Unit 2 - Blood Borne Parasites

Question 1

what are the 5 blood borne parasites and where they are?

Answer 1

1. Malaria - Africa
2. Babesia - CNY
3. Trypanosomes - Mexico, now in southern CA and AZ
4. Leishmania - soldiers returning overseas
5. Filarial infections - South America, Africa, and South Asia

Question 2

who is the intermediate host in most parasitic agents? where does sexual reproduction occur?

Answer 2

man is the intermediate host, with sexual reproduction occurring in vector associated with transmission of the agent

Question 3

what is the primary factor contributing to the resurgence of malaria?

Answer 3

appearance of drug-resistant strains of the parasite

Question 4

why is Africa the most affected country by malaria?

Answer 4

1. very efficient mosquito (Anopheles gambiae complex) is responsible for high transmission
2. predominant parasite is P. falciparum (most likely to cause severe malaria and death)
3. local weather conditions allow transmission to occur year-round
4. scarce resources and socio-economic instability have hindered efficient malaria control activities

Question 5

what are factors of more intense transmission?

Answer 5

places where the mosquito lifespan is longer and prefers to bite humans over animals

Question 6

what are links between genetics and immunological protection?

Answer 6

1. absence of Duffy Ag in RBC predominates in West Africans and derived populations, preventing P. vivax malaria
2. patients with hereditary elliptocytosis (glycophorin C deficiency = Leach phenotype) and sickle cell carriers are less susceptible to infection
3. certain thalassemias or G6PD deficiency offer protection
4. untreated infective patients eventually develop curative immunity against parasitizing strain

Question 7

why does hemolytic anemia occur in malaria?

Answer 7

• rupture of parasitized erythrocytes
• removal of parasitized and unparasitized RBC by spleen
• capillary sequestration
• bone marrow dyserythropoiesis

Question 8

what is the time from initial malaria infection until symptoms appear (incubation period) for the different species?

Answer 8

falciparum - 9-14 days
vivax/ovale - 12-18 days
malariae - 18-40 days
knowlesi - 11-12 days

but some can be within 7 days to as long as 8-10 months

Question 9

describe the malaria paroxysm

Answer 9

prodromal symptoms followed by febrile attacks

• cyclic periodicities of 48 hours (vivax/ovale/falciparum) or 72 hours (malariae)
• cold stage: feeling of intense cold with vigorous shivering due to RBC bursting (15-50 minutes)
• hot stage: intense heat and headache due to cytokine response/inflammatory response (2-6 hours)
• sweating stage: exhaustion and weakness cause sleepiness, and upon waking are asymptomatic until next parocysm

Question 10

explain malaria recrudescence

Answer 10

parasitemia falls below detectable levels and then later increases to a detectable parasitemia

Question 11

explain malaria relapse

Answer 11

sporozoites invade hepatocytes, in which they develop into schizonts and may not be observed in the circulation and the individual may be asymptomatic

• after a period of time, the hepatocyte ruptures
• each infected hepatocyte liberates 10-30K merozoites that invade circulating RBC
• growth and development of parasites in RBC result in subsequent waves of merozoite invasion

Question 12

what are most deaths directly attributable to malaria caused by?

Answer 12

severe manifestations of P. falciparum

-cerebral malaria, severe anemia, respiratory failure, renal failure, and severe malaria of pregnancy

Question 13

what is an important feature of P. falciparum pathogenesis? the most common metabolic complications?

Answer 13

ability to sequester in deep venous microvasculature

• metabolic (lactic) acidosis (due to reduced O2 delivery; primary cause of death)
• pulmonary edema and respiratory distress
• hypoglycemia (cause coma and convulsion, with significant morbidity)
• anemia (excess removal of RBC)

Question 14

what is the important difference between P. falciparum and other human malarias?

Answer 14

the way P. falciparum modifies surface of RBCs so that asexual parasites and gametoccytes can adhere to the endothelium and asexual parasites can adhere to placenta

• due to PfEMP-1 (P. falciparum erythrocyte membrane protein)
• CD36 is the major receptor for PfEMP-1

Question 15

describe cerebral malaria?

