Phylum Apicomplexa Chapters 8

1
Phylum Apicomplexa Chapters 8 9
Phylum Apicomplexa consists of 4 groups of
protozoan parasites 1. 2. 3. 4. We will
examine the first 3 groups, as they contain many
parasites of medical and veterinary importance.
We will omit the gregarines as they are
parasites of invertebrates and are not important.
2
Characteristics of the Phylum Apicomplexa
1. ______________________________________________
________________   2. Possess ___________________
____________________________________
- these organelles are concentrated at
_______________________________ - function?
____________________________________ - see
diagram in text p. 124 3. ______________________
_________________ 4. ___________________________
____________   - alternation of
_____________________________ - hosts?


3
Plasmodium and Malaria Chapter 9
Malaria is one of the most important diseases of
mankind. It has played an important part in the
rise and fall of nations and has killed untold
millions of persons. Today, ______________________
____are infected with malaria 1.5 billion people
(2/3 of the world's population) live in endemic
areas and are potential hosts. Malaria kills
_____________________ people each year.
4
Plasmodium and Malaria Chapter 9

• In areas of Africa with high malaria
  transmission, an estimated
  ________________people die of malaria each year
  over 2700 deaths per day or 1 death every 30
  seconds.
• Uganda 12 million infections/population 31
  million
• Tanzania 11 million infections/population 40
  million
• Ethiopia 9 million infections/population 78
  million

5
Species of Plasmodium

• The genus Plasmodium contains 127 species in
  lizards, birds, and mammals.
• life cycle worked out in a bird species
  (Plasmodium relictum)
• rodent species (P. berghei) important in
  research (we will do an experimental infection of
  this parasite in lab)
• several species in monkeys and apes are similar
  to human species - important in drug studies
• four species infect humans they are
• P. vivax, P. falciparum, P.
  malariae, P. ovale

6
Species of Plasmodium

• VECTOR _________________________________________
  ___
• several species can serve as vectors
• ___________________feed on blood and vector
  malaria
• RESERVOIR HOSTS ________________________________
  __
• SURVIVAL OF MALARIA is dependent upon
• 1. Many infected humans
• 2. Many Anopheles mosquitoes
• 3. Good contact between these 2 hosts

7
Life Cycle of Plasmodium
The life cycle is complex, so we will go through
it step by step to understand it.
8
Life Cycle of Plasmodium Human Cycle

• An infected Anopheles mosquito bites a human and
  _______________________________ into the
  bloodstream
• Within 30 minutes, the sporozoites enter
  _________________________ and begin the
  PRE-ERYTHROCYTIC INCUBATION (lasts for about a
  week).
• Within the liver cell, the sporozoite becomes a
  trophozoite
• divides by schizogony to form a multinucleate
  form called a ____________________________
• individual nuclei will form ______________________
  ______

9
Life Cycle of Plasmodium Human Cycle

• 4. Liver cell ruptures to release the
  merozoites 
• In 2 species of malaria, some of these
  merozoites will re-invade liver cells to begin a
  new cycle in the liver - called the
  EXO-ERYTHROCYTIC CYCLE.
• Cryptozoites in these liver cells become dormant
  and are called _________________________________
• Merozoites may break out of hypnozoites years
  later and enter rbc's causing a
  _________________________________
• In all species, most or all of the merozoites
  leave the liver and enter the bloodstream

10
Life Cycle of Plasmodium Human Cycle

• In the ERYTHROCYTIC CYCLE, a merozoite penetrates
  a rbc and transforms into a uninucleate
  _______________________________
• Trophozoite undergoes schizogony and becomes a
  multinucleate ______________________________
• 7. Schizont ruptures rbc to release
  ______________________________
• - This coincides with the onset of a
  fever followed by a period of chills.
•   - Length of time of fever/chill cycle
  varies by species
• 8. Merozoites re-invade erythrocytes
  initiating a new erythrocytic cycle. This
  process is repeated over and over again resulting
  in the destruction of rbc's.

