1. Chapter 23, Chapter 24
Microbial Diseases of the Cardiovascular and Lymphatic Systems
Microbial Diseases of the Respiratory System

2. The Cardiovascular System
Blood is a mixture of plasma and cells
Red blood cells carry oxygen
White blood cells are involved in the body’s defense against infection.
Figure 23.1

3. The Lymphatic System
Fluid that filters out of capillaries into spaces between tissue cells is called interstitial fluid.
Interstitial fluid enters lymph capillaries and is called lymph;
Vessels called lymphatic return lymph to the blood.
Figure 23.2

4. Sepsis and Septic Shock
Sepsis is an inflammatory response caused by the spread of bacteria or their toxin from a focus of infection.
Septicemia is sepsis that involves proliferation of pathogens in the blood.
Septic shock- low blood pressure which cannot be controlled
Lymphangitis -inflammation of the lymphatic channels that occurs as a result of infection at a site distal to the channel.
The most common cause of Lymphangitis
in humans is Streptococcus Pyogenes
Lymphangitis
Figure 23.3

5. Sepsis 1. Gram-Positive Sepsis 2. Gram-negative sepsis
Exotoxins, Nosocomial infections,
Staphylococcus aureus
Streptococcus pyogenes
Group B streptococcus
Enterococcus faecium and E. faecalis
2. Gram-negative sepsis
Endotoxins caused blood pressure decrease and septic shock .
Antibiotics can worsen condition by killing bacteria
3. Puerperal Sepsis (Childbirth fever)
Puerperal sepsis begins as an infection of the uterus following childbirth or abortion; it can progress to peritonitis or septicemia.
Puerperal sepsis was transmitted by the hands and instruments of midwives and physicians.
Puerperal sepsis is now uncommon because of modern hygienic techniques and antibiotics

6. Bacterial Infections of the Heart
Endocarditis
The inner layer of the heart is the endocardium.
Inflammation of the endocardium
Subacute bacterial endocarditis –
from microbes in the mouth.( Arises from a focus of infection, such as a tooth extraction).
Alpha-hemolytic streptococci
Staphylococci
Enterococci
Preexisting heart abnormalities are predisposing factors.
Signs include fever, anemia, and heart murmur.
Acute bacterial endocarditis
Staphylococcus aureus
The bacteria cause rapid destruction of heart valves

7. Rheumatic Fever
Rheumatic fever is an inflammatory disease that may develop after an infection with Streptococcus bacteria (such as strep throat or scarlet fever).
The disease can affect the heart, joints, skin, and brain
Symptoms
Abdominal pain
Fever
Heart (cardiac) problems, which may not have symptoms,
or may result in shortness of breath and chest pain
Joint pain, arthritis (mainly in the knees, elbows, ankles, and wrists)
Joint swelling; redness or warmth
Nosebleeds
Skin nodules
Streptococci might not be present at the time of rheumatic fever.
Prompt treatment of streptococcal infections can reduce the incidence of rheumatic fever (Penicillin is administered as a preventive measure against subsequent streptococcal infections.)

8. Zoonotic disease Tularemia- Brucellosis (Undulant Fever)
Francisella tularensis, gram-negative rod
Bacteria reproduce in phagocytes
Transmitted from rabbits and deer by deer flies
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

9. Anthrax Bacillus anthracis, Cutaneous anthrax
Gram-positive,
Endospore-forming aerobic rod
Found in soil
Multiply in macrophages and produce two exotoxins
Edema toxin
Lethal toxin
These toxins are the primary agents of tissue destruction, bleeding, and death of the host.
Cutaneous anthrax
Endospores enter through minor cut
20% mortality
Gastrointestinal anthrax
Ingestion of undercooked contaminated food
50% mortality
Inhalational anthrax
Inhalation of endospores
100% mortality
Cattle are routinely vaccinated
Treated with ciprofloxacin or doxycycline
Portal of entry
ID50
Skin
10-50 endospores
Inhalation
10,000-20,000 endospores
Ingestion
250,000-1,000,000 endospores

