MALARIA

Epidemiology
In 2012, malaria caused an estimated 627 000 deaths

(with an uncertainty range of 473 000 to 789 000),

mostly among African children(WHO, 2014).
3.4 billion people live in areas at risk of malaria
transmission in 106 countries and territories (CDC,
2014).
Males and females are affected equally. However,
malaria may be devastating during pregnancy to the
mother and the fetus. P falciparum is the primary
species responsible for increased morbidity and
mortality in pregnancy.
Young children aged 6 months to 3 years who live in
endemic areas are at an increased risk of death due
to malaria. Travelers without immunity are at an
increased mortality risk, regardless of age
(Medscape, 2014).

This map shows an approximation of the parts of the

world where malaria transmission occurs.

Etiology
Malaria is caused by the protozoan parasite
Plasmodium. Human malaria is caused by four
different species of Plasmodium:
P. falciparum (malaria tropica)
P. malariae (malaria quartana)
P. ovale (malaria ovale)
P. vivax (malaria tertiana)
P. Knowlesi (Humans occasionally become
infected with Plasmodium species that normally
infect animals, such as P. knowlesi)

Transmission
The malaria parasite is transmitted by female

Anopheles mosquitoes,
between dusk and dawn.

which

bite

mainly

Vector

Anopheles mosquito pumping blood

Pathogenesis

Malaria Life Cycle

 The malaria parasite life cycle involves two hosts. 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, inP. 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

Cont..
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.

Sign & Symptom

Patients with malaria typically become symptomatic a few weeks after infection,
although the host's previous exposure or immunity to malaria affects the
symptomatology and incubation period. In addition, each Plasmodium species
has a typical incubation period. Importantly, virtually all patients with malaria
present with headache. Clinical symptoms also include the following:

Headache (noted in virtually all patients with malaria)

Fatigue

Malaise
Shaking chills
Arthralgia
Myalgia

Paroxysm of fever, shaking chills, and sweats (every 48 or 72 h, depending

on species)
The classic paroxysm begins with a period of shivering and chills,

which lasts for approximately 1-2 hours and is followed by a high fever.
Finally, the patient experiences excessive diaphoresis, and the body
temperature of the patient drops to normal or below normal.

Cont..
Less common symptoms include the following:
Anorexia and lethargy
Nausea and vomiting
Diarrhea
Jaundice

Manifestasion of Plasmodium
Infection
Uncomplicated malaria

Severe malaria

Uncomplicated malaria
Uncomplicated malaria is defined as symptomatic malaria without signs of

severity or evidence (clinical or laboratory) of vital organ dysfunction. The

signs and symptoms of uncomplicated malaria are nonspecific. Malaria is,
therefore, suspected clinically mostly on the basis of fever or a history of
fever (WHO)
The classical (but rarely observed) malaria attack lasts 6-10 hours. It

consists of:
a cold stage (sensation of cold, shivering)
a hot stage (fever, headaches, vomiting; seizures in young children)
and finally a sweating stage (sweats, return to normal temperature,
tiredness).
Classically (but infrequently observed) the attacks occur every second
day with the "tertian" parasites (P. falciparum, P. vivax, and P. ovale) and every
third day with the "quartan" parasite (P. malariae).
More commonly, the patient presents with a combination of the following
symptoms:

-Chills

- headaches

Cont..
Physical findings may include:
Elevated temperatures
Perspiration
Weakness
Enlarged spleen
Mild jaundice
Enlargement of the liver
Increased respiratory rate
(CDC)

Severe malaria
Clinical features:
impaired consciousness or unrousable coma
prostration, i.e. generalized weakness so that the patient is unable
walk
or sit up without assistance
failure to feed
multiple convulsions more than two episodes in 24 h
deep breathing, respiratory distress (acidotic breathing)
circulatory collapse or shock, systolic blood pressure < 70 mm Hg in
adults
and < 50 mm Hg in children
clinical jaundice plus evidence of other vital organ dysfunction
haemoglobinuria
abnormal spontaneous bleeding
pulmonary oedema (radiological)

Laboratory findings:
hypoglycaemia (blood glucose < 2.2 mmol/l or < 40
mg/dl)
metabolic acidosis (plasma bicarbonate < 15 mmol/l)
severe normocytic anaemia (Hb < 5 g/dl, packed cell
volume < 15%)
haemoglobinuria
hyperparasitaemia (> 2%/100 000/l in low intensity
transmission areas or > 5%
or 250 000/l in areas of high stable malaria transmission
intensity)
hyperlactataemia (lactate > 5 mmol/l)
renal impairment (serum creatinine > 265 mol/l).

