Microbial Diseases of the Cardiovascular and Lymphatic Systems Chapter 23

ObjectivesKnow some infectious diseases of the cardiovascular & lymphatic systemsBacteriaProtozoanViral

The Cardiovascular System and Lymphatics SystemHeart: Pump blood to the rest of the bodyBlood and blood vessels Transports nutrients to and wastes from cellsMany of the bodys innate defensive systems are found in blood & lymphWBCs: Defend against infectionLymphatics: Transport interstitial fluid to bloodLymph nodes: Contain fixed macrophages to clear pathogens & T and B lymphocytesLymphoid organs:Tonsils, appendix, spleen & thymus

Sepsis and Septic ShockFigure 23.3Sepsis (septicemia): Whole-body inflammatory state (systemic) due to bacteria growing in the bloodAccompanied by fever, chills, rapid heart and respiratory rates (release mediators of inflammation)High count of white blood cellsOften accompanied by lymphangitis (inflamed lymph vessels), red streaks under the skin, along the arm or legSevere sepsis: Drop in blood pressure, failure of a body organSeptic shock (final stage): Low blood pressure cannot be controlled in spite of adequate fluid resuscitation

SepsisGram-negative sepsisEndotoxins cause blood pressure to decreaseAntibiotics can worsen condition by killing bacteria (Why?)Treatment involves attempts to neutralize the LPS components and inflammation causing cytokines (drugs to reduce clotting)Gram-positive sepsisNosocomial infections due to invasive procedures & intro of Gm+ m/osExotoxins, cell wall, or even bacterial DNAStaphylococcus aureus,Streptococcus pyogenes & Group B streptococcusEnterococcus faecium and E. faecalis (important group; inhabitants of colon; cause infections of wounds & urinary tract )Why is antibiotic (Peni) resistant enterococci of major concern? (Vancomycin resistant)Puerperal fever (childbirth fever)Streptococcus pyogenes (Group A b-hemolytic)Transmitted to mother during childbirth by attending physicians and midwives (infections from uterus to abdominal cavity & sepsis)Antibiotics and modern hygienic practices prevent such infection

Bacterial Infections of the HeartEndocarditis:Inflammation of the endocardiumInner layer of the heartLines the heart valves and muscleSubacute bacterial endocarditis: Major cause: a-hemolytic streptococci from mouthEnterococci and staphylococci may also be involvedArises from infection elsewhere in the body, i.e. teeth, tonsils, body piercingPathogens will clear except people with abnormal heart valvesFever, general weakness & heart murmurAcute bacterial endocarditis: More rapidly progressive typeMajor cause: Staphylococcus aureus from mouthLeads to rapid destruction of heart valvesPericarditis: (fluid enclosed sac surrounding the heart) Also caused by streptococci

Rheumatic FeverAutoimmune complication of Streptococcus pyogenes infections; aged 4-18Often follows a strep throat; short period of arthritis and fever; produces subcutaneous nodules at jointsInflammation of heart valves for ~50% of patients, probably from a misdirected immune Rx against streptococcal M proteinRenewed immunological damage with repeated sore throatsLeading cause of heart disease in the young in underdeveloped world

Figure 23.5

TularemiaFigure 23.6Francisella tularensisGram-negative rod, BSL-3 m/oBacteria reproduce inside phagocytestransmitted from rabbits and squirrels by deer flies or ticks; respiratory infection by dust contaminated with urine or feces of infected animalsTreatment: tetracycline for 10-15 daysExample of zoonotic diseaseCharacteristic clinical syndromes: ulceroglandular (common type ~ 75% of all forms). complicated by pneumonia, meningitis, or peritonitisReferred to as rabbit fever or deer fly fever

AnthraxCaused by Bacillus anthracis Gram-positive, endospore-forming, large aerobic rod, found in soilInfected cattleFulminating (sudden appearance) and fatal sepsis Cattle are routinely vaccinatedHumans also infected Cutaneous anthrax (20% mortality)90% of naturally occurring cases (preferred entry point)Endospores enter through minor cutIf the m/os enter the blood stream, 20% mortality but 50% mortality)Ingestion of undercooked food contaminated food (a rare form of anthrax)Symptoms: nausea, abdominal pain & bloody diarrhea, lesions in GI tractInhalational (pulmonary) anthrax (100% mortality)Inhalation of endosporesHigh probability to enter the bloodstreamIllness progresses in 2 or 3d and kills patient 24-36 h

