Vous êtes sur la page 1sur 33

Practice Essentials

Malaria is a potentially life-threatening disease caused by infection with


Plasmodium protozoa transmitted by an infective female Anopheles mosquito.
Plasmodium falciparum infection carries a poor prognosis with a high mortality if
untreated, but it has an excellent prognosis if diagnosed early and treated
appropriately.
Essential update: Revised guidelines for laboratory diagnosis of malaria
The British Committee for Standards in Haematology revised its Guidelines for the
Laboratory Diagnosis of Malaria, intended for use in the United Kingdom but also
potentially applicable to other nonendemic areas.[1] Recommendations include the
following:
Thick and thin films should be routinely used for malaria diagnosis; thick
films should be stained with Giemsa or Field stain, thin films with Giemsa
or Leishman stain
Two observers should examine thick films, with each viewing a minimum of
200 high-power fields; if the films are positive, the species should be
determined through examination of a thin film
In cases of P falciparum or Plasmodium knowlesi infection, the percentage
of parasitized cells or the number of parasites per microliter should be
estimated
Rapid diagnostic tests for malarial antigen can be used on a supplementary
basis when diagnosis is performed by inexperienced staff
Signs and symptoms
Patients with malaria typically become symptomatic a few weeks after infection,
though the symptomatology and incubation period may vary, depending on host
factors and the causative species. Clinical symptoms include the following:
Headache (noted in virtually all patients with malaria)
Cough

Fatigue
Malaise
Shaking chills
Arthralgia
Myalgia
Paroxysm of fever, shaking chills, and sweats (every 48 or 72 hours,
depending on species)
Less common symptoms include the following:
Anorexia and lethargy
Nausea and vomiting
Diarrhea
Jaundice
Most patients with malaria have no specific physical findings, but splenomegaly
may be present. Severe malaria manifests as the following:
Cerebral malaria (sometimes with coma)
Severe anemia
Respiratory abnormalities: Include metabolic acidosis, associated respiratory
distress, and pulmonary edema; signs of malarial hyperpneic syndrome
include alar flaring, chest retraction, use of accessory muscles for
respiration, and abnormally deep breathing
Renal failure (typically reversible)
See Clinical Presentation for more detail.
Diagnosis

The patient history should include inquiries into the following:


Recent or remote travel to an endemic area
Immune status, age, and pregnancy status
Allergies or other medical conditions
Medications currently being taken
The following blood studies should be ordered:
Blood culture
Hemoglobin concentration
Platelet count
Liver function
Renal function
Electrolyte concentrations (especially sodium)
Monitoring of parameters suggestive of hemolysis (haptoglobin, lactic
dehydrogenase [LDH], reticulocyte count)
In select cases, rapid HIV testing
White blood cell count: Fewer than 5% of malaria patients have
leukocytosis; thus, if leukocytosis is present, the differential diagnosis
should be broadened
If the patient is to be treated with primaquine, glucose-6-phosphate
dehydrogenase (G6PD) level
If the patient has cerebral malaria, glucose level to rule out hypoglycemia
The following imaging studies may be considered:

Chest radiography, if respiratory symptoms are present


Computed tomography of the head, if central nervous system symptoms are
present
Specific tests for malaria infection should be carried out, as follows:
Microhematocrit centrifugation (sensitive but incapable of speciation)
Fluorescent dyes/ultraviolet indicator tests (may not yield speciation
information)
Thin (qualitative) or thick (quantitative) blood smears (standard): Note that 1
negative smear does not exclude malaria as a diagnosis; several more smears
should be examined over a 36-hour period
Alternatives to blood smear testing (used if blood smear expertise is
insufficient): Include rapid diagnostic tests, polymerase chain reaction assay,
nucleic acid sequence-based amplification, and quantitative buffy coat
Histologically, the various Plasmodium species causing malaria may be
distinguished by the following:
Presence of early forms in peripheral blood
Multiply infected red blood cells
Age of infected RBCs
Schffner dots
Other morphologic features
See Workup for more detail.
Management
Treatment is influenced by the species causing the infection, including the
following:

Plasmodium falciparum
P vivax
P ovale
P malariae
P knowlesi
In the United States, 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 falciparum malaria with known chloroquine susceptibility (only a few
areas in Central America and the Middle East): Chloroquine
P vivax, P ovale malaria: Chloroquine plus primaquine
P malariae malaria: Chloroquine
P knowlesi malaria: Same recommendations as for P falciparum malaria
Pregnant women (especially primigravidas) are up to 10 times more likely to
contract malaria than nongravid women and have a greater tendency to develop
severe malaria. Medications that can be used for the treatment of malaria in
pregnancy include the following:
Chloroquine
Quinine
Atovaquone-proguanil

Clindamycin
Mefloquine (avoid in first trimester)
Sulfadoxine-pyrimethamine (avoid in first trimester)
Artemether-lumefantrine[2]
Artesunate and other antimalarials[3]
See Treatment and Medication for more detail.
Image library

Malarial merozoites in the peripheral blood. Note that


several of the merozoites have penetrated the erythrocyte membrane and entered
the cell.
Background
Malaria, which predominantly occurs in tropical areas, is a potentially lifethreatening disease caused by infection with Plasmodium protozoa transmitted by
an infective female Anopheles mosquito vector. Individuals with malaria may
present with fever and a wide range of symptoms (see the image below). (See
Etiology, Epidemiology, Presentation, and Workup.)

