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Systemic Protozoa Systemic Protozoa

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Page 1: Systemic Protozoa

Systemic ProtozoaSystemic Protozoa

Page 2: Systemic Protozoa

Toxoplasmosis (Toxoplasmosis (Toxoplasma Toxoplasma gondiigondii)     )     

• Morphology :  Morphology :  • trophozoitetrophozoite::

• intracellular parasitic stage intracellular parasitic stage • binary fissionbinary fission• early acute stage of infection - size 4-8 µmearly acute stage of infection - size 4-8 µm

• bradyzoitebradyzoite: : • an encysted form an encysted form • chronic latent (asymptomatic) infection; chronic latent (asymptomatic) infection; • persists for years in human tissues (brain, retina, persists for years in human tissues (brain, retina,

muscle etc.)muscle etc.)

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• oocystsoocysts:: • 10 µm form 10 µm form • stool of cats, stool of cats, • the product of the sexual reproductive cycle in the product of the sexual reproductive cycle in

cat gut epithelial cells. cat gut epithelial cells. • sporulate in 3 days after passage in stool and sporulate in 3 days after passage in stool and • infective in the environment for a year. infective in the environment for a year. • Man swallows oocysts to become infected.Man swallows oocysts to become infected.

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trophozoitetrophozoite

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bradyzoitebradyzoite

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EpidemiologyEpidemiology: :

• Very common throughout the worldVery common throughout the world• 50+% in other developed or developing 50+% in other developed or developing

countries.countries.• Definitive host : Cat (sexual reproductive Definitive host : Cat (sexual reproductive

cycle) cycle)

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• Humans become infected in several ways:Humans become infected in several ways:

• ingestion of oocystsingestion of oocysts• ingestion of bradyzoites in uncooked meat, ingestion of bradyzoites in uncooked meat, • transplacental wtransplacental w• blood transfusion, organ transplant. blood transfusion, organ transplant. • rare from contaminated drinking waterrare from contaminated drinking water

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• Clinical:Clinical:• asymptomaticasymptomatic• acute toxoplasmosisacute toxoplasmosis: :

• fever, lymphadenopathy fever, lymphadenopathy • can can rarelyrarely cause specific organ inflammation, e.g. cause specific organ inflammation, e.g.

encephalitis, myocarditis.encephalitis, myocarditis.• reactivation toxoplasmosisreactivation toxoplasmosis: :

• occurs in immunosuppressed such as AIDS, transplant occurs in immunosuppressed such as AIDS, transplant and cancer patients: presents with specific organ and cancer patients: presents with specific organ involvement e.g. encephalitis, pneumonitis.involvement e.g. encephalitis, pneumonitis.

• 44

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• choreoretinitis:choreoretinitis: • later in life in individuals ; congenitall toxoplasmosis;later in life in individuals ; congenitall toxoplasmosis;

• decreased visual acuitydecreased visual acuity

• congenital toxoplasmosiscongenital toxoplasmosis: : • transmission from mother to fetus transmission from mother to fetus

• Presents as hydrocephalus, hepatomegaly, cerebral Presents as hydrocephalus, hepatomegaly, cerebral calcifications, mental retardation with death at one end calcifications, mental retardation with death at one end of spectrum and mental retardation or just later of spectrum and mental retardation or just later choreoretinitis at the other end of spectrum.choreoretinitis at the other end of spectrum.

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toxoplasma retinal scar toxoplasma retinal scar

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toxoplasma cerebral abscesstoxoplasma cerebral abscess

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ToxoplasmosisToxoplasmosis

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Diagnosis:Diagnosis:

Serology or PCR is the usual means of diagnosis.Serology or PCR is the usual means of diagnosis.

Biopsy of organ, e.g. brainBiopsy of organ, e.g. brain

Biopsy of lymph nodes reveals suggestive pathology but Biopsy of lymph nodes reveals suggestive pathology but rarely trophozoites rarely trophozoites

Serology: in acute toxoplasmosis in routine screening of Serology: in acute toxoplasmosis in routine screening of pregnancy pregnancy

Immunofluorescent staining of biopsy sectionsImmunofluorescent staining of biopsy sections

PCRPCR

cultureculture

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• Treatment:Treatment:            - antifolates (pyrimethamine and             - antifolates (pyrimethamine and sulfadiazine)sulfadiazine)            - spiramycin            - spiramycin

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Pneumocystis cariniiPneumocystis carinii

• BiologyBiology - in two forms- in two forms

• cystscysts (5 mu), (5 mu),• a dormant form which contains 8 a dormant form which contains 8 trophozoitestrophozoites (5 x 1 m). (5 x 1 m).

• appears to be asexual binary division of trophozoites. appears to be asexual binary division of trophozoites.

