Malaria
Malaria is a protozoan disease transmitted by the bite of infected Anopheles mosquitoes. The most important of
the parasitic diseases of humans
Malaria is endemic throughout most of the tropics. In 2018, the World Health Organization (WHO) reported that
219 million cases of malaria occurred worldwide, down from 239 million cases in 2010 . However, data for 2015
to 2017 reflect that no substantial progress was made during this period. Malaria occurred most frequently in the
WHO African region (92 percent), followed by the WHO South-East Asian region (5 percent) and the Eastern
Mediterranean region (2 percent). (totally approximately 2000 deaths each day;)
5 species of the genus Plasmodium cause nearly all malarial infections in humans:
P. falciparum， P. vivax， two morphologically identical species of P. ovale (as suggested by recent evidence)
， P. malariae and in Southeast Asia-the monkey malaria parasite P. knowlesi . While almost all deaths are
caused by falciparum malaria， P. knowlesi and occasionally P. vivax also can cause severe illness.
Timely identification of the infecting species is extremely important, as P. falciparum infection can be fatal and is
often resistant to standard chloroquine treatment.
Mortality rates are decreasing as a result of highly effective control programs in several countries.
Malaria has been eliminated from the United States，Canada， Europe， and Russia;
P. falciparum _ mainly found in Africa, it's the most common type of malaria parasite and is responsible
for most malaria deaths worldwide. P. falciparum can cause severe malaria because it multiples rapidly
in the blood, and can cause severe blood loss (anemia). In addition, the infected parasites can clog small
blood vessels. When this occurs in the brain, cerebral malaria results, a complication that can be fatal
P. vivax – mainly found in Asia and South America, this parasite causes milder symptoms than
Plasmodium falciparum, but it can stay in the liver for up to 3 years, which can result in relapses
P. malariae is found in most endemic areas，especially throughout sub-Saharan Africa， but is much less
common. P. malariae, found worldwide, is the only human malaria parasite species that has a quartan
cycle (three-day cycle). (The three other species have a tertian, two-day cycle.) If untreated, P.
malariae causes a long-lasting, chronic infection that in some cases can last a lifetime. In some
chronically infected patients P. malariae can cause serious complications such as the nephrotic
syndrome.
.p. ovale – fairly uncommon and usually found in West Africa, it can remain in your liver for several years
without producing symptoms. It is biologically and morphologically very similar to P. vivax.
P. knowlesi – this is very rare and found in parts of southeast Asia . It has recently been shown to be a
significant cause of zoonotic malaria in that region, particularly in Malaysia. P. knowlesi has a 24-hour
replication cycle and so can rapidly progress from an uncomplicated to a severe infection; fatal cases
have been reported.
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Parasite morphology: Malarial par
asites form four developmental
stages in humans (hepatic schizonts
and then intraerythrocytic
trophozoites, schizonts and
gamonts) and three developmental
stages in mosquitoes (ookinetes,
oocysts and sporozoites).
1.Plasmodium-infected female Anopheles mosquito bites a human and transmits sporozoites into the
bloodstream. (2) Sporozoites migrate through the blood to the liver where they invade hepatocytes and divide
to form multinucleated schizonts (preerythrocytic stage). (3) Hypnozoites are a quiescent stage in the liver that
exist only in the setting of P. vivax and P. ovale infection. This liver stage does not cause clinical symptoms, but
with reactivation and release into the circulation, late-onset or relapsed disease can occur up to many months
after initial infection. (4) The schizonts rupture and release merozoites into the circulation where they invade
red blood cells. Within red cells, merozoites mature from ring forms to trophozoites to multinucleated schizonts
(erythrocytic stage). (5) Some merozoites differentiate into male or female gametocytes. These cells are
ingested by the Anopheles mosquito and mature in the midgut, where sporozoites develop and migrate to the
salivary glands of the mosquito.: The mosquito completes the cycle of transmission by biting another host.
transmitted by the bite of
infected Anopheles
mosquitoes. Other, less
common routes
of Plasmodium infection
are through blood
transfusion and maternal-
fetal transmission.
By this amplification process (known as intrahepatic or preeηthrocytic schizogony or
merogony)， a single sporozoite eventually may produce from 10，000 to >30，000
daughter merozoites. These merozoites then invade the red blood cells (RBCs) and
multiply six- to twenty fold every 48 h (P. knowl町， 24 h; P. malariae， 72 h). When the
parasites reach densities of -50/IlL of blood (-100 million parasites in the blood of an
adult)， the symptomatic stage of the infection begins. In P. vivax and P. ovale infec
tions， aproportion of the intrahepatic forms do not divide immediately ,but remain inert
for a period ranging from 3 weeks to :2: 1 year before reproduction begins. These
dormant forms， or hypnozoites， are the cause of the relapses that characterize
infection with these h矿o species. After entry into the bloodstream， merozoites rapidly
invade erythrocytes and become trophozoites.
All the clinical symptoms associated with malaria are caused by the asexual erythrocytic or blood stage
parasites.