Malarial merozoites in the peripheral blood. Note that


several of the merozoites have penetrated the erythrocyte membrane and entered
the cell.

The 5 Plasmodium species known to cause malaria in humans are P falciparum, P


vivax, P ovale, P malariae, and P knowlesi.[4, 5, 6] Timely identification of the
infecting species is extremely important, as P falciparum infection can be fatal and
is often resistant to standard chloroquine treatment. P falciparum and P vivax are
responsible for most new infections. (See Etiology, Prognosis, Treatment, and
Medication.)
The Plasmodium species can usually be distinguished by morphology on a blood
smear. P falciparum is distinguished from the rest of the plasmodia by its high
level of parasitemia and the banana shape of its gametocytes. (See Workup.)
Among patients with malaria, 5-7% are infected with more than a single
Plasmodium species. Co-infection with different Plasmodium species has also been
described in the parasites mosquito vectors.[5]
Each Plasmodium species has a defined area of endemicity, although geographic
overlap is common. At risk for contraction of malaria are persons living in or
traveling to areas of Central America, South America, Hispaniola, sub-Saharan
Africa, the Indian subcontinent, Southeast Asia, the Middle East, and Oceania.
Among these regions, sub-Saharan Africa has the highest occurrence of P
falciparum transmission to travelers from the United States. (See Epidemiology.)
Infection and reproduction
After a mosquito takes a blood meal, the malarial sporozoites enter hepatocytes
(liver phase) within minutes and then emerge in the bloodstream after a few weeks.
These merozoites rapidly enter erythrocytes, where they develop into trophozoites
and then into schizonts over a period of days (during the erythrocytic phase of the
life cycle). Rupture of infected erythrocytes containing the schizont results in fever
and merozoite release. The merozoites enter new red cells, and the process is
repeated, resulting in a logarithmic increase in parasite burden. (See the images
below.)

This micrograph illustrates the trophozoite form, or


immature-ring form, of the malarial parasite within peripheral erythrocytes. Red

blood cells infected with trophozoites do not produce sequestrins and, therefore,

are able to pass through the spleen.


A mature schizont
within an erythrocyte. These red blood cells (RBCs) are sequestered in the spleen
when malaria proteins, called sequestrins, on the RBC surface bind to endothelial
cells within that organ. Sequestrins are only on the surfaces of erythrocytes that
contain the schizont form of the parasite.
Other, less common routes of Plasmodium infection are through blood transfusion
and maternal-fetal transmission.
Complications
P falciparum can cause cerebral malaria, pulmonary edema, rapidly developing
anemia, and renal problems. 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. When a red blood cell (RBC)
becomes infected with P falciparum, the organism produces proteinaceous knobs
that bind to endothelial cells. The adherence of these infected RBCs causes them to
clump together in the blood vessels in many areas of the body, causing
microvascular damage and leading to much of the damage incurred by the parasite.
Patient education
Individuals traveling to malarial regions must be provided with adequate
information regarding prevention strategies, as well as tailored and effective
antiprotozoal medications. For patient education information, see Malaria, Foreign
Travel, and Insect Bites.
Etiology
Individuals with malaria typically acquired the infection in an endemic area
following a mosquito bite. Cases of infection secondary to transfusion of infected
blood are extremely rare. The risk of infection depends on the intensity of malaria
transmission and the use of precautions, such as bed nets, diethyl-meta-toluamide
(DEET), and malaria prophylaxis.

The outcome of infection depends on host immunity. Individuals with immunity


can spontaneously clear the parasites. In those without immunity, the parasites
continue to expand the infection. P falciparum infection can result in death. A
small percentage of parasites become gametocytes, which undergo sexual
reproduction when taken up by the mosquito. These can develop into infective
sporozoites, which continue the transmission cycle after a blood meal in a new
host.
The mechanisms that underlie immunity remain poorly defined. Additionally,
individuals who develop immunity to malaria who then leave the endemic area
may lose protection. Travelers who return to an endemic area should be warned
that waning of immunity may increase their risk of developing several malaria if
reinfected. These travelers returning to endemic areas are a special population,
sometimes termed visiting friends and relatives (VFRs).
Incubation
Each Plasmodium species has a specific incubation period. Reviews of travelers
returning from endemic areas have reported that P falciparum infection typically
develops within one month of exposure, thereby establishing the basis for
continuing antimalarial prophylaxis for 4 weeks upon return from an endemic area.
This should be emphasized to the patient to enhance posttravel compliance.
Rarely, P falciparum causes initial infection up to a year later. P vivax and P ovale
may emerge weeks to months after the initial infection. In addition, P vivax and P
ovale have a hypnozoite form, during which the parasite can linger in the liver for
months before emerging and inducing recurrence after the initial infection. In
addition to treating the organism in infected blood, treating the hypnozoite form
with a second agent (primaquine) is critical to prevent relapse from this latent liver
stage.
When P vivax and P ovale are transmitted via blood rather than by mosquito, no
latent hypnozoite phase occurs and treatment with primaquine is not necessary, as
it is the sporozoites that form hypnozoites in infected hepatocytes.
Life cycle
The vector, the Anopheles species mosquito, transmits plasmodia, which are
contained in its saliva, into its host while obtaining a blood meal. Plasmodia enter
circulating erythrocytes (red blood cells, or RBCs) and feed on the hemoglobin and
other proteins within the cells. One brood of parasites becomes dominant and is

responsible for the synchronous nature of the clinical symptoms of malaria.


