Parasitic Diseases of Humans (2/10)

Zhou Lecture 1 (Lecture 19)

medical parasitology

study of eukaryotic parasites

common property: cant live outside host, easy spread through travel

7/8 tropical disease

studies of infections and diseases by: protozoa and helminth worms

Protozoa

kingdoms: animals; fungi; protista (algae and protozoa)

single celled, animal like

examples: amoebae, cilitates, flagellates, sporozoans

structure: cytoplasmic membrane, cytoplasm, usually w flagellum

Life processes of protozoa

aquatic

obligate parasites

chronic/acute diseases:

• amebiasis (amebic dysentery): entamoeba

• sleeping sickness: trypanosoma bruci

• chagas disease: trypanosoma cruzi

• STD: trichomonas vaginalis

life cycle of protozoa

asexual reproduction: binary fission

sexual reproduction: conjugate; exchange DNA; segregate

Encystment

• adverse conditions

• cyst formation: round w protective coating, survive lack of food/water/high temperature

Classifications of protozoa (4 phyla)

amoebas, ciliates, flagellates, sporozoan

General properties of Infective amoebas

pseudopodia

trophozoite: actively growing

only binary fission

form cysts

major diseases: most not pathogenic

• amebiasis

• brain infection: naegleria, acanthamoeba

amoebiasis

entamoeba histolytica — intestinal disease

site of infection: intestinal mucosa

symptoms: mild diarrhea, dysentery (blood stools), abdominal pain, fever, fatigue, wt loss

tissue damage: cell ingestion due to enzymes dissolving tissue and ulcerations

severe cases of amoebiasis

liver, amoebic hepatitis

lung, pulmonary ameobiases

less freq: spleen, adrenals, kidney, skin brain

10% fatality rate

epidemiology of amoebiasis

tropical and subtropical disease:

• US 0.1-0.5% infection rate

• Tropical regions: 5-8%, sewage used as fertilizer

how is amoebiasis spread?

asymptomatic chronic carriers

encystment stage completed in health carriers

active dysentery: not infectious — cyst formation cant occur

Life Cycle of entamoeba histolytica

trophozoite: karyosome, nucleus, RBCs

mature cyst: chromatoidals, nucleus

excystment: nucleus

diagnosis and treatment of amoebiasis

diagnosis: ingested RBCs,4 nuclei in cysts, symptoms

treatment: drugs targeting parasite in feces and tissues

• Iodoquinol, metronidazole, dehydroemetine, chlorquine

Naegleria fowleria(nf) and acantheamoeba (acanth)

amoebic infection of the brain

common, free living protozoans, accidental parasites

live in lakes, hot springs, swimming pools, hot tubs, moist soil

Pathogenesis of nf and treatment

killer amoeba

“primary amoebic meningoencephalitis”

invades nasal mucosa

amoeba burrows in, multiplies, migrates to brain

primary acute meningoencephalitis: rapid massive destruction of brain and spinal tissue

symptoms: hemorrhage, coma, death in a week

advances too fast for effective treatment:

• amphotericin B,sulfadiazine, tetracycline, ampicillin if treated early can be helpful

pathogenisis of acanth

“granulomatous amoebic encephalitis”

invades broken skin, conjunctiva, lung and urogenitla epithelia

special risks: ppl w eye injuries or abrasions from contact lenses

course of infection longer than nf

balantidium coli is what type of organism? what disease and habitat is associated?

intestinal cilitate: movement, two nuclei (macro and micro), sexual and asexual production

disease: balantidiosis — infection in intestinal mucosa

natural habitat: large intestines of pigs, other domestic animals, primates (cysts in feces)

balantidium coli (infection/symptoms, treatment/prevention)

infection/symptoms: intestinal mucosa — irritation, injury, nausea, vomiting, diarrhea, dysentery and abdominal colic

healthy indiv are resistant

treatment: oral tetracycline, then dodoquinol, nitrimidazine or metronidazole

prevention: prevent food or drink contamination with pig manure

Common feature of mastrigophorans and its diseases

long filamentous flagellas “flagellates”

mild diseases: trichomoniasis and giardiasis

debilitating: trypanosomiasis and leismaniasis

trichomonads

small pear shaped protozoa, w 4 flagella and undulating membrane. no cysts

pathogen: trichomonas vaginalis — trichomoniasis, a STD

reservoir: human urogenital tract: 50% asymptomatic

transit: sexual contact, communal bath, public facilities, mother to child

trichomoniasis (symptoms and treatment)

2nd most prevalent STD (most common chlamydia — bacteria)

symptoms:

• females: foul smell, green to yellow vaginal discharge, vulvitis, cervicitis, urinary freq and pain

• males: urethritis, milky discharge, prostate infection

treatment: oral and vaginal metronidazole, both partner have to be treated

what is giardiasis caused by? outbreaks? what do you treat it with?

giardia lamblia — prominent cause of diarrhea

most common flagellate isolated in clinical specimens

2 nuclei in trophozoites and 4 in cysts

outbreaks: traveler’s diarrhea, hikers, campers, drinking from fresh mountain streams, children in day care centers

Treatment: quinacrine, metronidazole

vector borne blood parasites

hemoflagellates (blood and tissue)

major species: trypanosoma, leishmania

life threatening disease spread by blood sucking insects with complicated life cycles

what are the developmental stages of hemoflagellates (look at table in notes)

amastigote: lacks free flagellum

promasitgote: single free anterior flagellum

epimastigote: flagellate stage, with both flagellum and an undulating membrane

trypomoastigote: large, fully formed stage of Trypanosoma

not all hemoflagellates have all stages

trypanosomiasis

trypanosoma:

