Microbiology Flashcards
Malaria
Vector
Female anopheline mosquito
Malaria
Lifecycle
-
Sporozoites
- Transmitted form
- Innoculated from mosquito saliva
- Rapidly cleared from blood in 15-30 minutes
-
Sporozoites ⇒ merozoites in hepatocytes
- Asexual replication
- Parasites contained within a Schizont
- Non-pathogentic infection
- Merozoites released from Schizont ⇒ RBC
-
Merozoite ⇒ trophozoites (ring stage) in RBC
- Asexual replication inside RBC ⇒ release
- Responsible for pathology
- Asexual replication inside RBC ⇒ release
-
Merozoite ⇒ gametocyte
- Sexual stage
- Picked up by mosquitos that feeds
- Gametocytes mature into gametes in mosquito gut
- Fertilization ⇒ zygote ⇒ motile ookinete ⇒ penetrates gut ⇒ sporozoites ⇒ salivary glands
Plasmodium vivax
and
Plasmodium ovale
-
Tertian fever patterns
- Sx every 3 days
-
Latent state
- Long term persistance in the liver
- Potential for reactivation
- Prefers immature erythrocytes or reticulocytes
- Lower parasitemia
Plasmodium malariae
-
Quartan fever pattern
- Sx every 4 days
- Frequently becomes synchronous in vivo
- Periodic release of parasites with fever
- Low parasitemia
- Prefers senescent RBCs
- No latent phase
P. falciparum
- Asynchronous replication of blood-stage
- Irregular fever pattern
- Developmental period of 14 days
- Characteristic crescent shape
- Trophozoite and schizont forms occur in visceral capillaries ⇒ sequestration
- Infects all RBCs ⇒ high parasitemia
- Causes cerebral malaria
- Reponsible for the most deaths
Malaria
Host Cell Invasion
- Active process of the parasite
- Interactions between parasite surface molecules and host receptors
- Contents of apical organelles responsible
Malaria
Lifecycle Comparison
Malaria
Fever Generation
- Usually paroxysmal except for P. falciparum
- Coincides with parasite release from RBCs
- Parasite products induce cytokine production
- GPI anchors
-
Hemozoin
- Malarial pigment produced from digestion of heme
- Elevated TNF-α and IL-1
Malaria
Infectious Determinants
-
Host factors
-
Sickle cell trait & other hemoglobinopathies
- Heterozygosity confirs resistance
-
Duffy blood group system
- Duffy ⊖ cells resistant to P. vivax
-
Sickle cell trait & other hemoglobinopathies
-
Parasite factors
- Multiplication rate
- 1% parasitemia = 5x1010 in blood
- Parasite “toxins”
-
Cytoadherence-dependent tissue distribution
- Cerebral sequestration
- Placental sequestration
- Multiplication rate
Cytoadherence
- Specific receptor-ligand interactions
- Form knob-like structions on surface of RBCs ⇒ rosettes
- Contain late stage trophozoites and schizonts (merozoites inside)
-
Knob-associated parasite proteins
- PfEMP-1, rifin, stevor, clag
- Host cell receptors on endothelium, placenta, and uninfected RBCs
Malaria
Diagnosis
- History and clinical symptoms
-
Peripheral blood smears
- Thick smears ⇒ parasite detection
- Thin smears ⇒ species ID
-
P. falciparum ⇒ only see ring stages and banana shaped gametocytes in blood
- Due to sequestration of mature stages
-
Detection of circulating parasite Ag or nucleic acid
- HRP2 ⇒ secreted Ag
- Lactate dehydrogenase
- Dipstick and PCR
Uncomplicated Malaria
- Often cyclic high fever and chills
- Malaise
- Myalgia
- Dizziness
- HA
- Weakness
- Nausea
- Diarrhea
Recurrent Malarial Infections
-
Relapse from dormant liver stage ⇒ hypnozoites
- P. vivax and P. ovale only
- May occur within months to years after primary infection
-
Reinfection, multiple infections
- Frequent w/ P. falciparum
- Occurs w/ P. vivax
- Immunity is region specific
Malaria
Recrudescence
- Occurs esp. w/ P. falciparum
- Due to:
- Partially effective host immune response