Malaria-carrying female Anopheles species mosquitoes tend to bite only between
dusk and dawn.

Schema of the life cycle of malaria. Image courtesy of


the Centers for Disease Control and Prevention.
The protozoan brood replicates inside the cell and induces RBC cytolysis, causing
the release of toxic metabolic byproducts into the bloodstream that the host
experiences as flulike symptoms. These symptoms include chills, headache,
myalgias, and malaise, and they occur in a cyclic pattern. The parasite may also
cause jaundice and anemia due to the lysis of the RBCs. P falciparum, the most
malignant of the 5 species of Plasmodium discussed here, may induce renal failure,
coma, and death. Malaria-induced death is preventable if the proper treatment is
sought and implemented.
P vivax and P ovale may produce a dormant form that persists in the liver of
infected individuals and emerges at a later time. Therefore, infection by these
species requires treatment to kill any dormant protozoan as well as the actively
infecting organisms. This dormant infection is caused by the hypnozoite phase of
the life cycle, which involves a quiescent liver phase. (During this phase, the
infection is not typically eradicated by normal courses of antimalarials and requires
treatment with primaquine to prevent further episodes of disease.)
Malaria-causing Plasmodium species metabolize hemoglobin and other RBC
proteins to create a toxic pigment called hemozoin. (See the image below.)

An erythrocyte filled with merozoites, which soon will


rupture the cell and attempt to infect other red blood cells. Notice the darkened

central portion of the cell; this is hemozoin, or malaria pigment, which is a


paracrystalline precipitate formed when heme polymerase reacts with the
potentially toxic heme stored within the erythrocyte. When treated with
chloroquine, the enzyme heme polymerase is inhibited, leading to the hemeinduced demise of nonchloroquine-resistant merozoites.
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.
P falciparum
The most malignant form of malaria is caused by this species. P falciparum is able
to infect RBCs of all ages, resulting in high levels of parasitemia (>5% RBCs
infected). In contrast, P vivax and P ovale infect only young RBCs and thus cause
a lower level of parasitemia (usually < 2%).
Hemoglobinuria (blackwater fever), a darkening of the urine seen with severe RBC
hemolysis, results from high parasitemia and is often a sign of impending renal
failure and clinical decline.
Sequestration is a specific property of P falciparum. As it develops through its 48hour life cycle, the organism demonstrates adherence properties, which result in
the sequestration of the parasite in small postcapillary vessels. For this reason, only
early forms are observed in the peripheral blood before the sequestration develops;
this is an important diagnostic clue that a patient is infected with P falciparum.
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
the central nervous system (CNS), lungs, and kidneys.
Other manifestations of P falciparum infection include hypoglycemia, lactic
acidosis, severe anemia, and multiorgan dysfunction due to hypoxia. These severe
manifestations may occur in travelers without immunity or in young children who
live in endemic areas.

P vivax
If this kind of infection goes untreated, it usually lasts for 2-3 months with
diminishing frequency and intensity of paroxysms. Of 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
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
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
Autochthonous cases have been documented in Malaysian Borneo, Thailand,
Myanmar, Singapore, the Philippines, and other neighboring countries. It is
thought that simian malaria cases probably also occur in Central America and
South America. Patients infected with this, or other simian species, should be
treated as aggressively as those infected with falciparum malaria, as P knowlesi
may cause fatal disease.[4]
Epidemiology
Occurrence in the United States
Malaria was endemic in the southern United States until the 19th and early 20th
centuries, but it has since been eradicated. Almost all US cases of malaria are
imported from patients traveling from endemic areas. In very rare cases, infections
in individuals who have not traveled have occurred near airports (so-called airport

malaria). This is secondary to a local mosquito becoming infected through a blood


