Plasmodium
Pathogenic;
Non-pathogenic (commensals);
Cytopharynx
Micronucleus
Macronucleus
Food reserve
Cilia
Contractile vacuole
Cytoproct
Trophozoite
Entamoeba, Naegleria,
Lobosea
Acanthamoeba
Apicompl- Plasmodium, Toxoplasma,
Sporozoea Cryptosporidium, Isospora
exa
Kinetofragm-
Ciliophora Balantidium
inophorea
The four major groups of protozoa parasite in human
(conveniently listed as subphyla)
Life Cycle Stages
Trophozoite: Actively growing and
reproducing stage
Opportunistic pathogenicity
Not normally pathogens
Become pathogenic due to impairment of hosts resistance
Clinical importance of the AIDS epidemic, cancer patients,
Patients undergoing radiotherapy or chemotherapy and organ
transplant patients.
Ecological Niches in the Human Body
Skin: Leishmania;
Eye: Acanthamoeba;
Mouth: Amoebae and flagellates (usually non-pathogenic);
Gut: Giardia, Entamoeba (and invasion to liver),
Cryptosporidium, Isospora, Balantidium;
G.U. tract: Trichomonas;
Bloodstream: Plasmodium, Trypanosoma;
Spleen: Leishmania;
Liver: Leishmania; Entamoeba;
Muscle: Trypanosoma cruzi;
CNS: Trypanosoma, Naegleria, Toxoplasma, Plasmodium.
Plasmodium
Malaria parasite
SEATTLE, WA Congressman Jim McDermott (D-
WA) issued the below statement following Time
magazine's article yesterday that a major advance
toward the first-ever malaria vaccine was among the
top 10 Medical Breakthroughs of 2011. The trial
malaria vaccine was developed through the efforts
of two Seattle-based organizations PATH and the
Bill & Melinda Gates Foundation as well as
GlaxoSmithKline.
I want to congratulate the dedicated people at PATH Malaria
Vaccine Initiative, Bill & Melinda Gates Foundation,
GlaxoSmithKline, and researchers in Africa for bringing us close to
a first-ever malaria vaccine. It is fitting that Time magazine featured
this remarkable achievement second on a list of top ten medical
breakthroughs of 2011. On behalf of the people of Seattle, I want to
say that we are especially proud of the work of PATH and the Gates
Foundation recognized leaders in the field of global health that we
are fortunate to have right here in Seattle. Now comes the critical
part of sustained engagement the U.S. government should seize
this historic opportunity to end malaria by dedicating resources to
complete the work towards a vaccine. Now is not the time to pull
back on funding for USAID, a major funding agency for malaria
vaccine research.
Plasmodia habiting in RBC
Two cells burst open and merozoites released from them
Ruptured
Enlarged;
Pale;
Alleviated density.
Children under 5 are the major at
risk group in malarious regions.
Malaria is a major
public health problem
in warm climates
especially in
developing countries.
It is a leading cause of
disease and death
among children under
five years, pregnant
women and non-
immune travellers and
immigrants due to an
anopheles mosquito
taking a blood meal.
What is malaria ?
Malaria is a disease caused by the protozoan parasites of the
genus Plasmodium. The 4 species that commonly infect man are:
Malaria is transmitted by the female anopheles mosquito. Factors which affect mosquito ecology, such as temperature
and rainfall, are key determinants of malaria transmission. Mosquitoes breed in hot, humid areas and below altitudes of
2000 meters. Development of the malaria parasite occurs optimally between 25-30oC and stops below 16oC. Indigenous
malaria has been recorded as far as 64oN and 32oS.
Malaria has actually increased in sub-Saharan Africa in recent years. The major factor has been the spread of drug-
resistant parasites. Other important factors include the persistence of poverty, HIV/AIDS, mosquito resistance to
insecticides, weak health services, conflict and population migration.
Distribution of malaria in China in 1995
24,000 cases
reported with 39
deaths in 2000 in
China
Distribution of malaria in China in 1950
About 30 million
cases/year before
1949
History
An old disease, and an major health problems in the tropics today.
In 1880:
Laveran: found plasmodia in blood of a patient with malaria -
Nobel Prize of 1907.
In 1897:
Ross --- found only anopheles mosquitoes could transmit malaria -
Nobel Prize of 1902 (the first-ever medical Nobel Prize).
After 1950
World wide
Year Number of patients Morbidity(1/100,000) Death
China
Year Number of patients Morbidity(1/100,000) Death
4. Mature schizont
Nucleus divided into 12-24, and
cytoplasm also divided; each
nucleus was surrounded by a portion
of cytoplasm to form a merozoite;
malarial pigment clumped.
5. Male gametocyte
Oval in shape; one loose nucleus in the
centre; malarial pigments diffusing.
6. Female gametocyte
Oval in shape; one compact nucleus in
the side of it.
Morphological features of P.
falciparum
Early trophozoite (ring form)
1or 2 red nuclei on the ring-like light blue
cytoplasm; multiple infection in a cell.
Female gametocyte
New moon in shape; 1
compact nucleus in the
centre.
