23Microbial Diseases of the Cardiovascular and Lymphatic Systems

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.

The Cardiovascular System

Figure 23.1

The Lymphatic System

Figure 23.2

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

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

Sepsis Puerperal sepsis (childbirth fever)

Streptococcus pyogenes Transmitted to mother during childbirth by

attending physicians and midwives.

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

Bacterial Infections of the Heart

Figure 23.4

Rheumatic Fever Inflammation of heart valves Autoimmune complication of

Streptococcus pyogenes infections

Figure 23.5

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.

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

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.

Tularemia Francisella

tularensis, gram-negative rod

Transmitted from rabbits and deer by deer flies.

Bacteria reproduce in phagocytes.

Figure 23.6

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.

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

Anthrax Gastrointestinal

anthrax Ingestion of

undercooked food contaminated food

50% mortality. Inhalational

anthrax Inhalation of

endospores. 100% mortality.

Figure 23.7

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

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

Biological Weapons

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.

Animal Bites and Scratches

Pasteurella multocida Clostridium Bacteroides Fusobacterium Bartonella hensellae: Cat-scratch disease

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

Plague

Figures 23.10, 23.11

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

Lyme Disease Borrelia burgdorferi Reservoir: Deer Vector: Ticks

Figures 23.13b–c

Lyme Disease

Figure 23.13a

Lyme Disease First symptom:

Bull's eye rash Second phase:

Irregular heartbeat, encephalitis

Third phase: Arthritis

Figure 23.14

Figure 23.12

Ehrlichiosis

Ehrlichia, gram-negative, obligately intracellular (in white blood cells)

Reservoir: Deer, rodents

Vector: Ticks

Figure 23.15

Typhus Epidemic typhus

Rickettsia prowazekii Reservoir: Rodents Vector: Pediculus humanus corporis Transmitted when louse feces rubbed into bite

wound

Typhus Epidemic murine typhus:

Rickettsia typhi Reservoir: Rodents Vector: Xenopsylla cheopsis

Spotted Fevers (Rocky Mountain Spotted Fever)

Rickettsia rickettsii Measles-like rash

except that the rash appears on palms and soles too.

Figure 23.18

Spotted Fevers (Rocky Mountain Spotted Fever)

Figure 23.16

Tick Life Cycle

Figure 23.17

Human Herpes Virus 4 Infections

Ebstein Barr Virus EBVInfectious 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

Infectious Mononucleosis

Figure 23.20

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

Pathogen Portal of entry

Reservoir Method of transmission

Yellow fever Arbovirus Skin Monkeys Aedes aegypti

Dengue Arbovirus Skin Humans Aedes aegypti;

A. Albopictus

Marburg, Ebola, Lassa

Filovirus, arenavirus

Mucous membranes

Probably fruit bats; other mammals

Contact with blood

Hantavirus pulmonary syndrome

Bunyavirus Respiratorytract

Field mice Inhalation

Viral Hemorrhagic Fevers

Ebola Virus

Figure 23.21

American Trypanosomiasis (Chagas’ Disease) Trypanosoma cruzi Reservoir: Rodents,

opossums, armadillos

Vector: Reduviid bug

Figures 23.22, 12.33d

Toxoplasmosis Toxoplas

ma gondii

Figure 23.23

Malaria Plasmodium vivax, P. ovale, P. malariae, P.

falciparum Anopheles mosquito

Figure 12.31b

Malaria

Figure 23.25

Malaria

Figure 23.24

Malaria

Figure 12.19

OTHER PROTOZOA

BLOOD and TISSUE PROTOZOA Plasmodium Babesia Trypanosoma brucei Trypanosoma cruzi Toxoplasma gondii Leishmania

PROTOZOA FROM OTHER BODY SITES Free-living Amebae

Naegleria Acanthamoeba

Trichomonas vaginalis

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

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

P. falciparum: Blood Stage ParasitesThin 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).

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

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.

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

Plasmodium malariae: Blood Stage ParasitesThin 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). 

P. malariae gametocytes: round to oval with scattered brown pigment; may almost fill red blood cell (RBC).  The RBCs are normal to smaller than normal (3/4 ×) in size.

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.

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.

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.

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). 

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.

Plasmodium vivax: Blood Stage ParasitesThin 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). 

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.

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.

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

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

Positive IFA result with P. malariae schizont antigen.

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)

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

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

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

Tsetse fly. The vector of African trypanosomiasis

Winterbottoms sign

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

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

Trypanosoma cruzi crithidia

Trypanosoma cruzi: Leishmanial form

Riduviid bug: the vector of American trypanosomiasis

Ramana's sign: unilateral conjunctivitis and orbital edema 

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

- 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

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

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

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

A: Positive reaction (tachyzoites + human antibodies to Toxoplasma + FITC-labelled antihuman IgG = fluorescence.)

B: Negative IFA for antibodies to T. gondii.

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)

- 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

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

Disease Visceral leishmaniasis

Cutaneous leishmaniasis

Mucocutaneous leishmaniasis

Babesiosis

Fatal if untreated

Papule that ulcerates and scars

Disfiguring Replicates in RBCs

Causative agent

Leishmania donovani

L. Tropica L. Braziliensis Babesia microti

Vector Sandflies Sandflies Sandflies Ixodes ticks

Reservoir Small mammals

Small mammals Small mammals

Rodents

Treatment Amphotericin B or miltefosine

Amphotericin B or miltefosine

Amphotericin B or miltefosine

Atovaquone + azithromycin

Geographic distribution

Asia, Africa, Southeast Asia

Asia, Africa, Mediterranean, Central America, South America

Rain forests of Yucatan, South America

United States

Leishmaniasis

BABESIA Disease: Babesiosis Lab Dx: Giemsa stained thick and

thin blood smears

Babesiosis

Figures 23.26, 12.32

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. 

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. 

Schistosomiasis

Figure 23.28

S. haemotobium Granulomas in urinary bladder wall

Africa, Middle East

S. japonicum Granulomas in intestinal wall

East Asia

S. mansoni Granulomas in intestinal wall

African, Middle East, South American, Caribbean

Swimmer’s itch Cutaneous allergic reaction to cercariae

U.S. parasite of wildfowl

Schistosomiasis

Tissue damage (granulomas) in response to eggs lodging in tissues

Schistosomiasis

Figure 23.27a

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

Biomphalaria spp.

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

Male and female schistosomes.

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

Bulinus spp.

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

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.

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

Onchomelania, hupensis spp.

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

Cercaria

Schistosomiasis

Figure 23.27b