 
11
Life Cycle of Plasmodium Human Cycle
9. Not all the merozoites re-entering rbc's
become trophozoites - some transform into
gametocytes. _____________________________are
female _____________________________are
male. 10. Rbc's containing gametocytes are
infective to an Anopheles mosquito when she bites
and takes another blood meal.
 
12
Life Cycle of Plasmodium Mosquito Cycle

• 11. In the mosquito stomach
• macrogametocyte undergoes meiosis to become a
  __________________________
• microgametocyte undergoes meiosis to form 6 - 8
  elongate ___________________________ in a process
  called ___________________________
• The microgametes detach. Each swims to find a
  macrogamete, penetrates it, and
  syngamy occurs to form a ____________________
• 13. Zygote elongates to form an
  ___________________________which penetrates the
  stomach wall and comes to lie on the outside of
  the stomach.
•  

 
13
Life Cycle of Plasmodium Mosquito Cycle

• 14. Ookinete rounds up to form the
  _________________________
• 15. Within the oocyst, sporogony (a type of
  asexual multiple fission) occurs, resulting in an
  enlarged oocyst containing thousands of
  __________________________
• 16. Oocyst bursts releasing the sporozoites into
  the body cavity.
• Sporozoites migrate to the _______________________
  ___
• __________________________ and are
  injected into the human bloodstream with the next
  blood meal.

 
14
Life Cycle of Plasmodium Review of Human
Cyclefrom text page 150

 
15
Life Cycle of Plasmodium Review of Mosquito
Cyclefrom text page 150

 
16
Some Stages of Malaria in Anopheles
Feeding female Anopheles
Oocysts on outside of mosquito stomach
Exflagellation showing microgametes
Sporozoites from salivary gland
17
Some Stages of Malaria in the human
Cryptozoite in liver cell it will burst
releasing merozoites
Schizont multinucleate form in rbc
Trophozoite uninucleate form in rbc
Gametocyte uninucleate form in rbc
18
Plasmodium vivax

• Disease is _______________________________________
  _________________
•  "tertian" indicates that the parasite undergoes
  a ____________ erythrocytic cycle in human rbc's
  (parasites invade rbc's every third day, hence
  tertian)
• "benign" indicates that the species is
  ____________________________
• Has an exo-erythrocytic cycle resulting in
  ____________________________ occurring every 2-3
  years up to 8 years.
• Was once the most common and widely distributed
  species - occurred throughout tropical and
  temperate regions of the world.
• once occurred in Wisconsin

Habitat now -_____________________________________
_________________ This species is responsible
for ____________ of malaria in the world.
19
Plasmodium falciparum distribution (2005)
Plasmodium vivax distribution (2005)
20
Plasmodium vivax stages in human blood
Ring-stage Trophozoite - ________________________
________________________________________ -
cannot distinquish from other species Mature
Trophozoite - trophozoite ____________________
- ______________________________ due to ameboid
movement of parasite - reddish
______________________ appear (diagnostic!)
21
Plasmodium vivax stages in human blood

• Schizont
• ______________________________
• mature schizont forms ____ merozoites
• Schuffners dots present
• rbc enlarged
• Gametocyte (we will not distinguish between
  macro- and microgametocytes)
• ______________________________
• blue cytoplasm nearly fills rbc
• Schuffners dots present
• rbc enlarged

22
Plasmodium ovale

• Disease is _______________________________________
  ______________
• produces mild disease
• 48 hour erythrocytic cycle
• _______________________________________ - occurs
  in scattered areas of western Africa, India, and
  islands of the western Pacific (Philippines, New
  Guinea)
• Nearly identical to P. vivax and is difficult to
  differentiate from this species from P. vivax
• we will not distinguish between P. vivax and P.
  ovale in human blood smears examined in lab
• Is responsible for ___________________ of world
  malaria.