meal from an infected traveler or the arrival of an infected mosquito aboard a
plane; the mosquito then takes a blood meal from a local resident and transmits the
infection. The CDC has recently documented an increase in the number of reported
malaria cases in the United States. In 2010 there were 1,691 cases, representing a
14% increase from 2009 and a 30% increase from 2008.[7]
Each year, 25-30 million people travel to tropical areas, and approximately 10,00030,000 US and European travelers acquire malaria.
International occurrence
Malaria is responsible for approximately 1-3 million deaths per year, typically in
children in sub-Saharan Africa infected with P falciparum. Populations at an
increased risk for mortality due to malaria include primigravida individuals,
travelers without immunity, and young children aged 6 months to 3 years who live
in endemic areas.
Worldwide, an estimated 300-500 million cases occurring annually.[8] It is most
prevalent in rural tropical areas below elevations of 1000 m (3282 ft) but is not
limited to these climates. P falciparum is found mostly in the tropics and accounts
for about 50% of cases and 95% of malarial deaths worldwide. P vivax is
distributed more widely than P falciparum, but it causes less morbidity and
mortality; however, both P vivax and P ovale can establish a hypnozoite phase in
the liver, resulting in latent infection.
Human immunodeficiency virus (HIV) and malaria co-infection is a significant
problem across Asia and sub-Saharan Africa, where both diseases are relatively
common. Evidence suggests that malaria and HIV co-infection can lead to worse
clinical outcomes in both disease processes, with malarial infections being more
severe in patients infected with HIV and HIV replication increasing in malaria
infection.
Sex-related demographics
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. The prevalence of
malaria is higher in primigravidas than in nonpregnant women or multigravidas.

Maternal complications are thought to be mediated by pregnancy associated


decreases in immune function, as well as by placental sequestration of (P
falciparum) parasites. Anemia from malaria can be more severe in pregnant
women. Fetal complications include premature birth, anemia, low birth weight, and
death. Malaria during the first trimester of pregnancy increases the risk for
miscarriage.[3]
Age-related demographics
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.
Prognosis
Most patients with uncomplicated malaria exhibit marked improvement within 48
hours after the initiation of treatment and are fever free after 96 hours. P
falciparum infection carries a poor prognosis with a high mortality rate if
untreated. However, if the infection is diagnosed early and treated appropriately,
the prognosis is excellent.
Complications
Most complications are caused by P falciparum. One of them is cerebral malaria,
defined as coma, altered mental status, or multiple seizures with P falciparum in
the blood. 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. Other complications
of P falciparum infection include the following:
Seizures - Secondary to either hypoglycemia or cerebral malaria
Renal failure - As many as 30% of nonimmune adults infected with P
falciparum suffer acute renal failure
Hypoglycemia
Hemoglobinuria (blackwater fever) - Blackwater fever is the passage of dark
urine, described as Madeira wine colored; hemolysis, hemoglobinemia, and
the subsequent hemoglobinuria and hemozoinuria cause this condition

Noncardiogenic pulmonary edema - This affliction is most common in


pregnant women and results in death in 80% of patients
Profound hypoglycemia - Hypoglycemia often occurs in young children and
pregnant women; it often is difficult to diagnose because adrenergic signs
are not always present and because stupor already may have occurred in the
patient
Lactic acidosis - This occurs when the microvasculature becomes clogged
with P falciparum; if the venous lactate level reaches 45 mg/dL, a poor
prognosis is very likely
Hemolysis resulting in severe anemia and jaundice
Bleeding (coagulopathy)
Mortality
Internationally, malaria is responsible for approximately 1-3 million deaths per
year. Of these deaths, the overwhelming majority are in children aged 5 years or
younger, and 80-90% of the deaths each year are in rural sub-Saharan Africa.[8]
Malaria is the worlds fourth leading cause of death in children younger than age 5
years.
Malaria is preventable and treatable. However, the lack of prevention and treatment
due to poverty, war, and other economic and social instabilities in endemic areas
results in millions of deaths each year.
Host protective factors
The sickle cell trait (hemoglobin S), thalassemias, hemoglobin C, and glucose-6phosphate dehydrogenase (G-6-PD) deficiency are protective against death from P
falciparum malaria, with the sickle cell trait being relatively more protective than
the other 3. Individuals with hemoglobin E may be protected against P vivax
infection. A systematic review and meta-analysis analyzed the significance of some
of these hemoglobinopathies and their protective effects against malaria. However,
the degree of protection that these hemoglobinopathies confer is variable and they
provide mild or no protection against uncomplicated malaria and asymptomatic
parasitemia.[9]