Malaria-causing Plasmodium species metabolize hemoglobin and other RBC proteins to create a toxic
pigment called hemozoin. An important reason that the consequences of P falciparum infection are so
severe is that, due to its ability to adhere to endothelial cell walls, the species causes vascular obstruction.
The hemozoin and other toxic factors such as glucose phosphate isomerase (GPI) stimulate macrophages
and other cells to produce cytokines and other soluble factors which act to produce fever and rigors and
probably influence other severe pathophysiology associated with malaria.
Plasmodium falciparum-infected erythrocytes, particularly those with mature trophozoites, adhere to the
vascular endothelium of venular blood vessel walls and do not freely circulate in the blood. When this
sequestration of infected erythrocytes occurs in the vessels of the brain it is believed to be a factor in
causing the severe disease syndrome known as cerebral malaria, which is associated with high mortality.
The parasites derive their energy solely from glucose, and they metabolize it 70 times faster than the
RBCs they inhabit, thereby causing hypoglycemia and lactic acidosis. The plasmodia also cause lysis of
infected and uninfected RBCs, suppression of hematopoiesis, and increased clearance of RBCs by the
spleen, which leads to anemia as well as splenomegaly. Over time, malaria infection may also cause
thrombocytopenia.
Incubation period
Each Plasmodium species has a specific incubation period.
In most cases, the incubation period for P. falciparum infection is about 12 to 14 days (range 7 to 30 days);
most infections due to P. falciparum become clinically apparent within one month after exposure Longer
incubation periods are more likely in semi-immune individuals and individuals taking ineffective malaria
prophylaxis
The incubation period for relapsing species Plasmodium vivax and Plasmodium ovale is also about two
weeks ( 8- 27 days), but illness can occur months after the initial infection due to activation of residual
hypnozoites in the liver. Relapses generally occur within two to three years of infection; there is one report
of P. vivax infection presenting in a patient four years following departure from an endemic area
The incubation period for Plasmodium malariae is about 18 days( 16- 40 days), however, low-grade
asymptomatic infections can very rarely persist for years Following the bite of an infected
female Anopheles mosquito, the inoculated sporozoites go to the liver within one to two hours Individuals
are generally asymptomatic for 12 to 35 days but can commence symptoms as early as 7 days (depending
on parasite species), until the erythrocytic stage of the parasite life cycle ( Release of merozoites from
infected red cells when they rupture causes fever and the other manifestations of malaria.
P. falciparum and P. malariae have no dormant (hypnozoite) phase, hence do not relapse.
• The first symptoms of malaria are nonspecific: headache， fatigue， abdominal discomfortand
muscle aches followed by fever are all similar to the symptoms of a minor viral iIIness. In some
instance prominence of headache， chest pain，abdominal pain， cough， arthralgia，
myalgia， or diarrhea may suggest another diagnosis. Although headache may be severe in
malaria . Nausea， vomiting， and orthostatic hypotension are common.
• The classic malarial paroxysms， in which fever spikes， chills， and rigors occur at regular
intervals， are relatively unusual and suggest infection with P. vivax or P. ovale. The fever is
usually irregular at first (that of falciparum malaria may never become regular); the temperature
of nonimmune individuals and children often rises above 40C . with tachycardia and sometimes
delirium. Although childhood febrile convulsions may occur with any of the malarias，
generalized seizures are specifically associated with falciparum malaria and may herald the
development of encephalopathy (cerebral malaria) .
• Many clinical abnormalities have been described in aιute malaria， but most patients with
uncompliιated infections have few abnormal physical findings other than fever，malaise， mild
anemia， and (in some cases) a palpable spleen. Anemia is common among young children
living in areas with stable transmission， particularly where resistance has compromised the
efficacy 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.
Malaria disease can be categorized as uncomplicated or severe (complicated).
Severe malaria occurs when infections are complicated by serious organ failures or
abnormalities in the patient’s blood or metabolism. The manifestations of severe
malaria include the following:
Severe malaria is a medical emergency and should be treated urgently and
aggressively.
•Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures,
coma, or other neurologic abnormalities Cerebral malaria is the most common cause
of death in patients with malaria. If untreated, this complication is lethal. Even with
treatment, 15% of children and 20% of adults who develop cerebral malaria die. The
symptoms of cerebral malaria are similar to those of toxic encephalopathy.
• Severe anemia due to hemolysis (destruction of the red blood cells)
•Hemoglobinuria (hemoglobin in the urine) due to hemolysis
•Acute respiratory distress syndrome (ARDS), an inflammatory reaction in the lungs
that inhibits oxygen exchange, which may occur even after the parasite counts have
decreased in response to treatment
•Abnormalities in blood coagulation
•Low blood pressure caused by cardiovascular collapse
•Acute kidney injury
•Hyperparasitemia, where more than 5% of the red blood cells are infected by
malaria parasites
•Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in
association with hypoglycemia
•Hypoglycemia (low blood glucose). Hypoglycemia may also occur in pregnant
women with uncomplicated malaria, or after treatment with quinine.
