Human Parasitology

Plasmodium

Department of Parasitology, College of

Basic Medicine, Central South University
Medical Protozoology
Introduction to Medical Protozoa
General Concepts of Protozoa:
Generally unicellular
Eukaryotic organisms
Found in every conceivable damp habitat
Approximately 60,000 living species
Largest visible to the naked eyes
Smallest could only be seen with an EM
completing all necessary life activities independently
 Protozoa are one-celled animals found
worldwide in most habitats. Most species
are free living, but all higher animals are
infected with one or more species of
protozoa. Infections range from
asymptomatic to life threatening,
depending on species and strain of the
parasites and resistance of hosts.
 Medical Protozoa

The protozoa habit in lumens, body fluid, tissues or

cells and, according to the pathogenicity, can be
categorized into:

Pathogenic;

Non-pathogenic (commensals);

Whose pathogenicity are debatable.

 Structure
All protozoa cells possess a variety of
eukaryotic structures/organelles common
to all eukaryotic cells, including cell
membrane, nuclei, endoplasmic
reticulum, mitochondria, Golgi bodies,
lysosomes, centrioles, and food vacuoles.
 Basic structure
Cell membrane:
Cytoplasm:
Motile organelle (taxonomic marker of protozoa):
pseudopodium(-dia) - amoeba; flagellum (-lla) -
flagellate; cilium (-cilia) ciliate;
Nucleus: two kinds of nuclei:
vesicular; compact.
 Locomotion - grouping protozoa morphologically
according to the mechanism of locomotion

Motile with pseudopodium Amoeba,

Entamoeba histolytica, Naegleria fowleri;

Motile with flagellum Euglena, Giardia lamblia,

Trichomonas vaginalis;

Motile with cilia - Balantidium coli, Paramecium.

 The General Structure
Food vacuole
Cytostome

Cytopharynx

Micronucleus
Macronucleus
Food reserve
Cilia
Contractile vacuole

Cytoproct
Trophozoite

Outer ectoplasm Inner endoplasm

 Each cell is a self-sufficient unit capable
of carrying out all of the metabolic
functions of which multicellular
organisms are capable
 Classified under three phyla

Phylum: Class Genera:

Sarcomasti- Zoomastigop- Trypanosoma, Leishmania,

gophora hora Giardia, Trichomonas

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

Cyst: A dormant stage, enclosed in a

cyst coat resistant to an unfavourable
environment-medical importance of
infection
 Trophozoites of Cyst of Entamoeba
Entamoeba histolytica histolytica
 Nutrition

All parasitic protozoa require preformed

organic substances as holozoic as higher
animals.
 Reproduction
Binary fission, the most common form of
reproduction among medical protozoa, is asexual;

Multiple asexual division occurs in some forms;

Sexual reproduction: takes place within the

definitive host and usually results in the formation of
a zygote;

Both sexual and asexual reproduction occur in the

Apicomplexa.
 Characteristics of Pathogenesis
Proliferation
Only invading protozoa proliferate to a certain amount can
they result to impairment to host.

Disseminating effect (Diffusion)

As soon as invading protozoa set up a primary focus, they
could diffuse towards and impair to nearby tissues and organs.

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:

Species Major features

P. falciparum The most important species as it is responsible for 50% of
all malaria cases worldwide and nearly all morbidity and
mortality from severe malaria
Found in the tropics & sub-tropics
P. vivax The malaria parasite with the widest geographical
distribution
Seen in tropical and sub-tropical areas but rare in Africa
Estimated to cause 43% of all malaria cases in the world
P. ovale This species is relatively rarely encountered
Primarily seen in tropical Africa, especially, the west coast,
but has been reported in South America and Asia
P. malariae Responsible for only 7% of malaria cases
Occurs mainly in sub-tropical climates
 The burden of malaria
The direct burden of The indirect burden of
malaria morbidity and malaria
mortality Human development: Impaired
Every year, there are about 500 intellectual development,
million clinical attacks of developmental abnormalities
malaria. Of these, 2-3 million (especially following cerebral
are severe and about 1 million malaria), lost school attendance
people die (about 3000 deaths and productivity at work
every day). Economics: Malaria retards
Malaria in pregnancy accounts economic development in the
for about 25% of cases of developing world. The cost of a
severe maternal anaemia and single bout of malaria is
10-20% of low birthweight. equivalent to over 10 working
Low birthweight due to malaria days in Africa. The cost of
accounts for about 5-10% of treatment is between $US0.08
neonatal and infants deaths. and $US5.30, depending on the
type of drugs prescribed as
required by the local pattern of
drug resistance.
Geographical Distribution of Malaria
Although previously
widespread, today
malaria is confined
mainly to Africa, Asia
and Latin America.
About 40% of the
worlds population is at
risk of malaria. It is
endemic in 91 countries,
with small pockets of
transmission occurring
in a further 8 countries.

