Bacterial & Fungal Infections of Blood

&
Cardiovascular System
By the end of this chapter students should be able to:
- Distinguish among septicemia, bacteremia, and toxemia.
- Compare between action of endotoxin and exotoxins.
- Describe the signs, symptoms, causes, diagnosis, treatment, and prevention of
endocarditis, myocarditis, pericarditis and rheumatic fever.
- Compare and contrast the causative agents, vectors, reservoirs, symptoms, treatments,
and preventive measures for vector-borne diseases of cardiovascular system.
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Definitions:
• Bacteremia: presence of small number of bacteria in the blood which do not multiply
significantly.

• Septicemia
Presence of rapidly multiplying highly pathogenic bacteria in the blood.
A serious complication of septicemia is septic shock.

• Toxemia:
When bacteria remain fixed at a site of infection but release exotoxins into the blood,
the condition is toxemia.
A serious complication of toxemia is toxic shock.

• Fungimia: the presence of fungi in the blood.

• Viremia: the presence of viruses in the blood.

Source of blood stream infection:

- In hospital settings; direct inoculation of the organism into the blood as a result of
invasive procedures e.g. Intravenous catheterization.
- Via non-sterile needle use by drug users.
- From an infection elsewhere in the body, most common infections are urinary tract
infection, pneumonia, abdominal area, and surgical wound infections.

- Through small abrasions in the respiratory or digestive tracts.

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Common Causal Agents of blood stream infection:
1. Gram positive cocci: S. aureus, S. epidermidis (most common cause among Gram
positive cocci), S. pyogenes and S. pneumoniae.

2. Gram negative cocci: Neisseria meningitides.

3. Gram-positive bacilli: Clostridium causing gas gangrene, Bacillus anthracis.

4. Gram negative bacilli: as E. coli, Klebsiella species (most common cause among
enterobacteriaceae), Salmonella spp., Yersinia pestis, brucellae, Pseudomonas
aeruginosa.

5. Spirochete e.g Borrelia burgdorferi (Lyme disease), Borrelia causing relapsing fever.

6. Rickettsiae.

7. Fungi : e.g Candida, Dimorphic fungi e.g hispoplasma capsulatum .

8.viruses: Epstein-Barr virus, and parvovirus.

Pathogenesis of septicemia & septic shock:

- It is due to the excessive activation of the inflammatory immune response to molecules
from the microorganism that have caused the infection.
- Depending on the type of bacterium, these molecules may be lipopolysaccharide (LPS)
(Lipid A) molecules of Gram negative bacteria, or lipoteichoic acid of Gram positive
bacteria.
- a serious complication of septicemia is septic shock

Effects of Endotoxin
CliEffect of endotoxin
Fever
Hypotension (shock)
Inflammation
Disseminated intravascular
Coagulation
Mechanism
activating macrophages to produce:
interleukin-1 (IL-1),
tumor necrosis factor (TNF),
tumor necrosis factor (TNF)
Complement activation: C3a and C5a
activating tissue factor

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Signs and symptoms:
Septicemia: is characterized by:
- fever (over 38°C), chills, malaise,
- Nausea, vomiting, diarrhea,
- Shortness of breath,
- Petechia (minute hemorrhagic skin lesions) .
- Changes in mental status such as confusion and anxiety.

These signs and symptoms can progress rapidly to septic shock.

Septic shock: is caharacterized by:

- Extremely low blood pressure resulting from dilation of blood vessels,
- Decrease in body temperature,
- Decrease in or absence of urine output,
- Rapid breathing.
- Extremities become cool and pale.
- Bluish discoloration of the digits or lips (cyanosis)
- Increased heart rate, anxiety, and death.

Septicemia can lead to an infection of the lymphatic system in which inflamed lymphatic
vessels become visible as red streaks under the skin, a condition known as lymphangitis.
Lymphocytes, particularly in lymph nodes, act to limit infection of lymphatic vessels and
lymph nodes.