23
Plasmodium ovale stages in human blood
Ring-stage Trophozoite - nucleus and thin ring
of cytoplasm - cannot distinquish from other
species Mature Trophozoite - trophozoite
________________________ - reddish
__________________________ appear (diagnostic!)
24
Plasmodium ovale stages in human blood

• Schizont
• _____________________________
• mature schizont forms ____ merozoites
• Schuffners dots present
• rbc enlarged
• Gametocyte
• - single nucleus
• blue cytoplasm fills _______________
• Schuffners dots present
• rbc enlarged

25
Plasmodium malariae
Causes _________________________________ -
quartan indicates a ______________________
erythrocytic cycle Occurs throughout the tropics
but has a discontinuous distribution Also occurs
in chimpanzees but is not considered a zoonosis
as wild chimps and humans do not live together in
nature for disease transmission to occur between
them Relapse? ____________________________________
__________________ A human can be infected for
many years with no apparent symptoms, and the
parasite can suddenly become pathogenic. This
phenomenon is called _____________________________
_____. Fatalities are not uncommon. Is
responsible for ___________ of world's
malaria.  
26
Plasmodium malariae stages in human blood
Ring-stage Trophozoite - nucleus and thin ring
of cytoplasm - cannot distinquish from other
species Mature Trophozoite - trophozoite
often forms a __________________ across the rbc
(diagnostic!) - trophozoite does not enlarge
rbc - no Schuffners dots
27
Plasmodium malariae stages in human blood

• Schizont
• multinucleate
• mature schizont forms ____ merozoites
  (diagnostic)
• no Schuffners dots present
• no enlargement of rbc
• Gametocyte
• single nucleus
• blue cytoplasm nearly fills most of rbc
• no Schuffners dots present
• no rbc enlargement

28
Plasmodium falciparum

• Disease is _______________________________________
  ___________________
• "tertian" indicates a 40-48 hr. cycle in rbc's
• "malignant" indicates it is the most virulent of
  the 4 human species
• P. falciparum is the greatest killer of humanity
  in the tropics.
• it was responsible for the decline of the Greek
  civilization, the destruction of the Crusades,
  and caused more death in the Pacific in WWII than
  battles.
• it is the most dangerous because more rbc's are
  infected and destroyed - death occurs commonly
  8-10 months after infection.
• Relapse? _________________________________________
  _________________
• Occurs today throughout the tropics and is
  responsible for ___________
  
  of the world's malaria.

29
Plasmodium falciparum distribution (2005)
Plasmodium vivax distribution (2005)
30
Plasmodium falciparum stages in human blood

• Ring-stage Trophozoite
• single nucleus and thin ring of cytoplasm
• _______________________ in a rbc common
• Mature Trophozoites and Schizonts disappear from
  peripheral blood and are not seen
• Gametocyte
• single nucleus
• __________________________ (diagnostic!)
• can often see outline of rbc

31
History of Malaria

• Disease has been known since antiquity - one of
  first reports described fevers in 1550 BC.
• Malaria was commonly found in swampy areas and
  was thought to be contracted by breathing in "bad
  air" ( mal aria) in the swamps.
• Much effort was directed towards finding a
  causative agent in the water or air of these
  swamps.
• We now know that the mosquitoes that vector the
  disease lived in these swamps.

32
History of Malaria

• First breakthrough - French physician
  _______________________ identified the parasites
  in the rbc's of malaria patients in 1880.
• Laveran also witnessed an
  unusual step in the life
  cycle
  called exflagellation.
• _____________________ (1885) differentiated some
  species of Plasmodium and noted changes in the
  parasites associated with the fever - chill
  cycle.

33
History of Malaria

• Next breakthrough involved the mode of
  transmission.
• In the 1890's a famous British scientist
  ___________________________________ theorized
  that mosquitoes may be involved in malaria
  transmission.
• Manson had recently found that mosquitoes could
  vector filarial worms that caused elephantiasis
• So why couldn't they also vector malaria?

34
History of Malaria

• Manson convinced one of his
  
  students ________________________,
  a
  physician on leave from the Indian
  
  Medical Service, to test his hypothesis.
• Ross went back to India and began
  
  dissecting mosquitoes.
• After 2 years of dissecting mosquitoes,
  _____________
• __________________________________________________
  _
• In 1897 _________________________________________
  __
• __________________________________by feeding
  Anopheles mosquitoes on infected birds.
• Before Ross could prove transmission to humans,
  he was transferred to work on kala azar. He was
  awarded a Nobel Prize in Medicine in 1902.