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.

2000 years ago:

Symptom and therapy about malaria were described in ancient
Chinese medicine books

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

1950 25 million 1000 2.5 million

2002 50 million 920 1.5-2.7 million

China
Year Number of patients Morbidity(1/100,000) Death

1950 30million 750 0.30 million

1992 74,000 0.64 52

1999 29,000 0.24 67

2002 3.5298 0.34 42

 Etiology
There are four important species
that infect humans, causing malaria:
* P. vivax - benign tertian malaria accounts for ~
43% of cases;
* P. falciparum - malignant tertian malaria
accounts for ~ 50% cases;
* P. malariae - quartan malaria accounts for ~
7% of cases
* P. ovale - mild tertian malaria accounts for <
1% of cases.
Morphology
P. v P. f P. m P. o
 Wrights stain --- red nuclei, blue
cytoplasm and brown malarial
pigments;

Morphological features of P. vivax

1. Early trophozoite (ring form)

1 red nucleus on the ring-like light blue

cytoplasm; single infection in a cell.

The infected RBCs were basically as same

as normal RBCs.
 2. Late trophozoite
It was irregular in shape and alike
amoeboid form with pseudopodia;
within cytoplasm, brown pigment
granules (malarial pigment ---
haemozoin) appeared.

infected RBCs were pale in

color, and had schuffners dots
on it (fine red granules).
 3. Immature schizont
Oval in shape; nucleus divided into
2-4 or more; malarial pigment began
to concentrate in a mass.

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.

Infected RBC being alike normal RBC

Only the early trophozoites and
gametocytes of P. falciparum can be
seen in the peripheral blood .
 Male gametocyte
Banana in shape; 1 loose
nucleus in the centre;
malarial pigment diffusing.

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

Final host: female anopheles mosquito

Infective stage: sporozoite

Infective way: mosquito bite skin of human

Parasitic position: liver cells and red blood cells

Transmitted stage: gametocyte

Schizogonic cycle in red cells: 48 hrs/P.v

Sporozoite: tachysporozite (1-2 weeks) and

bradysporozite (3-6 months)
The time for one intraerythrocytic cycle
P. v.: 48h
P. f. : 36-48h
P. m.: 72h
Number and shape of merozoites in mature
schizont
P. v.: 12-24, irregular
P. f.: 8-36, irregular
P. m.: 6-12, daisy-like
 Gametocyte form

Intraerythrocytic phage of merozoites

macrogametocyte and microgametocyte
P. v.: 2-3d
P. f.: 7-10d
Without transmission significance as the
number of gametocytes < 12 per 1mm3 blood
Morphological changes of
parasited RBCs
P. v.: enlarged; Schuffners dots

P. f.: normal; Maurers dots

P. m.: normal; Simons dots

 The types of RBC
chosen by malaria spp.

