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Parasites and Infectious Diseases > Malaria - 5 (10/11) > Flashcards

Malaria - 5 (10/11) Flashcards

1
Q

Malaria

distribution

A

endemic in parts of

  • Asia
  • Africa
  • Latin America
  • Oceania

global warming = insect vector’s range broadening

  • 41% of the world’s population live in areas where malaria is transmitted
  • 219 million cases in 2010
  • 0.6-1.2 million deaths in 2010
    • 75% are kids in Africa
    • most are kids under 5
  • 1800-3300 deaths per day OR 1-2 deaths per minute
  • malaria is 4th leading cause of death after perinatal conditions, pneumonia and diarrheal diseases
    • may argue the major one because spread by only 1 organism
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2
Q

Malaria

transmission

A
  • causative agent is transmitted in the saliva of pregnant female mosquitoes (Anopheles) during blood feeding
    • mosquitoes (male/female) → vegetarian, feed on nectar, fruit juice, etc.
  • 30-40 different Anopheles speceis transmit the pathogen
    • Anopheles gambiae best known as it transmits the most common type of malaria
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3
Q

Malaria

superfunfaxxxx

A
  • mosquitoes are responsible for killing half the humans who have ever lived
    • 45 billion out of 90 billion
  • malaria
  • yellow fever
  • dengue fever
  • falariasis
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4
Q

Malaria

transmission

associated with

A
  • associated with “still” water
    • especially swamps
    • any puddle will do
  • mosquitoes utilize naturally occurring water bodies for breeding
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5
Q

Malaria

causative agent

A

disease caused by Apicomplexa

  • protozoan parasites
  • genus Plasmodium
  • Apicomplexan = large diverse phylum (>5000 named species)

includes

  • Babesia
  • Theileria
  • Cryptosporidium
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6
Q

Causative agent

Cryptosporidium

A
  • lives in GI tract
  • fecal-oral transmission
  • can live in humans and a whole raft of other mammalian vectors
    • eg in cows
      • poo with oocysts into water supplies
  • in mammals attach to intestinal cells and induce fusion of microvilli → encapsulation
    • doesn’t invade cells but promotes encapsulation of microvilli to surround parasite itself
  • in humans causes cryptosporidiosis
    • watery diarrhea (actually self-limiting)
  • important in immuno-compromised patients
  • problem in the UK - major cause of water-borne food poisoning
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7
Q

Causative agent

Toxoplasma

A
  • primary host - cat
  • intermediate host - rodents/birds
  • in human parasite infects macrophages anywhere in the body and form a cyst
    • can form in the brain
    • can change personality if parasite lodged in wrong part of the brain
    • schizophrenia, attention deficit disorder, bipolar, Parkinson’s disease
  • transmission from intermediate to primary host = ingestion
    • predator-prey
  • transmission from primary to intermediate host = fecal-oral
  • humans are accidental host
    • via fecal-oral or eating under-cooked meat
  • in humans - congenital transmission
  • disease is self-limiting
  • can be fatal to fetus or immunocompromised people
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8
Q

Causative agent

Babesia

A
  • single-celled eukaryotes
    • phylum Apicomplexan
    • all obligate parasites
  • transmitted by ticks
  • in mammals infects red blood cells
  • causes hemolytic infection called Babesiosis
    • mild fevers, diarrhea to severe anemia, organ failure
    • ticks → mammals
  • rare in humans, often confused with malaria
  • major problem in livestock
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9
Q

Causative agent

Theileria

A
  • transmitted by ticks
  • in mammals infects red and white blood cells
  • major problem in livestock (cattle, sheep, etc.)
  • infection called Theileriosis
    • fever, enlarged lymph nodes, GI tract problems, diarrhea
  • unlike Babesia and malaria - invades WBC and RBC
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10
Q

Apicomplexan parasites caused by cell biology

A

contain:

  • apicoplast
  • inner membrane complex
  • apical complex
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11
Q

Apicoplast

A
  • non-photosynthetic plastid related to chloroplasts
  • involved in synthesis pathways
    • fatty acid
    • isoprenoids
    • heme
  • chloroplast with lost ability to perform photosynthesis
  • drugs can target this because we don’t have it
  • taken up as secondary endosymbiotic event
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12
Q

