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Tropical, Vector-borne and Zoonotic Infectious Disease Pathology M. Kent Froberg, MD 2009.

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Presentation on theme: "Tropical, Vector-borne and Zoonotic Infectious Disease Pathology M. Kent Froberg, MD 2009."— Presentation transcript:

1 Tropical, Vector-borne and Zoonotic Infectious Disease Pathology M. Kent Froberg, MD 2009

2 Purpose To learn the etiological agents and life cycles of the major tropical, vector-borne and zoonotic parasites. To learn the major pathology associated with the important tropical, vector-borne and zoonotic pathogens.

3 CHAGAS’ DISEASE (AMERICAN TRYPANOSOMIASIS) TRYPANOSOMA CRUZI Organism: hemoflagellate (motile) Vector: Triatoma infestans (reduviid, kissing or assassin bug) Transmission: Vector lives in thatched or mud houses, biting sleeping victim at night, depositing infected feces in wounds. Zoonosis: between mammals and vector Dx: finding trypomastigotes in blood

4 Characteristic “U” or “C” shape of T. cruzi in peripheral blood Nuclei (green) and kinetoplasts(black) are stained blue with Geimsa

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7 Chagas Disease is most common in Central America and northern South America. Chagas is also a transfusion risk in the United States from infected blood donors who have immigrated from Latin America.

8 Reduviid “kissing” bug infects skin or mucous membranes of bite or other wounds by defecting in wound following a blood meal

9 CHAGAS’ DISEASE (2) Clinical: –Stage 1: Chagoma (local, transient inflammatory lump) at site of bite –Stage 2: Dissemination: Myocarditis; enlarged spleen, liver, & lymph nodes –Stage 3: Years later (10-30% infected persons): cardiac inflammation and fibrosis, dilated cardiomyopathy, apical aneurysm

10 CHAGAS’ DISEASE (3) Myenteric plexus damage  aperistalsis  mega-esophagus + mega-colon Prevalence: –Only in western hemisphere. –Most common cause of heart failure in Latin America –Up to 1/2 million in USA  transfusion hazard

11 Romana’s sign from acute conjunctival T. cruzi infection Dliated cardiomyopathy with destruction of the ventricular wall and an apical aneurysm 2  to Chagas Diseases

12 Virulence Factors Produces homolog of decay-accelerating factor (DAF) that inhibits formation of C3 convertase & blocks alternate pathway of complement Produces neuraminidase that cleaves sialic acids from host proteins lining lysosomes - destabilizes organelle Produces hemolysins that form pores in lysosomal membranes Burst host cells in going from amastigote to trypomastigote forms

13 Acute myocarditis from T. cruzi infection

14 Amastigotes of T. cruzi within myocytes

15 Amastigotes of T. cruzi within cardiac myocyte

16 Apical aneurysm from T. cruzi infection Left ventricle Right ventricle

17 African Trypanosomiasis Sleeping Sickness Trypanosoma brucei rhodesiense (East Africa). Acute, virulent. T. b. gambiense (West Africa), Chronic Transmission: Tsetse fly Within host, parasite undergoes successive changes of surface antigens, VSG (variable surface glycoprotein)  waves of parasitemia Zoonotic: wild mammals  man

18 African Trypanosomiasis Disease: –Waves of antibody-induced parasite deaths  recurrent fever. –Invasion  heart, liver, spleen, nodes  (lymphocytes, macrophages)  brain  often fatal lethargy  coma  death Brain: Leptomeningitis  demyelinating panencephalitis  plasma cells containing glycoprotein globules (flame cells)

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20 Distribution of African Trypanosomiasis

21 Tsetse fly of genus Glossina Chancre at site of Tsetse fly bite with transmission of Trypanosomes

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23 ONCHOCERCA VOLVULUS (FALARIAL NEMATODE) Transmission: Black flies: genus Simulium (tropical Africa) Cycle: Adult worms mate in skin  local infl. nodule  microfilariae  eye  keratitis and retinitis  blindness Rickettsia-like bacteria of genus Wolbachia live within nematode-probably cause pathology