35
History of Malaria
Two Italians ____________________________________(
1898) experimentally transmitted malaria from
mosquitoes to humans. It was not until 1948 that
the complete life cycle was known when the
pre-erythrocytic and exo-erythrocytic stages were
found in the liver of infected humans by
________________________________.
36
History of Malaria

• Last name important in the history of malaria is
  that of ________________________________, a
  sanitation officer (ENPH!) in the Panama Canal
  Zone.
• In 1906, he used the knowledge of mosquito
  transmission of malaria and yellow fever (a viral
  disease) to begin a ______________________________
  _______________.
• By 1913, the number of malaria cases had been
  greatly reduced and the building of the Panama
  Canal was undertaken.

37
Pathology of Malaria Infections
During the pre-erythrocytic and exo-erythocytic
cycles in the liver, there is no pathology and no
symptoms. Why? ____________________________
_______________________ Pathology of all 4
species occurs during the erythrocytic cycle by
the synchronous rupture of schizonts and release
of merozoites which destroy erythrocytes.
38
Pathology of Malaria Infections

• All 4 species show the following 3 pathological
  effects
• 1. ____________________________________ - as the
  rbc's are invaded and destroyed, there is a
  _______________________
• _________________________________________________
  .
• __________________________________________________
  
• - shown by a low hematocrit
• ___________________________________ - liver and
  spleen are overwhelmed in the breakdown and
  recycling of these destroyed rbc's
• results? ___________________________________
  ________

39
Pathological Differences among the 4
speciesPlasmodium vivax and Plasmodium ovale
In vivax and ovale malaria, merozoites primarily
invade __________________________ These malarias
rarely cause death but make a person quite ill
during a malarial paroxysm.
40
Pathological Differences among the 4
speciesPlasmodium vivax and Plasmodium ovale
Paroxysm lasts ________________ and represents
the time from invasion of rbcs by merozoites
until new merozoites are produced (length of
erythrocytic cycle)
41
Plasmodium vivax and Plasmodium ovale pathology

• These malarias cause a long-term disease because
  they have the ability to _________________________
  __.
• Relapse involves the ability of cryptozoites in
  the liver cells during the exo-erythrocytic cycle
  to become dormant for long periods. The dormant
  cryptozoites are called __________________________
  _______.
• Drug treatment or the immune system will
  effectively remove the erythrocytic forms, and
  the symptoms of malaria disappear - often for 2-3
  years.
• For some reason (we do not know why), the
  hypnozoites become active and release new
  merozoites to invade the rbcs - the person has a
  malarial relapse.

42
Plasmodium vivax and Plasmodium ovale pathology
Most individuals recover from these infections
and the parasites are __________________________.
Generally, the immune system totally eliminates
the parasites after about 8 years.
43
Plasmodium malariae pathology
In quartan malaria, merozoites of Plasmodium
malariae primarily invade ________________________
_. There is no exo-erythrocytic cycle, so all
the merozoites formed from cryptozoites invade
rbcs after the pre-erythrocytic incubation (no
relapse). Malarial paroxysms occur every
__________________ and represent the time from
merozoite invasion of rbcs to the formation of
new merozoites (length of erythrocytic cycle).

44
Plasmodium malariae pathology

• This parasite produces a phenonomen called a
  _____________________________________.
• Numbers of infected rbc's can become very low
  that a person shows no signs of the disease.
  This period may last for years and the person
  believes he/she is free of the disease.
• For some unknown reason, the parasites increase
  their numbers, invade many new rbcs, destroy
  them, and cause severe anemia.
• Longest lasting recrudescence was 53 years.
• recent problem in _______________________________
  ___
• How dangerous?____________________________________
  

45
Plasmodium falciparum pathology
Falciparum malaria is the most serious of the 4
species, usually resulting in a
fatality. Remember that only the ring-stage
trophozoites and gametocytes are found in
peripheral blood mature trophozoites and
schizonts are in rbcs of the spleen and bone
marrow. There is _________________________________
____, so all merozoites from the liver enter
rbcs - ______________________


