Week 5: Parasitology Part I Flashcards
learning objectives
For the parasitic organisms identify
- the geographic region of risk
- mode of transmission
- Life cycle
- Clinical symptoms
- Clinical complications of infection
- Laboratory diagnostic tests
- Appropriate treatment
- side effects of treatment
Case 1


Describe the distribution of Malaria

Question

Malaria is transmitted by the bite of the female Anopheles mosquito
Describe the mechanism of transmission of Malaria
- Malaria is transmitted by the bite of the female Anopheles Mosquito
- Sporozoites in the mosquito’s saliva are injected into the human bloodstream
- Vector-borne infection

Question

Merozoites
Describe the life-cycle of Malaria

Malaria is caused by?
Plasmodium species
Plasmodium characteristics
- Obligate intracellular protozoa
- Single-celled Eukaryotic
- The zygote is the only diploid stage in Plasmodium life-cycle
Tropism of Plasmodium
Blood protozoa with hepatic stage
Diploid stages of Plasmodium
The zygote is the only diploid stage in life-cycle
Definitive host of Plasmodium
Mosquito (sexual reproduction in the gut of the mosquito)
Intermediate host of Plasmodium
Human
(Asexual reproduction in liver and blood stages)
Plasmodium type and location of reproduction in definitive host
Mosquito (Sexual reproduction in the gut of the mosquito)
Plasmodium type and location of reproduction in intermediate host
Human (Asexual reproduction in liver and blood stages)
Factors associated with the pathogenicity of Plasmodium
4 listed
- Penetration of anatomic barrier via mosquito bite
- Avoidance of immune detection
- Antigenic variation, molecular mimicry, intracellular location, suppression of parasite-specific B & T-cell responses
- Replication in the host
- Endotoxin in P. falciparum
How do Plasmodium avoid immune detection
- Antigenic variation
- molecular mimicry
- Intracellular location
- suppression of parasite-specific B & T-cell responses
Question

D. Thick & thin peripheral blood smear
Thick and thin peripheral blood smear

Clinical symptoms of Malaria are caused by?
blood-stage parasites and the host immune response
Pathophysiology of Malaria infection
- RBC destruction
- Intravascular hemolysis -> severe microcytic, hypochromic anemia
- Cytokine release
- Schizont rupture -> macrophage stimulated to release TNF and IL-1 cytokines
- Sequestration of infected RBCs
- Adhere to capillary endothelial cells -> impair blood flow
- Splenomegaly
- Biochemical & electrolyte changes
- Hypoglycemia due to parasite glucose consumption, decreased hepatic gluconeogenesis, quinine causing pancreatic insulin release
- Metabolic acidosis from microvascular ischemia, parasite lactate production
- Hyponatremia

Pathophysiology of Malaria as a result of RBC destruction
Intravascular hemolysis -> severe microcytic hypochromic anemia
Pathophysiology of Malaria as a result of cytokine release
Schizont rupture -> macrophage stimulated to release TNF and IL-1 (cytokines)
Pathophysiology of Malaria as a result of sequestration of infected RBCs
- adhere to capillary endothelial cells -> impair blood flow
- Splenomegaly
Pathophysiology of Malaria as a result of biochemical & electrolyte changes
- Hypoglycemia due to parasite glucose consumption, decreased hepatic gluconeogenesis, quinine causing pancreatic insulin release
- Metabolic acidosis from microvascular ischemia, parasite lactate production
- Hyponatremia (SIADH)
What is SIADH
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a condition in which the body makes too much antidiuretic hormone (ADH). … ADH is a substance produced naturally in an area of the brain called the hypothalamus. It is then released by the pituitary gland at the base of the brain.
Clinical findings & complications of Malaria
- General
- Periodic every 48 to 72 hours (q48 or g72 hr) paroxysmal fever, chills and rigors caused by immune reaction from lysis of RBCs
- Muscle aches, malaise, nausea, vomiting
- Cerebral Malaria
- Symptoms: impaired consciousness, delirium, seizures
- Capillary plugging due to accumulation of malarial pigment and P. falciparum schizont sequestration
- Mortality 15-25%
- Blackwater fever
- Intravascular hemolysis with rapid destruction of RBC infected with P. falciparum causing hemoglobinuria and acute renal failure

List of Plasmodium species
- P. falciparum
- P. malariae
- P. ovale
- P. vivax
P. falciparum region
Global
P. falciparum incubation period
short 7-10 days
P. falciparum RBC infected
All
P. falciparum latent liver phase
No
P. falciparum Fever
Malignant tertian
*Most severe presentation*
P. malariae region
- Africa
- Haiti
- DR
P. malariae incubation period
Long 18-40 days
P. malariae RBC infected
old
P. malariae latent liver phase
No
P. malariae fever
Quartan
P. ovale region
- Africa
- Asia
- SA
P. ovale incubation period
10-17 days
P. ovale RBC infected
Young
P. ovale latent liver phase
Yes
P. ovale fever
Benign tertian
P. vivax region
Global; NOT Africa
P. vivax incubation period
10-17 days
P. vivax RBC infected
- Young
- Duffy Ag
P. vivax latent liver phase
Yes
P. vivax fever
Benign tertian
Question