Laboratory Diagnosis of septiceamia:

Blood culture: for isolation of causative organism from blood.

Treatment:
Treatment generally involves prompt diagnosis and treatment with appropriate
antimicrobial drugs against the specific bacterial cause;

Toxemia:
Manifests differently according to the action of the exotoxin.

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 Anthrax

Causative agent: Bacillus anthracis (B. anthracis)

B. anthracis is an aerobic spore forming, Gram positive large bacillus, arranged in chains,
capsulated, and non-motile.

Transmission of infections:
- Anthrax is primarily a disease of animals e.g. cattle and sheep.
- Spores play an important role in transmission; they can survive in soil or on the skin of
animals for years.
- Humans are infected by :

 Cutaneous anthrax: Contact with infected animals or contaminated animal

products (chapter 9).

 Pulmonary ( inhalation ) anthrax : Inhalation of spores, or

 Gastrointestinal anthrax: Ingestion of undercooked food containing anthrax

spores (zoonotic disease).

Anthrax is not contagious; it cannot be transmitted from person to person.

Pathogenesis:
- Infections by B. anthracis are initiated by endospores. Once introduced into the body,
they are taken up by alveolar macrophages.
- Spores are transported through lymph system to mediastinal lymph nodes where
Germination of spores occurs and toxin production Pulmonary edema (pleural
effusion) death.
- The organisms are not killed, but multiply, eventually killing the macrophage.
- The released bacteria then enter the bloodstream, replicate rapidly, and secrete toxins
Shock Death
- Lymphatic or hematogenous spread to C.N.S occurs causing meningitis Death

Virulence factors:
1. Capsule (formed of polypeptides): It is anti-phagocytic, not stimulate immune
system.

2. Anthrax toxin: (A-B subunit):

- A (Active) subunit: Formed of two toxins
 Lethal factor (protease): Kill cells; specially targets and kill macrophages, and
causes tissue necrosis.

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  Edema factor: is an adenylate cyclase; which causes elevation of intracellular
cAMP, this causes an outpouring of fluid from the cell into the extracellular
space, resulting in severe edema.
- B (binding) subunit: protective antigen.

Clinical forms of anthrax:

 Cutaneous anthrax (malignant pustule): (chapter 9).

 Inhalational anthrax (Wool sorters disease): begins with non specific influenza-
like symptoms, especially fever, a dry cough and chest discomfort. This rapidly
progresses to hemorrhagic mediastinitis, bloody pleural effusions, septic shock,
and death.
 Gastrointestinal anthrax (a rare clinical form) leads to abdominal pain and bloody
diarrhea.
If untreated; infection usually kills the patient within 24 to 36 hours. the mortality
rate is exceptionally high, approaching 100%.

Laboratory Diagnosis:
• Specimen :blood, respiratory secretions or cutaneous lesion
• Gram stain: Gram-positive rods in chains.
• Culture on blood agar: large, non-hemolytic colonies.
• Direct IF antibody test: that detects antigens of the organism in the lesion.
• Serology: ELISA test for antibodies.
• PCR.

Treatment: ciprofloxacin or doxycycline.

Prevention of anthrax:
1. Destroy animal carcasses by incineration or deep burial in quick lime.
2. Active immunization of animals by live attenuated vaccine.
3. Human anthrax vaccines: cell-free vaccine containing purified protective antigen (B
–subunit of anthrax toxin ) as immunogen.

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 Brucellosis (undulant fever- Malta fever) .

Causative agent:
- Brucellae are Small Gram-negative rods (coccobacilli), non capsulate.
- Facultative intracellular pathogen.

Reservoir:
• Brucellosis is a true zoonotic disease. It is primarily pathogens of animals and
transmitted from animals to humans.

• Brucellae are shed in large numbers in the animal's urine, milk, placental fluid, and
other body fluids.

The three major human pathogens and their animal reservoirs are Brucella melitensis
(goats and sheep), Brucella abortus (cattle), and Brucella suis (pigs).