P. v.: Immature RBCs

P. f.: All kinds of RBCs

P. m.: Aging RBCs

 Nutritional metabolism
Glucose metabolismthe main energy resource during
intraerythrocytic phase;

Protein metabolism: under the synergy of acidic endopeptidase and

aminopeptidase, hemoglobin in red cells were digested and
decomposed into globin and hemosiderin. The globin were
redecomposed into several amino acids under function of several
enzymes for synthesis of proteins necessary for the parasite. The
remaining hemosiderin deposited and eventually formed malaria
pigments.
Nucleic acid metabolism
Lipid metabolism:
 Endemicity

Endemicity refers to the amount or severity

of malaria in an area or community.
Malaria is said to be endemic when there is
a constant incidence of cases over a period
of many successive years.
 Endemic malaria may be present in various degrees.
Recognised categories of endemicity include :
A. Hypoendemicity - little transmission and the disease has little effect on the
population.
B. Mesoendemicity - varying intensity of transmission; typically found in the small,
rural communities of the sub-tropics.
C. Hyperendemicity - intense but seasonal transmission; immunity is insufficient to
prevent the effects of malaria on all age groups.
D. Holoendemicity - intense transmission occurs throughout the year. As people are
continuously exposed to malaria parasites, they gradually develop immunity to
the disease. In these areas, severe malaria is mainly a disease of children from the
first few months of life to age 5 years. Pregnant women are also highly
susceptible because the natural immune defence mechanisms are impaired during
pregnancy.
How is malaria
transmitted?
Malaria parasites are
transmitted from one person
to another by the bite of a
female anopheles mosquito.
The female mosquito bites There are about 380 species of
during dusk and dawn and anopheles mosquito but only
needs a blood meal to feed about 60 are able to transmit
malaria.
her eggs.
Like all mosquitoes, anopheles
Male mosquitoes do not
breed in water - hence
transmit malaria as they feed
accumulation of water favours
on plant juices but not blood. the spread of the disease.
 Pathogenesis
Incubation period:
The time necessary for completing the exoerythrocytic
development in addition to the time needed to arrive the
fever threshold.
Fever threshold:
The lowest blood protozoa density to result in fever.
Paroxysm:
Typical paroxysm:
A periodic chills and fevers resulted from fission
proliferation of intraerythrocytic phase of the protozoa;
 Typical paroxysm of P. v.

1-2h of chills

40h of interval 4-6h of fever

4 8h

2-4h of sweating and

bringing down a fever
 Relations between malaria fever types and the
development during intraerythrocytic phase
1th day 2th day 3th day 4th day

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

Chills and fevers

Atypical paroxysm:
Usually resulting misdiagnosis.
Reasons: initial paroxysm of malaria; mixed infection; children and non-
immunity population; improper treatment.
Relapse (relevant to liver stage):
It is a recurrence of symptoms which takes place after complete clear of
initial erythrocytic infection without reinfection and implies reinvasion
of the blood stream by merozoites transformed from activated
bradysporozoites in liver.
Recrudescence (relevant to erythrocytic stage):
It is a recurrence of symptoms in a patient whose parasite density in
blood stream is at such a low level that not to be clinically demonstrable
or there is not apparent symptoms, which is induced by non-standard
pathogenic therapy or drug resistant plasmodium (merozoites ).
Types of sporozoites and relapse
Relapse --- Appear clinic signs of malaria about three to six
months or longer after primary attack.
P. vivax and P. ovale:
Two types of sporozoites:
Tachysporozoites --- induce primary attack
Bradysporozoites --- result in relapse
P. malariae and P. falciparum:
Only tachysporozoite stage, without bradysporozoite stage,
no relapse in malaria caused by P. malariae and
P. falciparum.
Anemia
Directly destroy red cells by plasmodium;

Hypersplenism:

(1) Mechanism of self-protection demands spleen to produce more

phagocytes to clear invaded red cells, debris and metabolism
productions of plasmodium, which will result to 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;

(3) Big amount of red cells are sequestrated in enlarged spleen

 Depression of born marrow function;

Immunopathogenesis: exploration of hidden antigens on

red cell debris will stimulate immune system to produce
autoantibodies and further Ag-Ab complexes to resolve
debris. Similarly, the autoantibodies will also identify
the epitopes on normal red cells to lead to resolve
normal red cells
Splenomegaly

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.