Plasmodium Plasmodium Plasmodium
Plasmodium ovale Plasmodium know
falciparum vivax malariae
Tropical,
Tropical, endemic in
temperate
Tropical, temperate West Africa, present in Tropical, isolated
Geography zones, Southeast Asia
zones Philippines, Indonesia, pockets
absent from
and Papua New Guinea
West Africa
Young RBCs
Young RBCs
RBC preference RBCs of all ages (reticulocyte Older RBCs RBCs of all ages
(reticulocytes)
s)
Parasitemia Can be very high Usually <2% Usually <2% Usually very low Can be high
End organ
damage and
death less
End organ damage and Severe disease
Disease severity common Severe disease rare Severe disease can o
death can occur uncommon
than P.
falciparum b
ut can occur
Chloroquine
Yes Yes No Rare No
resistance
Relapses from
No Yes Yes No No
liver
14 days (10
18 days (15 to 35;
Incubation to 30;
12 days (8 to 25) 15 days (10 to 20) occasionally 11 days (9 to 12)
Definition of severe falciparum malaria
Manifestations Definitions
Glasgow coma score <11 in adults or Blantyre coma score <3 in
Cerebral malaria( coma)
children; inability to swallow
Generalized weakness so that a person is unable to sit, stand, or
Prostration
walk without assistance
Multiple convulsions More than two episodes within 24 hours
A base deficit of >8 mEq/L, a plasma bicarbonate level of <15
Acidosis mmol/L, or venous plasma lactate ≥5 mmol/L. Clinical indicators
of acidosis include rapid, deep, labored breathing.
Blood or plasma glucose <40 mg/dL (<2.2 mmol/L) for children
Hypoglycemia ≥5 years and adults; blood or plasma glucose <54 mg/dL (<3
mmol/L) for children <5 years
Hemoglobin concentration ≤5 g/dL or hematocrit ≤15 percent in
children <12 years of age (<7 g/dL and <20 percent, respectively,
Severe anemia
in adults) with parasite count >10,000/mcL (0.2 percent
parasitemia)
Plasma or serum creatinine >3 mg/dL (265 mcmol/L) or blood
Renal impairment
urea >20 mmol/L
Plasma or serum bilirubin >50 mcmol/L (3 mg/dL) with a parasite
Jaundice
count >100,000/mcL (0.2 percent parasitemia)
Radiographically confirmed or oxygen saturation <92 percent on
Pulmonary edema room air with respiratory rate >30/minutes, often with chest
indrawing and crepitation on auscultation
I
ncluding recurrent or prolonged bleeding (from the nose, gums,
Significant bleeding or venipuncture sites), hematemesis, or melena
Compensated shock is defined as capillary refill ≥3 seconds or
LABORATORY F I N DINGS
• Normochromic， normocytic anemia is usual.
• The leukocyte count is generally normal， although it may be raised in very severe
infections.
• The erythrocyte sedimentation rate， plasma viscosity， and levels of C-reactive
protein and other acute-phase proteins are high. The platelet count is usually reduced
to _ 1 05/μL.
Diagnosis
• The diagnosis of malaria rests on the demonstration of asexual forms of the parasite in stained
peripheral-blood smears( thin and thick) smears.
• When a patient in or from a malarious area presents with fever， thick and thin blood smears
should be prepared and examined immediately to confirm the diagnosis and identify the species of
infecting parasite . Repeat blood smears should be performed at least every 1 2-24 h for 2 days if the
first smears are negative and malaria is strongly suspected.
• Rapid， simple， sensitive， and specific antibody-based diagnostic stick or card tests that detect P.
fa1ciparum-specific， histidine-rich protein 2 (PfHRP2-)， lactate dehydrogenase or aldolase
antigens in finger-prick blood samples. PfHRP2-based tests may remain positive for several weeks
after acute infection.
• Molecular diagnosis by polymerase chain reaction (PCR) amplification of parasite nucleic acid is more
sensitive than microscopy or rapid diagnostic tests for detecting malaria parasites and defining
malarial species. While currently impractical in the standard clinical setting，PCR is used in reference
centers in endemic areas.
•
Patients with P falciparum infection are often treated on an inpatient basis to allow observation for
complications.
Patients with non– P falciparum malaria who are well can usually be treated on an outpatient basis.
General recommendations for pharmacologic treatment of malaria are as follows:
P falciparum malaria: Quinine-based therapy is with quinine (or quinidine) sulfate plus doxycycline or
clindamycin or pyrimethamine-sulfadoxine; alternative therapies are artemether-lumefantrine,
atovaquone-proguanil, or mefloquine
P vivax, P ovale malaria: Chloroquine plus primaquine
P malariae malaria: Chloroquine
P knowlesi malaria:
The treatment of falciparum malaria has changed radically in recent years. In all endemic areas， the World Health
Organization now recommends artemisinin-based combinations (ACTs) as first-line treatment for uncomplicated
falciparum malaria. These combinations are also highly effective for the other malarias.
