Id 4Y2: Protozoa

Front 1

Parasitic Protozoa

Unicellular/multicellular eukaryotes?

Intestinal/tissue parasites?

Direct/indirect transmission?

Reproduction may be _________ (binary fission or multiple organisms in a cyst) or ________ (definitive host)

Unlike most worms, protozoa multiply in ________ hosts and are generally not associated with ________

Back 1

One-celled animals - eukaryotes

Intestinal or tissue parasites

Direct or indirect transmission (vector)

Reproduction may be asexual (binary fission or multiple organisms in a cyst) or sexual (definitive host)

Unlike most worms, protozoa multiply in human hosts and are generally not associated with eosinophilia

Front 2

Groups of Parasitic Protozoa

Back 2

Sporozoans: Plasmodium, Toxoplasma, Cryptosporidium, Cyclospora*
Flagellates: Giardia, Trypanosoma, Leishmania, Trichomonas
Amoebas: Entamoeba, Naegleria
Ciliates: Balantidium*

* Organisms not discussed in this lecture

Front 3

Host factors and protozoan diseases

Severity and clinical manifestations may vary according to:

Back 3

Severity and clinical manifestations may vary according to:
- Age when infected
- Innoculum
- Nutritional status
- Coinfections
- Immune status (increased severity with HIV/AIDS)

Front 4

Therapy of Protozoan Infections

Shared metabolic pathways –
Sometimes unfavorable therapeutic ________

Some therapies improve ________ without _________ the infection

In the USA, antiparasitics are ________ drugs; many useful drugs are not registered here

_____ is a major barrier in the developing world

No good therapies are available for some infections at any cost !

Back 4

Shared metabolic pathways –
Sometimes unfavorable therapeutic ratios

Some therapies improve symptoms without eradicating the infection

In the USA, antiparasitics are orphan drugs; many useful drugs are not registered here

Cost is a major barrier in the developing world

No good therapies are available for some infections at any cost !

Front 5

A 3 year old boy in Ghana has fever, weakness, decreased responsiveness, pale conjunctiva, splenomegaly, no rash
Broad differential diagnosis

Blood smear shows ring forms in RBC’s; HgB 4 g%

Back 5

P. falciparum malaria

Front 6

Malaria: Numero Uno

Species? (4)

Back 6

4 species, Plasmodium falciparum, vivax, ovale, malariae

Front 7

Simplified Plasmodium Life Cycle

__-__ weeks from bite of anopheles mosquito to _________ (infectious gamete)

Thin, motile, spindle-shaped forms of the Plasmodia, called _______, swim to the ____ via the bloodstream – there they undergo asexual reproduction and form ___________ - as these grow they become a big mass with thousands of nuclei, called a _______ - a cytoplasmic membrane forms around each nuclei creating thousands of small bodies called ________.

The new, overloaded, liver cell bursts open, releasing the ________ back into the _______ and the _______. Some will now reinfect the ______ and others will enter ______ (and form a diamond shaped _________)

In the rbcs, nuclear division occurs forming another _______. Cytoplasm surrounds each nucleus forming new _________. Red cell lysis occurs releasing _________.

This final rbc _________ release is what causes an immune response manifested as _______, _______, and ______.

This cycle repeates every __-__ hours depending on the organism.

Back 7

2-4 weeks from bite of anopheles mosquito to sporozoite (infectious gamete)

Thin, motile, spindle-shaped forms of the Plasmodia, called sporozoites, swim to the liver (enter hepatocytes) via the bloodstream – there they undergo asexual reproduction and form trophozoites - as these grow they become a big mass with thousands of nuclei, called a shizont - a cytoplasmic membrane forms around each nuclei creating thousands of small bodies called merozoites.

The new, overloaded, liver cell bursts open, releasing the merozoites into the liver and the bloodsteam. Some will now reinfect the liver and others will enter rbcs (and form a diamond shaped trophozoite)

In the rbcs, nuclear division occurs forming another shizont. Cytoplasm surrounds each nucleus forming new merozoites. Red cell lysis occurs releasing merozoites.

