHMANIA
- Disease:
- L. tropica complex: Old Word Cutaneous
leishmaniasis (oriental sore, Aleppo boil, Delhi
ulcer, Baghdad boil)
- L. mexicana complex: New Word Cutaneous
leishmaniasis (chiclero ulcer, bay sore)
- L. braziliensis complex: Mucocutaneus
leishmaniasis (espundia, uta)
- L. donovani: Visceral leishmaniasis (kala-azar or
black disease, Dumdum fever)

93. - Lab Dx: Giemsa stained tissue sections or
impression smears
- Site in host: Monocytes/macrophages of
skin & mucosa
- Portal of entry: Skin
- Source of infection: Phlebotomus or
Lutzomiya fly

95. L. tropica amastigotes: ovoid in shape; large & eccentric
nucleus; small, rodlike kinetoplast positioned opposite
the nucleus; rodlike axoneme perpendicular to the
kinetoplast

96. Leishmaniasis
Disease Visceral Cutaneous Mucocutaneous Babesiosis
leishmaniasis leishmaniasis leishmaniasis
Fatal if Papule that Disfiguring Replicates in
untreated ulcerates and RBCs
scars
Causative Leishmania L. Tropica L. Braziliensis Babesia
agent donovani microti
Vector Sandflies Sandflies Sandflies Ixodes ticks
Reservoir Small Small mammals Small Rodents
mammals mammals
Treatment Amphotericin Amphotericin B Amphotericin B Atovaquone +
B or or miltefosine or miltefosine azithromycin
miltefosine
Geographic Asia, Africa, Asia, Africa, Rain forests of United States
distribution Southeast Mediterranean, Yucatan, South
Asia Central America, America
South America

97. BABESIA
 Disease: Babesiosis
 Lab Dx: Giemsa stained thick and thin
blood smears

98. Babesiosis
Figures 23.26, 12.32

100. Babesia microti infection, Giemsa stained thin smear. The
organisms resemble P. falciparum; however Babesia
parasites present several distinguishing features: they
vary more in shape and in size; and they do not produce
pigment.

101. Infection with Babesia. Giemsa stained thin smears
showing the tetrad, a dividing form pathognomonic for
Babesia. Note also the variation in size and shape of the
ring stage parasites and the absence of pigment.

102. Schistosomiasis
Figure 23.28

103. Schistosomiasis
 Tissue damage (granulomas) in response to eggs
lodging in tissues
S. haemotobium Granulomas in urinary Africa, Middle East
bladder wall
S. japonicum Granulomas in intestinal East Asia
wall
S. mansoni Granulomas in intestinal African, Middle East,
wall South American,
Caribbean
Swimmer’s itch Cutaneous allergic U.S. parasite of
reaction to cercariae wildfowl

104. Schistosomiasis
Figure 23.27a

105. SCHISTOSOMA MANSONI
- Disease: Schistosomiasis, intestinal
schistosomiasis, bilharziasis “snail fever”
- Site in host: veins of LI
- Portal of entry: skin
- Definitive host: humans, baboons & rodents
- Intermediate host: snail (Biomphalaria sp &
Tropicorbis sp)
- Infective stage: cercariae
- Lab Dx: eggs in stool; rectal or liver biopsy

107. Biomphalaria spp.

108. Schistosoma mansoni eggs: large (length 114 to 180 µm)
and have a characteristic shape, with a prominent lateral
spine near the posterior end. The anterior end is tapered
and slightly curved. When the eggs are excreted, they
contain a mature miracidium

113. Male and female schistosomes.

114. SCHISTOSOMA HAEMATOBIUM
- Disease: Urinary schistosomiasis,
schistosomal hematuria, urinary bilharziasis
- Site in host: veins of urinary bladder
- Portal of entry: skin
- Definitive host: humans, monkeys & baboons
- Intermediate host: snail (Bulinus, Physopsis,
and Biomphalaria sp)
- Infective stage: cercariae
- Lab Dx: eggs in stool; cystoscopy

115. Bulinus spp.

116. S. haematobium eggs: large and have a prominent
terminal spine at the posterior end

118. S.haematobium: adult schistosomes live in pairs in the pelvic veins
(especially in the venous plexus surrounding the bladder); males are
10-15 mm in lenght by 0,8-1 mm in diameter, and have a ventral
infolding from the ventral sucker to the posterior end forming the
gynecophoric canal. Adult male with female in the copulatory groove.

119. SCHISTOSOMA JAPONICUM
- Disease: Schistosomiasis, Katayama fever
- Site in host: veins of SI
- Portal of entry: skin
- Definitive host: humans, dogs, cats,
horses, pigs, cattle, deer, caribou &
rodents
- Intermediate host: snail (Oncomelania)
- Infective stage: cercariae
- Lab Dx: eggs in stool; liver biopsy

120. Onchomelania, hupensis spp.

121. S. japonicum egg: typically oval or subspherical, and
has a vestigial spine (smaller than those of the other
species)

124. Cercaria

128. Schistosomiasis
Figure 23.27b