• trypanosoma brucei: african sleeping sickness

  • T. b. gambiense: West Africa

  • T. b. rhoesiense: East Africa

• T. cruzi: Chagas disease

Vector: tsete flies

Infections by T. brucei

Tsetse flies get infected by feeding on infected reservoir hosts (antelope, lion, cow, goat, human)

Trypanosomes multiply in fly gut

migrate to salivary glands, develop into infectious stage

transfer into bite wounds on new hosts, to lymphatics and blood

what is the difference between rhodesian form and gambian form T.b infections?

rhodesian: T.b. rhoesiense — acute, effects brain in 3-4 wks

gambian: T.b. gambiense — chronic, may not affect the brain for several yrs

Pathology of Sleeping Sickness (T.b)

intermittent fever, enlarged spleen, swollen lymph nodes, joint pain

personality change, sleep disturbances (sleepy day, sleepless at night)

advanced neurological disorders:

• muscular tremors, shuffling gait, slurred speech, epileptic seizures, paralysis

• death: coma, secondary infections, heart damage

Treatment/prevention of T.b

chemotherapy admin before brain damage

expensive:

• melarosprol-toxic arsenic based drug

• difluroomethylornithine (DFMO) less toxic

control: insecticides (difficult)

sudan and zaire: 20-40% of population infected

Why can’t the immune system defeat trypanosome?

they produce large #s of surface antigens in succession

antibodies produced by host fail to stop bugs with new antigen

hosts eventually overwhelmed

difficult to immunize: >100 antigenic variations

Chagas Disease

trypanosoma cruzi

insect host: kissing bugs with trypanosomes in the hind gut and discharge it in feces

central/south america and share habitat with humans

infection occur when bug defecates near bite wounds, incoulation by rubbing bug feces into wounds

pathology and treament for chagas disease

symptoms: fever, swelling lymph nodes, spleen, and liver

pathology: favored targets are heart muscle, large intestine —> heart enlarged —> death in 2 yrs

treatment: nifurtimox and benzonidazole admin early, side effects damaging

leishmaniasis

leishmania

cutaneous leishmanisis: capillary infections

trasmit among mammals by phlebotomine flies (sand)

endemic to equatorial regions

special risks: travelers and immigrants

death by destruction of tissues

leishmania life cycle

sand fly

promastigote stages in gut of sand fly

human/mammal

free and intracellular amastigotes in the spleen

apicocomplexan parasites

sporozoans: lack locomotor organelles in mature stage

sexual and asexual reproduction

human pathogens:

• plasmodium: malaria

• toxoplasma: toxoplasmosis (muscle aches/brain lesions/birth defects)

• cryptosporidium: cryptosporidiosis (diarrhea)

what is malaria? cause? symptoms?

plasmodium, obligate intracellular sporozoan

dominant protozoan disease

exposure to bad air from swamps: mosquitoes

symptoms:

• chills, fever at regular intervals, following by sweating (48-72hrs) due to synchronous rupturing of RBCs

• anemia in children, organ ruptrure from accumulated cell debris (spleen, liver, kidneys)

• long recovery: <5years

malaria species and transmission

P. malarae; P. vivax; P. falciparum; P. ovale

most severe: falciparum — persistent fever, rapid pulse, cough, weakness for weeks wo relief, high death rate in acute phase

transmission:

• mostly by female anopheles mosquitoes

• occasionally by sharing needles

• blood transfusions

• mother to child

asexual phase of plasmodium life cycle: exoerythrocytic development

injection of anticoag saliva into the capillar y

asexual plasmodium injection (sporozoites)

sporozoites reach liver and undergo schizogony (asexual division), generate daughter parasites (merozoites)

eruption of liver cells, release numerous mature merozoites into circulation

asexual phase of plasmodium life cycle: erythrocytic development

release merozoites invade RBCs, feed on Hb, producing cells called schizonts (filled w merozoites)

RBC burst releasing more merozoites

merozoites develop into macrogametocytes (female) and microgametocytes (male)

sexual phase of plasmodium life cycle: gametocyte phase

mosquitoes draw gametes into stomach

fertilization

diploid cells (oocyst) implants stomach wall and undergo multiple mitotic divisions, releasing sporozoites

sporozoites migrate to salivary glands and aval for next infection

hemoglobin C vs S warding off malaria

C: protection with no fitness cost

S: protection with a cost — sickle cell anemia in s/s individuals

malaria diagnosis and control

diagnosis: stained blood smear, antibodies, DNA-PCR analysis

control:

• pesticides: DTT — resistance

• treatment:

  • non-resistant strains: chloroquine has less toxic side fx

  • resistant strains: mefloquine, quinine

  • eliminate parasite from liver: primaquine or proguenil

toxoplasmosis exposure rate, symptoms

toxoplasma gondii

order coccidorida of the apicomplexa

exposure rate 90%

most cases: mild, sore throat, lymph node enlargement, low grade fever

Immunodef pts: brain lesions, fetal disruption of heart and lungs

toxoplasmosis in pregnant women

transmit to fetus 33% chance

still birth, liver failure, hydrocephalus, convulsions, retina dmg, blindness

summary of parasitic diseases of humans

Infective amoebas:

• amoebiasis: entaomoeba histolytica

• brain infections: nf and acanth

Intestinal Cilitates: balantidium coli

The Flagellates:

• trichomoniasis: trichomonads

• giardiasis-intestinal disease: giardia lamblia

• trypanosomiasis: sleeping sickness

• trypanosoma: chagas disease

• leishmania: leishmaniasis

Apicomplexan parasites

• plasmodium: malaria

• toxoplasma gondii: toxoplasmosis