Massive RBC rupture and hemolysis shows hyperhemoglobinemia,

lumbago (backache), malarial hemoglobinuria, anemia, jaundice,
acute renal failure.
 Nephropathic syndrome

Usually occurs in cases of p. malariae infection.

Patients with hypertension, edema, massive
protein in urine, etc.
 Severity of disease and host factors
In addition to parasite factors, several host
factors determine the outcome of exposure to
malaria:
Naturally-acquired immunity: People who are constantly
exposed to malaria gradually acquire immunity, firstly against clinical
disease and later against parasite infection. Clinical manifestations of
malaria are most severe in the non-immune. In holoendemic areas,
these are children aged <5 years and pregnant women (especially
primigravidae). People of any age from areas that are free from
malaria, or have limited malaria transmission, are at risk when they
are exposed to malaria.
 Red cell and haemoglobin variants:
Well known examples of inherited factors that protect against malaria are
Haemoglobin S carrier state, the thalassaemias and Glucose-6-phosphate
dehydrogenase (G6PD) deficiency. Malaria provides the best known example
whereby an environmental factor (malaria) has selected human genes because of
their survival advantage.

Foetal haemoglobin (HbF):

High levels of HbF occur in neonates, and in some people with inherited
haemoglobin variants, protect against severe forms of P. falciparum malaria.
Duffy blood group:
P. vivax requires the Duffy blood receptor to enter red blood cells. Therefore, people
who do not carry the Duffy blood group are resistant to this malaria species. This
explains the rarity of P. vivax in Africa, as most Africans are Duffy blood group
negative.
The clinical course of P. falciparum
Following a bite by an infected mosquito, many
people do not develop any signs of infection. If
infection does progress, the outcome is one of three
depending on the host and parasite factors:

Asymptomatic parasitaemia (clinical immunity)

Acute, uncomplicated malaria

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.

Fever is the most constant symptom

of malaria. It may occur in
paroxysms when lysis of red cells
releases merozoites resulting in fever,
chills and rigors (uncontrollable
shivering).
 Other features of simple, uncomplicated
malaria include:
o Vomiting
o Diarrhoea more commonly seen in young children and,
when vomiting also occurs, may be misdiagnosed as viral
gastroenteritis;
o Convulsions commonly seen in young children. Malaria
is the leading cause of convulsions with fever in African
children.
o Pallor resulting mainly from the lysis of red blood cells.
Malaria also reduces the synthesis of red blood cells in the
bone marrow.
o Jaundice mainly due to haemolysis.
 Malaria is a multisystem disease. Other common
clinical features are:
o Anorexia
o Cough
o Headache
o Malaise
o Muscle aches
o Splenomegaly
o Tender hepatomegaly
These clinical features occur in mild malaria.
However, the infection requires urgent diagnosis
and management to prevent progression to severe
disease.
 C. Severe and complicated malaria
Nearly all severe disease and the estimated >1 million deaths from
malaria are due to P. falciparum. Although severe malaria is both
preventable and treatable, it is frequently a fatal disease.
The following are 8 important severe manifestations of malaria:

5. Acute renal failure

1. Cerebral malaria
6. Pulmonary oedema
2. Severe malaria anaemia
7. Circulatory collapse, shock
3. Hypoglycaemia
or algid malaria
4. Metabolic acidosis
8. Black water fever

Note: It is common for an individual patient to have

more than one severe manifestation of malaria!
Summary of differences in the clinical
features of severe malaria in adults and
children Frequency of occurrence

Clinical Manifestation Children Adults

Similar in adults and children
Prostration +++ +++
Circulatory collapse + +
More common in children
Cerebral malaria +++ ++
Severe anaemia +++ +
Multiple convulsions +++ +
Metabolic acidosis +++ +
Hypoglycaemia ++ +/-
More common in adults
Jaundice + +++
Pulmonary oedema +/ - ++
Haemoglobin uria +/ - +
Abnormal bleeding +/ - +
Renal failure +/ - +
 Diagnosis

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 and thin blood smear (Giemsa stain)

