Microbial Diseases of the Cardiovascular and Lymphatic Systems

Bacterial Infections of the Cardiovascularand Lymphatic Systems• Subacute Bacterial Endocarditis• Rheumatic Fever• Tularemia• Brucellosis• Anthrax• Gas Gangrene• Bite WoundsCopyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

MVinMA

Brucellosis (Undulant Fever)• B. abortus (cattle, elk, bison), B. suis (swine), B.melitensis (goats,sheep, camels)• Brucella, gram-negative rods, grow in phagocytes• Undulating fever spikes to 40°C each evening• The bacteria enter through minute breaks in the mucosaor skin, reproduce in macrophages, and spread vialymphatics to liver, spleen, or bone marrow.• Contact with infected animals (slaughterhouse workers,veterinarians, farmers, dairy workers) – also via ingestionof milk or milk products.100-200 cases/y; worldwide incidence ~ 500,000.• Mortality rate ~ 2 % (endocarditis)Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Well-formed hepatic granuloma from apatient with brucellosis

Methylene blue stain: Cultured human macrophage infected withBrucella melitensis. coccobacillary bacteria replicate inphagolysosomes(original magnification x 1,000). Photograph: Courtesy of Robert Crawford, Ph.D., SeniorScientist, American Registry of Pathology, Washington, DC.

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Vivero volante en producción.Pálmacesde Jadraque, Guadalajara.Cultivo manual de planta raíz z desnuda en eras hipógeasgeas.Fototeca forestal

generally occurs at woundor surgical site painfulswelling and tissuedestruction. Rapidlyprogressive, often fatal.

Animal Bites and ScratchesAnaerobic bacteria infect deepanimal bitesPasteurella multocida – normalflora of oral and nasopharyngeal cavity of dogs andcats; may cause septicemiaBartonella henselae – (rickettsia) Cat scratchdisease. Relatively common (~20,000 cases in US)– mostly in young – occasionally seriousHuman bites – (not in book) normal mouth flora (incl.S. aureus, hemolytic S. viridans, H. influenza andvarious anaerobes)Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Clenched Fist Bite Injury . . .This gentleman presented witha draining sinus on the dorsalaspect of his proximal phalanx,about one month aftersustaining a clenched fist biteinjury. He could not clearlyrecall details of his initialtreatment.

. . .leading to OsteomyelitisCopyright © 2006 Pearson Education, Inc., publishing as Benjamin CummingsEvidence of osteomyelitiswith bone erosion andsubperiosteal boneformation (arrows).

Vector-Transmitted Diseases• Plague• Relapsing Fever• Lyme Disease• Ehrlichiosis• Typhus• Epidemic Typhus• Spotted FeversCopyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

PlaguePlague suitCopyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings“Black death”: Yersinia pestis,G- rod, bipolar stainingEndemic in Southwest sylvaticplagueReservoir: Rats, groundsquirrels, and prairie dogsVector: infected fleas• Bubonic plague:Bacterial growth in bloodand lymph• Septicemia plague:Septic shock• Pneumonic plague:Bacteria in the lungs

The Black DeathFig 23.11

Copyright © 2006 Pearson Education, Inc., publishing as Benjamin CummingsFemoral bubo:Most common site of,tender, swollen,lymph node inpatients with plague

Bipolar staining: Darkstained bipolar ends inWright's stain (blood fromplague victim)

Lyme DiseaseZoonosis caused by Borrelia burgdorferiReservoir: mice, deer; Vector: Ixodes ticks3 stages with various symptoms1. Early localized stage: Bull’s eye rash= erythema (chronicum) migransECM; flu-like symptoms2. Early disseminated stage: Heart andNervous system symptoms; also skinand joints affected3. Late stage: Chronic arthritisCopyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Diagnosis• Symptoms alone: often misdiagnosis• In most cases not possible to isolate andculture B. burgdorferi indirectserological tests (ELISA and Westernblot)• PCRPreventionTreatment in early stages!Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Ixodes pacificusIxodes scapularis / pacificus

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Life Cycleof the TickCompare toFig 23.13a

EhrlichiosisFirst described in 1986Caused by Ehrlichia species andtransmitted by Ixodes ticks –diseases of animals andhumansObligately intracellular (in whiteblood cells)• Monocytic Ehrlichiosis (HME)• granulocytic Ehrlichiosis (HGE)Nonspecific symptoms (similar toother diseases)Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

HME and HGE

Lyme Disease andEhrlichiosis

Rocky Mountain SpottedFever (RMSF)• Rickettsia rickettsii• Zoonosis –• Reservoir: mammals• Vector: ticks• Characteristic hemorrhagicrash – maculopapular –starts on palms and soles(unlike measles!)• Can damage vital organsCopyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Rocky Mountain WoodTick (Dermacentorandersoni)

Red structures indicate immunohistological staining ofRickettsia rickettsii in endothelial cells of a blood vessel froma patient with fatal RMSF

Spotted Fevers (Rocky MountainSpotted Fever)Copyright © 2006 Pearson Education, Inc., publishing as Benjamin CummingsFigure 23.16

VIRAL DISEASES OF THE CARDIOVASCULARAND LYMPHATIC SYSTEMS• Infectious Mononucleosis• Viral Hemorrhagic FeversCopyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Infectious Mononucleosis• “Kissing disease” – caused by Epstein-Barr virus(EBV) of Herpesviridae, also known as HHV-4• Well-established relationship between HHV-4 andoncogenesis (Burkitt’s Lymphoma etc.)• Virus multiplies in parotid glands and is present insaliva. It causes the proliferation of atypicallymphocytes (life-long infection) – Transmission viasaliva• Most people (~95%) infected. Childhood infectionusually asymptomatic. Adolescent infection Mononucleosis.• Characteristic triad: fever, pharyngitis, andlymphadenopathy (+spleno- and hepatomegaly)lasting for 1 to 4 weeks.Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

TriadSwollen lymph nodes, sore throat, fatigue and headache are some of thesymptoms of mononucleosis. It is generally self-limiting and most patientscan recover in 4 to 6 weeks without medications.