Individuals who are heterozygotic for RBC band 3 ovalocytosis are at reduced risk
of infection with P falciparum, P knowlesi, and, especially, P vivax malaria. West
African populations lacking RBC Duffy antigen are completely refractory to
infection by P vivax. Polymorphisms in a hosts TNF (tumor necrosis factor) gene
can also be protective against malaria.
Persons living in areas of malaria endemicity may develop partial immunity to
infection with time and repeated exposure. This limited immunity reduces the
frequency of symptomatic malaria and also reduces the severity of infection.
Immunity to malaria infection can be lost over long periods of time spent away
from endemic areas with limited exposure. As a result, those individuals born in
malaria-endemic regions who move abroad for work or study and then return home
may be at increased risk for developing severe malaria and complications of
infection.
History
In patients with suspected malaria, obtaining a history of recent or remote travel to
an endemic area is critical. Asking explicitly if they traveled to a tropical area at
anytime in their life may enhance recall. Maintain a high index of suspicion for
malaria in any patient exhibiting any malarial symptoms and having a history of
travel to endemic areas.
Also determine the patient's immune status, age, and pregnancy status; allergies or
other medical conditions that he or she may have; and medications that he or she
may be using.
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:
Cough
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.
Many patients, particularly early in infection, do not present the classic paroxysm
but may have several small fever spikes a day. Indeed, the periodicity of fever
associated with each species (ie, 48 h for P falciparum, P vivax, and P ovale [or
tertian fever] ; 72 h for P malariae [or quartan fever]) is not apparent during initial
infection because of multiple broods emerging in the bloodstream. In addition, the
periodicity is often not observed in P falciparum infections. Patients with longstanding, synchronous infections are more likely to present with classic fever
patterns. In general, however, the occurrence of periodicity of fever is not a reliable
clue to the diagnosis of malaria.
Less common malarial symptoms include the following:
Anorexia and lethargy
Nausea and vomiting
Diarrhea
Jaundice
Notably, infection with P vivax, particularly in temperate areas of India, may cause
symptoms up to 6-12 months after the host leaves the endemic area. In addition,
patients infected with P vivax or P ovale may relapse after longer periods, because
of the hypnozoite stage in the liver.
P malariae does not have a hypnozoite stage, but patients infected with P malariae
may have a prolonged, asymptomatic erythrocytic infection that becomes
symptomatic years after leaving the endemic area.

Tertian and quartan fevers are due to the cyclic lysis of red blood cells that occurs
as trophozoites complete their cycle in erythrocytes every 2 or 3 days, respectively.
P malariae causes quartan fever; P vivax and P ovale cause the benign form of
tertian fever, and P falciparum causes the malignant form. The cyclic pattern of
fever is very rare.
Travelers to forested areas of Southeast Asia and South America have become
infected by Plasmodium knowlesi, a dangerous species normally found only in
long-tailed and pigtail macaque monkeys (Macaca fascicularis and M nemestrina,
respectively). This species can cause severe illness and death in humans, but, under
the microscope, the parasite looks similar to the more benign P malariae and has
sometimes been misdiagnosed.
Because P malariae infection is typically relatively mild, Plasmodium knowlesi
infection should be suspected in persons residing or traveling in the above
geographical areas who are severely ill and have microscopic evidence of P
malariae infection. Diagnosis may be confirmed via polymerase chain reaction
(PCR) assay test methods.
Physical Examination
Most patients with malaria have no specific physical findings, but splenomegaly
may be present. Symptoms of malarial infection are nonspecific and may manifest
as a flulike illness with fever, headache, malaise, fatigue, and muscle aches. Some
patients with malaria present with diarrhea and other gastrointestinal (GI)
symptoms. Immune individuals may be completely asymptomatic or may present
with mild anemia. Nonimmune patients may quickly become very ill.
Severe malaria primarily involves P falciparum infection, although death due to
splenic rupture has been reported in patients with non P falciparum malaria.
Severe malaria manifests as cerebral malaria, severe anemia, respiratory
symptoms, and renal failure.
In children, malaria has a shorter course, often rapidly progressing to severe
malaria. Children are more likely to present with hypoglycemia, seizures, severe
anemia, and sudden death, but they are much less likely to develop renal failure,
pulmonary edema, or jaundice.
Cerebral malaria

This feature is almost always caused by P falciparum infection. Coma may occur;
coma can usually be distinguished from a postictal state secondary to generalized
seizure if the patient does not regain consciousness after 30 minutes. When
evaluating comatose patients with malaria, hypoglycemia and CNS infections
should be excluded.
Severe anemia
The anemia associated with malaria is multifactorial and is usually associated with
P falciparum infection. In nonimmune patients, anemia may be secondary to
erythrocyte infection and a loss of infected RBCs. In addition, uninfected RBCs
are inappropriately cleared, and bone marrow suppression may be involved.
Renal failure
This is a rare complication of malarial infection. Infected erythrocytes adhere to
the microvasculature in the renal cortex, often resulting in oliguric renal failure.
Renal failure is typically reversible, although supportive dialysis is often needed
until kidney function recovers. In rare cases, chronic P malariae infection results in
nephrotic syndrome.
Respiratory symptoms
Patients with malaria may develop metabolic acidosis and associated respiratory
distress. In addition, pulmonary edema can occur. Signs of malarial hyperpneic
syndrome include alar flaring, chest retraction (intercostals or subcostal), use of
accessory muscles for respiration, or abnormally deep breathing
Approach Considerations
In returning travelers from endemic areas, malaria is suggested by the triad of
thrombocytopenia, elevated lactate dehydrogenase (LDH) levels, and atypical
lymphocytes. These findings should prompt obtaining malarial smears.
In general, blood cultures should be drawn in a febrile patient. Patients from
tropical areas may have more than 1 infection; maintaining a high suspicion for
additional infections should be considered when patients do not respond to
antimalarials.
Assess hemoglobin (decreased in 25% of patients, often profoundly in young
children), platelet counts (thrombocytopenia in 50-68% of patients), and liver

