The Disease
The average incubation period from mosquito bite to onset
of disease is 2 weeks or longer. Symptoms of malaria will
vary depending on which species of Plasmodium is
involved. Classic malaria symptoms involve the occurrence
of cyclic paroxysms, during the erythrocytic stage of Plasmodium
life cycle. Cyclic paroxysms are periodic attacks of chills
and fevers (40°C to 42°C). These symptoms are caused
by the sudden release of Plasmodium merozoites, toxins,
and erythrocyte debris into the bloodstream. Other symptoms
of malaria may include profuse sweating, dehydration, diarrhea
(not bloody) and vomiting, headache, muscle pains, anorexia,
jaundice, exhaustion, enlargement of the liver (hepatomegaly),
enlargement of the spleen (splenomegaly), and anemia.
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P. falciparum is the cause of almost all severe
and fatal malaria, and patients suspected of having malaria
should be always be screened for P. falciparum infection
as soon as possible. This parasite invades a much higher percentage
of host red blood cells and reproduces faster than the other
Plasmodium species. P. falciparum produces
a protein which is expressed on the red blood cell membrane
that causes the RBC to adhere to endothelial cell surface
receptors. This obstructs blood circulation in vital organs
such as the brain and kidney.
P. falciparum infections produce cyclic paroxysms
every 36-48 hours, however there are some instances where
patients exhibit a constant fever instead of a periodic one.
Potentially life-threatening complications include cerebral
malaria, pulmonary insufficiency, jaundice, anemia, and renal
failure. High parasitemia is associated with this type of
malaria. This type of malaria has a mortality rate of >20%
and most deaths will occur within 3 days of disease onset.
To make matters worse, P. falciparum strains resistant
to the anti-malarial drug chloroquine are becoming more common.
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P. vivax is rarely lethal. Since P. vivax
only invades new blood cells, it is rare if more than 1% of
host red blood cells become infected. Cyclic paroxysms occur
every 48 hrs. Some P. vivax drug resistance is present
in Oceania, but most strains outside these areas are susceptible
to chloroquine. P. vivax is capable of long term
latent infection of hepatocytes after elimination of parasites
from the bloodstream. The parasites can stay dormant in the
liver, and re-emerge months to years later.
P.ovale is rarely lethal and rarely invades more
than 1% of host red blood cells. This type of malaria is rare
outside of Africa and drug resistance is rare. Cyclic paroxysms
occur every 48 hrs. Like P. vivax, this parasite
is capable of establishing long term latent infections of
hepatocytes and can re-emerge months to years later.
This type of malaria produces the mildest and most chronic
symptoms. P.malariae only infects older mature red
blood cells, resulting in low parasitemia. Attacks might reoccur
for 30 to 50 years later, but severity will decrease over
time. Cyclic paroxysms occur every 72 hours. P. malariae
has widespread sporadic distribution.
Once a person contracts malaria, the most important determinants
of survival are early diagnosis and prompt initiation of appropriate
therapy. A fever in a person returning from the tropics should
be treated as a case of malaria until proven otherwise. There
are three general methods to demonstrate the presence of parasites
within erythrocytes:
Microscopy
Blood samples are taken twice daily over several days from
a finger-prick. Thick blood smears are used to identify the
presence of Plasmodium. Thin smears are used to identify
the species of Plasmodium. One negative smear does
not rule out malaria. Thick smears offer greater sensitivity,
as more red blood cells are on a single slide. Thin smears
have less blood cells and shows undistorted parasites, making
it easier to examine the morphological changes that are characteristic
to each species of Plasmodium.
| Identifying Plasmodium
Species using Microscopic Observations |
| Organism |
Parasitemia |
RBC types affected |
Infected RBC Morphology |
| P. falciparum |
high |
Most RBC types |
Does not cause enlargement of infected RBC's. |
| P. vivax |
rarely above 1% |
Reticulocytes |
Causes infected RBC's to enlarge. |
| P. ovale |
rarely above 1% |
Reticulocytes |
Causes infected RBC's to enlarge. 20%-70% of infected
RBC's have oval shape with jagged edges. |
| P. malariae |
low |
Older, mature RBC types |
Does not cause enlargement of infected RBC's. |
Of the three techniques for malaria detection, only microscopy
can quantify parasite densities (parasitemia) which is useful
in determining the effectiveness of treatments and progression
of disease. The blood smears produced by this method can be
used as a permanent record of infection. The reliability of
microscopic techniques is dependent on the availability of
skilled and experienced technicians.
Serological methods
Several rapid diagnostic tests have been developed which
detect malaria parasite antigens in lysed blood using monoclonal
antibodies. Histidine-rich protein II (HRP2) and parasite
lactate dehydrogenase (pLDH) are examples of antigens used
for detection of malaria parasites. Kits which detect HRP2
can only detect this protein from samples containing P.
falciparum.
Rapid diagnostic tests are easier and faster to perform and
interpret. They are more suitable for use in the field because
they do not require electricity, special equipment, or technicians
skilled in microscopy. These kits do not require special conditions
when being shipped or stored.
Unfortunately, there are currently no rapid diagnostic tests
on the market which can differentiate P. vivax, P.
ovale, or P. malariae. These tests are not quantitative
and will not provide any information concerning levels of
parasitemia. Antigen persistence, is also a problem. When
treatment for malaria is successful, rapid diagnostic tests
will still be positive, since the antigens which the test
detects is still persistent in the bloodstream.
Molecular Detection
PCR testing offers a rapid, sensitive, and less subjective
method to determine the presence and species of Plasmodium.
Unfortunately, PCR-based malaria tests are expensive and not
yet commercially available. PCR testing for malaria is not
well-suited for application in the field, since it is the
most expensive, requires electricity, specialized equipment,
an very clean laboratory conditions.
Correct therapy requires an accurate diagnosis. The aim
of therapy is to terminate the acute attacks and prevent relapse.
Chloroquine is drug of choice for all malaria infections except
chloroquine-resistant P.falciparum. Chloroquine is
a safe drug when used in the proper doses. Side effects of
chloroquine use include a bitter taste, nausea, headache,
and overdoses are frequently fatal.
Chloroquine is effective in treating the parasites within
red blood cells, but it does not kill parasites that exist
outside red blood cells. In order to kill parasites outside
red blood cells, other drugs like primaquine must be used.
In severe and complicated cases, a combination of anti-malarial
drugs is applied intravenously. Severe infections have a mortality
rate of 20% or higher. Due to the increasing resistance to
chloroquine, there is a need to develop new anti-malarial
agents.
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