Transmission:
• Ingestion of raw milk and unpasteurized milk products like fresh cheese.

• Direct contact: of skin abrasions/ mucosal surfaces with tissues or organs of infected
animals.

• Inhalation of contaminated aerosols or dried remnants of infected animal tissues or

secretions.

• No human to human infection.

Virulence Factors:
• Endotoxin.
• Facultative intracellular pathogens: that can survive and multiply within host
phagocytic cells.

Pathogenesis:
• Acute stage: From the portal of entry the organisms reach the blood stream via
lymphatics and cause bacteremia
• From blood the organisms reach organs that are involved in the reticuloendothelial
system, including the liver, spleen, kidneys, bone marrow, and other lymph nodes;
where they multiply intracellularly.
• Chronic stage: The organisms stimulate cell mediated immunity with the
formation of granulomatous nodules, which can progress to form focal abscesses.
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Clinical Findings : I.P 1 to 3 weeks . Acute or gradual onset;
- Nonspecific symptoms such as fever, chills, fatigue, malaise, anorexia, and weight
loss occur.
- Undulating (rising-and-falling) fever pattern that gives the disease its name (often
in evening), in untreated patients.
- Enlarged lymph nodes, liver, and spleen are frequently found.
- Osteomyelitis is the most frequent complication.

Laboratory Diagnosis of Brucellosis:

Brucella is difficult to culture in a laboratory, diagnosis is confirmed by serological tests
showing a rising level of antibodies against Brucellae.

Direct methods Indirect methods

(Acute stage) (Acute & chronic stage)

1. Specimen: blood, bone marrow sample.

2. Blood Culture: Castaneda medium; Serum Agglutination test:

Trypticase-soy broth & agar , 5-10 %
CO2 (for 3 weeks).
3. Colonies are identified by:
- Gram stained film, B.R
( four fold increase in antibody
titer; or >1:160 considered
positive)

Treatment
As the organism is intracellular pathogen, a combined prolonged course of treatment with:
- Deoxycycline and rifampicin (for at least 6 weeks) for adults.
- Cotrimoxazole and rifampicin for children.

Prevention And Control:

1. Pasteurization of milk is the most important measure.
2. Health education for farmers, veterinarians and slaughterhouse workers for
occupational hazards
3. Active immunization of animals with live-attenuated strains.

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 Plague (Black Death)

Causative agent : Yersinia pestis (Y. pestis)

- Small Gram-negative rods.
- Facultative intracellular parasite.
- Non-lactose fermenting members of the enterobacteriaceae.

Transmission:
• Plague is enzootic in wild rodents (e.g. rats). Transmitted among them by fleas
(Xenopsylla cheopis) (urban plague).

• Infection is transmitted from infected rats to humans by flea bites mainly.

• In case of pneumonic plague spread can occur from human to human by respiratory
droplets (epidemic plague).

Virulence Factors:
It is one of the most virulent bacteria known (i.e., 1 to 10 organisms are capable of
causing disease).

1. Polypeptide capsule: anti-phagocytic- not immunogenic.

2. Endotoxin.
3. Exotoxin.
4. Yersinia outer proteins: inhibit phagocytosis.
5. V and W antigens: allow the organism to survive and grow intracellularly.

Clinical diseases:
1. Bubonic plague, the most frequent form, begins with pain and swelling of the
lymph nodes (buboes) draining the site of the flea bite. Buboes are typically located
in the groin but may also occur in axillae or on the neck.They started red and as
the patient's condition worsened they would become a dark purple or black colour
- and leak blood and pus.

2. Pneumonic plague: From blood, the bacilli reach many organs especially the lungs
causing secondary pneumonic plague.

3. Septicemic plague: The endotoxin-related symptoms, including disseminated

intravascular coagulation and cutaneous hemorrhages.