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• Epidemiology:Epidemiology:• Acquired in childhood by almost everyone,Acquired in childhood by almost everyone,• probably airborne and possibly (unknown) probably airborne and possibly (unknown)

without overt illness. without overt illness. • Remains in latent nonpathogenic form in Remains in latent nonpathogenic form in

human pulmonary interstitium human pulmonary interstitium • overt illness in the immune compromized overt illness in the immune compromized

(premature infants, AIDS)(premature infants, AIDS)

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Silver stain of Silver stain of P. carinii in P. carinii in bronchoalveolar lavage (BAL)bronchoalveolar lavage (BAL)

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• Clinical:Clinical:1. interstitial plasma cell pneumonia of 1. interstitial plasma cell pneumonia of infants (especially premature). infants (especially premature). • epidemics, usually in hospitals; 50% mortality if epidemics, usually in hospitals; 50% mortality if

untreated.untreated.

2. pneumonia in immunocompromized - e.g. 2. pneumonia in immunocompromized - e.g. leukemia, lymphoma, AIDS; 100% mortality if leukemia, lymphoma, AIDS; 100% mortality if untreated. Most common cause of mortality in untreated. Most common cause of mortality in AIDS AIDS

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• Diagnosis:Diagnosis:- Open lung biopsy, brush biopsy, and - Open lung biopsy, brush biopsy, and

at times sputum stainsat times sputum stains• Grocot, silver stain will stain thick Grocot, silver stain will stain thick

cyst wall.cyst wall.• Giemsa stain will stain trophozoites.Giemsa stain will stain trophozoites.

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• Treatment:Treatment: Antifolates (trimethoprim Antifolates (trimethoprim andsulfamethaxazole) andsulfamethaxazole) PentamidinePentamidineClindamycin and primaquineClindamycin and primaquineAtovaquoneAtovaquone

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HemoflagellatesHemoflagellates      

• HemoflagellatesHemoflagellates                      • Phylum:   SarcomastigophoraPhylum:   Sarcomastigophora• Genera:    2 important medically - Genera:    2 important medically -

TrypanosomaTrypanosoma and and LeishmaniaLeishmania

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• Overview:Overview:    - Important pathogens of humans and livestock- Important pathogens of humans and livestock- All pathogenic species transmitted by insects- All pathogenic species transmitted by insects- All have more or less complex cycles alternating - All have more or less complex cycles alternating from one morphologic form to anotherfrom one morphologic form to another- Distinguishing structural characteristics: - Distinguishing structural characteristics: flagellum, kinetoplastflagellum, kinetoplast- Basic morphologic stages: -flagylated - Basic morphologic stages: -flagylated trypomastigote, promastigote or amastigote    trypomastigote, promastigote or amastigote   

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Genus TrypanosomaGenus Trypanosoma

• Two different species of medical Two different species of medical importanceimportance• Trypanosoma cruziTrypanosoma cruzi: causes Chagas' disease in : causes Chagas' disease in

South AmericaSouth America• Trypanosoma bruceiTrypanosoma brucei: causes African : causes African

trypanosomiasis (African sleeping sickness)trypanosomiasis (African sleeping sickness)

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Genus LeishmaniaGenus Leishmania

- many species grouped by clinicalmany species grouped by clinical

presentation: cutaneous, mucocutaneous and presentation: cutaneous, mucocutaneous and visceral visceral

visceral  visceral  Leishmania donovani Leishmania donovani             cutaneouscutaneous Leishmania tropica, major, Leishmania tropica, major,

mexicana etcmexicana etc          mucocutaneousmucocutaneous Leishmania Leishmania

braziliensis etcbraziliensis etc

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Trypanosoma cruziTrypanosoma cruzi (Chagas' (Chagas' Disease, American Disease, American TrypanosomiasisTrypanosomiasis

• reservoirs of armadillo, opossums, reservoirs of armadillo, opossums, raccoonsraccoons

• transmitted to man by the reduvid bug (e.g. transmitted to man by the reduvid bug (e.g. in Mexico in Mexico Rhodnius prolixusRhodnius prolixus). ).

• Reduvid bug bites human while asleep and Reduvid bug bites human while asleep and passes feces containing parasite passes feces containing parasite (trypomastigote form, 20 m) onto skin near (trypomastigote form, 20 m) onto skin near the bite. Human rubs faeces and parasite the bite. Human rubs faeces and parasite into wound or eye.into wound or eye.

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• Parasite causesParasite causes• local infection and inflammation (chagoma) local infection and inflammation (chagoma)

then circulates in blood of host then circulates in blood of host tissue cells tissue cells (muscle and mononuclear phagocytic system of (muscle and mononuclear phagocytic system of spleen, liver, 1ymph nodes and CNS) where it spleen, liver, 1ymph nodes and CNS) where it changes into amastigotes (2-4 mu) and divides changes into amastigotes (2-4 mu) and divides by binary fission.by binary fission.