E. All of the above
because they all cause chronic low-grade anemia so there are less cells for the plasmodium to infect and reproduce in
Treatment of Malaria
- Blood schizonticide
- Tissue schizonticide
Blood schizonticides kill Plasmodium in what stage?
Trophozoite in RBC
Tissue schizonticide kill Plasmodium in what stage
Dormant hypnozoites in the liver (prevents relapse of OVALE and VIVAX)
Blood schizonticides
- Chloroquine
- Quinine
- Mefloquine
- Artemesins
- Atovaquone-proguanil
Tissue schizonticides
- Primaquine
Quinine indications
Treatment for severe malaria
Quinine MOA
- facilitates the aggregation of cytotoxic heme. Free cytotoxic heme accumulates in the parasites, causing their deaths.
- (toxic heme buildup and cell lysis)
Quinine side-effects
- arrhythmia
- Hemolysis in G6PD deficiency
- Cinchonism
Chloroquine indications
Many areas with resistant P. falcuparum and P. vivax
Chloroquine MOA
Blocks detox of heme buildup from parasite blood meal -> disrupts parasite membrane function -> lysis of parasite
Chloroquine side effects
- GI toxicity
- itching
- retinal toxicity
Examples of Artemesinin group antimalarials
Artesunate
Artemesinin group indications
- first-line treatment for P. falciparum in combination with another blood schizonticide
Artemesinin group MOA
Inhibits P. falciparum EXP1 membrane glutathione S-transferase
Artemesinin group side effects
no significant side effects
Mefloquine indications
Second-line for P. falciparum and P. vivax
Mefloquine MOA
inhibition of heme polymerase
Mefloquine side effects
neuropsych
Atovaquone-Proguanil MOA
Inhibits parasitic electron transport chain
Atovaquone-Proguanil Side effects
GI toxicity
Blood schizonticides overview

Question

American trypanosomiasis
American trypanosomiasis AKA
Chagas Disease
How is Chagas Disease transmitted?
Bite from reduviid bug (Triatomines) which transmits typomastigote
Chagas Disease Region
Endemic in Mexico, Central America and South America
What is Trypanosoma cruzi?
Flagellated protozoa
Describe the life-cycle of Trypanosoma cruzi
- Bugs bite humans and infect humans by defecating on humans and the wound is rubbed causing infection
- In humans, trypomastigotes lose flagellum and undulating membrane and become smaller oval intracellular amastigotes which multiply via binary fission and transform into trypomastigotes and burst out of the cell into the blood
- Triatomine bug takes a blood meal from infected human and epimastigotes use asexual reproduction and can infect another human via bite and defacation

Trpanosoma cruzi vector
Reduviid bug
Describe Trypanosoma cruzi stage in reduviid bug
metacytic trypomastigotes
Describe thick and thin smear
- thin smear - see the red cells and see the organism in its phase that is inside RBCs
- thick smear - to catch the gametocytes
- Get 3 thick and thin smears because this test is 100% operator dependent

Describe Trypanosoma cruzi stage in humans
in humans
trypomatigotes in blood and Amastigotes in tissue
Reduviid bug AKA
Kissing bug
Definitive host of Trypansoma cruzi
wild-animal reservoir
Signs & symptoms of Acute Chagas Disease
- Chagoma at the inoculation site
- Fever, chills, malaise, myalgias, lymphadenopathy
- Rarely: arrhythmia, meningoencephalitis
- Romaña’s Sign

Prognosis of Chagas disease
Most recover & then remain in asymptomatic indeterminate phase w/ persistent low-level parasitemia unless immunosuppressed then chronic Chagas Disease
Signs & symptoms of Chronic Chagas Disease
- 20-30% of people infected progress to chronic disease with significant manifestations
- Destruction of nerve cells (Auerbach plexus)
- Dilated cardiomyopathy
- Megacolon
- Megaesophagus
Diagnosis of Acute Chagas Disease
Peripheral blood smear, culture or xenodiagnosis
Diagnosis of Chronic Chagas Disease
- Serology: antibody titer
- Biopsy of infected organ
- Peripheral blood-smear
- Xenodiagnosis
Acute Chagas disease treatment
Drugs available are not FDA approved and need to be obtained with special permission from the CDC
(Benznidazole, Nifurtimox)
Chronic Chagas Disease Treatment
Drugs available are not FDA approved and need to be obtained with special permission from the CDC
(Benznidazole, Nifurtimox)
When to treat Acute Chagas Disease?
All acute and congenital cases should be treated
When to treat Chronic Chagas Disease?
- Only immunosuppressed patients and children
- Symptomatic treatment of GI and cardiac issues
Question