Young adults presentwith fever,pharyngitis,lymphadenopathy,and tonsillitis.

• Proliferation of infected B cells results in massiveactivation and proliferation of T c cells (CD8 cells) characteristic lymphoid hyperplasia.• Transformation of B cells to immortal plasmacytoidcells secrete a wide variety of IgMs = heterophileantibodies (Monospot test)• Commercially-available test kits are 70-92% sensitiveand 96-100% specific"Downy cell“: lymphocytes infectedby EBV or CMV in infectiousmononucleosis. Cytoplasmic rim isintensely blue and has tendency to"stream" around adjacent red cells.

Pathogenesis of infectious mononucleosis

Viral Hemorrhagic Fevers• Enveloped RNA viruses: Arenaviruses,filoviruses, bunyaviruses, and flaviviruses• Viruses geographically restricted to wheretheir host species live• For some viruses, after accidental transmissionfrom host, humans to human transmission• Human cases or outbreaks sporadic andirregular. Not easily predictable‣ Marburg VHF: 1967 outbreak in Marburg (D) –imported from Africa; Mortality rate 25%‣ Ebola HF: 1995 major outbreaks in Zaire andSudan; Mortality rate 50 – 90%Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Classic Viral Hemorrhagic Fevers: YellowFeverCaused by arbovirus (flaviviridae)transmitted by mosquitoesDirect damage to liver and heart jaundice, hemorrhaging, weak heart circulatory and kidney failureAfrican and American tropical junglesDiagnosis: test for presence of virusneutralizingantibodiesNo treatment Highly effectiveattenuated vaccineCopyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Hantavirus Pulmonary Syndrome (HPS)Korean hemorrhagic fever caused byHantaan virus of BunyaviridaeHPS first reported in US in spring of 1993.Transmission through urine, droppings, or salivaof infected rodents humans breathe inaerosolized virus. No person to persontransmission in USSudden respiratory failureMortality rate > 35%Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Hanta Virus Cases

PROTOZOAN DISEASES OF THECARDIOVASCULAR ANDLYMPHATIC SYSTEMS• American Trypanosomiasis (Chagas’Disease)• Toxoplasmosis• Malaria• Babesiosis

American Trypanosomiasis orChagas DiseaseTrypanosoma cruziReservoir: Rodents, opossums,armadillosVector: night feeding reduviid bugs (kissing bugs)Symptoms in 1% of infected. Acute phase (feveretc.) to chronic phase (heart damage)Antigenic variation persistent evasion ofimmune system Cyclic parasitemia(7-10 days)Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Course of trypanosome infection: emergence of variant surfaceCopyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummingsglycoproteins (VSG) - Host antibodies indicated with Y's.

Millions in Latin America affected. No cureand little effective treatmentRomaña's sign: pathogonomic, early sign ofChagas disease.→ Unilateral severe conjunctivitis, swelling ofeyelid, inflammation of teargland, swelling of regionallymph nodes.

ToxoplasmosisToxoplasma gondii> 60 mio people infected in US (mostly asymptomatic)Zoonosis – Transmission via undercooked meat, catfeces, drinking water. Flu-like symptomsCan cross placenta Congenital risk (TORCH) braindamage or vision problemsRisk of new infection or reactivation in theimmunosuppressedT. gondii undergoes sexual reproduction in the intestinaltract of domestic cats, and oocysts are eliminated in catfeces.Toxoplasmosis can be identified by serological tests, butinterpretation of the results is uncertain.Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Compare to Fig. in book

Malaria• Four species of Plasmodium: P. falciparum (malignant)• Vector: Anopheles mosquito• Worldwide 300-500 million cases; ~ 1.5 – 3 millionpeople die; ~ 1,200 cases in US• Plasmodium infects red blood cells microscopicdiagnosis• Symptoms: chills, fever, vomiting,headache; at intervals of 2 to 3 days• New drugs are being developedas the protozoa develop resistanceto drugs such as chloroquine.Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Microscopic DiagnosisCopyright © 2006 Pearson Education, Inc., publishing as Benjamin CummingsFigure 23.25

MalariaCopyright © 2006 Pearson Education, Inc., publishing as Benjamin CummingsFigure 23.24

Copyright © 2006 Pearson Education, Inc., publishing as Benjamin CummingsCompareto Fig12.19

Distribution of MalariaCopyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

BabesiosisBabesia microtiVector Ixodes tick - ZoonosisHemoprotozoan rupture of RBCs hemolytic anemiaIn malaria-endemic areasmisdiagnosis as PlasmodiumCopyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Schistosomiasis / Bilharzia(sis)• Schistosoma mansoni, S. haematobium, and S.japonicum• 250 million people infected worldwide• Cercaria penetrates skin when exposed tocontaminated water worms grow inside bloodvessels and produce eggs eggs travel to liver(liver damage), intestine or bladder.• Treatment available (praziquantel)Fig 17.2Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Other Schistosomes: Swimmer’s Itch orCercarial DermatitisSchistosome cercariaaccidentally enters human skin(bird is definitive host for adultparasite)Almost every state in US (Mostpredominant in the north). Also inmore than 30 countries.Disappears without treatment ( 7days) – no internal organsinvolvedCopyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings

Parasites die afterentering dermatitis inpreviously sensitizedindividuals. Sensitivityrarely disappears; usuallygets worse in subsequentexposures.Widely scattered fromMichigan lakes to Alaska.

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