Plasmodium species are found in thick and thin blood smear,
or bone marrow smear.
--------Definitive diagnosis
Thick and thin blood smear are very simple and important
Malaria Thick Smear
Plasmodium falciparum: Blood Stage
Parasites - Thin Blood Smears

1: Normal red cell

2-18: Trophozoites
( 2-10: ring-stage trophozoites)
19-26: Schizonts ( 26 is ruptured
schizont)
27, 28: Mature macrogametocytes
(female)
29, 30: Mature microgametocytes
(male)
Plasmodium vivax: Blood Stage
Parasites - Thin Blood Smears
1: Normal red cell
2-6: Young trophozoites
(ring stage parasites)
7-18: Trophozoites
19-27: Schizonts
28, 29: Macrogametocytes
(female)
30: Microgametocyte
(male)
Plasmodium ovale: Blood Stage
Parasites - Thin Blood Smears
1: Normal red cell
2-5: Young trophozoites
6-15: Trophozoites
16-23: Schizonts
24: Macrogametocytes
(female)
25: Microgametocyte
(male)
Plasmodium malariae: Blood Stage
Parasites - Thin Blood Smears
1: Normal red cell
2-5: Young trophozoites
(rings)
6-13: Trophozoites
14-22: Schizonts
23: Developing
gametocyte
24: Macrogametocyte
(female)
25: Microgametocyte
(male)
 Diagnosis
Malaria is a multisystem disease. It presents with a wide variety of
non specific clinical features: there are no pathognomonic symptoms
or signs. Many patients have fever, general aches and pains and
malaise and are initially misdiagnosed as having flu.
P. falciparum malaria can be rapidly progressive and fatal. Prompt
diagnosis saves lives and relies on astute clinical assessment:
A good history
Residence or a recent visit (in the preceding 3 months) to a malaria
endemic area
History of fever (may be paroxysmal in nature)
Recognise significance of non-specific clinical features such as
vomiting, diarrhoea, headache, malaise
Physical examination
Identify signs consistent with malaria: fever, pallor,
jaundice, splenomegaly

Exclude other possible causes of fever (e.g. signs

of viral and bacterial infections)

The diagnosis of malaria should be considered

in any unwell person who has been in a
malarious area recently
 Investigations

Blood Film Examination

Thick and thin blood films (or smears) have remained the gold standard for the
diagnosis of malaria. The films are stained and examined by microscopy.

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

Severe toxemia symptoms, with primary

inflammation focus
Positive blood bacterial culture.
Without periodic paroxysm and intermittent
period.
 Leptospirosis

The history of contacting contaminated

water or wet soil;
enlargement of lymph nodes, persistent
high fever, myalgia of the calf muscle;
Positive agglutination-lyse test for
antibodies against leptospira species.
 Typhoid fever:
Insidious onset, sustained fever, relative
bradycardia, rose spots, positive Widals reaction
and positive blood culture for salmonella typhi.

Biliary ducts inflammation:

Sudden onset, with high fever, colic pain in right
upper part of abdomen, jaundice. Utrasonography
will be very helpful for making the diagnosis.
 Japanese encephalitis and toxic
form of shigellosis:
Should be considered in differential
diagnosis of cerebral malaria.
 Prognosis
Good in ordinary cases.

Poor in cerebral malaria and Black Water

Fever.
 Treatment
1. Symptomatic and supportive treatment
2. Etiologic treatment:
A. Control paroxysm treatment
B. Prevent relaps
C. Prevent transmission
 Symptomatic and supportive treatment
High fever, convulsion, cerebral edema, black water
fever, etc.
Keep warm for shaking chill;
Physical and chemical defervescent methods for high
fever, such as ice bag, air condition. Corticosteroid may
be given , if necessary.
Diazepam and wintermin for convulsion.
 20% Mannitol injection fluid intravenous quickly for
cerebral edema;

Dextran also is useful for cerebral malaria.

For black water fever, withdraw all anti malaria drug,

and giving dexamethason, small amount of blood
transfusion. Giving sodium bicarbonate, and must
keep more than 2000ml urine output per day.
Etiologic treatment
Treatment principle:
1. Combination anti-paroxysm treatment with
preventing from relapse and transmission treatment

2. Ordinary examining G-6-PD before giving

primaquine.