function (results abnormal in 50% of patients). Also monitor renal function,


electrolytes (especially sodium), and parameters suggestive of hemolysis
(haptoglobin, LDH, reticulocyte count). Rapid HIV testing may also be indicated
in select cases. Importantly, fewer than 5% of patients with malaria have an
elevated white blood cell (WBC) count. If leukocytosis is present, the examiner
should entertain a broader list of differential diagnoses. The British Committee for
Standards in Haematology has guidelines on the laboratory diagnosis of malaria.[10]
If the patient is to be treated with primaquine, a G-6-PD level should be obtained
because primaquine can result in severe hemolysis in these patients.
If the patient has cerebral malaria, obtain a blood glucose level to rule out
hypoglycemia as a cause of mental-status changes. Note that intravenous (IV)
quinine can induce hypoglycemia; therefore, blood glucose should be monitored
when IV quinine is used.
Imaging studies
Chest radiography may be helpful if respiratory symptoms are present. If CNS
symptoms are present, a computed tomography (CT) scan of the head may be
obtained to evaluate evidence of cerebral edema or hemorrhage.
Microhematocrit centrifugation
Using this method with the CBC tube is a more sensitive method of detection of
malaria infection. However, microhematocrit centrifugation does not allow the
identification of the species of Plasmodium. To determine species, a peripheral
blood smear must be examined.
Fluorescent dyes/ultraviolet indicator tests
Several different dyes allow laboratory results to be obtained more quickly. These
methods require the use of a fluorescent microscope. Fluorescent /ultraviolet tests
may not yield speciation information.
Polymerase chain reaction assay
PCR assay testing is a very specific and sensitive means of determining if species
of Plasmodium are present in the blood of an infected individual. PCR assay tests
are not available in most clinical situations. However, they are very effective at

detecting the Plasmodium species in patients with parasitemias as low as 10


parasites/mL of blood.
Lumbar puncture
If the patient exhibits mental-status changes, and even if the peripheral smear
demonstrates P falciparum, a lumbar puncture should be performed to rule out
bacterial meningitis.
Blood Smears
A diagnosis of malaria should be supported by the identification of the parasites on
a thin or thick blood smear. In rare occasions, P falciparum infection can present
without detectable parasitemia. If no alternative diagnosis is found in an at-risk
patient with possible cerebral malaria (ie, unrevealing lumbar puncture findings),
initiate therapy for presumptive malaria and continue to obtain additional blood
smears to confirm the diagnosis.
When reading a smear, 200-300 oil-immersion fields should be examined (more if
the patient recently has taken prophylactic medication, because this temporarily
may decrease parasitemia). One negative smear does not exclude malaria as a
diagnosis; several more smears should be examined over a 36-hour period.
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.
Alternatives to Blood Smear Testing

Alternative diagnostic methods typically are used if the laboratory does not have
sufficient expertise in detecting parasites in blood smears.
Rapid diagnostic tests (RDT)
Immunochromatographic tests based on antibody to histidine-rich protein-2
(PfHRP2), parasite LDH (pLDH), or Plasmodium aldolase appear to be very
sensitive and specific.[11, 12] Some RDTs may be able to detect P falciparum in
parasitemias that are below the threshold of reliable microscopic species
identification. Only one RDT (BinaxNOW) has been approved to date for the
diagnosis of malaria in the United State.[13]
In one study, RDTs were found to perform better than microscopy under routine
conditions. RDTs performed by the health facility staff were 91.7% sensitive and
96.7% specific. Microscopy was 52.5% sensitive and 77% specific.[14] A recent
sudy using loop-mediated amplification technique (LAMP)also suggests that RDTs
have accuracy similar to that of nested PCR, with a greatly reduced time to result,
and was superior to expert microscopy.[15]
In a study from Tanzania, d'Acremont et al reported that antimalarials could be
safely withheld from febrile children (< 5 y) who had negative results from an
RDT based on PfHRP2.[16]
RDTs are less effective when parasite levels are below 100 parasites/mL of blood,
and, in rare instances, an RDT test is negative in patients with high parasitemias.
For these reasons, confirm RDT test results with a second type of screening test
when possible. A false-positive result from an RDT may occur up to 2 weeks or
more after treatment due to persistence of circulating antigens.
Other tests
In addition to the RDT listed above, new molecular techniques, such as PCR assay
testing and nucleic acid sequence-based amplification (NASBA), are also available
for diagnosis. They are more sensitive than thick smears but are expensive and
unavailable in most developing countries.[17]
The quantitative buffy coat (QBC) is a technique that is as sensitive as thick
smears. Because results cannot be used to speciate Plasmodium, a thin smear must
be examined.

