Malaria

Introduction:
Malaria is a disease caused by one of four types of Plasmodium usually
transmitted to humans by the bite of an infected female Anopheles mosquito that
previously sucked the blood from a person with malaria. Malaria is one of the
leading causes of disease and death in the world. It is estimated that there are
300-500 million new cases every year, with 1.5 to 2.7 million deaths worldwide.
It occurs extensively in tropical and subtropical regions. Malaria may have
contributed to the decline of the Roman Empire, and was so pervasive in Rome
that it was known as the "Roman fever".The term malaria originates from
Medieval Italian: mala aria — "bad air";

Etiologic Agent:-
There are four species that commonly cause disease among humans:
P. vivax, P. falciparum, P. ovale, and P. malariae. Mixed infections are possible. It
is important to understand significant differences among the several species in
terms of clinical illness, treatment, prophylaxis, and geographical distribution.
Malaria due to P. falciparum causes the most severe symptoms and requires
prompt intervention. Malaria parasites have a complex life cycle. After injection
into the human host from anopheline mosquitoes, the parasites mature in the
liver before being released into the bloodstream and invading red blood cells.
The parasites multiply inside the red blood cells, eventually rupturing the cells,
releasing more parasites into the bloodstream with accompanying high fevers.
Some parasites differentiate into sexual forms (gametocytes) which, if ingested
by another mosquito, can lead to the development of another generation of
parasites, ready for transmission to another human host. The bloodstream cycle
can persist for weeks to years, depending on the species involved. In malaria due
to P. vivax and P. ovale, a dormant stage (hypnozoites) can persist indefinitely in
the liver. Four species of Plasmodium can infect and be transmitted by humans.
Severe disease is largely caused by Plasmodium falciparum. Malaria caused by
Plasmodium vivax, Plasmodium ovale and Plasmodium malariae is generally
a milder disease that is rarely fatal.

pecies Appearance Periodicity Liver persistent

Plasmodium vivax tertian yes

Plasmodium ovale tertian yes

Plasmodium falciparum tertian no

Plasmodium malariae quartan no

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 Disease Severity and Duration
vivax ovale malariae falciparum
Severe
Initial Paraoxysm moderate to moderate to
mild
Severity severe severe
50,000-
Average
20,000 9,000 6,000 500,000
Parasitemia (mm3)

Symptom Duration
(untreated) 3-8 weeks 2-3 weeks 3-24 weeks 2-3 weeks

Maximum
Infection Duration 12-20
5-8 years 20-50+ years 6-17 months
(untreated) months

Anemia ++ + ++ ++++
Complications renal cerebral

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 Life Cycle of Malaria:-

In nature, malaria parasites spread by infecting successively two types of

hosts: humans and female Anopheles mosquitoes. In humans, the parasites grow
and multiply first in the liver cells and then in the red cells of the blood. In the
blood, successive broods of parasites grow inside the red cells and destroy them,
releasing daughter parasites ("merozoites") that continue the cycle by invading
other red cells.

The blood stage parasites are those that cause the symptoms of malaria. When
certain forms of blood stage parasites ("gametocytes") are picked up by a female
Anopheles mosquito during a blood meal, they start another, different cycle of
growth and multiplication in the mosquito.

After 10-18 days, the parasites are found (as "sporozoites") in the mosquito's
salivary glands. When the Anopheles mosquito takes a blood meal on another
human, the sporozoites are injected with the mosquito's saliva and start another
human infection when they parasitize the liver cells.

Thus the mosquito carries the disease from one human to another (acting as a
"vector"). Differently from the human host, the mosquito vector does not suffer
from the presence of the parasite

During a blood meal, a malaria-infected female Anopheles mosquito

inoculates sporozoites into the human host . Sporozoites infect liver cells and
mature into schizonts , which rupture and release merozoites . (Of note, in P.
vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and
cause relapses by invading the bloodstream weeks, or even years later.) After
this initial replication in the liver (exo-erythrocytic schizogony ), the parasites
undergo asexual multiplication in the erythrocytes (erythrocytic schizogony ).
Merozoites infect red blood cells . The ring stage trophozoites mature into
schizonts, which rupture releasing merozoites . Some parasites differentiate into
sexual erythrocytic stages (gametocytes) . Blood stage parasites are responsible
for the clinical manifestations of the disease.

