The plasmodia are sporozoa in which the sexual and
asexual cycles of reproduction are completed in
different host species.
The sexual phase occurs within the gut of the female
anopheles mosquito. The sexual cycle is called
Sporogony, as it results in the generation of
The asexual cycle occurs in humans and is called
Schizogony, as it results in the formation of
The life cycle of plasmodia begins with the release of
sporozoites from the saliva of the infecting mosquito
into the blood stream.
These released sporozoites circulate in the subcutaneous capillaries and circulate in the peripheral
Within 30 minutes or an hour, they attach to and
invade the hepatocytes, a process believed to be
mediated by a ligand present in the sporozoite outer
After attachment, the merozoite invaginates the cell
membrane and is slowly endocytosed.
The intracellular parasite initially occurs as a ring shaped
trophozoite, which emlarges and becomes more active and
irregular in outline.
Within a few hours, nuclear division occurs producing the
multi-nucleated schizont. Cytoplasm condenses around
each nucleus of the schizont to form a cluster of 6-24
merozoite daughter cells.
About 48-72 hours after the initial invasion the infected
erythrocytes rupture releasing the merozoites and
producing the first clinical manifestations of the disease.
The newly released daughter cells invade other RBC’s, where
most repeat the asexual cycle. Fever, the hallmark of malaria
appears to be initiated with the release of merozoites.
It is believed that the parasite-derived pyrogens may be the
reason. Alternatively, fever may result from the release of
interleukin-1 and/or TNF from the macrophages involved in the
ingestion of the parasite or erythrocytic debris.
Early in malaria, RBS’s appear to be infected at several different
stages of the development of the parasite, as each induces
sporulation at different times. The resulting fever, thus is
irregular and hectic, that may reach 40-41.7 degree centigrade.
This kind of temperature destroys mature parasites and
ultimately a single population emerges, sporulation is
synchronized and fever occurs in distinct paroxysms at 48 or 72
Other daughter cells that do not invade RBC’s are transformed
into sexual forms or gametocytes that differentiate into female
microgamete and male macrogametes. These do not lyse RBC’s
and continue to circulate in the peripheral blood until ingested
by the mosquito.
Sporogony, or the sexual cycle begins in the gut of the
mosquito, when the gametocytes mature and effect fertilization.
The resulting zygote penetrates the gut wall and vacuolates to
form an oocyst where thousands of sporozoites are formed.
The enlarging cyst finally ruptures, releasing the sporozoites
into the body cavity of the mosquito which then penetrates the
salivary glands rendering the mosquito infectious at the next
Pathogenesis and clinical findings:
All the pathological findings of malaria result from the destruction of RBC’s.
The incubation period between the bite of the mosquito and onset of disease
is approximately 2 weeks.
The clinical manifestations vary with the species of plasmodia but typically
include chills, fever, splenomegaly and anemia.
Anemia manifests due to the parasitized erythrocytes engulfed by the
stimulated reticuloendothelial system or are destroyed at the time of
Depression of marrow function,sequestration of erythrocytes within the
enlarging spleen, and accelerated clearance of non-parasitized cells all appear
to contribute to anemia (mechanism unclear).
The enlarged spleen characteristic of malaria is due to the congestion of the
sinusoids with erythrocytes coupled with hyperplasia of lympohocytes and
Infection with P.falciparum is far more severe and it is characterized
by infection of far more red cells than other plasmodia spp.
Untreated P.falciparum infection, results in the blocking of capillaries
with the aggregates of parasitized red cells. This may lead to
intravascular hemolysis, which when massive results in
hemoglobinuria resulting in dark urine and hence the name
blackwater fever. Hemoglobinuria can also lead to acute renal failure.
The blocking of capillaries impair the microcirculation and precipitate
tissue hypoxia, lactic acidosis and hypoglycemia. Although deep
tissues are involved, the brain is the most commonly affected. This
manifests in cerebral malaria. The patient may develop delerium,
convulsions, paralysis,, coma and rapid death, usually within 3 days.
Acute pulmonary insufficiency frequently accompanies cerebral
malaria and may be the leading cause of death in such cases.