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T.cruziT.cruzi trypomastigote trypomastigote

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• EpidemiologyEpidemiology: : Transmission: ..by reduvid bug biteTransmission: ..by reduvid bug bite                       ..vertical (in utero)                       ..vertical (in utero)                       ..blood transfusion                       ..blood transfusion

•           12 million persons affected; 35 million 12 million persons affected; 35 million at risk; Central and South America.    at risk; Central and South America.                                                                                                                                                                                                                                                                                                             

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• Clinical:Clinical:AcuteAcute: local inflammation at site of : local inflammation at site of innoculation (chagoma) generalized innoculation (chagoma) generalized lymphadenopathy, hepatosplenomegaly fever.lymphadenopathy, hepatosplenomegaly fever.ChronicChronic: up to several decades after acute : up to several decades after acute stage myocardopathy - heart failure, stage myocardopathy - heart failure, arrhythmias megaintestine - megaoesophagus, arrhythmias megaintestine - megaoesophagus, achalasia, megacolonachalasia, megacolon

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• Diagnosis:Diagnosis:                            - blood smear for                            - blood smear for trypanosomes (Giemsa stain)trypanosomes (Giemsa stain)                           - serology, PCR                           - serology, PCR                           - biopsy                           - biopsy                           - xenodiagnosis                           - xenodiagnosis

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• Treatment:   Treatment:   - Nifurtimox (Lampit) a - Nifurtimox (Lampit) a nitrofurone, poorly effective in chronic nitrofurone, poorly effective in chronic ChagasChagas

• Control:  Control:  - Concrete walls and floors - Concrete walls and floors prevent reduvid bug infestations prevent reduvid bug infestations                          - antiparasitic agents added                          - antiparasitic agents added to transfused to transfused

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African Trypanosomiasis (African African Trypanosomiasis (African Sleeping Sickness)Sleeping Sickness)

• A hemoflagylate A hemoflagylate • AfricaAfrica• Resevoir: antelope, cattleResevoir: antelope, cattle• transmitted from resevoir animal to man by transmitted from resevoir animal to man by

the vector tsetse fly (e.g. the vector tsetse fly (e.g. Glossina palpalisGlossina palpalis). ). • In west African : transmitted by tsetse In west African : transmitted by tsetse

human to human..human to human..

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• Two species: Two species: •     Trypanosoma brucei gambienseTrypanosoma brucei gambiense (Africa west (Africa west

of Rift valley)of Rift valley)•         Trypanosoma brucei rhodesiense Trypanosoma brucei rhodesiense (Africa (Africa

east of Rift valley)east of Rift valley)

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• PathogenesisPathogenesis• Tsetse bites man Tsetse bites man multiply locally producing multiply locally producing

a local lesion a local lesion intravascular space where the intravascular space where the trypanosome multiplies by binary fision trypanosome multiplies by binary fision extracellularly producing fever and extracellularly producing fever and lymphadenopathy lymphadenopathy central nervous system central nervous system producing a meningoencephalitis producing a meningoencephalitis

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• Clinical pictureClinical picture- trypanosomal chancre- trypanosomal chancre- parasitemia with lymphadenopathy fever - parasitemia with lymphadenopathy fever - central nervous system signs of variable - central nervous system signs of variable focal nature and eventually coma and death focal nature and eventually coma and death

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encephalitis of African Sleeping encephalitis of African Sleeping Sickness Sickness

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• Diagnosis Diagnosis         - motile organisms on wet preparations of fresh - motile organisms on wet preparations of fresh blood or CSFblood or CSF    - stained smears (Giemsa) may reveal organism     - stained smears (Giemsa) may reveal organism

         - high levels of protein (IgG and IgM) in - high levels of protein (IgG and IgM) in CSF                     CSF                         - lymphocytosis in CSF    - lymphocytosis in CSF - PCR- PCR

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• Treatment    Treatment    - Pentamidine- Pentamidine                          - Suramin                          - Suramin                          - Eflornithine                          - Eflornithine                          - Melarseprol                          - Melarseprol

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LeishmaniasisLeishmaniasis

• There are two distinct groups of clinical There are two distinct groups of clinical presentations.presentations.

1. 1. Visceral leishmaniasis:Visceral leishmaniasis:systemic illness of feversystemic illness of feversplenomegaly splenomegaly lymphadenopathy (caused by lymphadenopathy (caused by Leishmania Leishmania

donovanidonovani))other names Kala azar, Dum Dum fever.other names Kala azar, Dum Dum fever.