This final rbc merozoite release is what causes an immune response manifested as fevers, chills, and sweats.

This cycle repeates every 48-72 hours depending on the organism.

Front 8

Plasmodium Blood Stages

Thin smear with ____ and a ______ (banana shaped)

___________ (ring & mature)

Back 8

Thin smear with rings and a gametocyte (banana shaped)

Trophozoites (ring & mature)

Front 9

Plasmodium falciparum

How common?

How deadly?

Merozoites bind to _______, can infect all _____’s (regardless of age) leading to high levels of __________

_______ immunity protects young infants.

High mortality in ______ and ______.

Older children and adults have ______ immunity (fatal/non-fatal? attacks)

What confers partial resistance?

Back 9

Most common species in many areas

Deadly- Merozoites bind to glycophorin, can infect all RBC’s (regardless of age) leading to high levels of parasitemia

Maternal immunity protects young infants.

High mortality in older infants and toddlers.

Older children and adults have partial immunity (nonfatal attacks)

Certain hemoglobinopathies (sickle trait, thalassemia, G6PD deficiency) confer partial resistance

Front 10

Other Plasmodium Species (3 aside from falciparum)

Back 10

P. vivax
P. ovale
P. malariae

Front 11

Other Plasmodium Species

P. vivax –

Symptoms?
Fatal?

Merozoites bind to ______ antigen on ____.

Late relapses (up to a year or more) because of ____-_______ stages (hypnozoites) in liver.

Back 11

Flu-like illness with fever, malaise, splenomegaly.

Rarely fatal.

Merozoites bind to Duffy antigen on RBC. Infects young RBC, lower % parasitemia.

Late relapses (up to a year or more) because of extra-erythrocytic stages (hypnozoites) in liver.

Front 12

P. ovale - Does it require Duffy receptor for entry into cells?

Back 12

P. ovale - very similar to P. vivax, but does NOT require Duffy receptor for entry into cells. Primarily in Africa.

Front 13

P. malariae -

Common?
Causes acute/chronic infection?

Prefers what cells?

Associated with what syndrome/disease?

Back 13

P. malariae
- rarer,
- causes a chronic infection,
- prefers senescent cells, low level parasitemia for many years.

*Recrudescence of clinical symptoms rather than relapse.

Nephrotic syndrome.


*FYI: Recrudescence is the reappearance of a disease after it has been quiescent. For example, a clinical attack after parasites in the blood have dropped markedly and the disease has subsided. The parasites, e.g. Plasmodium, which are responsible for the disease Malaria, can persist in the blood without causing apparent symptoms for a few months. It occurs mainly due to suppression of the immune system. This is an important difference between recrudescence and relapse (which occurs due to reactivation of hypnozoites in the liver).

Front 14

Malaria Pathogenesis

Anemia: why?

Which parasite antigens on the surface of red blood cells (“knobs”) cause adherence to endothelium (via CD__) leading to obstruction and infarction?

Cytokines (________ which one?) cause fever and hypotension

Increased risk in ________ ?

Back 14

Anemia: Clearance and lysis of infected RBC; also decreased RBC production

Pf - Parasite antigens on the surface of red blood cells (“knobs”) cause adherence to endothelium (CD36) leading to obstruction and infarction

Cytokines (TNF alpha) cause fever and hypotension

Increased risk in pregnancy for mother and fetus

Front 15

Malaria: Clinical Manifestations

_____ / ______ /_______,

Onset? __-__ days after infection –

Periodicity may not be evident in __-_____ patients

P.falciparum cycles every ___-___ hours

P. ovale and vivax cycle every __ hours

P. malariae cycles every __ hours

Back 15

Chills / Fever / Sweats,

Onset 7-14 days after infection –

Periodicity may not be evident in non-immune patients


P.falciparum cycles every 36-48 hours

P. ovale and vivax cycle every 48 hours

P. malariae cycles every 72 hours

Front 16

Malaria: Clinical Manifestations (2)

Anemia? WBC? platelets?

Other presentations?