Inner membrane complex

A
  • pellicle of 3 membrane layer (alveolar structure)
  • series of membranous structures under the membrane
  • protects cell
  • allows cell to retain shape during locomotion
  • involved in cell invasion in myosin motors
    • allows cell to move/glide over certain surfaces
    • stick to particular cell type and glide over
  • also RBC invasion
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13
Q

Apical complex

A

composed of

  • conoid and polar rings
  • microtubules
  • rhoptry
  • micronemes
  • dense granules
  • sescretory bodies
  • series of secretory molecules
  • for introducing molecules on the outside and cell evasion, gliding
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14
Q

Apicomplexan parasites

(picture)

A
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15
Q

In humans, 4 different Plasmodium species cause malaria

A
  • Plasmodium falciparum
    • ​clinically most important
    • 15% of malaria infections
    • 90% of deaths
    • causes severe complications in terms of its pathology that can affect virtually every organ in the patient’s body and cause it to break down
  • Plasmodium vivax
    • ​most common
    • 80% of malaria infectous
  • Plasmodium malariae
  • Plasmodium ovale
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16
Q

Malaria life cycle

  1. sporozoites

in saliva → blood

A
  • found in mosquito’s salivary gland
  • stage transmitted by mosquitoes
    • mosquito takes blood meal
    • saliva into patient as well as sporozoite form of parasite
    • single cell
    • through epidermis
  • once in the blood the sporozoites will find vessels of the circulatory sytem
  • travel to the liver
    • must go through liver before can get into RBC
    • in liver sinusoids (liver blood supply) sporozoites glide over endothelial cells
    • circumsporozoite released from apical complex
    • parasite surface circumsporozoite protein interacts with sulfated heparin secreted by stellate cells
    • glides over by breaking and reforming heparin-sporozoite interaction
    • parasite crosses sinusoid layer by invading and transverse across Kupffer cells (macrophages)
      • sporozoite invades it and uses it to cross the epithelial layer to be delivered into hepatocytes that lie below the space between the epithelial layer and hepatocytes that
      • taken up, transferred into hepatocyte
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17
Q

Malaria life cycle

  1. sporozoite

in liver

A
  • travel to the liver
    • must go through liver before can get into RBC
  • in liver sinusoids (liver blood supply) sporozoites glide over endothelial cells
  • circumsporozoite released from apical complex
    • parasite surface circumsporozoite protein interacts with sulfated heparin secreted by stellate cells
    • glides over by breaking and reforming heparin-sporozoite interaction
  • parasite crosses sinusoid layer by invading and transverse across Kupffer cells (macrophages)
    • sporozoite invades it and uses it to cross the epithelial layer to be delivered into hepatocytes that lie below the space between the epithelial layer and hepatocytes that
    • taken up, transferred into hepatocyte
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18
Q

Malaria life cycle

  1. sporozoites

hepatocytes

A
  • sporozoites transverse several hepatocytes until it becomes established in one
    • once in hepatocyte can move amongst them until finds one it likes
  • parasite found in a parasitophorous vacuole
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19
Q

Malaria life cycle

bite → hepatocyte invasion takes

A

30-60 minutes

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20
Q

Malaria life cycle

  1. liver schizont

definitions - schizogony, schizont

A
  • sporozoite develops into a liver (or exoerythrocytic) schizont
  • schizogony - nucleus divides asynchronously without cytoplasmic division
  • schizont - a multinucleated parasite
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21
Q

Malaria life cycle

  1. liver schizont

1 schizont →

A

liver exoerythrocytic schizont develops into merozoites

  • schizont undergoes budding producing many mononucleated merozoites
    • form of asexual reproduction
  • 1 schizont → thousands of merozoites
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22
Q

Malaria life cycle

  1. Merozoites
A
  • budding - migration of nucleus and other organelles to cell membrane, becomes incorporated into merging merozoite
  • hepatocyte becomes packed out with budded versions of itself - merozoites
  • merozoites cause the hepatocyte to die to form a merosome
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23
Q

Malaria life cycle

  1. Merosome
A
  • dying hepatocytes release membrane-bound aggregates of merozoites (merosomes) into the bloodstream
    • merozoites associated with membranous material from the hepatocyte to form a merosome
  • merosomes - may protect merozoites from phagocytosis by Kuffper cells
  • merosomes break up releasing individual merozoites
    • membrane material breaks down
    • parasite is released into the bloodstream where merozoites go on to infect RBC
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24
Q