The gametocytes, male (microgametocytes) and female (macrogametocytes), are

ingested by an Anopheles mosquito during a blood meal . The parasites’
multiplication in the mosquito is known as the sporogonic cycle . While in the
mosquito's stomach, the microgametes penetrate the macrogametes generating
zygotes . The zygotes in turn become motile and elongated (ookinetes) which
invade the midgut wall of the mosquito where they develop into oocysts . The
oocysts grow, rupture, and release 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.

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 Signs and symptoms:-

The classic signs and symptoms of malaria are recurrent bouts of fever,
chills, sweats, and headache. Other symptoms can occur, depending on the
severity of infection, including gastrointestinal symptoms (vomiting, diarrhea),
respiratory symptoms (cough, shortness of breath), muscle aches, etc. Fevers can
recur at regular intervals (48 or 72 hours, depending on the malarial species)
that coincide with a synchronized rupture of red blood cells. This periodicity may
be masked. The severity of symptoms varies with the species of parasite
involved, the stage of infection, the immunological history of the patient, and
other factors. Persons in endemic areas may develop “concomitant” immunity—
a relative resistance to symptoms that persists only with continued exposure,
persistent low-level parasitemia, or frequent infections.

P. falciparum infections are potentially life-threatening because the the

proportion of red blood cells containing parasites can be greater than 10% which
results in venous thrombosis or sludging in the capillaries. Complications of
inadequately treated falciparum malaria include anemia, renal failure, shock,
adult respiratory distress syndrome, encephalopathy, and acidosis. Disease
caused by the other malarial species is rarely fatal, and can be quite mild.

The classical presentation of malaria is:

1. The ‘cold stage’ associated with rigors (shaking).

2. The ‘hot stage’ where the patient becomes febrile, oftenexceeding 40oC
associated with nausea and vomiting.

3. The ‘sweating’ stage where the temperature returns to normal The fever is
referred to as a ‘swinging fever’ and the duration between fevers may point to
a malaria.

The Malarial Paroxysm

cold stage hot stage sweating stage
• intense heat • profuse sweating
• feeling of intense
• dry burning skin • declining temperature
cold
• throbbing • exhausted and weak →
• vigorous shivering
headache sleep
• lasts 15-60 minutes
• lasts 2-6 hours • lasts 2-4 hours

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 • P. ovale/P. vivax 38-42 hours between fevers (‘tertian fever’)
• P. malariae 62-66 hours between fevers (‘quartan fever) . This clinical
presentation is due to red blood cell rupture and subsequent merozoite release
into the circulation. However in P. falciparum the timing of fevers tends to be less
periodic. Other features include
• headache
• abdominal pain and on rare occasions may suggest an “acute abdomen”,
• vomiting considered in the differential diagnosis.

** other Signs of malaria include:

• conjunctival pallor (a sign of anaemia)
• mild jaundice which is caused by haemolysis. P. falciparum may be associated
with severe jaundice
and is caused by liver damage
• splenomegaly (the spleen is palpable). It takes only afew days for the spleen to
enlarge in an acute attack of malaria. However, there are many causes of
anaemia, jaundice and splenomegaly
• hepatomegaly (liver enlargement).
Other more general signs may include tachycardia (fast heart rate) with a
bounding pulse, and tachypnoea (fast breathing rate) especially in children.