Back 16

Anemia, normal WBC, decreased platelets

Headache

Splenomegaly

Nausea, vomiting, diarrhea

Acute renal failure – Pf (hemolysis)

Cough / respiratory distress - Pf

Coma, seizures (cerebral malaria) - Pf

Front 17

Malaria Diagnosis

___________ (acridine orange)

____________ (detects parasite's ____________ ) and/or LDH

____ useful but not widely used

Back 17

Malaria

Blood smears (acridine orange)

Antigen detection (detects parasite's histidine-rich protein (HRP)) and/or LDH

PCR useful but not widely used

Front 18

Malaria Prevention

Mosquito ____ (preferably insecticide impregnated)

Repellents: _____

Avoiding mosquito ____: mosquitoes prefer to bite at _____. protective measures?.

_________ medication! - VERY important

Back 18

Mosquito nets (preferably insecticide impregnated)

Repellents: DEET

Avoiding mosquito bites: mosquitoes prefer to bite at dusk. Protective clothing.

Prophylactic medication! - VERY important

Front 19

Malaria prophylaxis

Mainstay (as long as not resistant)?

Alternatives for P. falciparum?

Alternatives for p.vivax/ovale that have a hypnozoite stage of latent liver infection (exo-erythrocytic cycle)?

Back 19

Chloroquine - mainstay

Alternatives for P. falciparum –
- mefloquine (CNS, QTc)
- Doxycycline (photosensitivity, Candida, GI)
- Malarone (atovaquone/proguanil) $$$

Vaccines (work in progress)

Primaquine is used to clear hypnozoites from liver to prevent late relapses

Front 20

Chloroquine:

Blocks detoxification of _____ into _________ pigment.

___________ is resistant to CQ in most areas (PfCRT gene)

Back 20

Blocks detoxification of heme into hemozoin pigment.

P. falciparum is resistant to CQ in most areas (PfCRT gene)

Front 21

Malaria Treatment

Chloroquine resistant strains? - _______ with _________?

- Artemesinin derivatives may be superior to quinine (call CDC for _________). These are also used with a second agent. ______ (artemether/lumefantrine) used in Africa
- _________ : BP support, transfusions, correct hypoglycemia. (quinine can increase insulin release). Consider exchange transfusion for patients with cerebral malaria or parasitemia > 5%.

Back 21

P. falciparum:
- Quinine/quinidine (anti-arrhythmic drug) with doxycycline or clindamycin

- Artemesinin derivatives may be superior to quinine (call CDC for artesunate) especially in children and adults. These are also used with a second agent. Co-artem (artemether/lumefantrine) used in Africa

- Supportive care: BP support, transfusions, correct hypoglycemia. (quinine can increase insulin release). Consider exchange transfusion for patients with cerebral malaria or parasitemia > 5%.

Front 22

Malaria: Special issues

Risk in Pregnancy?

_______ ________ treatment (__T) of high risk populations in endemic areas

Back 22

Pregnancy: Increased risk for pregnant women. Placental microvasculature, increased fetal loss; Congenital infections are usually self-limited

Intermittent presumptive treatment (IPT) of high risk populations in endemic areas

Front 23

Malaria Treatment

Other Plasmodium species:
Generally sensitive to chloroquine and Malarone; P. vivax is resistant to CQ in some areas. __________ is used to clear hypnozoites from liver to prevent late relapses

Back 23

Other Plasmodium species:
Generally sensitive to chloroquine and Malarone; P. vivax is resistant to CQ in some areas. Primaquine is used to clear hypnozoites from liver to prevent late relapses

Front 24

Chagas Disease - American Trypanosomiasis

Clinical finding: _______ ________ ______ in Latin America – Romaña’s sign

Diagnosis: Acute Trypanosoma cruzi infection

Back 24

Clinical finding: Unilateral orbital edema in Latin America – Romaña’s sign

Diagnosis: Acute Trypanosoma cruzi infection

Front 25

Trypanosomes

Family of parasites?

Transmitted by?

Characteristic feature of organism?

