Chapter 20

Microbial Diseases of the Cardiovascular and Lymphatic System

Cardiovascular system

•       Composed of three parts

–       Heart

–       Blood

–       Blood vessels

•       Heart pumps blood into arteries that are connected to veins via capillaries

–       Arteries carry blood away from the heart

–       Veins carry blood to the heart

Lymphatic system

•       Plasma can leave the blood vessels and circulate in the interstitial space (space between tissue cells).

•       Plasma collects metabolic products and carries them to lymphatic system (it can also pick up the microbes and disseminate the infection).

•       When inside the lymphatic system, plasma is called – lymph.

Bacterial diseases

•       Blood is normally sterile

•       Bacteria can infect the blood, blood vessels, and heart

•       Bacteremia – presence of bacteria in the blood

•       Septicemia – microorgansims are actively multiplying in the blood

•       Septic shock – condition in which Gr- bacteria release the endotoxin (can be caused by antibiotic treatment)

•       Lymphangitis - Infection and inflammation of the lymphatic vessels

Bacterial infection of the heart

Endocarditis

•       Involves inflammation of endocardium and heart valves

•       Endocardium – the inner layer of heart muscle

•       Two types of endocarditis

–       Acute

–       Subacute

Subacute bacterial endocarditis

•       The disease develops slowly

•       Bacteria grow on preexisting lesions

•       If not treated, the disease is fatal within a few months

•       Caused by a-hemolytic streptococci.

•       The microorganisms enter the blood during the tooth extraction or tonsillectomy. Prophylactic antibiotic treatment

Acute bacterial endocarditis

•       Staphylococcus aureus is transferred from original infection site to the heart (traumatic injury or surgical procedure)

•       Colonize heart valves  (vegetations) – cardiac malfunction

•       It causes a rapid destruction of heart valves

•       If untreated, can be fatal within a few days

 Plague (Black Death)

•       Caused by Yersinia pestis – Gr- rod shaped bacteria

•       Normally infects rats (other rodents)

•       Transmitted by rat flea and airborne droplets

•       Bacterium is injected by the bite of the flea

•       Bacterium enters the blood and lymph where it proliferates.

•       Symptoms: enlargement of lymph nodes in armpit and groins – buboes – bubonic plague. Mortality 50-75%.

  Bubonic plague

•       Characterized by enlarged, inflamed lymph nodes called buboes

•       Pneumonic plague

•       Occurs when the bacterium spreads to the lungs - mortality 100%

•       Treatment: streptomycin, tetracycline.

•       Vaccine is available

•       Prevention - through rodent and flea control and good personal hygiene

Rheumatic fever

•       Is an autoimmune reaction of the organism initiated by streptococcal infection

•       Rheumatic fever is preceded by a sore throat (primary streptococcal infection).

•       Symptoms: arthritis, fever, and nodules at joints. The immune reaction is misdirected towards the heart valves

 Anthrax

•       Causative agent: Bacillus anthracis – gr+ endospore forming bacterium

•       The bacterium is found in soil – the endospores are ingested by animals

•       Can be contracted by those who handle animals

•       Endospore can enter the body through  broken skin – Cutaneous anthrax - here the pustule is formed (mortality rate 20%)

•       respiratory tract – pulmonary anthrax – mortality rate 100%

•       ingestion – gastrointestinal anthrax – mortality rate more than 50%

•       The released exotoxin causes septicemia

•       Treatment: penicillin (not effective against the toxin)

Gangrene

•       Occurs when the blood supply to the tissue is interrupted

•       The dying tissue provides anaerobic conditions for the growth of Clostridium

•       Toxin produced by the bacterium causes necrosis of neighboring tissue (muscles)

•       Gas is also produced that swells the tissue

•       Treatment: Penicillin, surgical removal of necrotic tissue, hyperbaric chamber.

Plague (Black Death)

•       Caused by Yersinia pestis – Gr- rod

•       Normally infects rats (other rodents)

•       Transmitted by

–       The bite of the rat flea

–       Airborne droplets

–       Direct contact with the infected person

•       Bacterium enters the blood and lymph where it proliferates

•          Symptoms: enlargement of lymph nodes in armpit and groins – buboes – bubonic plague. Mortality 50-75%.

–       Bubonic plague

Characterized by enlarged, inflamed lymph nodes called buboes

–       Pneumonic plague

•       Occurs when the bacterium spreads to the lungs - mortality 100%

–       Treatment: streptomycin, tetracycline.

–       Vaccine is available

–       Prevention - through rodent and flea control and good personal hygiene

Lyme disease

•       The causative agent is Borrelia burgdorferi – a spirochete

•       The infection has three phases:

–       Expanding red rash that often resembles a bull’s eye

•       Flu-like symptoms, antibiotics effective

–       Neurological symptoms

•       Heart is effected, facial paralysis, meningitis

–       Severe arthritis

•       Months or years later

•       The vector is the deer tick of the genus Ixodes

•       Involves two hosts: white tailed deer and white footed mouse

•       The larva feeds on white-footed mouse – picks up the bacteria

•       The adult tick lives on deer

•       Prevention: protective clothing

•       Treatment: Doxycycline, penicilin

Epidemic typhus

•       Caused by Rickettsia prowazekii

•       Transmitted by the human body louse

•       The microbe is excreted from the intestinal tract of the body louse

•       Infection occurs when the feces of louse are rubbed into the skin, when the   host scratches the bite.

•       The microbe infects endothelial cells of vascular system – causing rapture of small blood vessels – hemorrhaging – red spots on the skin.

•       Disease is characteristic for crowded unsanitary conditions.

•       Symptoms: high fever, stupor and rash. Mortality high if not treated.