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2. Cutaneous leishmaniasis:2. Cutaneous leishmaniasis:skin ulcer or ulcers skin ulcer or ulcers caused by caused by Leishmania tropicaLeishmania tropica, , mexicanamexicana, ,

and and braziliensisbraziliensisreservoir : dog or rodent reservoirreservoir : dog or rodent reservoirtransmitted to man by sandfly bite transmitted to man by sandfly bite

((Phlebotomus spPhlebotomus sp). ). distributed throughout the distributed throughout the tropicstropics

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• Organism:Organism:Two morphological forms,Two morphological forms,

1. promastigote 1. promastigote - found in the sandfly vector - found in the sandfly vector

2. amastigote2. amastigote- in man- in man- intracellularly in macrophages in skin - intracellularly in macrophages in skin

lesions (in cutaneous leishmaniasis) or in the lesions (in cutaneous leishmaniasis) or in the reticuloendothelial system of blood, liver, reticuloendothelial system of blood, liver, lymphnodes, spleen (in visceral leishmaniasis).lymphnodes, spleen (in visceral leishmaniasis).

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                    Promastigotes Promastigotes

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Amastigotes, also called Leishmania Amastigotes, also called Leishmania Donovani bodies Donovani bodies

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• Pathophysiology/life cyclePathophysiology/life cycle::- sandfly bites human - sandfly bites human invade invade macrophages, becoming amastigotesmacrophages, becoming amastigotes multiplymultiply new macrophages new macrophages• lymphocytes to the local infection, a local lymphocytes to the local infection, a local

subcutaneous 1-3 cm. nodule is produced which subcutaneous 1-3 cm. nodule is produced which ulcerates and is contained locally by the cell ulcerates and is contained locally by the cell mediated immune system in cutaneous mediated immune system in cutaneous leishmaniasis or spreads systemically in leishmaniasis or spreads systemically in visceral leishmaniasis.visceral leishmaniasis.

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• Clinical pictureClinical picture::visceral leishmaniasis:visceral leishmaniasis: ( (L. donovaniL. donovani))• early nodule at site of sandfly bite seen at timesearly nodule at site of sandfly bite seen at times• usually presents with chronic feverusually presents with chronic fever• splenomegaly (very large)splenomegaly (very large)• lymphadenopathy and dark skin = Kala, azar.lymphadenopathy and dark skin = Kala, azar.• High mortality from anemia and bacterial High mortality from anemia and bacterial

superinfections.superinfections.

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Clinical pictureClinical picture::cutaneous leishmaniasis:cutaneous leishmaniasis:- several variants basically with skin - several variants basically with skin nodules which ulcerate.nodules which ulcerate.

        L. tropicaL. tropica complex - in Asia, Africa, and complex - in Asia, Africa, and Mediterranean (called Oriental sore, Delhi Mediterranean (called Oriental sore, Delhi or Bagdad boil).or Bagdad boil).      L. mexicanaL. mexicana complex and others - in complex and others - in Central and South America Central and South America

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cutaneous leishmaniasis     cutaneous leishmaniasis    

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throat mucocutaneous leishmaniasis throat mucocutaneous leishmaniasis (2 years duration) (2 years duration)

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• mucocutaneous leishmaniasismucocutaneous leishmaniasis::begins as a cutaneous ulcer and begins as a cutaneous ulcer and metastasizes to mucosa of nose and pharynx metastasizes to mucosa of nose and pharynx leading to destruction, obstruction and leading to destruction, obstruction and death. death.

L. braziliensisL. braziliensis - in South  and Central - in South  and Central America (called espundia).America (called espundia).

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DiagnosisDiagnosis::

• Cutaneous and mucocutaneousCutaneous and mucocutaneous1. aspirate material from edge of ulcer and stain (Giemsa).1. aspirate material from edge of ulcer and stain (Giemsa).2. biopsy and stain with Giemsa - pathology sections show 2. biopsy and stain with Giemsa - pathology sections show granulomatous lesion and organisms (amastigotes = granulomatous lesion and organisms (amastigotes = Leishmania donovani bodies =LD bodies) are seen in Leishmania donovani bodies =LD bodies) are seen in macrophages.macrophages.3. culture aspirate or biopsy material in special media 3. culture aspirate or biopsy material in special media producing promastigotes.producing promastigotes.4. serology4. serology5. PCR5. PCR

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• VVisceralisceral1. aspirate bone marrow or spleen and stain 1. aspirate bone marrow or spleen and stain (Giemsa) or culture material.(Giemsa) or culture material.2. serology.2. serology.3. PCR3. PCR

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• Treatment:Treatment:- relatively toxic drugs, e.g. antimonials - relatively toxic drugs, e.g. antimonials (Pentostam), Pentamidine, Amphoteracin B. (Pentostam), Pentamidine, Amphoteracin B.

- resistance to all drugs in some geographic - resistance to all drugs in some geographic areas.areas.

• Scientific Challenges:Scientific Challenges:      - defining the many variants in species.      - defining the many variants in species.            - finding less toxic drugs.            - finding less toxic drugs.