Back 25

Flagellates (Kinetoplastida)

Transmitted by insects

Have nucleus and kinetoplast (energy power station for flagella)

Flagellum on free edge of undulating membrane

Front 26

T. Cruzi Life Cycle

1. __________ bug takes a blood meal (passes metacyclic trypomastigoes in insect _______, trypomastigotes enter bite wound or mucosal membrane, such as ____________)

2. Penetrate cells at bite site

3. Multiply by __________ at bite site

4. Intracellular _________ (no flagella) transform into _________ (with flagella) and burst out of cells into __________

5. Triatomine bug takes another blood meal

cycle continues

Back 26

1. Tratomine bug (kissing bug) takes a blood meal (passes metacyclic trypomastigoes in feces, trypomastigotes enter bite wound or mucosal membrane, such as conjunctiva)

2. Penetrate cells at bite site

3. Multiply by binary fission (asexual) at bite site

4. Intracellular amastigotes transform into trypomastigotes and burst out of cells into blood stream

5. Triatomine bug takes another blood meal

cycle continues

Front 27

Epidemiology of T. cruzi infection

Host(s)?

Bugs live in cracks in mud and thatch walls and roofs of ______. Improved _______ is decreasing the incidence of Chagas’ disease in Latin America

Back 27

Zoonosis: Small mammals are the reservoir

Bugs live in cracks in mud and thatch walls and roofs of houses. Improved housing is decreasing the incidence of Chagas’ disease in Latin America

Present in triatomes and rodents in USA. However, our bugs do not live in houses, and autochthonous cases are very rare here.

Front 28

Clinical Manifestations of Chagas’ Disease

Acute: Only ___% of infected people have early symptoms
- inflammation at site of inoculation (2 places)
- _ or _ weeks later, fever / malaise / anorexia
- symptoms often resolve (with/without) therapy?

Chronic: __-__%, often after _-_ years
- Heart findings: (3)?
- GI tract – (2)?

Back 28

Acute: Only 30% of infected people have early symptoms
- inflammation at site of inoculation (skin or conjunctiva)
- 2 or 3 weeks later, fever / malaise / anorexia
- symptoms often resolve without therapy

Chronic: 15-40%, often after 10-20 years
- Dilated cardiomyopathy: conduction defects, CHF, thromboembolic disease
- GI tract – Mega-esophagous (aspiration pneumonia), Mega-colon (severe constipation)

Front 29

Clinical Approach to Chagas’ Disease

Diagnosis:?

Therapy:?
for acute disease?
for chronic disease?

Back 29

Diagnosis
- detect trypomastigotes in blood or at the inoculation site
- chronic disease by [serology!], xenodiagnosis, or PCR

Therapy
- nifurtimox or benznidazole improve acute disease symptoms but only cure 50-70% of acutely infected individuals

- no effective therapy for chronic infection

Front 30

Clinical Approach to Chagas’ Disease

Therapy
- ______ or ________ improve acute disease symptoms but only cure 50-70% of acutely infected individuals

- Therapy for chronic infection?

Back 30

Therapy
- nifurtimox or benznidazole improve acute disease symptoms but only cure 50-70% of acutely infected individuals

- no effective therapy for chronic infection

Front 31

Clinical Approach to Chagas’ Disease

What is an emerging threat in the USA?

Back 31

Blood transfusion risk

Front 32

42 year old Mexican man with a hand lesion

with an ulcer with a heaped-up border

Diagnosis?

Back 32

Diagnosis: Cutaneous leishmaniasis

Front 33

Leishmaniasis

Kinetoplastid parasites transmitted by ______ _________ (Phlebotomus, Luzomyia)

At least 19 species (5 old world, 14 new world) cause __ major clinical syndromes: name them

Generally a zoonosis (reservoir ___and _____); human reservoir for some species

Back 33

Kinetoplastid parasites transmitted by dipteran sandflies (Phlebotomus, Luzomyia)

At least 19 species (5 old world, 14 new world) cause 3 major clinical syndromes

Cutaneous, mucocutaneous, and visceral leishmaniasis

Generally a zoonosis (reservoir dogs and rodents); human reservoir for some species