AnthraxVirulence factorsEndosporesSurvive and multiply in macrophagesEdema toxin (causes local edema & swelling, interferes phagocytosis by macrophages)Lethal toxin (targets and kills macrophages)Capsule (not polysaccharide but amino acid residues, does not stimulate an immune response)Bacteria proliferate in the blood w/o any effective inhibition; these toxin-secreting bacteria ultimately kill the hostTreatmentAntibiotics such as ciprofloxacin or deoxycycline, long period that up to 60 daysLive, a single dose of attenuated vaccine for cattleInactivated form of toxin to vaccinate humans, 6X injections in 18 months, followed by annual booster

GangreneIschemia: Loss of blood supply to tissueNecrosis: Death of tissueGangrene: Death of soft tissueGas gangrene: Death of muscle tissue with gas productionClostridium perfringens, gram-positive, endospore-forming anaerobic rod, grows in necrotic tissue with gas productionToxin to kill cells & produce necrotic tissue; enzymes to degrad collagen & proteinaceous tissue for spreadingImproperly performed abortions due to the invasion of uterine wallTreatment includes surgical removal of necrotic tissue; hyperbaric chamber; penicillin

PlagueYersinia pestis Gram-negative rodBacteria can survive and grow in phagocytesReservoir: Rats, ground squirrels, and prairie dogsVector: rat fleas (Xenopsylla cheopsis) Bubonic plague: Bacterial growth in blood and lymph; most common form (80-95% of cases today); 50-75% mortality rateSepticemic plague: Septic shockPneumonic plague: Bacteria in the lungs; 100% mortality rateEasily spread by aerosol dropletsVirulence factors: capsule, ability to survive and grow in phagocytic cells, ability to sense temp (37oC or 25oC) and Ca2+ (high or low) to turn on or off virulence factorsTreatment: streptomycin & tetracyclineDiagnostic: Look for capsular AgVaccine: available for field and lab workers

Brucellosis (Undulant Fever)Brucellosis is the most common bacterial zoonotic disease, endemic in Middle EastBrucella Gram-negative coccoid rods that grow in phagocytesB. abortus (elk, bison, cows)B. suis (swine)B. melitensis (goats, sheep, camels)Undulating fever Gibraltar fever, Malta fever, Mediterranean feverFever spikes to 40C each eveningTransmitted via milk from infected animals or contact with infected animals

TyphusEpidemic typhusRickettsia prowazekiiGram-negative cocci; obligate intracellular parasites of eukaryotesReservoir: RodentsVector: Body louse Pediculus humanus corporisTransmitted when louse feces rubbed into bite woundTreatments: tetracycline & chloramphenicolEndemic murine typhus:Rickettsia typhiReservoir: RodentsVector: rat flea (Xenopsylla cheopsis)

Spotted Fevers (Rocky Mountain Spotted Fever)Rickettsia rickettsiiCan be passed from one generation of ticks to another through eggsBest-known rickettsial disease in USMeasles-like rash except that the rash appears on palms and soles (mistaken for measles)Mortality (20%) if treatment is not promptTetracycline and chloramphenicol are effective

Figure 23.18

Human Herpesvirus 4 InfectionsEpstein-Barr virus (EB)Infectious MononucleosisChildhood infections are asymptomaticIntense immunological response in young adulthoodTransmitted via saliva (kissing)Characterized by proliferation of monocytes (unusual lobed nuclei)Diagnostic: IgM detection using fluorescent techniqueBurkitts lymphomaNasopharyngeal carcinomaCauses cancer in immuno-suppressed individuals and malaria and AIDS patientsCommon childhood cancer in Africa

Human herpesvirus 5 InfectionsCytomegalovirus (CMV), a very large herpes-virusInfected cells swell (cyto-, mega-)Latent in white blood cells, replicating very slowCarriers shed the virus in saliva, semen & breast milkMay be asymptomatic or mild in adultsTransmitted across the placenta; may cause mental retardation up to 40-50% if infection during pregnancyTransmitted sexually, by blood, or by transplanted tissue