- Incomplete treatment and development of resistance
Severe Malaria
P. vivax
- Severe anemia
- Splenomegaly
- Splenic rupture
Severe Malaria
P. malariae
Immune complex glomerulonephritis associated with persistent low level of parasitemia
Severe Malaria
P. falciparum
- Splenomegaly
- Lactic acidosis
- Hypoglycemia
- Severe anemia
- Cerebral malaria
- Acute renal failure
- Pulmonary edema
- Hyperparasitemia
- Multi-organ failure
Cerebral Malaria
- Severe complication of P. falciparum
- Affects children 3-5 y/o
- Parasitized RBC cytoadhere to endothelium of brain microvasculature
- pRBCs form rosettes with uninfected RBCs
-
Pathogenesis
-
Ischemia/hypoxia
- Occlude capillaries ⇒ impair flow of blood, oxygen, nutrients to brain
-
Inflammation
- Inflammatory response ⇒ ↑ vascular permeability ⇒ tissue damage
-
Ischemia/hypoxia
-
Symptoms
- Impaired consciousness
- Cerebral dysfunction
- Coma
- Death ⇒ mortality rate 15-30% w/ tx
Severe Malarial
Anemia
- Criteria
- Hb < 7 g/dL or Hct < 20%
- Presence of any malarial parasitemia
- Almost always d/t P. falciparum
- Mainly affects children < 1 y/o in sub-Saharan Africa
Malaria
Immunity
- Acquired very slowly
-
Transient
- Wanes rapidly if person leaves the area
- Specific to region and strains
- Likely involves both Ab and cell-mediated immunity but poorly understood
Malaria
Vaccines
Still in development
- Sporozoites
- Circumsporozoite surface protein target
- Being tested
- Circumsporozoite surface protein target
- Erythrocytic stage
- Major merozoite surface protein
- Rhoptry proteins
- Cytoadherence molecules
- Gametocyte and zygotes
- Transmission blocking immunity
Malaria
“Anti-disease” Immunity
- People in endemic areas w/ persistent parasitemia may appear asymptomatic
- Sterilizing immunity may not be possible
- If possible, may be short lived and cause ↑ severity w/ subsequent infection
Hemoflagellates
- Flagellated, insect-transmitted protozoa
- Infects blood and tissues
- Have kinetoplasts ⇒ specialized mitochondria at base of flagella
-
Contains maxicircle and minicircle DNA
- Drug target and strain ID
-
Contains maxicircle and minicircle DNA
-
Leishmania and Trypanosoma
- Two major genera that cause human & domestic animal disease
Leishmania
Vector and Reservoirs
Vector ⇒ sandfly
(Phlebotomus and Lutzomyia)
Reservoirs ⇒ rodents, dogs, foxes, small mammals
Animal-vector-human cycle
Human-vector-human cycle
Leishmania
Lifecycle
- Extracellular promastigotes in sandfly vector
- Differentiate in salivary glands to metacyclic promastigotes ⇒ infectious form
-
Metacyclic promastigotes innoculated by sandfly during blood meal
- Motile and resistant to complement
- Metacyclic promastigotes invade macrophages
- Differentiate into amastigote form
-
Amastigotes multiply within phagolysosome of Mφ
- Cell lysis releases parasite for further spread
- Amastigotes transferred to sandfly when infected host bitten
- Differentiates back into promastigotes
Cutaneous Leishmaniasis
Organisms
Caused by 4 geographically specific species:
-
L. mexicana & L. braziliensis
- South and central America
- Can become visceral
-
L. major & L. tropica
- Asia, Africa, Mediterreanan, Middle East, Russia
- Typically remains cutaneous
Cutaneous Leishmaniasis
Pathogenesis
-
Red papule develops @ site of bite after 1 wk - 2 months
- Secondary bacterial infections problematic
- Becomes hard and crusted
-
Usually self-limiting but may persist for months to years
- Resolution associated with protective immunity
Diffuse Cutaneous Leishmaniasis
- Occurs with ineffective immune responses
- Esp. cell-mediated
- See massive, disseminated nodular skin lesions
- Resembles leprosy