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Laboratory Diagnosis of plague:
Clinical specimens and cultures are hazardous

Direct methods Indirect methods

1. Specimen: blood, L.N aspirate, sputum.

Detection of antibodies
2. Stained film with:
- Gram’s: Gram negative coccobacilli.
to the capsular antigen
- IF. by:

3. Isolation and identification by:

Culture at 270C for 2-3 days on: ELISA
Blood, or selective medium. (titer of ≥ 16)

4. The organism is identified by: B.R

Treatment
A combination of streptomycin and doxycycline.

Prevention & Control:

1. Anti-rats measures and Anti-fleas measures (insecticides).
2. strict isolation (quarantine) of patient for 72 hours after antibiotic therapy is
started
3. Chemoprophylaxis: for contacts with cases of pneumonic plague e.g. Tetracyclines.
4. Formalin killed vaccine: for persons at risk. provides partial protection against
bubonic but not pneumonic plague

Relapsing Fever

Causative rganism:
Borrelia recurrentis, and Borrelia hermsii
Borreliae are Gram negative., large irregular wide spirals, highly flexible, and motile.

Relapsing fever
− Relapsing fever occurs in 2 forms: Epidemic and Endemic.

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.Table 12.1 comparison between epidemic and endemic relapsing fever
Epidemic Relapsing Endemic Relapsing Fever
Fever
Causative organism Borrelia recurrentis Borrelia hermsii
Vector lice ticks
Natural hosts Obligate human pathogens Rodents
(zoonosis)
− B.recurrentis is transmitted from person to person by the human body louse;
Humans are the only hosts.

− While B.hermsii are transmitted to humans by soft ticks (Ornithodoros), Rodents

are the main reservoirs (Zoonosis).

− Infection started by the arthropod bite that introduces spirochetes to blood; where
it multiply and spread to many tissues, producing fever, chills, headaches, myalgia,
and multiple-organ dysfunction.
− Relapsing fever is characterized by several cycles of apparent recovery, each
followed by a relapse.
− A most striking property of the organism is its ability to change surface protein
antigens.
− As antibodies appear, organisms disappear from the blood and are replaced by a
different antigenic variant within a few days.

Fig. Clinical stages of relapsing fever.

Laboratory diagnosis
1. Blood smears stained by Giemsa’s stain :diagnosis is usually based on the appearance
of loosely coiled spirochetes in the blood during the febrile stage of the disease.
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2. Blood culture : is not used routinely as a method of diagnosis.

3. Serologic tests: is rarely useful (due to antigenic variation)

Treatment
Tetracycline may be beneficial early in the illness and may prevent relapses.

Prevention:
1. Maintain good personal hygiene and delousing.
1. Insecticides for eradication of ticks.

VASCULITIS
Rickettsial Diseases

Distinguishing Features of Rickettsia

- Small, aerobic, Gram negative coccobacilli
- Obligate intracellular parasites of eukaryotic cells, because they are unable to
produce sufficient energy to replicate extracellularly.
- All are maintained in mammalian reservoirs.
- Transmitted by arthropod vectors (e.g ticks, mites, lice or fleas);except Q fever.
- Humans are accidentally infected.
- They are the causative agents of typhus, spotted fevers, and Q fever.

Table. Diseases caused by Rickettsia

Arthropod Mammalian
Disease Organism
vector Reservoir
Rocky mountain R. ricketsii Ticks Dogs, rodents
spotted fever (zoonosis)
Epidemic Typhus R. prowazekii Lice Humans
Endemic typhus R. typhi Fleas Rodents
(zoonosis)

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Pathogenesis of Rickettsial Infection:
The typical lesion caused by the rickettsiae is a vasculitis
1. Rickettsia infect endothelial cells lining the small blood vessels.
2. Once in the host cell the bacteria lyse the phagosome membrane with a phospholipase
 get into the cytoplasm where they replicate.
3. Pathogenesis is primarily due to destruction of endothelial cells by the endotoxin of
replicating bacteria  leakage of blood  organ and tissue damage due to loss of blood
into the tissue spaces.
4. Damage to blood vessels of the skin causes characteristic rash.

