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1. 4.3.2. Plasmodium species

2. Plasmodium species
Causative agent of Malaria: an acute and/or chronic
infection caused by protozoans of the genus
Plasmodium
Four plasmodium species causing human malaria
Plasmodium falciparum (P. falciparum)
P. vivax
 P.malariae
P.ovale
2

3. Plasm…
• Widespread species
• P. falciparum: most prevalent in the hotter and
more humid regions of the world.
• P. vivax: more common in temperate region than
in the tropics
• Less widespread species
P. malariae: : confined mainly to tropical Africa (25%)
P. Ovale: : Low & restricted distribution
 Occurs primarily in tropical west Africa (10%)
3

4. General feature of Plasmodium species
Intracellular obligate parasites. (liver cell & RBC)
Life cycle,
Alternation of generation ~ alternation of hosts
Requires two hosts::

Man (IH)

Female Anopheles mosquitoes (DH)
Sexual and asexual reproduction
No animal reservoir host except P.malariae
4

5. Burden of malaria
endemic in 109 countries, 45 within African region
in 2008
An estimated 3.3 billion people were at risk of malaria in 2006
2.1 billion were at low risk (< 1 reported case per 1000
population), 97% of whom were living in regions other
than Africa
1.2 billion at high risk were living mostly in the WHO
African (49%) & South-East Asia (37%)
5

6. 6
Geographic distribution

7. Bur…
 estimated 247 million malaria cases in 2006, 86% of
them were in the African Region
 80% of the cases in Africa were in 13 countries,
and
over half were in Nigeria, Democratic Republic of
Congo, Ethiopia, United Republic of Tanzania and
Kenya.
7

8. Estimated incidence of malaria per 1000 population, 2006
8

9. Bur…
an estimated 881 000 malaria deaths in 2006,
 of which 91% were in Africa and 85% were of < 5
children
One child dies of malaria in Africa every 20 sec
one malarial death every 12 sec in the world
9

10. Estimated deaths from malaria per 1000 population, 2006
10

11. Bur…Bur…

KKills in 1 year what AIDS killed in 15 years
16% growth in malaria cases annually (WHO)
Every year ~ 30000 visitors to endemic areas develop
malaria
1% of them may die.
11

12. Burden of malaria in Ethiopia
¾ landmass malarious
68% of the population at risk
Annual clinical cases estimated 4-5 million
10-40% of all outpatient consultations
13-26% of all inpatient admissions
12

13. Bur. Mal. Eth.
Plasmodium species
P.falciparum =60%
P.vivax = nearly 40%
P.malariae =1% cases ,focal distribution like in
Humera
P.ovale = less than 1% cases , found in Setit Humera ,
Gambela & Arbaminch
13

14. Epidemiology of Malaria in Ethiopia
The risk of malaria varies highly from season to season and
from place to place
Transmission- seasonal (Unstable)
Mainly depends on rain fall and Temp
Two major transmission periods
Major - September to December after main rainy
season
Minor- April to June following small showers of
rain in autumn.
14

15. Epid…
Characteristics of stable malaria:
~ Constant incidence over several years
Includes seasonal transmission
Immunity and disease tolerance developed by adult
Usually affects children
15

16. Epid…
Characteristics of unstable malaria:
Malaria incidence varies from week to week, month to
month, year to year, day to day.
Communal immunity of the population low.
Makes the region prone to malaria epidemics.
High morbidity and mortality
16

17. 17
Morphological Stages
Sporozoite: develops in the mosquito salivary gland
Hepatic schizont
   a
ctively dividing, multinucleated, parasite
form in hepatocytes
Trophozoite: metabolically active form living within the RBC
Sometimes called the ring form
Erythrocytic schizont: multinucleated stage in a RBC
resulting from asexual multiplication of trophozoite
Each schizont contains a species determined number of
merozoites

18. 18
Morph…
Merozoite: infective schizont components that break out of
hepatocyte or RBC
Gametocyte: morphologically distinctive sexual (male or
female) form which develops from some trophozoites in RBCs

19. Transmission and life cycle of
Malaria
Principal mode of
Transmission
bites of female anopheles
mosquito
60 species of mosquito
sucks the gametocytes during
blood meal
bites between 5 PM and 7 AM,
with maximum intensity at
midnight.
Anopheles
19

20. Tran…
In Ethiopia : A.gambiae, A.funestus, A.nili,
A.arebiansis & A.pharonensis are
main vectors
 A. arabiensis is responsible for most
epidemics in the country
20

21. Tran…
Other modes of transmission
11. . Blood transfusion (Transfusion malaria):
This is fairly common in endemic areas

Following an attack of malaria, the donor may
remain infective for:
1-3 years in P. falciparum,
3-4 years in P. vivax, and
15-50 years in P. malariae
21

22. Tran…
Most infections occur:
 in blood stored for less than 5 days and
 rare in blood stored for more than 2 weeks
 Frozen plasma is not known to transmit malaria
blood transfusions malaria
Infective stage-trophozoites / merozoites
shorter incubation period, because no exo-erythrocytic
shizogony
22