Malaria life cycle

dormant stage

A
  • in some P. vivax and P. ovale infections, sporozoites don’t immediately form schizonts
  • in livers tage parasite becomes dormant part way through schizogony
  • infection enters dormant - hypnozoite - stage
  • hypnozoite can reactivate and undergo schizony resulting in relapse
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25
Q

Malaria life cycle

  1. merozoites - continued

merozoite facts

A
  • small (~1nm diameter)
  • pear-shaped
  • pointed (apical) end contains apical complex
  • specifically infects erythrocytes
  • infection is rapid (~20 seconds)

parasite: mosquito → liver → RBC

  • merozoites designed to invade RBC
  • process of RBC invasion has 4 stages
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26
Q

Malaria life cycle

  1. merozoites

RBC invasion - 4 steps

A
  1. attachment
  2. reorientation
  3. junction formation
  4. invasion
  • reorient because anywhere on spherical body but need apical end to be in contact with RBC membrane
  • parasite talking with RBC by secreting effectof molecules that form a tight junction
    • tight junction can split and pass up and over parasite, invade
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27
Q

Malaria life cycle

merozoites

  1. attachment
A
  • intial interaction - random collision
  • involves reversible interactions between merozoite “adhesins” and erythrocyte ligand

interaction between:

  • GPI-anchored merozoite surface protein-1 (MSP-1)
  • Band 3 (anion transporter)

other interactions between:

  • erythrocyte binding antigen (EBAs) and
  • reticulocyte-binding-like (RBL) proteins
  • bind to glycosylated (sialic) proteins on erythrocyte surface

^ P. falciparum 5xEBAs and 6xRBLs

eg EBA-175 binds to glycophorin A

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28
Q

Malaria life cycle

merozoites

  1. attachment

different attachment pathways operate in different parasite lines/geographical locations

A

EBL-175/glycophorin A pathway predominates in India/Gambia

EBL-175/glycophorin A pathway only in a minority of cases in Brazil

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29
Q

Malaria life cycle

merozoites

  1. reorientation
A
  • stick anywhere across parasite cell surface
  • must move itself around such that the apical end comes into contact with RBC membrane
  • parasite linked via adhesin to receptor on RBC membrane
  • parasite adhesins undergo proteolysis
  • at that point the link between parasite and RBC is broken
  • parasite shifts slightly
    • wobbles a bit and promotes slight movement of parasite in one direction so that next adhesin contacts adjacent/subsequent effector
  • adjacent parasite adhesins interact with adjacent RBC ligands
  • “apical end” makes contact with erythrocyte membrane
  • effectively rotates by proteases snapping the adhesin on the parasite surface → rotation of parasite so apical end contacts the erythrocyte membrane
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30
Q

Malarial life cycle

  1. junction formation
A
  • secretory bodies release contents
  • parasite protein complexes insert into erythrocyte membrane while components of complex remaining bound to the parasite
  • bridge between host and pathogen cells called tight junction
  • appears as electron-dense zone at parasite/erythrocyte boundary
  • apical end contacts RBC membrane then forms junction
  • the parasite secretes membrane complexes - some of which are inserted into the erythrocyte membrane, some of which are held on to by the parasite itself
  • the complexes that held on to by the parasite by itself interact with complexes when it’s produced and inserted into erythrocyte membrane
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31
Q

Malaria life cycle

merozoites

  1. junction formation

tight junction proteins include

A

rhoptry neck proteins - RON2, 4, 5

  • RONs inserted in erythrocyte membrane to form RON complex
  • inserted at point of contact into erythrocyte membrane

apical membrane antigen-1 (AMA-1)

  • transmembrane protein (crosses parasite membrane)
  • extracellular region binds to RON complex
  • inner cellular region interacts with aldolase in parasite cytoplasm
    • aldolase binds to F-actin
    • actin interacts with myosin located in inner membrane complex
    • fixes the parasite onto the RBC surface at the apical end to promote junction formation
  • the AMA-1 C-terminuses exposed in the cytoplasm of the parasite
    • interacts with aldolase
    • aldolase interacts with actin
    • actin can interact with myosin
    • myosin can then sit on the inner membrane complex (interacts with) which is all around the cell
  • actually linked RBC membrane to the underlying structure within parasite unlerlying cell membrane of the parasite
  • myosin acts as ATP-driven motor
    • flips back and forth across surface of actin
    • this drives the parasite into the RBC
32
Q