Chronic malaria:-

The persistence of malaria in the blood, especially in people who live in

subtropical regions, leads to ‘chronicmalaria.’ Symptoms may include attacks of
‘ acute m alaria’ interspersed with anaemia, weight loss or other infections

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 Diagnosis:-

The first symptoms of malaria (most often fever, chills, sweats, headaches,
muscle pains, nausea and vomiting ) are often not specific and are also found in
other diseases (such as influenza and other common viral infections). Likewise,
the physical findings are often not specific (elevated temperature, perspiration,
tiredness). In severe malaria (typically caused by P. falciparum), clinical findings
(confusion, coma, neurologic focal signs, severe anemia, respiratory difficulties)
are more striking and may increase the suspicion index for malaria.

Laboratory diagnosis :-

*The mainstay of malaria diagnosis has been the microscopic examination

of blood. used to make a diagnosis, Detection of malaria parasites in thick or thin
peripheral blood films. Using Giemsa-stained, Only Ring forms and gametocytes
can be found in blood film.

*Detection of species specific parasite DNA in a sample of peripheral

blood using a polymerase chain reaction test (PCR) . PCR (and other molecular
methods) is more accurate than microscopy. However, it is expensive, and
requires a specialized laboratory. Moreover, levels of parasitemia are not
necessarily correlative with the progression of disease, particularly when the
parasite is able to adhere to blood vessel walls. Therefore more sensitive, low-
tech diagnosis tools need to be developed in order to detect low levels of
parasitemia in the field.

*For areas where microscopy is not available, or where laboratory staff are
not experienced at malaria diagnosis, there are commercial antigen detection
tests that require only a drop of blood. Immunochromatographic tests (also
called: Malaria Rapid Diagnostic Tests, Antigen-Capture Assay or "Dipsticks")
have been developed, distributed and field tested. These tests use finger-stick or
venous blood, the completed test takes a total of 15–20 minutes, and the results
are read visually as the presence or absence of colored stripes on the dipstick, so
they are suitable for use in the field.. One disadvantage is that dipstick tests are
qualitative but not quantitative – they can determine if parasites are present in
the blood, but not how many.

Treatment:-

When properly treated, a patient with malaria can expect a complete recovery.
The treatment of malaria depends on the severity of the disease; whether
patients who can take oral drugs have to be admitted depends on the assessment
and the experience of the clinician. Uncomplicated malaria is treated with oral
drugs. Severe malaria requires the parenteral administration of antimalarial
drugs. Until recently the most used treatment for severe malaria was quinine but
artesunate has been shown to be superior to quinine in both children and adults.
Treatment of severe malaria also involves supportive measures.

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 Infection with P. vivax, P. ovale or P. malariae is usually treated on an outpatient
basis. Treatment of P. vivax requires both treatment of blood stages (with
chloroquine or ACT) as well as clearance of liver forms with primaquine. In
general, chloroquine is the drug of choice for all Plasmodium except for
chloroquine-resistant P. falciparum and chloroquine-resistant P. vivax.
Primaquine, a drug that is active specifically against the liver stages, may be
added for treatment of malaria due to P. vivax and P. ovale to prevent relapse but
should not be used during pregnancy and can also cause complications in
persons with G6PD de iciency.

Treatment of P. falciparum is more complicated, because of widespread

resistance to chloroquine, and, increasingly, mefloquine. Treatment is often with
quinine plus a second drug, but it is essential to get up-to-date treatment
recommendations particularly the appropriate recommendations for children,
pregnant women, and persons with G6PD de iciency. Because of the potential for
rapid clinical deterioration, clinicians should strongly consider hospitalizing
patients with falciparum malaria, at least until the success of therapy is assured.
For prophylaxis recommendations during travel.

Prevention and Control in Endemic Areas:-

Prevention is an important component of malaria control in endemic countries.
It is achieved through:

•vector control
•personal protection measures such as insecticide-treated bed nets
•preventive treatment with antimalarial drugs of vulnerable groups such as
pregnant women, who receive intermittent preventive treatment.

*Travelers from non-endemic countries should take precautions against

acquiring malaria when they visit a malaria risk area.

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