Malaria is a reportable disease. Identification of parasites by any of the above


techniques should prompt notification to the local or state health department.
Histologic Findings
The table below compares histologic findings for P falciparum, P vivax, P ovale,
and P malariae.
Table 1. Histologic Variations Among Plasmodium Species (Open Table in a new
window)
Table 1. Histologic Variations Among Plasmodium Species
Findings
P falciparum
P vivax
P ovale
P malariae
Only early
Yes
No
No
No
forms present
in peripheral
blood
MultiplyOften
Occasionally
Rare
Rare
infected RBCs
Age of
RBCs of all ages Young RBCs
Young RBCs Old RBCs
infected RBCs
Schffner dots No
Yes
Yes
No
Other features Cells have thin
Late trophozoites Infected
Bandlike
cytoplasm, 1 or 2 develop
RBCs
trophozoites
chromatin dots,
pleomorphic
become oval, are distinctive.
and applique
cytoplasm.
with tufted
forms.
edges.
Approach Considerations
Failure to consider malaria in the differential diagnosis of a febrile illness in a
patient who has traveled to an area where malaria is endemic can result in
significant morbidity or mortality, especially in children and in pregnant or
immunocompromised patients.
Mixed infections involving more than 1 species of Plasmodium may occur in areas
of high endemicity and multiple circulating malarial species. In these cases,
clinical differentiation and decision making will be important; however, the
clinician should have a low threshold for including the possible presence of P
falciparum in the treatment considerations.

Occasionally, morphologic features do not permit distinction between P


falciparum and other Plasmodium species. In such cases, patients from a P
falciparum endemic area should be presumed to have P falciparum infection and
should be treated accordingly.
In patients from Southeast Asia, consider the possibility of P knowlesi infection.
This species frequently causes hyperparasitemia and the infection tends to be more
severe than infections with other non P falciparum plasmodia. It should be treated
as P falciparum infection.
P falciparum is resistant to chloroquine treatment except in Haiti, the Dominican
Republic, parts of Central America, and parts of the Middle East. Resistance is rare
in P vivax infection, and P ovale and P malariae remain sensitive to chloroquine.
Primaquine is required in the treatment of P ovale and P vivax infection in order to
eliminate the hypnozoites (liver phase).
In the United States, patients with P falciparum infection are often treated on an
inpatient basis in order to observe for complications attributable to either the
illness or its treatment.
Pregnancy
Pregnant women, especially primigravid women, are up to 10 times more likely to
contract malaria than nongravid women. Gravid women who contract malaria also
have a greater tendency to develop severe malaria. Unlike malarial infection in
nongravid individuals, pregnant women with P vivax are at high risk for severe
malaria, and those with P falciparum have a greatly increased predisposition for
severe malaria as well.
For these reasons, it is especially important that nonimmune pregnant women in
endemic areas use the proper pharmacologic and nonpharmacologic prophylaxis.
If a pregnant woman becomes infected, she should know that many of the
antimalarial and antiprotozoal drugs used to treat malaria are safe for use during
pregnancy for the mother and the fetus. Therefore, the medications should be used,
since the benefits of these drugs greatly outweigh the risks associated with leaving
the infection untreated.
Pediatrics

In children, malaria has a shorter course, often rapidly progressing to severe


malaria. Children are more likely to present with hypoglycemia, seizures, severe
anemia, and sudden death, but they are much less likely to develop renal failure,
pulmonary edema, or jaundice.
Cerebral malaria results in neurologic sequelae in 9-26% of children, but of these
sequelae, approximately one half completely resolve with time.
Most antimalarial drugs are very effective and safe in children, provided that the
proper dosage is administered. Children commonly recover from malaria, even
severe malaria, much faster than adults.
Diet and activity
Patients with malaria should continue intake and activity as tolerated.
Monitoring
Patients with non P falciparum malaria who are well can usually be treated on an
outpatient basis. Obtain blood smears every day to demonstrate response to
treatment. The sexual stage of the protozoan, the gametocyte, does not respond to
most standard medications (eg, chloroquine, quinine), but gametocytes eventually
die and do not pose a threat to the individual's health.
Pharmacologic Therapy
IV preparations of antimalarials are available for the treatment of severe
complicated malaria, including artesunate and quinidine gluconate, which is used
as a substitute for the IV quinine available in countries outside of the United States.
In a 2010 randomized study done in 11 African centers, children (age < 15 years)
with severe P falciparum malaria had reduced mortality after treatment with IV
artesunate, as compared with IV quinine. Development of coma, seizures, and
posttreatment hypoglycemia were each less common in patients treated with
artesunate.[18]
Evidence from a meta-analysis including 7429 subjects from 8 trials shows a
decreased risk of death using parenteral artesunate compared to quinine for the
treatment of severe malaria in adults and children.[19]

P falciparum drug resistance is common in endemic areas, such as Africa. Standard