Malaria life cycle

merozoites

  1. invasion
A
  • tight junction formation causes invagination of erythrocyte membrane
  • parasite forcibly enters through invagination
  • tight junction functions as biological (myosin) motor
  • as invasion progresses, tight junction forms a “ring of contact” with erythrocytes
  • eventually parasitophorous vacuole formed within which the parasite lives
  • as invasion progresses, components of tight junction are degraded by serine protease, PfSUB2 (“sheddase”)
33
Q

Malaria life cycle

  1. asexual cycle

trophozoite

A
  • merozoite differentiates into a trophozoite stage
  • young trophozoite called ring stage because of Giemsa staining pattern
  • ring morphology disappears as parasite feeds on hemoglobin
34
Q

Malaria life cycle

  1. asexual cycle

trophozoite

feeeeeding

A
  • ring stage trophozoite
    • hemoglobin taken up by pinocytosis over whole parasite surface
  • mature trophozoite
    • hemoglobin taken up by endocytosis via cytosome
    • hemoglobin-containing vesicles fuse to form food vacuole
    • food vacuole acidifies (pH 5-5.4) and recruits several distinct classes of proteases
35
Q

Malaria life cycle

  1. asexual cycle

trophozoites

digesting the noms

A

proteases digest hemoglobin in semi-ordered, sequential process

  • plasmepsins (aspartic acid proteases) make initial cleavage
  • release heme and globin
  • proteases digest globin to peptides then to amino acids
  • peptides and amino acids transported from food vacuole to parasite cytoplasm
  • used to make new proteins/energy source
36
Q

Malaria life cycle

  1. asexual cycle

trophozoites

heme watchu doin son?

A
  • heme (toxic) polymerizes to hematin
  • hematin polymerizes to hemozoin (inert)
  • chloroquine blocks polymerization
37
Q

Malaria life cycle

  1. asexual cycle

trophozoite stage ends when…

A
  • trophozoite stage ends when schizogony (nuclear division) starts
  • trophozoite differentiates into erythrocytic schizont
  • schizont formation involves 3-5 rounds of nuclear division
  • budding occurs - producing mononucleated merozoites
  • erythrocytes burst, releasing merozoites into the bloodstream
  • invade new erythrocyte
  • starts new asexual cycle
  • asexual cycle is usually synchronous in a given host
  • simultaneous rupture of erythrocytes and release of merozoites
  • antigens (host and parasite) and waste products cause relapsing fever
  • P. falciparum mature trophozoite- and schizont-infected erythrocytes adhere to capillary endothelial cells
    • leads to severe malaria pathologies
38
Q

Malaria life cycle

  1. Sexual cycle
A
  • some merozoites - upon invading the erythrocyte - develop into gametocytes
    • micro-gametocytes
    • macro-gametocytes
  • do not cause pathology
  • cleared from bloodstream if not taken up by mosquito
  • in mosquito gut RBC breaks down
  • gametocytes released, differentiate into gametes (gametocytogenesis)
  • micro-gametocytes → micro-gametes
  • macro-gametocytes → macro-gametes
39
Q

Malaria life cycle

  1. sexual cycle

gametocytes

A

micro-gametocytes undergo

  • 3 x nuclear division
  • flagella formation (exflagellation)

macro-gametocytes - no morphological changes

40
Q

Malaria life cycle

  1. sexual cycle

zyote formation

A
  • micro-gamete (nucleated flagella) separate
  • fuse with macro-gamete → diploid zygote
  • zygote develops into motile ookinete
  • ookinete crosses mosquito gut lining/wall, emerging on basal side of epithelium
41
Q

Malaria life cycle

  1. sexual cycle

ookinete

A
  • zygote develops into motile ookinete
  • ookinete crosses mosquito gut lining/wall, emerging on basal side of epithelium
  • ookinete develops into oocyst → insect stages
42
Q

Malaria life cycle

  1. insect stages

oocyst

A
  • ookinete develops into oocyst
  • oocyst undergoes meiosis followed by binary fission (sporogony)
  • produces thousands of sporozoites
43
Q

Malaria life cycle

  1. insect stages

sporozoites

A
  • oocyst ruptures releasing spozoites into hemocel
  • motile sporozoites have specificity to the salivary gland
  • transverse the salivary gland epithelial cells, reside in lumen
44
Q