23. Tran…
no relapses possible (vivax/ovale)
clinical features & management of cases are
the same as naturally acquired infection
Donor blood should be screened
2. Mother to the growing fetus (congenital
malaria)
23

24. Tran…
3. Needle stick injury:
Accidental transmission can occur among drug
addicts who share syringes and needles
24

25. Life cycle
Require two host
Man:-
intermediate host
Asexual reproduction
Liver cell
RBC
Mosquitoes:-
Definitive host
Sexual
reproduction
25

26. Mosquitoes cycle
A- Sporogony
Human cycle
Two phases
B- exo-erythrocytic
schizogony in liver
C- Erythrocytic
schizogony &
gametocytogenesis in
RBC
26

27. Lif…
IN THE MOSQUITO
 During a blood meal on man, female Anopheles mosquito
picks up mature gametocytes
In the mosquito's mid gut, a micro gamete(male)
penetrates a macro gamete(female) and form a zygote
The zygotes inturn become motile and elongated form
called ookinetes
27

28. Lif…
 invade the midgut wall of the mosquito where they
develop into oocysts
The oocysts expanding by asexual multiplication, grow,
rupture, and release motile sporozoites , which make
their way to the mosquito's salivary glands
 

Inoculation of the sporozoites into a new human host
perpetuates the malaria life cycle
28

29. 29
Lif…
IN MAN
During a blood meal, malaria-infected female Anopheles
mosquito inoculates sporozoites and salivary fluid
The sporozoites remains in the circulating
blood for only 30 minutes
The kupfer cells of the liver kill and clear
many sporozoites from blood stream

30. When the female mosquito bites a person, she pierces the skin and injects
saliva (which contains anticoagulants to stop the blood clotting whilst she
takes her meal 30

31. Lif…
Fraction sporozoites escape destruction are carried rapidly
via the blood stream and invade hepatic parenchymal cells
of the liver
 begin their initial asexual replication : Exo- erythrocytic/
Intrahepatic / Pre-erythrocytic schizogony
within 5-15 days mature into pre-erytrocytice(PE)
schizonts containing 10,000-30,000 merozoites

rupture the swollen liver cells & release merozoites in to
blood stream
31

32. Lif…
P. falciparum
mature and released simultaneously
from liver, no relapse
P. malariae
P .vivax
may remain latent in the liver and
relapse
P.ovale
32

33. Lif…
A proportion of the merozoites are phagocytosed &
destroyed
The remaining Enter in to red cells starts erythrocytic
schizogony which to complete takes 36-48 hours (P. falcipar
um),48 hours (P. ovale/ vivax) &72 hours (P. malariae).
At this time the intracellular merozoites develop in to
trophozoites (‘ring form’)
When the trophozoites fully developed ,then
schizogony takes place resulting in the formation of
schizont containing 8-32 merozoites

33

34. Lif…
development to erythrocytic schizont in P. falciparum takes place in
the capillaries of deep tissue ,
The mature schizont rapture from red blood cells
releasing merozoites , malaria pigment and toxins in to
plasma
Merozoites ,which are not destroyed by host immune system
infect new red blood cells, initiates further cycle of erythrocytic
schizogony with more red blood cells begin destroyed.
34

35. Lif…
After several erythrocytic schizogony cycle , some of the
trophozoites in the red blood cells develop into male
female gametocytes
P. vivax , P. ovale and P. malariae at least two cycle
eryhrocytic schizgony
 P. falciparum ,the asexual parasites in the circulation
for ten days
The gametocytes are now ready to be ingested by an
Anopheles mosquito during a blood meal
35

36. Lif…
Life Cycle:
  
                                                                 
36

37. 37
 
                 

38. Comparison of malarial parasites
  
PfPf PvPv PoPo PmPm
Tissue schizogonyTissue schizogony
8 - 25 days8 - 25 days
8 - 27 8 - 27
daysdays
9 - 17 9 - 17
daysdays
15 - 30 days15 - 30 days
Erythrocytic phaseErythrocytic phase
48 hours48 hours 48 hours48 hours 48 hours48 hours 72 hours72 hours
Red cells affectedRed cells affected
AllAll
ReticulocyReticulocy
testes
ReticulocReticuloc
ytesytes
Mature RBC'sMature RBC's
Merozoites per Merozoites per
schizontschizont 8 - 328 - 32 12 - 2412 - 24 4 - 164 - 16 6 - 126 - 12
Relapse from Relapse from
HypanozoitesHypanozoites
NoNo YesYes YesYes
No, but blood No, but blood
forms can forms can
persist up to persist up to
30 years30 years
38

39. Clinical Features & pathology
Characterized by acute febrile attacks (malaria
paroxysms)
•caused by the release of toxins (when erythrocytic
schizonts rupture) stimulate the secretion of
cytokines from leucocytes and other cells
Manifestations and severity depend on parasite species,
parasitemia and host status, i,e immunity, general health,
nutritional state, genetics
Without treatment, P.vivax, P. ovale, P. malaria ultimately
may result in spontaneous cure
P. falciparum can develop severe complications
39