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

11. Vector transmitted disease - Plague
Plague - enterobacteria Yersinia pestis
gram-negative rod
grow in blood and lymph
plague bacteria secrete several toxins
Transmitted by rat flea
Septicemia plague - Septic shock
Pneumonic plague - Bacteria in the lungs
Treatments - antibiotics

12. Vector transmitted disease - Lyme Disease
Borrelia burgdorferi
Reservoir - Deer
Vector - Ticks
First symptoms
may include fever, headache, fatigue, depression
a characteristic circular skin rash called erythema migrans (bull's eye rash)
eliminated by antibiotics, especially if the illness is treated early
Second phase
Irregular heartbeat
Encephalitis
Third phase
Arthritis (Borrelia causes autoimmunity)
Figure 23.14

13. Figure 23.14

14. Vector transmitted disease - Rickettsias
Epidemic typhus
Rickettsia prowazekii
gram negative, bacillus, obligate intracellular parasitic, aerobic bacteria
transmited by human body louse Pediculus humanus corporis
causes tickborne typhus fever
prevalent in crowded and unsanitary living conditions that allow the proliferation of lice
signs of typhus - rash, prolonged high fever, and stupor
Treatment - tetracycline and chloramphenicol
Endemic murine typhus
a less severe disease caused by Rickettsia typhi and transmitted from rodents to humans by the rat flea.
Spotted Fevers (Rocky Mountain spotted fever)  
Rickettsia rickettsii is a parasite of ticks (Dermacentor spp.) in the southeastern United States, Appalachia, and the Rocky Mountain states
chloramphenicol and tetracycline effectively treat Rocky Mountain spotted fever, or tick-borne typhus.
Serological tests are used for laboratory diagnosis.

15. Viral Diseases of the Cardiovascular and Lymphatic Systems
Infectious Mononucleosis
Mononucleosis is caused by Epstein-Barr virus.
Human herpes virus 4
The virus multiplies in the parotid glands and is present in saliva.
It causes the proliferation of atypical lymphocytes.
The disease is transmitted by the ingestion of saliva from infected individuals.
Childhood infections are asymptomatic
Diagnosis is made by an indirect fluorescent-antibody technique.
EB virus may cause other diseases,
including cancers and multiple sclerosis.

16. Viral Diseases of the Cardiovascular and Lymphatic Systems
Burkitt lymphoma is a cancer of the lymphatic system (in particular, B lymphocytes).
It is named after Denis Burkitt, a surgeon who first described the disease in 1956 while working in equatorial Africa.
Epstein-Barr virus (Human herpes virus 4)
The endemic variant occurs in equatorial Africa. It is the most common malignancy of children in this area.
Children affected with the disease often also had chronic malaria
Disease characteristically involves the jaw or other facial bone, distal ileum, cecum, ovaries, kidney or the breast.
The sporadic type of Burkitt lymphoma (also known as "non-African") is another form found outside of Africa.
It is believed that impaired immunity provides an opening for development of the Epstein-Barr virus.
Immunodeficiency-associated Burkitt lymphoma is usually associated with HIV infection or occurs in the setting of post-transplant patients who are taking immunosuppressive drugs.

17. Viral Diseases of the Cardiovascular and Lymphatic Systems
Cytomegalic Inclusion Disease
Cytomegalovirus (Human herpes virus 5)
Infected cells swell (cyto-, mega-)
Latent in white blood cells
Cause formation of distinctive inclusion bodies
May be asymptomatic or mild.
Transmitted across the placenta, may cause mental retardation, sexually, by blood, by transplanted tissue
Viral hemorrhagic fevers are caused by viruses from four distinct families.
Range in severity from relatively mild to life-threatening.
Begin with fever and muscle aches.
Some viral hemorrhagic fevers progress to far more serious problems, including severe internal and external bleeding (hemorrhage), widespread tissue death (necrosis), and shock.
No current treatment can cure viral hemorrhagic fevers, and immunizations exist for only two of the many VHFs