Life cycle
Reproduction Patterns
1. Sporozoite / liver,
2-5. Mitosis, liver cell lysis,
6. Trophozoite / red blood cell,
7-11: Mitosis,
12. Gametocytes (via meiosis),
13,14. Gametes via mitosis
(midgut),
15,16. Ookinetes, zygotes via
conjugation, cross the midgut
epithilium,
17. Oocysts, mitosis,
18-20. Cross salivary epithelium.
Infective sporozoite in female anopheles
(exoerythrocytic phase)
Schizont containing merozoites in
human liver cells (reproduce asexualy)
(intraerythrocytic phase)
Mature schizont (merozoites) in human RBC
(reproduce asexualy)
Periodic
gametocytes paroxysm
RBC rupture release merozoites
Anopheles parasite debris, pigments and metabolites paroxysm
(reproduce sexualy)
Life cycle of plasmodium in human
(In female anopheles) infective sporozoite
blood circulation of human human liver cells :
schizont containing merozoites (tachysporozoites for
1-2 weeks, bradysporozoites for 3 - 6 months relapse,
exoerythrocytic phase) pour into blood circulation
by liver cell rupture invade RBC: merozoite
ring form trophozoite schizont containing
merozoites (intraerythrocytic phase)
Periodic paroxysm
gametocytes female anopheles
RBC rupture , release merozoites
parasite debris, pigments and metabolites
clinical paroxysm (chill and fever) human body
Development of plasmodium in
anopheles
Gametocytes in blood circulation of human
bitted by female anopheles, sexual reproduction:
(gametocytes zygote ookinete
oocyst containing sporoblasts infective
sporozoite ) humans blood circulation by
bite
Three Main (Human) Stages
Stage I : Upon infection by the mosquito, the malaria parasites move
rapidly into the liver (within ~ 30 minutes ), and reproduce rapidly
(mitosis) for 5 days or more, depending on the species ( P. falciparum or P.
vivax).
Stage II : The malaria parasites release from liver cells, enter the
bloodstream and within minutes invade red blood cells where they grow
and divide. Every 48-72 hours (time differences depend on the species) a
batch of infected red blood cells rupture and disperse more parasites
along with waste products/toxins into blood stream of human. This step
causes fever, chills and anemia in the victim. The released parasites then
invade other red blood cells, begin the cycle again.
Stage III: After invading red blood cells some
parasites develop into a sexual form-male or female
gametocytes. As soon as anopheles mosquitoes bite
human hosts, the gametocytes are sucked, and then
mate each oher and reproduce inside the mosquitoes.
Afterwards, zygotes (ookinetes) make their way to the
salivary glands of the mosquitoes and ready to infect
another victim when the mosquitoes take their next
blood meal.
Characteristic of life cycle
Intermediate host: human
1-2h of chills
40
P. v.
36
40
P. f.
36
Mechanism of typical paroxysm
Merozoites
Swallowed by Endogenous
Erythrocytic debris
WBC / M heat-inducers
Metabolic productions
Hypothalamic
thermoregulatory
center
Hypersplenism:
(2) Phagocytes not only clear invaded red cells through recognition of
receptors on the infected red cells but also swallow large number of
normal red cells driven by incorrect identification mechanism;
Mechanism:
(1) Proliferation of mononuclear phagocytes
results to hyperemia of spleen;
(2) Repeated infection leads to proliferation
of fibrous tissue
Complications
Hemolytic urinemic syndrome
(Black water fever)
Often occurs in patients with G-6-PD (Glucose -6 - phosphate
dehydrogenase) deficiency and may be induced by primaquine
treatment, heavy infection (high parasitemia) of P. falciparum or
an atypical immune response during reinfection.
Severe malaria
A. Asymptomatic parasitaemia
This is usually seen in older children and adults
who have acquired natural immunity to clinical
disease as a consequence of living in areas with
high malaria endemicity. There are malaria
parasites in the peripheral blood but no symptoms.
These individuals may be important reservoirs for
disease transmission.
Some individuals may even develop anti-parasite
immunity so that they do not develop parasitaemia
following infection.
B. Simple, uncomplicated malaria
This can occur at any age but it is
more likely to be seen in individuals
with some degree of immunity to
malaria. The affected person, though
ill, does not manifest life-threatening
disease.
Epidemiological data
Clinical manifestations
Laboratory findings
Epidemiological data
History of living in or traveling to epidemic
areas.
History of blood transfusion.
Neonates born by malaria mothers.
Clinical manifestations
Periodic paroxysms with shaking chills, high
fever, sweating.
Anemia and splenomegaly may present.
Fever patterns may be irregular in some cases.
Laboratory findings
WBC, RBC, Hb:
Normal white blood cell count, decreased red blood cell
count and hemoglobin level.
Thick blood film - Used for detecting malaria: a larger volume of blood is
examined allowing detection of even low levels of parasitaemia. Also used for
determining parasite density and monitoring the response to treatment.
Thin blood film Gives more information about the parasite morphology and,
therefore, is used to identify the particular infecting species of Plasmodium.
Serologic tests : not so important
Test antibody against plasmodium
Test DNA of plasmodium by PCR:
high sensitivity
Therapeutic trial is not advocated
because of the side effects of
chloroquine and primaquine.
Differential diagnosis
septicemia
leptospirosis
typhoid fever
bile duct infection
Japanese encephalitis
toxic form of shigellosis
Septicemia
3. Individual protection
Immunity
Congenital immunity