40. Prodromal Symptoms
Malaria paroxysm preceded by Prodromal period
2-3 days before 1st paroxysm
includes: malaise, fatigue, headache, muscle pain,
nausea, anorexia (i.e., flu-like symptoms)
can range from none to mild to severe
40

41. Febrile Attack (Malaria
Paroxysm), 4-8 hr
periodic febrile episodes alternating with symptom-free periods
initially fever may be irregular before developing periodicity
may be accompanied by splenomegaly, hepatomegaly (slight
jaundice), anemia
P. falciparum can be lethal in non-immune
paroxysms comprises of three successive stage: cold stage,
hot stage and sweating stage
41

42. cold stage
•feeling of intense cold
•vigorous shivering, rigor
•lasts 15-60 min
42

43. hot stage
•intense heat
•dry burning skin
•throbbing headache
•lasts 2-6 hours
43

44. sweating stage
•profuse sweating
•declining temperature
•exhausted, weak  sleep
•lasts 2-4 hours
44

45. •paroxysms associated with
synchrony of merozoite
release
•between paroxysms
temperature is normal and
patient feels well
•falciparum may not exhibit
classic paroxysms
•continuous fever
•24 hr periodicity
Malaria Paroxysm
tertian malaria
quartan malaria
45

46. Complication of Acute Malaria
46

47. Malaria caused by P.falciparum
Falciparum/subtertian/malignant malaria
Most pathogenic of all species
Almost all deaths are due to falciparum malaria
47

48. Factors for Malignance of P.falciparum
Rapid multiplication
Infected red blood cells become "stick"
Infects all age group of red blood cells
A single red blood cell can be infected by more than one
parasites
Erythrocytic schizogonic reproduction takes place in the deep
capillaries of organs such as brain, lung, heart, spleen, bone-
marrow, placenta, intestine, etc.
48

49. 1.Higher Parasitemia in Falciparum
Malaria
•all erythrocytes invaded
•up to 36 merozoites
•Pv/Po = reticulocytes
•Pm = senescent RBC
P.falciparum.
-Up to -Up to 30-40% of RBC of RBC
- sever if - sever if > 5% RBC are infected. RBC are infected.
P.vivax & P.ovale rarely exceeds rarely exceeds 2%
P.malariae.. Usually Usually < 1%
Pathogenecity of P.
falciparum
49

50. • avoidance of
spleen
• low oxygen
tensions
• better invasion
2. Cytoadherence of
infected
erythrocytes
-trophozoite and schizont
stages
-primarily in brain, heart,
lungs, and gut
complications
-immune evasion (spleen
avoidance
50

51. Severe Falciparum Malaria
Complications
Features Indicating Poor Features Indicating Poor
PrognosisPrognosis
cerebral malaria
blackwater fever
anemia
hypoglycemia
GI and liver syndromes
pulmonary edema
algid malaria (shock))

impaired consciousnessimpaired consciousness

repeated convulsionsrepeated convulsions

respiratory distressrespiratory distress

shockshock

acidosis/hyperlactemiaacidosis/hyperlactemia

hypoglycemiahypoglycemia

jaundice or other liver jaundice or other liver
malfunctionsmalfunctions

renal impairmentrenal impairment

high parasitemia high parasitemia
(>500,000/mm(>500,000/mm
33
))
51

52. Predisposing factors for
complications of P. falciparum
malaria
(1.) Extremes of age.
(2.) Pregnancy, especially in primigravidae and in
2nd half of pregnancy.
(3.) Immunosuppressed - patients on steroids, anti-
cancer drugs, immunosuppressant drugs
(4.) Splenectomy.
(5.) Lack of previous exposure to malaria (non-immune) or
lapsed immunity
(6.) Pre-existing organ failure.
52

53. Cerebral malaria
severe complication of falciparum malaria
mortality of 30-50%
associated with sequestration in micro-vasculature of
brain
a diffuse encephalopathy with loss of consciousness
53

54. Mal…
Infections caused by P. vivax, P. ovale or P. malariae are rarely life
threatening
 no Cytoadherence of parasitized cells
 parasitic densities are lower
Relapses are a feature of vivax and ovale malaria
Recrudescences are a feature of P. malariae
P. malariae is nephritic syndrome which may progress to renal failure.
 

54

55. Genetic factors That Provide
Protection Against Malaria
1.Nature of hemoglobin
Hgb S (Sickle cell anemia trait) –p.f
Thalassemia Hgb-P.f
Fetal Hgb – all sps
Hgb E – P.v
2. Enzyme content of erythrocyte
Glucose-6-phosphate dehydrogenase deficiency ,-P.f
3. Presence or absence of certain factor
 Ovalocytosis -P.f & P.v
 Duffy blood group antigens (i.e., Fya and Fyb) negative
RBCs-P.v
55

56. Laboratory Diagnosis
56

57. Laboratory diagnosis
Clinical Diagnosis
Microscopic
•Thin film
•Thick film
• QBC
Immunological
Ag /enzyme
•RDT.ICT Malaria PfICT Malaria Pf
ParaSight FParaSight F
OptiMALOptiMAL
Ab- ELISA
Molecular
PCR
etc.
Malaria Diagnosis
MALALRIA Diagnostics approachesMALALRIA Diagnostics approaches
57