46
Plasmodium falciparum pathology
The erythrocytic cycle lasts from ______________
hours. Malarial paroxysm is unusual
____________________________ _____________________
________________________________


47
Plasmodium falciparum pathology

• Falciparum malaria is the most pathogenic for the
  following reasons
• 1. Merozoites invades __________________________
  _____ - thus, more rbc's are infected and
  destroyed.
• More destroyed rbcs leads to serious
  _____________________.
• With more destroyed rbcs to recycle, liver and
  spleen enlarge - _______________________________-
  and often fail.
• Infected blood becomes viscous, often plugging
  capillaries in the brain causing
  ______________________________________

48
Plasmodium falciparum pathology

• 5. Massive rbc destruction results in high
  levels of hemoglobin removed by the kidneys.
  Urine often becomes dark. Result?
  _________________________________________
• 6. ______________________________________
  occurs when plasma fills the lungs
• 7. ______________________________________occurs
  failure of many organs leads to shock
• A combination of any of these pathologies leads
  to death in 8-10 months.

49
Sickle Cell Anemia
Presence of falciparum malaria has resulted in
the maintenance of another disease which affects
black persons in Africa. Cause

50
Sickle Cell Anemia

Persons who are ___________________________ have
rbcs that are sickle shaped, and die of other
factors by age 30. They are hh. H - normal
gene h - sickle cell gene
51
Sickle Cell Anemia

Persons who are ___________________________ have
rbcs that are sickle shaped, and die of other
factors by age 30. However, if a person is
___________________________ for the sickle-cell
anemia, rbcs are normal shaped but are protected
from invasion of merozoites of P. falciparum
thus, the person is protected from falciparum
malaria.
52
Sickle Cell Anemia cont.

• Selective pressure of malaria in Africa has led
  to the maintenance of an otherwise undesirable
  gene in the population.
• Problem occurs ___________________________ where
  malaria is no longer endemic __________of
  African Americans are heterozygotes (Hh) and
  could transfer the trait to their offspring.

53
Diagnosis and Treatment of Malaria
DIAGNOSIS - identify parasites within human
erythrocytes in a s
stained blood smear (this is what
we are doing in lab)
54
Treatment of Malaria

• 1. _________________________
• used from ______________________
• from bark of cinchona tree
• Disrupts __________________________
• used as final resort now

55
Diagnosis and Treatment of Malaria

• 2. Artemisinin
• Derived from artemisin plant
• Disrupts erythrocytic schizogony
• New form - artemether-lumefantrine introduced in
  2005 to treat uncomplicated Plasmodium falciparum
• New problem
•  

56

• 3. ______________________________________________
  ______ - synthetic drugs developed in WWII and
  used today
•  
• chloroquine (Aralen) and mefloquine (Lariam)
  destroys
• __________________________________________________
  
• primaquine destroys _____________________________
  ___
• (used only to eliminate relapse in
  __________________________________________)

57

• 3. Chloroquine, mefloquine and primaquine -
  synthetic drugs developed in WWII and used today
•  
• used in mixtures of chloroquine-primaquine or
  mefloquine-primaquine for ________________________
  _____________
• chloroquine or mefloquine used individually for
  ___________________________
• The average cost for potentially life-saving
  treatments of malaria are estimated to be US
  0.13 for chloroquine.

58
Treatment of Malaria

• Chloroquine and mefloquine can be taken as a
  preventative - ______________________________
  - by anyone travelling into a malarious area to
  reduce risk of infection. See Health Information
  for International Travelers from CDC or on the
  web at http//www.cdc.gov/travel/
• Chloroquine is effective against
  vivax, ovale,
  and most malariae

59
Chloroquine resistant P. falciparum common
Chloroquine resistant P. malariae in
_______________________
60
Treatment of Malaria

• Mefloquine (Lariam) was developed
  in 1993 to
  combat chloroquine-resistant
  P. falciparum it is
  effective against
  all 4 species
• Recent problems
• Mefloquine has been implicated
  in a number of
  serious
• ___________________________
  
• ___________________________
  is developing
  drug
  resistance to mefloquine
  in SE Asia

61

• 4. _______________________________
• used as both a preventative and a treatment
• Works by _____________________________________
• side effects include sunburning, nausea,
  diarrhea, and vaginal yeast infections in women.
• Not for pregnant women and children under 8
• used as in areas of chloroquine and mefloquine
  resistance to P. falciparum
• used as an alternative for travelers who cannot
  or choose not to take mefloquine or Malarone.