24 Dermatitis from Onchocerca adults in skin

25 Keratitis & blindness associated with microfilarial infection of eye

26 Filariasis WUCHERERIA BANCROFTI Brugia malayi Mosquito is vector. Tropics. Larva circulates in blood  mature worm in lymphatics Humans only reservoir Nematode worm  intense inflammation, necrosis, destructive scarring Resulting lymphatic obstruction  massive edema (elephantiasis) Wuchereria bancrofti  90% of infections

27 Tropical distribution of filarial nematodes

28 Cross section of adult filarial nematode within lymphatic channel

29 Diagnosis is made by finding microfilaria in blood smear

30 Massive lymphedema from filariasis

31 “Elephantiasis”

32 Massive edema of scrotum and penis when adult nematodes block lymphatics

33 Leishmaniasis (1) Mucocutaneous Leishmaniasis (Espundia) Etiology: Leishmania braziliensis (protozoan) Transmission: Sandfly. Only in tropical New World Thrive in macrophage phagolysosomes, proton pump raises pH, lipophosphoglycans inhibit lysosomal enzymes Glycolipid gp63 = complement-cleaving proteinase Cell-mediated immunity protective, parasite causes Th1  Th2 switch which inhibits macrophage activation Dense glycocalyx binds C3b and resists lysis by C5-9.

34 Leishmania Life Cycle: amastigotes can survive within macrophages

35 MUCOCUTANEOUS LEISHMANIASIS (ESPUNDIA) (2) Clinical: –Disfiguring –destructive inflammation, nose –anus –vulva Pathology: Parasite-laden macrophages in granulomatous inflammation

36 Distribution of visceral & mucocutaneous leishmaniasis

37 Espundia

38 Mucocutaneous leishmaniasis

39 VISCERAL LEISHMANIASIS (KALA-AZAR: BLACK DISEASE) Etiology: –L. donovani (Old World) –L. chagasi (New World) Clinical: Systemic dissemination  nodes, liver, spleen  Pathology: Like mucocutaneous but involving viscera Death: Bacterial infection, pancytopenia, progressive wasting

40 Enlarged liver & spleen in Pt with visceral leishmaniasis

41 Fatal hemorrhage (green arrow) from splenic (black arrow) biopsy in patient with visceral leishmaniasis

42 Kupffer cell containing amastigotes in visceral leishmaniasis

43 SCHISTOSOMA MANSONI, S. JAPONICUM, S. HEMATOBIUM Life cycle: complex: Snail  larvae  human (via skin)  mature adult worms in portal & pelvic veins  eggs  granulomas with eosinophils - so Th1 & Th2 responses Disease: –S. mansoni, S. japonicum  liver cirrhosis & portal hypertension –S. hematobium  bladder  hemorrhage & carcinoma

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45 Eosinophilic & granulomatous inflammation around Schistosome eggs in bladder

46 Squamous cell carcinoma of bladder in pregnant Pt with Schistosomiasis SCC

47 Zoonoses Pathogens that are spread to humans from other animals Transmission may involve insect/arthropod vectors, direct or indirect transmission

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49 RICKETTSIA Rickettsia: small aerobic gram negative coccobacilli Vector-borne obligate intracellular parasites Infect endothelial & smooth muscle cells Endotoxin Abrupt onset fever, chills, headache, myalgia, rash Rx: tetracyclines

50 Q FEVER (1) Q fever: Coxiella burnetti, worldwide Droplet inhalation or direct contact Reservoir: cattle, sheep, goats Clinical: subacute, fever, HA, malaise –lungs: interstitial pneumonitis –liver:  LFP, hepatomegaly, 1/3 jaundice

51 Q FEVER (2) Epidemiology: slaughterhouse & farm animals Pathology: –lung  UIP –liver & BM  ring granulomas –DX: serology –Rx: tetracycline –Prognosis: rarely fatal

52 Ring granuloma in bone marrow of Pt with Q fever

53 Ring granuloma

54 Ring granuloma in Q fever Pt presenting with FUO

55 EPIDEMIC TYPHUS (1) Rickettsia prowazekii, ~worldwide Vector: body louse (Pediculus corporis) Louse lives only on humans or in human clothes Clinical: fever, vasculitis  rash, cerebral damage Mortality 5-25%

56 EPIDEMIC TYPHUS (2) Pathology: –skin  necrosis & gangrene –heart, lungs, etc.  ecchymosis –brain  typhus nodule Epidemiology:  prevalence if clothing not changed –war, poverty Brill-Zinsser: recurrent typhus after long latent interval