Laboratory Diagnosis
- Laboratory diagnosis of rickettsial diseases is based on serologic tests rather than
isolation of the organism.
e.g ELISA and IFA test are most widely used; fourfold increase in titer is diagnostic.
- Although rickettsiae can be grown in cell culture or embryonated eggs, this is a
hazardous procedure that is not available in the standard clinical laboratory.

Treatment: doxycycline.

Prevention:
- De-lousing, Rodents control, and Prevention of tick bites.
- doxycycline for exposed persons
- Vaccine: Formalin killed vaccine: for epidemic typhus.
-

. Table . Changes in Blood Cells

Symptoms and Signs Most Common Causal Agents
Anemia Chronic infections
Increases in PMNs in many extracellular bacterial
infections
Increases in mononuclear Viruses and other intracellular
leukocytes (monocytes or organisms: Listeria, Legionella,
lymphocytes)
Lymphocytosis with paroxysmal Bordetella pertussis
cough, stridor on inspiration

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 Cardiac Bacterial & Fungal Infections

Type Infection Common Causal Agents

Endocarditis Staphyloccoccus aureus

Acute
endocarditis

Subacute - Viridans streptococci (Most common cause,

endocarditis 50%)
- Other bacteria: S. epidermidis and S. aureus, , S.
pneumoniae,Enterococcus, Escherichia, Neisseria,
Pseudomonas, Mycobacterium, and Mycoplasma.
- Fungus: candia
Myocarditis - Viral causes : Coxsackie viruses are the
most common cause .

-S. aureus, -Enterococcus faecalis

( as complication of endocarditis)
-C.diphtheria toxin
-Borellia burgdorferi
Fungi: candida, aspergillus, histoplasam
capsulatum
Pericarditis -S. aureus and S.pneumoniae are most
common
-Mycobacterium tuberculosis
-Fungi: systemic mycosis e.g Histoplasma
capsulatum
Rheumatic fever Streptococcus pyogenes

Endocarditis
Definition:
An inflammation of the endocardium ( inner layer of the heart) .It is two types; acute or
subacute endocarditis
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 1. Acute Bacterial endocarditis:

Causative organisms: Staphyloccoccus aureus

Most common in hospitalized patients or intravenous drug user.

Source of infection: organism travel through bloodstream to heat .

Clinical picture
High fever, chills, new or increasing heart murmurs, fatigue, and emboli manifested
by Janeway lesions (painless, macular, haemorrhagic lesions that occur most commonly
on the palms or soles).

II. Subacute Bacterial endocarditis

Causative organisms:
- Viridans streptococci : most common cause ( 50% of cases).

- Other organisms are :

 Staphylococcus epidermidis and S. aureus, candia from the skin,
 Streptococcus pneumoniae from the pharynx,
 Enterococcus and Escherichia from the digestive tract.
 Neisseria, Pseudomonas, Mycobacterium, and Mycoplasma.

Viridans Streptococci Endocarditis

Causative organism:
- Gram-positive cocci arranged in chains, producing α- haemolytic colonies on blood
agar (viridans =green).
- The organisms are normal flora of human oropharynx.

Pathogenesis:

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 - During oral surgical procedure e.g. tonsillectomy or teeth extraction the organism
reaches the blood. In healthy individual the organism cleared from the circulation by
the immune system.
- In patients with previously damaged valve e.g. rheumatic heart disease, conjenital heart
defect, or artificial prosthetic heart valve the organism may settle on the surface of
heart valves causing subacute bacterial endocarditis.
Virulence factors:
Virulence of the organism is due to its ability to synthesize dextrans from glucose
(biofilm), which allows it to adhere to damaged heart valves.

Clinical picture
Low-grade fever, with weight loss, night sweats, increasing heart sounds, fatigue,
emboli to others sites manifested as splinter hemorrhages (under the finger nail).