•       Treatment: tetracycline and chloramphenicol.

 Viral diseases

Infectious Mononucleosis (Mono)

•       Caused by EB (Epstein-Barr) virus

•       The virus multiplies in the lymph glands

•       Transmission: Saliva (kissing), drinking vessels

•       Symptoms: swelling of lymph nodes and spleen, proliferation of special type of lymphocytes; rapture of spleen possible

•       Recovery in a few weeks

•       Treatment focuses on relieving symptoms, resting

Viral Hemorrhagic Fevers

Yellow fever

•       Caused by Arbovirus, transmitted by mosquitos (Aedes aegypti)

•       Limited to tropical areas of Central and South America and Africa. Monkeys serve as reservoir.

•       Symptoms: fever, nausea, vomiting

•       Yellowing of the skin as result of liver damage

•       Action: Control of mosquito population

Viral hemorrhagic fevers

•       Marburg virus, brought to Europe (Germany) together with African monkeys

–           Symptoms: headache, fever, internal and external bleeding

•               Lassa fever – appeared in Africa   

•                   Symptoms: chest pain, hemorrhaging

- Reservoir – rodents

- Rodent’s urine is the source of human infection

Ebola virus first emerged in Africa

–       Reservoir probably in fruit bats

–       The infection spread by blood and body fluids

–       The virus lives in the bloodstream – causes capillary fragility

–       Massive internal and external bleeding

–       Mortality rate: between 25-100%

Acquired Immunodeficiency Syndrome (AIDS)

•            In 1981 a number of cases of rare pulmonary infections and skin cancers were linked to homosexual young men. They all showed loss of immunity

•            In 1983 a virus was identified as a causative agent of AIDS - known today as HIV (human immunodeficiency virus)

•            Origin: Hybrid of two simian immunodeficiency viruses of monkeys (Central Africa) – cross over to human population

Virus structure

•            Virus selectively infects T cells (type of white blood cells)

•            HIV is a retrovirus, its components are:

–            Two strands of RNA

–            The enzyme reverse transcriptase

–            Envelope - lipoprotein with spikes - gp120

HIV reproduction

•            Virus enters through the mucus membrane

•            Glycoprotein spikes (gp120) on the virus surface recognize the CD4 receptors on the T cell surface

•            Co-receptors are also required (Chemokin-CCR5)

•            Virus penetrates the T cell

•            After uncoating, the reverse transcriptase produces double stranded DNA

•            This DNA is now incorporated into host DNA (provirus) – remains latent

•            Reactivated provirus produces viral mRNA

•            Synthesis of coat proteins, mature virus is released by budding

•            New virus particle may not be released – latent virion

The stages of HIV infection

•            Category A - Swollen lymph nodes are the only symptoms

•            Category B - Yeast infection of mouth, throat or vagina

•            Category C - All symptoms of AIDS - yeast infections, tuberculosis,        Kaposi’s sarcoma.

Other characteristics of AIDS:

•            The number of T cells is an indicator of AIDS progression.

•            Normal number of T cells = 800-1000/mm3

•            Bellow 200 /mm3 - AIDS

•            About 5% of infected persons do not develop symptoms of AIDS (less virulent virus strain or T cells more effective, deletion in CCR5)

Diagnostic Methods

•            ELISA – for HIV antibodies

•            Disadvantage of the method –

–            Positive results needs to be confirmed with Western blot

–            Antibodies detectable after 3 months (seroconversion)

•            Plasma viral load test – PCR of viral RNA

Transmission of HIV

•            Not transmitted by casual contact

•            Possible transmission routs:

•            sexual contact, breast milk, transplacental infection of a fetus, blood transfusion, organ transplants, blood contaminated needles (39 health care workers have been infected - most by needlestick)

HIV vaccines

•            Development of efficient HIV vaccine is hindered by:

•            Lack of suitable animal host

•            Rapid mutation

•            Virus has developed clades – different in different geographic regions

Chemotherapy

•            Treatment includes combination of drugs

–Nucleoside reverse transcriptase inhibitors

–Protease inhibitors (inhibition of coat synthesis)

•            Other potential targets:

–Fusion inhibitors

–Integrase inhibitors (cDNA must be integrated into host DNA)

 Protozoan diseases

Toxoplasmosis

•       Caused by the protozoa Toxoplasma gandii.

•       It has a complex life cycle

•       Human infection starts

–       with eating raw meat of an infected animal or

–       ingesting the oocysts from urine or feces of infected cat

•       Symptoms: older children and adults suffer from flue-like symptoms.

•       Infection of a pregnant woman may result in death of the fetus or congenital defects (brain damage, blindness, and mental retardation).

 Malaria

•       Causative agent: protozoan - Plasmodium

–       Four Plasmodium species cause malaria

•       P. falciparum, P. vivax, P. ovale, P. malariae

•       Disease severity depends on the species

•       Signs and Symptoms

–       Cyclic symptoms that correlate with the parasite’s life cycle: Fever and chills recur every two to three days as erythrocytes lyse

–       Other symptoms include anemia, fatigue, and jaundice

•       Diagnosis

–           Blood smear - Presence of trophozoites or other Plasmodium stages

•       Treatment

–           Standard drug is chloroquine except with drug resistant cases

–           Usually effective except in severe falciparum cases

•       Prevention

–       Limiting contact with mosquitoes

–       Use of insecticides

•       Spread by female mosquito – Anopheles

•       Sporozoits – asexual phase of plasmodium is injected into human’s bloodstream

•       Invade liver cells - develop into merozoits

•       Enter erythrocytes – reproduce within erythrocytes – burst out

•       Ingested by another mosquito

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