57 Louse business parts

58 Typhus nodule in CNS

59 ROCKY MOUNTAIN SPOTTED FEVER (1) Rickettsia rickettsia: U.S., esp. SE & SC Vector: Dermacentor ticks (wood, dog, lone star) Reservoir: dogs & wild rodents Clinical: rash incl. soles & palms, fever, chills, myalgia, DIC Mortality 3%

60 ROCKY MOUNTAIN SPOTTED FEVER (2) Pathology: –skin  vascular necrosis & thrombosis –brain  perivascular inflammation –lungs  pneumonitis Epidemiology: –90% April  September –Most common in children

61 CDC incidence data of RMSF from 2002: red states have the highest incidence Dermacentor ticks are the most common vector of RMSF

62 Erythematous maculopapular rash of RMSF. Rash often involves soles and palms. Immunostaining of Rickettsia rickettsia within endothelial cells of blood vessel in fatal case of RMSF (red stains)

63 Denuded endothelium & thrombosis from RMSF

64 Vascular occlusion (typhus nodule) in CNS of Pt with RMSF

65 Anaplasmosis (Ehrlichiosis) Ehrlichia canis, Anaplasma phagocytophilum, E. ewingii, E. chaffeensis, U.S. Vector: ticks (deer, wood, dog) Reservoir: unknown Clinical: like RMSF: F, HA, rash 20% Pathology: like RMSF but less severe, thrombocytopenia Dx: “purple blobs” in WBCs

66 Morulae in WBCs in Pts with Anaplasmosis

67 LYME DISEASE (1) Borrelia burgdorferi, spirochete, US, Europe & Japan Vector: hard-shelled ticks (Ixodes scapularis) Reservoirs: deer, deer mice Clinical: –tick bite  erythema migrans –dissemination  cranial neuritis, meningo- encephalitis, heart block, myocarditis –late chronic  chronic, destructive arthritis, neuropathy

68 LYME DISEASE (2) Dx: serology, PCR, culture Pathology: –skin  PV lymphocytes & plasma cells –meninges  hypercellular CSF, IgGs vs. Borrelia –joints  like RA  plasma cell synovitis  “onionskin”- like arteries  erosion of cartilage

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72 Erythema migrans

73 Perivascular dermatitis in EM lesion

74 LEPTOSPIROSIS Spirochetes, multiple serotypes, worldwide Spread: contaminated water or occupational exposure Reservoirs: wild & domestic animal Clinical: most inapparent, fever, myalgia –meningitis  ~aseptic –liver  10% jaundice, mortality ~10% –lungs  pneumonitis, hemorrhage Pathology: scant inflammation

75 TULAREMIA (1) Francisella tularensis –small gram-negative coccobacillus –worldwide Spread: contact, ticks, inhalation Reservoirs: rabbits, ticks, beaver Clinical: protean, fever, chills, malaise –ulceroglandular  ulcer, draining nodes  –systemic  bacteremia, pneumonia

76 TULAREMIA (2) Pathology: –early = neutrophilic infl., then granulomatous infl., stellate abscess Dx: serology, culture Rx: streptomycin Mortality < 1% with antibiotics

77 Cutaneous ulcer from tularemia

78 Stellate abscess (granulomas) of Tularemia

79 PLAGUE (1) Yersinia pestis –gram-negative rod, intracellular –~ worldwide Vectors: –urban plague, rats (Rattus rattus)  rat flea (Xenopsylla cheopsis)  humans –sylvatic plague  rodents, rabbits (SW US) Clinical: high fever & painful bubo –bubonic = lymph node abscess –pneumonic = rapidly develop pulmonary signs

80 PLAGUE (2) Pathology: neutrophilic response –lymph nodes  ulcerating lymphadenitis –lungs  hemorrhagic, necrotizing bronchopneumonia, fibrinous pleuritis Mortality: without antibiotics –bubonic ~75% –pneumonic ~90% USA ~30 cases/yr

81 Xenopsylla cheopsis

82 Bubo with central area about to ulcerate

83 Necrotic lymph node from plague

84 Manner of dress of royal surgeon of medieval times when dealing with Pts with plague


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