18. Protozoan Diseases of the Cardiovascular and Lymphatic Systems
Chagas’Disease - Trypanosoma cruzi
Reservoir-Rodents, opossums, armadillos
Vector- Reduviid bug
Leishmaniasis -Leishmania spp.
Vector- Sandflies. The protozoa reproduce in the liver, spleen, and kidneys.
Antimony compounds are used for treatment.
Babesiosis - Babesia microti
transmitted to humans by ticks.
Figure 23.22, 12.33d

19. Toxoplasmosis Toxoplasmosis is caused by Toxoplasma gondii.
T. gondii undergoes sexual reproduction in the intestinal tract of domestic cats, and oocysts are eliminated in cat feces.
In the host cell, sporozoites reproduce to form either tissue-invading tachyzoites or bradyzoites.
Humans contract the infection by ingesting tachyzoites or tissue cysts in undercooked meat from an infected animal or contact with cat feces.
Congenital infections can occur. Signs and symptoms include severe brain damage or vision problems.
Toxoplasmosis can be identified by serological tests, but interpretation of the results is uncertain.

20. Malaria
Malaria is transmitted by Anopheles mosquitoes. The causative agent is any one of four species of Plasmodium.
The signs and symptoms occur at intervals of 2 to 3 days.
chills,
fever,
vomiting,
headache, which
Sporozoites reproduce in the liver and release merozoites into the bloodstream, where they infect red blood cells and produce more merozoites.
New drugs are being developed as the protozoa develop resistance to drugs such as chloroquine.

21. Learning objectives
Identify the role of the cardiovascular and lymphatic systems in spreading and eliminating infections.
List the signs and symptoms of septicemia, and explain the importance of infections that develop into septicemia.
Differentiate gram-negative sepsis, gram-positive sepsis, and puerperal sepsis.
Describe the epidemiologies of bacterial endocarditis and rheumatic fever.
Discuss the epidemiology of tularemia. Brucellosis and antrax.
Discuss the epidemiology of gas gangrene.
List three pathogens that are transmitted by animal bites and scratches.
Compare and contrast the causative agents, vectors, reservoirs, symptoms, treatments, and preventive measures for plague, Lyme disease, and Rocky Mountain Spotted Fever.
Identify the vector, etiology, and symptoms of five diseases transmitted by ticks.
Describe the epidemiologies of epidemic typhus, endemic murine typhus, and spotted fevers.
Describe the epidemiologist of CMV inclusion disease, Burkitt’s lymphoma, and infectious mononucleosis.
Compare and contrast the causative agents, modes of transmission and reservoirs, for toxoplasmosis, malaria, leishmaniasis, and babesiosis.

22. Structure and Function of the Respiratory System
The upper respiratory system consists of :
Nose
Pharynx
Sinus
Middle ear and auditory tubes.
Coarse hairs in the nose filter large particles from air entering the respiratory tract.
The ciliated mucous membranes of the nose and throat trap airborne particles and remove them from the body.
Lymphoid tissue, tonsils, and adenoids provide immunity to certain infections.

23. Microbial Diseases of the Upper Respiratory System
Upper respiratory normal microbiota may include pathogens
Laryngitis:
S. pneumoniae,
S. pyogenes,
viruses
Tonsillitis:
Sinusitis:
Bacteria
Epiglottitis:
H. influenzae

24. Streptococcal pharyngitis
Strep throat
Streptococcus pyogenes
Resistant to phagocytosis
Streptokinases lyse clots
Streptolysins are cytotoxic
Scarlet Fever ( scarlatina )
Erythrogenic toxin produced
by lysogenized S. pyogenes
Diagnosis by indirect agglutination
Figure 24.3

25. Diphtheria Corynebacterium diphtheriae. Diphtheria
exotoxin-producing
Diphtheria
A membrane, containing fibrin and dead human
and bacterial cells, forms in the throat and can
block the passage of air.
The exotoxin inhibits protein synthesis,
Heart, kidney, or nerve damage may result.
Laboratory diagnosis is based on isolation of the bacteria and the appearance of growth on differential media.
Antitoxin must be administered to neutralize the toxin, and antibiotics can stop growth of the bacteria.
Routine immunization in the United States includes diphtheria toxoid in the DTaP vaccine.
Slow-healing skin ulcerations are characteristic of cutaneous diphtheria.

