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Parasite 'turns women into sex kittens' By Jane Bunce, December 26, 2006 05:27pm, Article from: AAP

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Parasite 'turns women into sex kittens' By Jane Bunce, December 26, 2006 05:27pm, ... it can make men behave like alley cats and women behave like sex kittens' ... – PowerPoint PPT presentation

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Title: Parasite 'turns women into sex kittens' By Jane Bunce, December 26, 2006 05:27pm, Article from: AAP


1
Parasite 'turns women into sex kittens'By Jane
Bunce, December 26, 2006 0527pm, Article from
AAP
A COMMON parasite can increase a women's
attractiveness to the opposite sex but also make
men more stupid, an Australian researcher
says. About 40 per cent of the world's
population is infected with Toxoplasma gondii,
including about eight million Australians. Until
recently it was thought to be an insignificant
disease in healthy people, Sydney University of
Technology infectious disease researcher Nicky
Boulter said, but new research has revealed its
mind-altering properties. "Interestingly, the
effect of infection is different between men and
women,'' Dr Boulter writes in the latest issue of
Australasian Science magazine. "Infected men
have lower IQs, achieve a lower level of
education and have shorter attention spans. They
are also more likely to break rules and take
risks, be more independent, more anti-social,
suspicious, jealous and morose, and are deemed
less attractive to women. "On the other hand,
infected women tend to be more outgoing,
friendly, more promiscuous, and are considered
more attractive to men compared with non-infected
controls. "In short, it can make men behave like
alley cats and women behave like sex kittens''.
(http//www.news.com.au/story/0,10117,20975555-2
9277,00.html)
2
Apicomplexan invasion
  • Active, parasite driven process
  • Depends on parasite actin/myosin motility
    (conveyor belt model)
  • Involves secretion of micronemes (attachment,
    motility), rhoptries (PV MJ formation) and
    dense granules (makes PV into a suitable home)
  • Sets up a parasitophorous vacuole which initially
    is derived from the host cell cell-membrane
  • A moving junction is formed which screens out
    host membrane proteins from the PV, the PV is
    fusion incompetent and the parasite protected

3
Malaria II
  • Malaria the disease
  • Pathogenesis of severe falciparum malaria
  • Drugs used to treat malaria and the development
    of drug resistance

4
Malaria the disease
  • Human malaria is primarily a blood disease,
    however it causes pathology in a variety of
    organs tissues
  • All disease is due to the parasites development
    within the red blood cell (merozoite,
    trophozoite, schizont).
  • Other stages are important for transmission but
    they do not contribute to pathogenesis

5
Malaria the disease
  • 9-14 day incubation period
  • Fever, chills, headache, back and joint pain
  • Gastrointestinal symptoms (nausea, vomiting, etc.)

6
Malaria the disease
7
Malaria the disease
  • Malaria tertiana 48h between fevers (P. vivax
    and ovale)
  • Malaria quartana 72h between fevers (P.
    malariae)
  • Malaria tropica irregular high fever (P.
    falciparum)

8
Malaria the disease
  • Symptoms intensify
  • Irregular high fever
  • Anxiety, delirium and other mental problems
  • Sweating, increased pulse rate, severe exhaustion
  • Worsening GI symptoms
  • Enlarged spleen and liver

9
Malaria the disease
3 Severe manifestations
Cerebral malaria
Severe anemia
Renal failure
Irritability, loss of reflexes, neurological
symptoms similar to menigitis, coma 20 fatality
Progressive severe drop of hematocrit, poor
oxygen Supply for organs and tissues
Dwindling urine, high urea Level in serum,
hyperventilation Coma, poor prognosis
10
Malaria the disease
WHO-TDR
11
Pathogenesis of malaria
  • In highly endemic areas high mortality among
    children due to severe anemia, children who
    survive beyond the first years show decreasing
    parasitemia and disease (this immunity is not
    sterile and depends on constant exposure)
  • In areas with less infection pressure malaria is
    an epidemic disease with varying intensity.
    Adults and children are equally susceptible and
    death in adults is mostly due to cerebral malaria

12
Pathogenesis of malaria
Age
13
Pathogenesis of cerebral malaria
  • Cerebral malaria is characterized by multiple
    brain hemorrhages
  • Excessive serum and tissue levels of TNFa and
    INFg (two important cytokines) are associated
    with severe malaria
  • Some researchers believe this inflammation is the
    main cause for pathology (remember the immunology
    introduction an overshooting immune response
    against a chronic pathogen that can not be
    cleared can cause severe disease)

14
Sequestration cytoadherence
  • The second model suggests sequestration to be the
    main culprit
  • In P. falciparum infections only early stages
    (rings) are found in the peripheral blood
  • Trophozoites and schizonts are sequestered to the
    post-capilary venules by attachment to the
    endothelium

Ring stages
15
Pathogenesis of falciparum malaria
  • Parasite infected RBC become sticky and adhere
    to endothelial cells
  • This phenomenon takes about 10-12 hours to
    develop after parasite invasion
  • Under high flow (here modeled using a
    microfluidic device) this first results in
    rolling and then in attachment

16
Pathogenesis of falciparum malaria
  • Rosetting (adhesion of infected RBCs to other
    RBCs) and clumping (adhesion between infected
    cells) was first observed in in vitro culture
  • Rosetting was also found in 50 of field isolates
    and correlated strongly with the severity of the
    observed disease