Front 34

Life Cycle of Leishmania


1. ______ bites, trasfers _________ into bloodstream, invades __________ and transforms into non-motile _____________
2. _________ multiplies within the ___________ in the lymph node, spleen, liver, and bone marrow (reticuloendothelial system)

Back 34

Carried by rodents, dogs, and foxes
Transmitted to humans by sandfly
Disease found in S. and central America, Africa, and Mid East

1. Sandlfy bites, trasfers PROmastigote into bloodstream, invades phagocytic cells (macs) and transforms into non-motile AMAStigotes
2. Amastigote multiplies within the phagocytic cells in the lymph node, spleen, liver, and bone marrow (reticuloendothelial system)

Front 35

Epidemiology of Leishmaniasis

90% of all cases of visceral leishmaniasis occur in (countries?)

90% of all cases of cutaneous leishmaniasis occur in which countries?

Back 35

90% of all cases of visceral leishmaniasis occur in Bangladesh, India, Nepal and Sudan

90% of all cases of cutaneous leishmaniasis occur in Afghanistan, Brazil, Iran, Peru, Saudi Arabia and Syria.

Front 36

_______ - Vector of Leishmaniasis

Back 36

Sandfly - Vector of Leishmaniasis

Front 37

Cutaneous Leishmaniasis

Areas of the world?

Onset?

________ papule develops into a ______ that ulcerates with a _____ border

May have _____ lesions, sporotrichoid spread (along ______ vessels)

Resolution? does it leave a scar?

Parenteral, toxic medications: _______ (Sodium stibogluconate) or ______ (liposomal Amphotericin B).
Or you can just ______

Back 37

Latin America, Middle East

Onset weeks after infection

Erythematous papule develops into a nodule that ulcerates with a raised border

May have satellite lesions, sporotrichoid spread (along lymphatic vessels)

Self-healing (months) leaves an atrophic scar

Parenteral, toxic medications: Pentostam (Sodium stibogluconate) or Ambisome (liposomal Amphotericin B).
Or you can just wait.

Front 38

Mucocutaneous Leishmaniasis

Common?

May present _______ after resolution of cutaneous lesions.
- What countries?
- Where does it infect?

- Responsive to therapy?

Back 38

Uncommon (2-3%) late complication of L. braziliensis infection.

May present years after resolution of cutaneous lesions.
- Equador, Bolivia, Brazil
- Soft palate, nose, lips

- Poorly responsive to therapy with Pentostam

Front 39

Visceral Leishmaniasis - Kala Azar

Countries?

Amastigotes spread to ____ cells throughout the body

________ onset of illness with ______ and _________ (TNF mediated)

Marked _______ and _________

Invasion of bone marrow and hypersplenism with (3)

_______ from secondary infection, anemia, hemorrhage

Back 39

India, E. Africa, Brazil

Amastigotes spread to RE cells throughout the body

Subacute onset of illness with fever and weight loss (TNF mediated)

Marked hepatomegaly and splenomegaly

Invasion of bone marrow and hypersplenism with anemia, leukopenia, thrombocytopenia

Death from secondary infection, anemia, hemorrhage

Front 40

Clinical approach to leishmaniasis

Diagnosis

Back 40

Diagnosis
Microscopy (amastigotes in macrophages in biopsies of skin or mucosal lesions; (liver, spleen, bone marrow in kala azar)

Culture and PCR provide species information

Serology: Rapid format, sensitive for kala azar

Front 41

Clinical approach to leishmaniasis

Treatment

Back 41

Therapy
Pentavalent antimony compounds are effective but toxic and difficult to use (i.v., 21 days)

Amphotericin or Ambisome

Miltefosine, the first oral therapy for Kala Azar

Itraconazole and paromomycin have activity in cutaneous leishmaniasis

Front 42

29 year old man with HIV presents with subacute onset of headache, confusion, fever
LP, CSF is normal
MRI shows multiple ring enhancing lesions with edema (T2 weighted image)

Toxo antibody test positive
CSF PCR positive for

Back 42

Toxoplasma gondii

Front 43

Toxoplasma gondii

Family of parasites?