26. Common cold
Rhinoviruses (50%)
Coronaviruses (15-20%)
Rhinoviruses attached to ICAN-1 on nasal mucous

27. Infection of he middle ear
Otitis Media
S. pneumoniae (35%)
H. influenzae (20-30%)
M. catarrhalis (10-15%)
S. pyogenes (8-10%)
S. aureus (1-2%)
Treated with broad-spectrum antibiotics
Incidence of S. pneumoniae reduced by vaccine

28. Structure and Function of the Respiratory System
The lower respiratory system consists of:
Trachea
Bronchial tubes
Alveoli.
The ciliary escalator of the lower respiratory system helps prevent microorganisms from reaching the lungs.
Microbes in the lungs can be phagocytized by alveolar macrophages.
Respiratory mucus contains IgA antibodies.

29. Pertussis (Whooping Cough)
Bordetella pertussis:
Gram-negative coccobacillus
Capsule
Tracheal cytotoxin of cell wall damaged ciliated cells
Pertussis toxin - inhibit the function of the host's immune system
Stages
Catarrhal stage, like common cold
Paroxysmal stage: Violent coughing siege
Convalescence stage
Prevented by DTaP vaccine (acellular Pertussis cell fragments)
Figure 24.8

30. Microbial Diseases of the Lower Respiratory System
Bacteria, viruses, & fungi cause:
Bronchitis - inflammation of the bronchi.
Symptoms include: Coughing up extra mucus, sometimes with blood, Wheezing, Difficulty breathing, Runny nose
Bronchiolitis - inflammation of the bronchioles, the smallest air passages of the lungs.
Pneumonia -inflammatory illness of the lung. Frequently, it is described as lung parenchyma/alveolar inflammation and abnormal alveolar filling with fluid.
The alveoli are microscopic air-filled sacs in the lungs responsible for absorbing oxygen.
Typical symptoms associated with pneumonia include cough, chest pain, fever, and difficulty in breathing

31. Tuberculosis Mycobacterium tuberculosis: M. bovis M. avium
Acid-fast rod.
Transmitted from human to human
M. bovis
<1% U.S. cases,
Not transmitted from human to human
M. avium
Intracellular complex
Infects people with late stage HIV infection
Symptoms: a chronic cough with blood-tinged sputum, fever, night sweats, and weight loss.
Infection of other organs causes a wide range of symptoms.
Treatment of Tuberculosis: Prolonged treatment with multiple antibiotics
Vaccines: BCG, live, avirulent M. bovis. Not widely used in U.S.
Figure 24.9

32. The Pathogenesis of Tuberculosis

33. Tuberculosis Diagnosis: Tuberculin skin test screening
Positive reaction means current or previous infection
Followed by X-ray or CT exam, acid-fast staining of sputum, culturing of bacteria
Figure 24.11

34. Pneumonias
Pneumonia
An illness of the lungs and in which the alveoli (microscopic air-filled sacs of the lung responsible for absorbing oxygen) become inflamed and flooded with fluid.
Pneumonia can result from a variety of causes – bacteria, viruses, fungi or parasites
Typical pneumonia is caused by S. pneumoniae.
Atypical pneumonias are caused by other microorganisms.
Typical symptoms
cough,
chest pain,
fiver,
breathing difficulty,
rust-colored sputum.
Diagnostic tools include x-rays and examination of the sputum.
Treatment depends on the cause of pneumonia; bacterial pneumonia is treated with antibiotics.