Answer 15

most severe neurological complication of infection with P. falciparum

• intense sequestration of parasites (infected erythrocytes) in cerebral microvasculature, often accompanied by hemorrhages, perivascular leukocyte infiltrates, and immunohistochemical evidence for endothelial cell damage, causing breakdown of BBB and apoptosis of endothelial cells –> damage and death
• sequestration of parasites stimulates local production of inflammatory cytokines and mediators causing varying degrees of functional obstruction that leads to reduced local delivery of O2 and glucose

Question 16

explain malaria of pregnancy

Answer 16

maternal morbidity and mortality, intrauterine growth retardation, premature delivery, low birth weight, increased newborn mortality
-mature parasites accumulate in monocytes in placenta due to interaction with syncytiotrophoblastic chondroitin sulfate A(CSA), hyaluronic acid, and Igs

Question 17

what are the only 2 receptors that provide stable stationary adherence of parasitized RBC to PfEMP-1

Answer 17

1. CD36 - major sequestration receptor on microvascular endothelial cells
2. condroitin sulphate A (CSA) - receptor on placental intervillous space

Question 18

rapid diagnostic test for malaria?

Answer 18

only US brand is Binax

• detects 1 Ag specific for P. falciparum, and another found in all 4 human species
• however, cannot tell if double infection

Question 19

why do P. vivax and ovale have low mortality rates?

Answer 19

strongly favor reticulocytes (as opposed to all RBC like falciparum, or older RBC like malariae)

• don’t exhibit sequestration
• parasitemia <1%

infections with P. vivax and ovale are considered similar to each other clinically

Question 20

describe P. malariae?

Answer 20

most difficult to diagnose b/c doesn’t have the same intensity as the others

• infects older RBC so parasitemia is low (<2%)
• longest incubation (40 days), but parasites may be found several days (up to a week) before symptoms
• patients present with proteinuria or nephrotic syndrome
• ring forms look like a large signet ring, and infected RBCs are normal or smaller
• merozoites form daisy head arrangement

Question 21

what is important to know about P. knowlesi?

Answer 21

primate malaria parasite in SE Asia

• emerging infection reported in humans in 1965
• accounts for 70% of malaria cases in SE Asia where it’s mostly found
• replicates and completes blood stage in 24 hour cycles, so high loads of parasite in short periods of time
• similar to P. malariae and unlikely to be diagnosed correctly other than using molecular detection assays

Question 22

clinical disease of babesia in NE US VS MW and W US

Answer 22

NE: similar picture of P. vivax
MW/W: fulminate, febrile, hemolytic disease

both caused predominantly by Babesia microti (although additional species in MW)

• only ixodid ticks identified as vectors
• severity of infections varies (maybe mild or asymptomatic, or severe)

Question 23

what are the disease manifestations of human babesiosis caused by?

Answer 23

asexual reproductive stage of organsim in erythrocyte of host and subsequent lysis of host cells
–very broad clinical spectrum probably directly reflective of level of parasitemia in blood

Question 24

describe anaplasmosis?

Answer 24

first symptoms of anaplasmosis typically start within 1-2 weeks after bite of infected tick

• fever, headache, muscle pain, malaise, chills, nausea/abdominal pain, cough, confusion
• can be fatal if not treated correctly, even in previously healthy people
• -difficulty breathing, hemorrhage, renal failure, neurological problems

Question 25

what are the causative agents of African sleeping sickness?

Answer 25

2 out of 60 species are pathogenic to men
-Trypanosoma cruzi - American/Chagas disease (kissing Reduvid bugs)
Trypanosoma brucei gambiense and rhodensiense - African sleeping sickness (African trypanosomiasis)

*Trypanosoma brucei brucei causes disease in animals, but not humans

Question 26

what are the two forms of Chagas disease?

Answer 26

1. acute - death within a few weeks

2. chronic - symtpoms may not present until 5-15 years later