Thrombocytopenia is common in malaria and may be related to both
splenic pooling and a shortened platelet life span.
Involvement of visceral capillaries may result in vomiting, abdominal
pain and diarrhea with or without bloody stools
The clinical findings include the malarial paroxysm.
This begins with a cold stage, which persists for 20-60 minutes. The
patient experiences continous rigours and feels cold.
With the consequent increase in the body temperature, vasodilation
commences, ushering in a hot stage. The temperature may rise a
maximum of 104-107 degrees farenheit before it begins to fall.
The wet stage consists of a decrease in fever and profuse sweating. It
leaves the patient exhausted, otherwise well, till the next onset of
Typical paroxysms first appear in the second or third
week of fever, when the parasite sporulation becomes
In falciparum malaria, the synchronization may never
take place and the fever remains hectic and
Other symptoms include headache, myalgias and
A quick species and strain specific immunity is possible
due to the high levels of antibodies developed that
typically limits the parasite multiplication and
moderates the clinical manifestations of the disease
known as Premunition, with eventual recovery.
Individuals with sickle-cell trait are protected as their
RBC’s appear to have too little ATPase activity and
cannot produce sufficient energy to support the growth
of the parasite.
Individuals homozygous recessive for duffy antigen.
Individuals with G6PD deficiency .
Laboratory diagnosis involves the microscopic
examination of peripheral blood stained with
Thick smears for presence of parasites.
Thin smear for species identification.
The appearance of each of the 4 species is sufficiently
different for identification on which the treatment
The parasitized erythrocyte in vivax and ovale infection is pale, enlarged and
contains numerous red nuclear chromatin, known as Shuffner’s dots. All
asexual stages (trophozoite, schizont, merozoite) may be seen simultaneously.
Ovale infected cells are elongated, frequently irregular and fimbriated in
Maliariae infected cells are not enlarged and do not contain granules. The
trophozoites are seen as band forms and the merozoites are arranged in
rossettes around a clump of central brownish-black malarial pigment or
hemozoin, a hemoglobin degradation product.
The trophozoites of falciparum have small rings with the infected cells often
showing more than one parasite lying against the margins of the cell.
Intracytoplasmic granules known as Maurer’s dots may be present, fewer in
number than the Schuffner’s dots.
Schizonts and merozoites are not present in the peripheral blood.
Gametocytes of falciparum are large and sausage or banana or crescent
shaped. Other plasmodia gametocytes are spherical.
If more than 5% of red cells are parasitized is indicative of falciparum.
An ELISA test detects a protein HPR2, specific for
PCR based test for plasmodium nucleic acids are also
Another rapid test “Optimal” to detect parasite
lactate dehydrogenase is available and is able to
distinguish between falciparum and vivax.
Treatment and Prevention:
Chloroquine is the drug of choice for acute malaria.It
kills the merozoites.
P.falciparum strains resistant to chloroquine are
increasing. Chloroqine also does not affect the
hypnozoites of vivax and ovale in the liver (cause of
Primaquine effective against the hypnozoites, but can
induce severe hemolysis in G6PD deficient
individuals. Hence, individuals should be tested for
G6PD deficiency before administering primaquine.
Chloroquine and Mefloquine(schizonticidal agent)
resistant strains of falciparum treated with Malarone
(combination of atovaquone and proguanil).
In severe falciparum cases, intravenous quinidine or
quinine along with another anti-malarial such as
Doxycycline or Clindamycin can be used.Artemisinins
like artesunate or artemether are inexpensive with
fewer side effects. Resistance to artesunate emerging
from falciparum .
Artemether and Lumefantrine in combination can be
useful in such cases.
Prevention includes chemoprophylaxis of doxycycline or
mefloquine or Malarone for travellers to chloroquine
resistant falciparum endemic places.
For other plasmodia, chloroquine starting 2 weeks before
arrival and 6 weeks after departure from endemic places.
Followed by 2 week course of primaquine to kill
Mosquito nets, repellents etc… useful.
DDT and other insecticide sprays not effective any more.
Drainage of stagnant water pools effective to prevent
breeding of mosquitoes.
No vaccine yet.