17
Pathogenesis of falciparum malaria
  • Cytoadherence seems to be the main culprit for
    pathogenesis
  • Infected RBCs will adhere to the endothelium as
    well as to each other and cause clogging and
    hemorhaging
  • Note that high cytokine levels induce expression
    of endothelial adhesins -- inflammation makes the
    endothelia stickier
  • Adherence and inflammation reinforce each other
    in an unholy circle causing pathology

18
Knobs and cytoadherence
  • Cytoadhrence and rosetting correlates with the
    presence of knobs (left column) on the surface
    of the infected RBC
  • The right column shows a RBC infected with a
    knob-less strain which does not cause cerebral
    malaria
  • Knobs are made up of parasite derived proteins

knobs
knob-less
19
Knobs and cytoadherence
20
Knobs and cytoadherence
  • PfEMP1 (P. falciparum erythrocyte membrane
    protein) is found in knobs and is responsible for
    cytoadherence and rosetting
  • PfEMP1 is a large membrane protein anchored in
    the RBC membrane with the bulk extending into the
    blood stream
  • Various domains of PfEMP1 have been shown to bind
    to ligands on the endothelia of the vasculature
    and the placenta (Rathod I-CAM movie)
  • PfEMP1 is an important pathogenesis factor

21
Knobs and cytoadherence
  • The parasite exports PfEMP1 and other proteins
    (this picture is showing Knob associated protein)
    into the RBC and its surface to form knobs
  • F in early rings protein is in the parasites,
    G,H in trophozoites it is found first within the
    RBC cytoplasm and then at the RBC membrane (I).

22
Knobs and cytoadherence
  • How precisely the parasite transports proteins
    through the RBC is still under study
  • However it is clear that the parasite has not
    only to provide the cargo but also the transport
    machinery as the RBC has reduced its capability
    for membrane transport and secretion
  • All these proteins are initially secreted by the
    parasite into the parasitophorous vacuole what
    happens next remains poorly characterized
  • Maurers clefts (parasite induced membranous
    structures in the RBC) appear to be an important
    bridgehead acting in the sorting and trafficking
    of exported proteins

23
Immunity to malaria
  • There is no sterile immunity to malaria
  • Patients produce strong antibody responses to
    PfEMP1 which is exposed to the immune system on
    the surface of the infected RBC.
  • Why is the immunity to malaria relatively weak?
  • PfEMP1 is encoded by a large multigene family
    (VAR genes) and parasites switch to new variants
    (antigenic variation again)
  • The parasite genome encodes 60 VAR genes, only
    one is expressed at a time (allelic exclusion)
  • This phenomenon appears to depend on the VAR
    promoter

24
Immunity to malaria
  • Successful vaccination in humans has been
    achieved with large doses of irradiated
    sporozoites, however that is likely not practical
  • Many approaches have been and are explored to
    stimulate immunity against sporozoites (infection
    blocking), merozoites (disease blocking) or
    gametocytes (transmission blocking)
  • None has yielded a satisfactory and safe human
    vaccine yet
  • The most promising new strategies use genetic
    manipulation to engineer attenuated parasites
    strains (parasites that enter cells and induce
    immunity yet fail to develop fully and cause
    disease)
  • Currently, control depends heavily on drug therapy

25
Chinchona the source of quinine
  • Peruvian Indians appear to have been the first to
    know about the medicinal effects of quinine, they
    chewed Chinchona bark while working in the mines
    as forced laborers for the Spanish
  • Jesuits brought the bark back to Europe to treat
    febrile diseases
  • In the early 1600s the bark was used to treat the
    fever of the Countess of Chinchon and became well
    known as Jesuits powder or Peruvian bark
  • Initial preparations were often quite variable in
    the amount of active ingredient resulting in
    varying effects

26
Chichona the source of quinine
  • High demand had brought the Chinchona tree almost
    to extinction in the wild
  • Charles Ledger a trader in Peru send out Manuel
    Incra Macrami to collect seeds from a stand of
    special trees they had found earlier
  • After three years Manuel came back with 15 kg of
    seeds which they sold for 100 guilders to the
    Dutch consul as the British were not interested
  • C. ledgeriana formed the basis of a very
    profitable Dutch quinine monopoly which lasted
    until World War II

27
Chloroquine the wonder drug
  • Chloroquine a synthetic quinine analog developed
    by German and American chemists during WWII was a
    very potent drug that was cheap to make, stable
    and had no serious side effects
  • Chloroquine was a major component of the 60/70s
    malaria eradication campaign
  • None of the drugs developed since come close to
    chloroquine

28
Chloroquine the wonder drug
  • During its development within the RBC the malaria
    parasite ingests the cytoplasma of its host
  • Note that in this schematic (and in real
    micrographs) the red color of the blood cell gets
    considerably lighter -- at the same time malaria
    pigment accumulates
  • The parasite digests large ammounts of hemoglobin
    to cover part of its amino acid needs

29
Chloroquine the wonder drug
  • RBC cytoplasm is taken up by endocytosis
  • The endocytosis vesicle fuse with the food
    vacuole (a homolog of the secondary lysosome)
    were hemoglobin digestion occurs
  • Digestion frees large ammounts of heme
  • Heme is toxic to the parasite and is neutralized
    by polymerization into the malaria pigment or
    hemozoin
  • Chloroquine accumulates in the food vacuole (its
    a weak base and like all lysosomes the FV is an
    acidic compartment)
  • Chloroquine is thought to interfere with the
    polymerization and detoxification of heme
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