Staphylococcus epidermidis endocarditis

Causative organism:
- Gram positive cocci arranged in clusters, coagulase negative, nonhemolytic, and
novobiocin sensitive.
- It is a commensal on the skin.

Pathogenesis:
Virulence factors::
The organism produce a glycocalyx that adhere to biomedical devices e.g intravascular
catheter and prosthetic devices;
causing septicemia prosthetic heart valves endocarditis.

Diagnosis of Endocarditis
- blood culture: for isolation of causative organism from blood
- According causative agent:
 On blood agar form α-hemolytic colonies of S. viridans (catalase –ve) must be
distinguished from S. pneumoniae (pneumococci), which is also α-hemolytic.
Viridans group streptococci are bile insoluble and optochin resistant.
 Non hemolytic colonies of S. epidermidis: catalase +ve, coagulase –ve,
novobiocin sensitive.

Treatment:
Penicillin or vancomycin + aminoglycosides (gentamycin) for endocarditis

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Prevention:
Prophylactic antibiotics amoxicillin prior to dental work or surgery for individuals with
damaged heart valve.

Myocarditis

Definition:
Myocarditis is inflammation of the heart muscle (myocardium)

Causative organisms
- Viral causes : Coxsackie viruses are the most common cause .
- Bacterial causes: Staph. aureus, Enterococcus faecalis (as a complication of
endocarditis), C.diphtheriae (toxin), Borrelia burgderferi.
- Fungi: candida, aspergillus, histoplasam capsulatum (in immunocompromised
patients).

Clinical picture:
Patients present with signs and symptoms of heart failure.

Pericarditis
Definition:
Inflammation of the sac around the heart (the pericardium).

Causative organisms
- Staphylococcus aureus and Streptococcus pneumoniae are most common.
- Mycobacterium tuberculosis
- Fungi: e.g Histoplasma capsulatum

Mode of transmission:
Pathogens reach the pericardium by either :
-Hematogenous or
-Direct spread from adjacent intrathoracic structures or,
-rarely directly from infected myocardium.

Clinical picture:
Chest pain is the most common manifestation of pericarditis. Pain often worsens with
inspiration or coughing.

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 Rheumatic fever
Post-streptococcal immune-mediated (non-suppurative) disease

Causative organism: streptococcus pyogenes

.
Pathogenesis:
Occurs 2-4 weeks after respiratory tract infection usually pharyngitis by S. Pyogenes
rheumatogenic strains; bearing certain M proteins.

It is autoimmune disease- Type II hypersensitivity reaction-: It is due to immunologic

reaction between cross-reacting antibodies to certain streptococcal M proteins and
antigens of joint, heart, and brain tissue.

C/P: Fever, malaise, migratory polyarthritis, endocarditis, myocarditis, and rheumatic

chorea. Recurrence is common, causing heart damage.

Lab.Diagnosis:

 Non specific tests : elevated Erythrocyte sedimentation rate (ESR) and C-reactive
protein.

 Specific test: Anti-streptolysin O (ASO) test : ASO titers (>200 Todd units/ml).

Treatment: No Benefit from penicillin treatment after the onset of rheumatic fever.

Prevention of rheumatic fever: possible prophylactic antibiotics for at least 5 years

post-acute rheumatic fever with benzathine penicillin; once each month.

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 Vector-borne diseases of the cardiovascular system

Arthropod Mammalian
Disease Organism
vector Reservoir
Plague Yersinia pestis Fleas; Rodents (zoonosis)

Lyme disease Borrelia ticks Field mice(zoonosis)

burgdorferi
Rocky mountain R. ricketsii Ticks Dogs, rodents
spotted fever (zoonosis)

Epidemic Typhus R. prowazekii Lice Humans

endemic typhus R. typhi Fleas Rodents (zoonosis)

Epidemic Relapsing lice Humans

Borrelia
Fever
recurrentis
Endemic Relapsing ticks Rodents (zoonosis)
Fever Borrelia hermsii

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