62
Treatment of Malaria

• 5. _______________________________ developed
  in 1980 to destroy erythrocytic forms of P.
  falciparum
• Causes side effects as skin rash, poor healing,
  excessive bleeding, and diarrhea
•  
• Problem -

63
Treatment of Malaria

• 6. ________________________________ new drug
  that became available in July, 2000 to combat
  drug resistant P. falciparum
• Has been shown to be 98 effective in treating P.
  falciparum
• Kills schizonts of P. falciparum
• Problem -
• Question?

64
Distribution of Malaria in the World
Extent of malaria in the world before any
eradication programs were started.
65
Distribution of Malaria in the World
66
Malaria in the U.S.
About ______________cases of malaria are

diagnosed in the U.S. each year. How were
Americans infected?
67
Malaria in the U.S.

• Malaria was once a major problem in southern
  midwestern U.S.
• Species present were ____________________________
  _______.
• Wisconsin had both species.

68
Malaria in the U.S.
By the 1950's malaria was eradicated from the
U.S. due to 1. 2.
69
Malaria Eradication
Because malaria eradication was successful in the
U.S., the World Health Organization began a
worldwide eradication program in 1956. What did
they have for

eradication? 1. 2. It was thought that this was
it for malaria.  
70
Malaria Eradication

• Eradication was successful during much of the
  1960's but problems began to occur in the 1970's
  and continue today.
• Example
• in 1947, 7 million cases of malaria reported in
  India
• in 1966, 40,000 cases of malaria in India
  (height of control)
• in 1977, 5 million cases were diagnosed
• in 1990s, 3 million cases
• Eradication was failing. Why?
•  

71
Malaria eradication failed. Why?
1. Money was not available to combat mosquitoes
or treat human cases. (Energy crisis of 1970's
took alot of money away from malaria
eradication) 2. Disease occurs in third-world
countries where the disease is poorly understood
by the masses. 3. Trained medical personnel and
hospitals are few in number in these
countries. 4. Resistance of P. falciparum to
chloroquine, mefloquine, and Fansidar. 5.
Resistance of Anopheles mosquitoes to
____________and other insecticides
72
Malaria Prevention
1. Avoid mosquito bites use insecticides,
repellents, netting Probably the cheapest and
most effective way to reduce malaria is the use
of insecticide-treated bed nets. A bed net costs
10 and can last up to 4 years Malaria No More
is a non-profit agency that provides bed nets to
Africa.
73
Malaria Prevention

• ___________________________ with chloroquine,
  mefloquine, and Fansidar but this a problem in
  areas with P. falciparum resistant strains
• New finding
• In October, 2000, researchers at the US Institute
  of Allergy and Infectious Diseases announced they
  found that the mutation of a single gene in the
  Plasmodium parasite is responsible for the
  emergence of chloroquine resistance. Formerly it
  was believed that a number of mutations spread
  over a number of genes was likely responsible.
• If this result holds up, it should make it easier
  to potentially alter chloroquine in such a way as
  to evade the parasite's new-found resistance and
  make chloroquine an effective treatment for
  malaria once again.

74
Malaria Prevention

• 3. Malaria vaccine
• a circumsporozoite vaccine (called SPf66) has
  been developed, but human trials have not been
  promising (under 50 protection)
• A new vaccine consisting of Plasmodium genes and
  hepatitis antigens that works with T lymphocytes
  has been developed. Preliminary tests rated it
  as being 65 effective against P. falciparum.
  More extensive tests are currently underway.
• Recent funding available from the
  ____________________________Foundation
• Several Nobel prizes in medicine await
  for the
  development of effective malaria
  vaccines.

75
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76
Despite all these advances, malaria will likely
be with us as long as there are humans on this
earth.