Global distribution?

_____ are definitive hosts; mice and a wide range of mammals (lamb, cattle) are intermediate hosts.

______ are accidental intermediate hosts

Directly transmitted by _____ from ____ _______ or by ingestion of cysts in ________ of intermediate hosts

Back 43

Sporozoan parasite with world-wide distribution

Cats are definitive hosts; mice and a wide range of mammals (lamb, cattle) are intermediate hosts.

Humans are accidental intermediate hosts

Directly transmitted by oocysts from cat feces or by ingestion of cysts in muscle (undercooked meat) of intermediate hosts

Front 44

Toxoplasma Gondii Sources

Undergoes sexual reproduction in ____ (host) and is excreted in the ______ as the infectious cyst

Humans are infected by ingestion of cysts in __________ or food contaminated with household _____ ________

Back 44

Undergoes sexual reproduction in cat and is excreted in the feces as the infectious cyst

Humans are infected by ingestion of cysts in undercooked meats (raw pork) or food contaminated with household cat feces

Front 45

Toxoplamsa gondii

Treated with _________ and ________ with folinic acid

Back 45

Treated with pyramethamine and sulfadiazine with folinic acid

Front 46

Toxoplasma gondii

Symptoms?
Can cause a _________ syndrome in healthy people

________ infection risk 40% when women have primary infections early in pregnancy (significant risk of 3 manifestations).

Can cause severe disease in _________ ________ (cardiomyopathy, pneumonia, encephalitis)

Patients with advanced _____ present with CNS toxo (necrotizing brain lesions by MRI).

Most patients have antibodies to Toxo. This is usually ________ of latent infection.

Back 46

Infections are often asymptomatic. Toxo can cause a mononucleosis like syndrome in healthy people

Congenital infection risk 40% when women have primary infections early in pregnancy (significant risk of brain damage, blindness, fetal death).

Spiramycin.

Can cause severe disease in immunocompromised patients (cardiomyopathy, pneumonia, encephalitis)

Patients with advanced AIDS present with CNS toxo (necrotizing brain lesions by MRI).

Most patients have antibodies to Toxo. This is usually reactivation of latent infection.

Front 47

7 year old child has bloody diarrhea

Diagnostic study: Microscopy of stool sample showed Entamoeba trophozoites. Single nucleus, center is nucleolus - dissolves red cell and damages white cells

Diagnosis?

Back 47

Diagnosis: amebic dysentery

Front 48

Life Cycle of Entamoeba histolytica

Back 48

1. cysts and tophozites passed in feces

2. Mature cysts ingested

Cycle repeats

Front 49

Clinical Summary--Amebiasis

_________ --bloody small volume stools, +/- fever. Colon ulcers. Can be complicated by intestinal perforation, hemmorhage.

____________– R lobe, male predominance, often no history dysentery
- Symptoms include?
- Complications?
- Fatal?

Back 49

Amebic dysentery--bloody small volume stools, +/- fever. Colon ulcers. Can be complicated by intestinal perforation, hemmorhage.

Amebic liver abscess– R lobe, male predominance, often no history dysentery

- Symptoms include fever, RUQ pain, hepatic tenderness, shoulder pain
- Complications: Perforation into peritoneum, pleural space, pericardium; Death !

Front 50

Clinical approach to Amebiasis

Diagnosis?

Treatment?

Back 50

Diagnosis
- amebic dysentery--stool exam; microscopy / ELISA
- Amebic liver abscess: serology/radiology (ultrasound or CT)

Treatment
- Metronidazole, nitazoxanide
- Luminal agent such as iodoquinol or tetracycline (to prevent relapse)

Front 51

23 y/o medical student with a history of diarrhea for 2 weeks, flatulence, and weight loss after returning from a rotation in Haiti

Diagnosis

Back 51

Giardia lamblia cysts in stool

Front 52

Epidemiology of Giardiasis

Major cause of _________ _________in U.S.A.

Can be contracted in ______
Transmission?

Many, especially _______, are asymptomatic carriers

_______ and _________ are also at increased risk (beavers, dogs)

Back 52

Major cause of waterborne diarrhea in U.S.A.