Malaria relapse
In P. vivax and P. ovale infections, patients having

recovered from the first episode of illness may

suffer several additional attacks ("relapses") after
months or even years without symptoms.
Relapses occur because P. vivax and P.
ovale have dormant liver stage parasites
("hypnozoites") that may reactivate.

Incubation period
Plasmodium falciparum

Plasmodium vivax

9 14 days
12 17 days

12mo
Plasmodium ovale
16 18 days
Plasmodium malariae 18 40 days
Plasmodium knowlesi 9 12 days

P. falciparum
Malaria tropica
Incubation period 9 14 days
P falciparum is able to infect RBCs of all ages, resulting in high levels of

parasitemia (>5% RBCs infected).

Hemoglobinuria (blackwater fever), seen with severe RBC hemolysis, is

often a sign of impending renal failure and clinical decline.

Sequestration is a specific property of P falciparum. As it develops through

its 48-hour life cycle, the organism demonstrates adherence properties,

which result in the sequestration of the parasite in small postcapillary
vessels.
Sequestration of parasites may contribute to mental-status changes and

coma, observed exclusively in P falciparum infection. In addition, cytokines

and a high burden of parasites contribute to end-organ disease. End-organ
disease may develop rapidly in patients with P falciparum infection, and it
specifically involves CNS, lungs, and kidneys.
Other manifestations of P falciparum infection include hypoglycemia, lactic

acidosis, severe anemia, and multiorgan dysfunction due to hypoxia.

P. vivax
Malaria tertiana
Incubation period 12 17 days
If this kind of infection goes untreated, it usually lasts

for 2-3 months with diminishing frequency and

intensity of paroxysms.
Patients infected with P vivax, 50% experience a
relapse within a few weeks to 5 years after the initial
illness.
Splenic
rupture
may
be
associated
with P.vivax infection secondary to splenomegaly
resulting from RBC sequestration.
P vivax infects only immature RBCs, leading to limited
parasitemia.

P. ovale
Malaria ovale

Incubation period 16 18 days

These infections are similar to P.vivax infections,

although they are usually less severe.

P.ovale infection often resolves without treatment.
Similar to P.vivax, P.ovale infects only immature

RBCs, and parasitemia is usually less than that

seen in P falciparum.

P. malariae
Malaria quartana

Incubation period 18 40 days

Persons

infected
with
this
species
of Plasmodium remain asymptomatic for a much
longer period of time than do those infected
with P vivax or P ovale.
Recrudescence is common in persons infected
with P malariae. It often is associated with a
nephrotic syndrome, possibly resulting from
deposition of antibody-antigen complex on the
glomeruli.

P. knowlesi
have been documented in Malaysian Borneo,

Thailand, Myanmar, Singapore, the Philippines,

and other neighboring countries.
It is thought that similiar malaria cases probably
also occur in Central America and South America.
Patients infected with this, or other similiar
species, should be treated as aggressively as
those
infected
with
falciparum
malaria,
as P.knowlesi may cause fatal disease

Diagnosis
Clinical sign and symptom
Microscopic examination remains the "gold standard" for laboratory

confirmation of malaria.
Blood smears (thick and thin smear)
Thick smears
Three thick and thin smears 12-24 hours apart should be
obtained. The highest yield of peripheral parasites occurs during or soon
after a fever spike; however, smears should not be delayed while
awaiting fever spikes. Thick smears are 20 times more sensitive than
thin smears, but speciation may be more difficult. The parasitemia can
be calculated based on the number of infected RBCs. This is a
quantitative test.
Thin smears
Thin smears are less sensitive than thick smears, but they allow
identification of the different species. This should be considered a
qualitative test.
RDT (Rapid diagnostic Test) -> Immunochromatographic tests based on

antibody

Treatment
ACT options now recommended for treatment of
uncomplicated falciparum malaria in alphabetical
order are:
artemether plus lumefantrine,
artesunate plus amodiaquine,
artesunate plus mefloquine,
artesunate plus sulfadoxine-pyrimethamine,
dihydroartemisinin plus piperaquine.

Treatment

Differential diagnosis
Dengue Fever

Influenza
Leptospirosis
Meningitis
Typhoid Fever
Pneumonia

Thankyou