Malaria life cycle

  1. re-infection
A
  • mosquito is primary or definitive host
    • host where parasites rewaches maturity and sexually reproduces
  • mammals/humans are intermediate hosts​​
    • used to get from insect to insect
45
Q

Primary/definitive host

A

host where parasite reaches sexual maturity and sexually reproduces

46
Q

Intermediate host

A

used to get from insect to insect

(between primary/definitive hosts)

47
Q

Malaria pathology

  1. onset

after infection and pre-patent time

A
  • 6-18 days after infection by mosquito parasites appear in blood
  • pre-patent time
    • time to complete liver stage
    • no symptoms with liver infection
48
Q

Malaria pathology

  1. onset

different plasmodium species have different pre-patent times

A
  • P. falciparum* → 6-9 days
  • P. vivax* → 8-12 days
  • P. ovale* → 10-14 days
  • P. malariae* → 15-18 days
49
Q

Malaria pathology

  1. onset

incubation period

A

the time between RBC infectoin and onset of symptoms

50
Q

Malaria pathology

  1. onset

different plasmodium species - different incubation periods

A
  • P. falciparum → 7-14 days
  • P. vivax → 12-17 days
  • P. ovale → 16-18 days
  • P. malariae → 18-40 days
51
Q

Malaria pathology

  1. development

classical symptoms

A

last 4-8 hours

  • chills/rigor
    • intense feeling of cold but displaying elevated temperature
    • vigorous shivering
  • fever
    • intense heat + severe headache
    • fatigue
    • dizziness
    • nausea
  • sweating
  • fever starts to decline
  • patient exhausted, falls asleep, wakes up well

symptoms repeated every 2/3 days

52
Q

Malaria pathology

  1. development

cyclical nature of fever

A
  • P. vivax and P. ovale - every 2 days
  • P. malariae - every 3 days
  • P. falciparum - almost continous fever
53
Q

Malaria pathology

  1. development

cyclical nature of fever

why cyclical?

A
  • synchronous development of parasites in human host
  • all parasites in RBC at approximately same stage of development
54
Q

Malaria pathology

  1. development

cyclical nature of fever

symptoms

A
  • lysis of infected RBC
  • parasite antigens released into bloodstream
  • stimulate macrophages + immune effector cells to produce TNF-α and other cytokines
  • causes febrile episodes

symptoms become less severe as patient gets older (immunity)

55
Q

Malaria pathology

  1. development

further symptoms

A
  • symptoms intensify
  • irregular high fever
  • anxiety, delirium, other mental problems
  • sweating, increased pulse rate, severe exhaustion
  • worsening GI symptoms
  • enlarged spleen/liver
56
Q

Malaria pathology

  1. severe malaria
A
  • 10% falciparum cases
  • up to 50% mortality rate
  • several manifestations can arise simultaneously or sequentially
    • cerebral malaria
    • severe anemia
57
Q

Malaria pathology

  1. severe malaria

cerebral malaria

A
  • non-specific fever followed by loss of consciousness
  • severe headache
  • drowsiness
  • neurological abnormalities
  • convulsions
  • vomiting
  • coma
58
Q

Malaria pathology

  1. severe malaria

severe anemia

A
  • drop in hematocrit
    • destruction of RBCs (infected)
    • non-infected RBCs destroyed
    • reduced RBC formation (cytokines, etc.)
  • poor oxygen supply for organs and tissues
59
Q

Severe malaria pathology

sequestration/cytoadherence

ring stages

A
  • P. falciparum infections only
  • ring stage parasite found in peripheral blood
60
Q

Severe malaria pathology

sequestration/cytoadherence

schizonts

A

mature trophozoite- and schizont-infected erythrocytes are “sicky” and attach to the endothelium of venules (cytoadherence)

mature trophozoite- and schizont-infected erythrocytes not found in peripheral blood (sequestration)

61
Q

Severe malaria pathology

sequestration/cytoadherence

rosetting

A

adherence of infected RBCs to non-infected RBCs

62
Q

Severe malaria pathology

sequestration/cytoadherence

clumping

A

adhesion between infected RBCs

63
Q

Severe malaria pathology

sequestration/cytoadherence

rosetting and clumping

A
  • first observed in in votro culturing
  • observed in 50% of field isolates and correlates strongly with disease severity
64
Q