Can be contracted in daycare
Fecal oral / person to person transmission

Many, especially children, are asymptomatic carriers

Campers and travelers are also at increased risk (beavers, dogs)

Front 53

Giardia Lamblia

Do they survive in the environment?

Metabolism?

Mitochondria?

Active nuclei? how many in trophozoites? how many in cysts?

Replication?

Back 53

No

Aerotolerant anaerobes

Ventral disc

No mitochondria

Trophs have 2 transcriptionally active nuclei; 4 nuclei in cysts

Binary fission

Front 54

Attack rate and symptoms

If 100 people ingest Giardia cysts:
- approximately ___ will not develop infections

- approximately __-__ will be asymptomatic cyst passers

- about __ will develop self-limited, symptomatic watery diarrhea

- about __ will develop chronic diarrhea with malabsorption, weight loss, flatulence.

Back 54

If 100 people ingest Giardia cysts:
- approximately 50 will not develop infections

- approximately 10-15 will be asymptomatic cyst passers

- about 30 will develop self-limited, symptomatic watery diarrhea

- about 10 will develop chronic diarrhea with malabsorption, weight loss, flatulence.

Front 55

Clinical approach to Giardiasis

Diagnosis?

Treatment?

Post-giardiasis, one can develop __________ intolerance

Back 55

Diagnosis
Stool microscopy and antigen detection

Therapy
Metronidazole (drug resistant Giardia may be becoming more frequent); nitazoxanide
Post-giardiasis malabsorption, lactose intolerance

Front 56

Nitazoxanide

Used to treat?
Chemically related to?

Back 56

Approved 2002 for treatment of Giardia and Cryptosporidium
- Chemically related to metronidazole

Active against a variety of
Protozoans: E. histolytica, Cyclospora
Helminths: Ascaris, Fasciola, ? Echinococcus
Bacteria: H. pylori, C. difficile
Oral, safe

Front 57

27 y/o vet assistant
with 10 days of watery
diarrhea, malaise, anorexia, and low grade fever

Acid fast, 4 to 5 microns

Intracellular, just under the membrane

Back 57

Cryptosporidium parvum

Front 58

Cryptosporidium parvum

What kind of parasite?

Intra/extracellular parasite?

Characterize diarrhea:

_____ diarrhea in children in developing countries

______, ________ diarrhea in AIDS patients (several liters/day)

Back 58

Sporozoan / coccidian parasite

Intracellular

Secretory diarrhea; self-limited in immunocompetent hosts.

Chronic diarrhea in children in developing countries

Severe, chronic diarrhea in AIDS patients (several liters/day)

Front 59

Cryptosporidiosis

Immunocompetent
- Incubation period __days , mean duration ___ days

Immunocompromised (CD_ deficiency)
- severe _____, “______-like” diarrhea (> 10L/day).
- Can cause ______ __________in AIDS pts
- Therapy?
- Some patients improve with paromomycin or nitazoxanide

Back 59

Immunocompetent
- 30 oocysts can cause disease
- Incubation period 9d, mean duration 12 days
- Asymptomatic vs watery diarrhea with malaise, anorexia, low grade fever, nausea

Immunocompromised (CD4 deficiency)
- severe watery, “cholera-like” diarrhea (> 10L/day).
- Can cause acalculus cholecystitis in AIDS pts
- No consistently effective therapy
- Some patients improve with paromomycin or nitazoxanide

Front 60

24 y/o female with yellow vaginal discharge, itching and dysuria

Wet mount--
motile organism
with flagella

Back 60

Trichomonas vaginalis

Front 61

Trichomoniasis

Symptoms?

Describe cyst stage.
Treatment?
Describe

Back 61

Vaginal discharge (yellow, may have bubbles)

Cervicitis (strawberry cervix), dysuria, dyspareunia

Men--rarely have symptoms (dysuria)

Wet mount, motile pear-shaped cells
Release cytotoxic acid hydrolases

Sexually-transmitted disease: No cyst stage

Treatment—metronidazole for patient and partner