Viral Hemorrhagic Fevers

PathogenPortal of entryReservoirMethod of transmissionYellow feverArbovirusSkinMonkeysMosquito(Aedes aegypti)DengueArbovirusSkinHumansMosqioto(Aedes aegypti;A. Albopictus)Marburg, Ebola, LassaFilovirus, arenavirusMucous membranesProbably fruit bats; other mammalsContact with bloodHantavirus pulmonary syndromeBunyavirusRespiratorytractField miceInhalation

ProtozoansNote the following about each disease:Organism involvedReservoirs: hosts (definitive and intermediate)Mode of transmissionDisease symptomsTrypanosomiasisToxoplasmosisMalariaSchistosomiasis

Lyme DiseaseIn 1976 a group of children in Lyme Connecticut, thought to have at first juvenile rheumatoid arthritis, were suspected rather to have a tick- transmitted multisystem disease.In 1981 Willy Burgdorfer and colleagues found an unidentified spirochetal bacterium, Borrelia burgdorferi, in a nymphal Ixodes scapularis tick. B. burgdorferi is a vigorously motile spirochete with its cytoplasmic membrane surrounded by peptidoglycan and flagella.

Enzootic Life Cycle of Borrelia burgdorferiTransmitted by Ixodes scapularis in eastern and central North AmericaTransmitted by Ixodes pacificus in western N.A.The small animals that larvae feed on can be squirrels, chipmunks, other rodents, and birds.Most human infections of B. burgdorferi are transmitted by the tiny nymphal stage (1mm) in the spring summer of the 2nd year who feed agressively.

Distribution in North AmericaDo these ticks get turned back at the Canada-U.S border?In B.C. areas where people have been infected: Vancouver Island, the Lower Mainland especially the Harrison-Hope area, Okanagan, and Kootenay area

B.C. and Future ProjectionsFigure 1. Geographic extent of suitable temperature conditions for Ixodes scapularis in eastern and central Canada

Initial Infection Upon receiving a tick bite the characteristic bulls eye rash called erythema migrans (EM) develops in 3 32 days in 70 80% of people. This is accompanied by flu-like symptoms including, fever, fatique, malaise, headache, slight muscle and joint pain. A six-week regime of antibiotics such as biaxin, flagyll, or high levels of amoxicillin, can eradicate the disease at this point

http://www.youtube.com/watch?v=aJHjUMZVRKA&feature=related

Immune Response to B. burgdorferiThe first line of host defense is complement-mediated lysis of the spirochete. Histological examination of the EM skin lesions reveals lymphocytes, macrophages and plasma cells.Patients develop IgG and IgM antibodies against many components of the organismBy changing or minimizing antigenic expression (hiding in tissues) B. burgdorferi can evade the hosts immune responses.

Second Phase and Chronic Lyme Disease (Third Phase)In the second phase the infection disseminates widely with many possible expressions:Acute lymphocytic menigitis, cranial neuropathy, atrioventricular nodal block, musculoskeletal pain in joints, bursae, tendon, muscle, bone and eye manifestationsPatients have major sleep disturbances, concentration and memory blocks, panic, anxiety, depression, hearing loss, shortness of breath, persistent headache or pressure.Chronic Lyme Disease Expressed as one of two conditions: autoimmune with debilitating joint pain (wheelchair) or neuroborreliosis.Because of the very slow division of the spirochete 10-14 days of antibiotics for other bacteria would take 1 years. Controversy over treating with antibiotics for years.

***http://www.lyme.org/burgdorfer.htmlhttp://www.sciencephoto.com/image/11578/530wm/B2201002-Borrelia_burgdorferi_bacteria-SPL.jpghttp://www.cmaj.ca/content/180/12/1221.full

**http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5710a1.htm http://www.cmaj.ca/content/180/12/1221.fullhttp://www.lymeinfo.ca/lymedisease-geographicdistribution.aspx

http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/08vol34/dr-rm3401a-eng.php

**http://www.bio.davidson.edu/people/sosarafova/Assets/Bio307/meprasse/Assets/Host%20mechanisms%20of%20spirochetal%20killing.jpg

*http://www.lyme.org/img/gallery/joint-swelling_schwartz.jpg