Severe malaria pathology

sequestration/cytoadherence

mature trophozoite-infected and schizont-infected erythrocytes have

A

altered surface morphology

  • electron-dense protrusions (knobs)
65
Q

Severe malaria pathology

knobs contain parasite proteins

A
  • PfEMP1 - P. falciparum Erythrocyte Membrane Protein 1
  • PfEMP2 - P. falciparum Erythrocyte Membrane Protein 2
  • KAHRP - knob-associated histidine rich protein

all produced and secreted by parasite then transferred toward erythrocyte surface

66
Q

Severe malaria

knobs

PfEMP2 and KAHRP

A
  • not exposed on outer surface of erythrocyte
  • localized toward erythrocyte cytoplasm
  • function unknown - reorganizing erythrocyte cytoskeleton?
67
Q

Severe malaria

knobs

PfEMP1

A
  • is exposed to the outer surface of the erythrocyte
  • functions as ligand to bind receptors on host epithelial cels
  • is immunogenic
  • expressed by var gene family
  • parasite genome contains 40-60 var genes
  • at least 40-60 immunogenic PfEMP1 isoforms
68
Q

Severe malaria

knobs

Pfemp1

(picture)

A
69
Q

Severe malaria

knobs

PfEMP1

A
  • 40-60 PfEMP1s exhibit high degree of sequence variability
  • have similar overall conserved, multi-domain structure
  • NTS = N-terminal segment
  • cysteine rich domains
  • TM - transmembrane domains
  • duffy binding like (DBL)
  • cysteine-rich interdomain regions (CIDR)
  • number and order of DBLs and CIDRs varies between PfEMP1 isoforms
70
Q

Severe malaria

knobs

PfEMP1

different DBLs and CIDRs bind to different host cell receptors

A

CD36 complement receptor 1 - ICAM1

  • variable domain composition and extensive sequence polymorphism thought to provide great flexibility in binding properties
71
Q

Severe malaria

knobs

PfEMP1

allelic exclusion

A
  • out of 40-60 var genes only 1 expressed by a population (allelic exclusion)
  • knobs only contain 1 PfEMP1 isoform
  • each PfEMP1 isoform is antigenically distinct
  • in response to immune system parasites switch to new PfEMP1 variants (antigenic variation)
  • switching is promoter-driven
  • switching frequency of ~2% of the population switch per cycle
  • switching to new, antigenically distinct PfEMPs results in new infected erythrocyte having different adhesion phenotype
72
Q

Severe malaria pathology

sequestratio/cytoadherence

anemia

A
  • cytoadherence - non-infected and infected RBCs stick to each other AND the blood vessel endothelium (PfEMP1 mediated)
  • blood vessels become clogged and hemorrhage (common in cerebral malaria)
  • induces production of cytokines
    • causes expression of endothelial adhesins and makes endothelial cells more “sticky”
  • reduces blood flow → anemia
73
Q

Malaria

acquired immunity

A
  • people living in endemic areas acquire immunity through natural exposure to the parasite
  • acquired (or natural) immunity occurs only after continued exposure from multiple infections over time
  • acquired immunity limits high-density parasitemia
    • however it does not lead to sterile protection
  • clinical immunity provides protection against severe effects of malaria but fails to provide strong protection against infection with malaria parasites

explains why kids and people from non-malarious regions are more susceptible to malaria

74
Q

Malaria

diagnosis

A

microscopy

  • thin/thick blood films
  • tell 4 species apart

antigen

  • can’t distinguish between all types of malaria
  • rapid diagnostic tests

PCR

  • expensive
75
Q

Malaria

drugs

A
  • quinine
  • chloroquine
  • mefloquine (Lariam)
  • sulfadoxine-pyrimethamine (Fansidar)
  • atovaquone-proquanil (Malarone)
  • doxycycline
  • artemisin

MAJOR PROBLEM IS COUNTERFEIT DRUGS

COMPOUNDS SOLD AS ANTI-MALARIAL WITH NO/REDUCED ACTIVE INGREDIENT

76
Q

Malaria

control measures

A

insecticide sprays

  • adult insects/larval stages
  • ecological considerations

bed nets containing insecticide

  • cheap
  • insecticide is “contained”

drainage

  • ecological considerations

wear socks

  • mosquitoes like smelly feet
77
Q
A

Parasites and Infectious Diseases (8 decks)

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