Primaquine only is given in these patients without G-

6-PD deficiency
 Anti-paroxysm
kill reproducting plasmodia in RBC
Prevent relapse
kill bradysporozoite;
primaquine, for 8 days;
Prevent transmission:
kill gametocyte
primaquine, for 3days
 For P. vivax and P. ovale malaria
Anti- paroxysm drugs and primaquine
( for 8 days) must be given to control
paroxysm, prevent from relapse and
transmission.
 For P. falciparum and P.
malariae - caused malaria
Anti-paroxysm drugs and primaguine
(for 2-4 days) must be given to control
paroxysm and to kill gametocyte for
prevent from transmmision although
prevent from relapse is not necessary.
 Control drugs and treatment of
paroxysm
Drugs
chloroquine - first choice for sensitive plasmodia

artesunate - first choice for cerebral malaria

artemisinine, pyromaridine phosphate, mefloquine,

quinine sulfate, benflumethtolum, arteflene,
naphthoquine phosphate.
Choice of drugs
1) Treatment of vivax, malariae, ovale and
chloroquine - sensitive falciparum malaria:
chloroquine

2) Radical cure of vivax or ovale malaria:

chloroquine + primaquine

3) Treatment of chloriquine - resistant falciparum

malaria: artemisinin or mefloquine or quinine
 Prophylaxis
1. Treatment of patients and
carriers

2. Control mosquito vectors

3. Individual protection
 Immunity

Congenital immunity

Duffy-negative erythrocytes are resistant to

P.v in West Africans.
 Immunity
Premunition: (similar to concomitant
immunity described in S.j)
An acquired nonsterilizing immunity;
Certain resistance against reinfection;
Dynamic effects of immunity being positively related
to protozoan burden in host;
Being able to kill most protozoa.
 Immunity
Immune evasion :
An ability of malaria parasite to evade host immunity.

Possible mechanism of evasion

1) Antigenic variation and antigen polymorphism;
2) Histological sequestration (avoiding exposure to immune
attack from host);
3) Poor immunogenicity of its antigens (analogy exists between
parasitic antigens and host molecules);
4) Alteration of immune response of host.
 vaccine
Until now, a practical vaccine against malaria spp.
isnt available. Undoubtedly, the news reported in
Times will not only bring benefits to the people
suffering from the disease, but also direct a right
way for other researches. It should be believed
that a effective vaccine is around the corner.
 Summary
Malaria is a parasitic diseases caused by plasmodium
species, and transmitted by the bite of infected female
anopheles mosquitoes;
Four top medical important species of plasmodium :
P. vivax, P. ovale, P. malariae and P. falciparum;
Primarily cccur in tropic and subtropic area;
All person are susceptible, and no last immunity;
Life cycle of plasmodium:
two hosts, two types of reproductions
 Summary
The clinical features
periodic paroxysm: shaking chills, high fever, heavy
sweating.
Anemia, splenomegaly and cerebral malaria in some of
cases.
Relapse and Recrudescence
Definite diagnosis: Plasmodium species is found in
thick and thin blood smear, or bone marrow smear.
 Summary
Etiologic treatment principle:
1.Combination anti-paroxysm with prevent replase and
transmission treatment
2. Examining G-6-PD before giving primaquine.
Control paroxysm treatment
1.chloroquine-sensitive plasmodia
first choice: chloroquine
2.chloroquine -resistant plasmodia
3. Control paroxysm for cerebral malaria
artesunate, first choice
chloroquine (sensitive plasmodia)
slowly intravenous drip ,then orally
 Summary
Prevent relapse: kill bradysporozoite:
primaquine, for 8 days
Prevent transmission: kill gametocyte:
primaquine, for 3days
primaguine only is given in the patients without
G-6-PD deficiency.
Prophylaxis: No vaccine is available
1.Treatment of patients and carriers
2.Control mosquito vectors
3. Individual protection:
Avoid mosquito bite
chemoprophylaxis