35. Pneumomoccal Pneumonia
Streptococcus pneumoniae:
Gram-positive encapsulated diplococci
Diagnosis by culturing bacteria
Penicillin is drug of choice
Figure 24.13

36. Pneumonia Haemophilus influenzae Mycoplasma pneumoniae
Gram-negative coccobacillus
Alcoholism, poor nutrition, cancer, or diabetes are predisposing factors
Second-generation cephalosporins
Mycoplasma pneumoniae
It is an endemic disease.
Diagnosis is by PCR or serological tests.
Legionella pneumophila
Aerobic gram-negative rod.
The bacterium can grow in water
such as air-conditioning cooling towers,
and then be disseminated in the air.
This pneumonia does not appear to be transmitted from person to person.
Bacterial culture, FA tests, and DNA probes are used for laboratory diagnosis.

37. Obligate intracellular pathogens
Chlamydophila pneumoniae
Has a complex life cycle and must infect another cell in order to reproduce.
It is transmitted from person to person.
Tetracycline is used for treatment.
Coxiella burnetii causes Q fever.
The disease is usually transmitted to humans through unpasteurized milk or inhalation of aerosols in dairy barns.
Laboratory diagnosis is made with the culture of bacteria in embryonated eggs or cell culture.

38. Viral Pneumonia
Viral pneumonia as a complication of influenza, measles, chickenpox
Viral etiology suspected if no cause determined
Respiratory Syncytial Virus (RSV)
Common in infants; 4500 deaths annually
Causes cell fusion (syncytium) in cell culture
Symptoms: coughing
Diagnosis by serologic test for viruses and antibodies
Treatment: Ribavirin

39. Influenza -Influenza virus
Family: Orthomyxaviradae (ssRNA)
Hemagglutinin (H) spikes - used for attachment to host cells
Neuraminidase (N) spikes - used to release virus from cell
Antigenic shift
Changes in H and N spikes - probably due to genetic recombination between different strains infecting the same cell
Antigenic drift
Mutations in genes encoding H or N spikes (may involve only 1 amino acid)
Allows virus to avoid mucosal IgA antibodies
Influenza serotypes
A: causes most epidemics, H3N2, H1N1, H2N2
B: moderate, local outbreaks
C: mild disease
Chills, fever, headache, muscle aches (no intestinal symptoms), 1% mortality due to secondary bacterial infections
Treatment: Amantadine (interference with a viral protein, M2,which is required for the viral particle to become "uncoated" once taken inside a cell by endocytosis)
Vaccine for high-risk individuals

40. Fungal Diseases of the Lower Respiratory System
Fungal spores are easily inhaled;
They may germinate in the lower respiratory tract.
The incidence of fungal diseases has been increasing in recent years.
The mycoses in the sections below can be treated with amphotericin B.

41. Fungal Diseases of the Lower Respiratory System
Histoplasmosis
Histoplasma capsulatum
subclinical respiratory infection that only occasionally progresses to a severe, generalized disease.
Coccidioidomycosis
 Coccidioides immitis -
Most cases are subclinical,
tuberculosis can result.
Pneumocystis Pneumonia 
Pneumocystis jiroveci is found in healthy human lungs,
causes disease in immunosuppressed patients.
Opportunistic fungi can cause respiratory disease in immunosuppressed hosts, especially when large numbers of spores are inhaled - Aspergillus, Rhizopus, and Mucor.

42. Learning objectives
Describe how microorganisms are prevented from entering the respiratory system.
Characterize the normal microbiota of the upper and lower respiratory systems.
Differentiate among pharyngitis, laryngitis, tonsillitis, sinusitis, and epiglottitis.
List the causative agent, symptoms, prevention, preferred treatment, and laboratory identification tests for streptococcal pharyngitis, scarlet fever, diphtheria, cutaneous diphtheria, and otitis media.
List the causative agents and treatments for the common cold.
List the causative agent, symptoms, prevention, preferred treatment, and laboratory identification tests for pertussis and tuberculosis.
Compare and contrast the seven bacterial pneumonias discussed in this chapter.
List the causative agent, symptoms, prevention, and preferred treatment for viral pneumonia, RSV, and influenza.
List the causative agent, mode of transmission, preferred treatment, and laboratory identification tests for four fungal diseases of the respiratory system.