D. Tsetse fly
Vector of African Sleeping Sickness
Tsetse fly
Reduviid bug bite pain level
painful
Tsetse fly bite pain level
painful
African Sleeping Sickness pathogen
Trypanosoma brucei
Describe the life-cycle of Trypanosoma brucei
- Tsetse flys take a blood meal from infected animal or human, trypomastigotes perform Asexual reproduction in Tsetse fly.
- Tsetse fly bites human and trypomastigotes enters bloodstream and does asexual reproduction in body fluids (blood, lymph and spinal fluid) and are not intracellular
- Tsetse fly bites infected human and trypomastigotes continue infection
Infective stage of Trypanosoma brucei
trypomastigotes injected into human by Tsetse fly
Diagnostic stage of Trypanosoma brucei
Trypomastigotes in human bloodstream
Trypanosoma brucei causes
African Sleeping Sickness
Trypanosoma brucei type
- Flagellated blood protozoa
Trypanosoma brucei vector
Tsetse fly
Trypanosoma brucei reservoirs
Humans and game
African Sleeping sickness diagnosis
Trypanosoma brucei trypomastigote in blood smear
Trypanosoma brucei rhodesiense region
East Africa
Trypanosoma brucei gambiense region
West Africa
Signs & symptoms of African Sleeping sickness
Days to weeks after infection
- Recurring fever (due to antigenic variation), headache and joint pain
Several months after infection
- Parasitemia -> fever, diffuse lymphadenopathy, confusion, numbness and trouble sleeping
Months to years later
- Parasites invade the CNS causing symptoms: headache, somnolence, confusion and coma
Question

C. Leishmania braziliensis
Describe Leishmania life-cycle
- Sandfly takes a blood meal from infected human or animal and ingests infected macrophages with amastigotes
- amastigotes transform into promastigote stage in midgut of Sand fly and do asexual reproduction
- Sandfly takes a blood meal from human and promastigotes get phagocytosed by human macrophages
- Promastigotes transform into amastigotes inside macrophages
- Amastigotes multiply by binary fission invade other cells

Leishmaniasis pathogen
- Leishmania donovani (old world/Eastern hemisphere)
- Leishmania brasiliensis (New world/Western hemisphere)
Leishmania donovani or brasiliensis type
Flagellated blood protozoa
Vector of Leishmania
Phlebotomine sand flies
Leishmania reservoir
- Rodents
- dogs
- infected humans
Leishmania donvani causes
Visceral Leishmaniasis
Leishmania brasiliensis causes
Mucosal Leishmaniasis
Signs & Symptoms of Mucosal Leishmaniasis
Cutaneous Leishmaniasis with dissemination to naso-oropharyngeal mucosa (nose, mouth, nasal septum)
Signs & Symptoms of Visceral Leishmaniasis
- Fever
- HSM
- Pancytopenia
Visceral Leishmaniasis AKA
Kalazar
Photos of Leishmaniasis

Diagnosis of Cutaneous Leishmania
Skin biopsy for histology > culture or PCR
Diagnosis of Visceral Leishmaniasis
Bone marrow or spleen aspirate for:
- Smear: macrophages with intracellular amastigotes
- Culture (rarely used)
- PCR
- Serology
Ampho
- Amphotericin B
- Miltefosine
Treatment of Visceral Leishmaniasis
- Amphotericin B
- Miltefosine
Question

D. Toxoplasma gondii
What is Toxoplasma gondii?
Tissue protozoa
Describe the life-cycle of Toxoplasma gondii
- Organisms develop in the intestinal cells of cat & during extraintestinal cycle with passage to the tissue via the blood stream
- Organisms from intestinal cycle are passed in cat feces and mature into infective cysts within 3-4 days in the environment
- Oocysts (containing sporozoites) are ingested by humans (meat, cat feces) and produce acute and chronic infection

Question

A. Cat
Plasmodium species clinical disease
Malaria
Plasmodium species vector
Female anopheles mosquito
Plasmodium species diagnosis of acute disease
- peripheral thick and thin smear (in febrile phase or will miss because RBCs are not rupturing when afebrile)
- Trophozoite in RBCs
Trypanosoma cruzi clinical disease
Chagas Disease
Trypanosoma cruzi vector
Reduviid bug
Trypanosoma cruzi diagnosis of acute disease
- Peripheral smear
- trypomastigote
Trypanosoma brucei clinical disease
African Sleeping Sickness
Trypanosoma brucei vector
Tsetse fly
Trypanosoma brucei diagnosis of acute disease
- Peripheral smear
- Trypomastigote
Leishmania donovani clinical disease
Visceral leishmaniasis (Kala-Azar)
Leishmania donovani vector
Sandfly
Leishmania donovani diagnosis of acute disease
- Peripheral smear
- Amastigotes in macrophages
Leishmania brasiliensis clinical disease
Mucosal leishmaniasis
Leishmania brasiliensis vector
Sandfly
Leishmania brasiliensis diagnosis for acute disease
- Biopsy for histology
- Amastigotes
Toxoplasma gondii clinical disease
Toxoplasmosis;
Acute: mono
Reactivation: CNS
Toxoplasma gondii vector
- none
- Oral-fecal contamination
Toxoplasma gondii Diagnosis of acute disease
Serology