antimalarials, such as chloroquine and antifolates (sulfadoxine-pyrimethamine), are
ineffective in many areas. Because of this increasing prevalence of drug resistance
and a high likelihood of resistance development to new agents, combination
therapy is now becoming the standard of care for treatment of P falciparum
infection worldwide. In April 2009, the US Food and Drug Administration (FDA)
approved the use of artemisinins, a new class of antimalarial agent.[20]
Despite the activity of artemisinin and its derivatives, monotherapy with these
agents has been associated with high rates of relapse. This may be due to the
temporary arrest of the growth of ring-stage parasites (dormancy) after exposure to
artemisinin drugs. For this reason, monotherapy with artemisinin drugs is not
recommended.[21] Rectal artesunate has been used for pretreatment of children in
resource-limited settings as a bridge therapy until the patient can access health
care facilities for definitive IV or oral therapy.[22]
Despite their being a fairly new antimalarial class, resistance to artemisinins has
been reported in some parts of southeast Asia (Cambodia).[23]
In the United States, artemether and lumefantrine tablets (Coartem) can be used to
treat acute uncomplicated malaria. Artesunate, a form of artemisinin that can be
used intravenously, is available from the Centers for Disease Control and
Prevention (CDC). Other combinations, such as atovaquone and proguanil HCL
(Malarone) or quinine in combination with doxycycline or clindamycin, remain
highly efficacious. Malaria vaccine production and distribution continues to be in
the research and development stage.[24, 25, 26]
When making treatment decisions, it is essential to consider the possibility of
coinfection with more than 1 species. Reports of P knowlesi infection suggest that
coinfection is common.[5] It has also been demonstrated that up to 39% of patients
infected with this species may develop severe malaria. In cases of severe P
knowlesi malaria, IV therapy with quinine or artesunate is recommended.[6]
The following is a summary of general recommendations for the treatment of
malaria:
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 falciparum malaria with known chloroquine susceptibility (only a few


areas in Central America and the Middle East) - Chloroquine
P vivax, P ovale malaria - Chloroquine plus primaquine; however, a 2012
study of Indonesian soldiers demonstrated that primaquine combined with
newer nonchloroquine antimalarials killed dormant P vivax parasites and
prevented malaria relapse;[27, 28] the combination of dihydroartemisininpiperaquine with primaquine had 98% efficacy against relapse, suggesting
that this regimen could become a useful alternative to primaquine plus
chloroquine, the clinical utility of which is being threatened by worsening
chloroquine resistance
P malariae malaria - Chloroquine
P knowlesi malaria Recommendations same as those for P falciparum
malaria.
In July 2013, the FDA updated its warning about mefloquine hydrochloride to
include neurologic side effects, along with the already known risk of adverse
psychiatric events such as anxiety, confusion, paranoia, and depression. The
information, which is included in the patient medication guide and in a new boxed
warning on the label, cautions that vestibular symptoms, which include dizziness,
loss of balance, vertigo, and tinnitus, can occur.[29, 30]
The FDA also warns that vestibular side effects can persist long after treatment has
ended and may become permanent. In addition, clinicians are warned against
prophylactic mefloquine use in patients with major psychiatric disorders and are
further cautioned that if psychiatric or neurologic symptoms arise while the drug is
being used prophylactically, it should be replaced with another medication.
Pharmacologic treatment in pregnancy
Medications that can be used for the treatment of malaria in pregnancy include
chloroquine, quinine, atovaquone-proguanil, clindamycin, mefloquine (avoid in
first trimester), sulfadoxine-pyrimethamine (avoid in first trimester) and the
artemisinins (see below). Briand et al compared the efficacy and safety of
sulfadoxine-pyrimethamine to mefloquine for intermittent preventive treatment
during pregnancy. In their study, 1601 women of all gravidities received either
sulfadoxine-pyrimethamine (1500 mg of sulfadoxine and 75 mg of pyrimethamine)
or mefloquine (15 mg/kg) in a single dose twice during pregnancy. There was a

small advantage for mefloquine in terms of efficacy, although the incidence of side
effects was higher with mefloquine than with sulfadoxine-pyrimethamine.[31, 32]
In addition to mefloquine and sulfadoxine-pyrimethamine, other medications have
been used in the treatment of the pregnant patient with malaria. In a recent study in
African patients, artemether-lumefantrine was as efficacious and as well tolerated
as oral quinine in treating uncomplicated falciparum malaria during the second and
third trimesters of pregnancy.[2]
Artesunate and other antimalarials also appear to be effective and safe in the first
trimester of pregnancy, when development of malaria carries a high risk of
miscarriage.[3]
Inpatient Care
Patients with elevated parasitemia (>5% of RBCs infected), CNS infection, or
otherwise severe symptoms and those with P falciparum infection should be
considered for inpatient treatment to ensure that medicines are tolerated.
Obtain blood smears every day to demonstrate a response to treatment. The sexual
stage of the protozoan, the gametocyte, does not respond to most standard
medications (eg, chloroquine, quinine), but gametocytes eventually die and do not
pose a threat to the individual's health or cause any symptoms.
Deterrence and Prevention
Avoid mosquitoes by limiting exposure during times of typical blood meals (ie,
dawn, dusk). Wearing long-sleeved clothing and using insect repellants may also
prevent infection. Avoid wearing perfumes and colognes.
Adult-dose 95% DEET lasts up to 10-12 hours, and 35% DEET lasts 4-6 hours. In
children, use concentrations of less than 35% DEET. Use sparingly and only on
exposed skin. Remove DEET when the skin is no longer exposed to potential
mosquito bite. Consider using bed nets that are treated with permethrin. While this
is an effective method for prevention of malaria transmission in endemic areas, an
increasing incidence of pyretrhoid resistance in Anopheles spp has been reported.
[33]
Seek out medical attention immediately upon contracting any tropical fever or
flulike illness.
Consider chemoprophylaxis with antimalarials in patients traveling to endemic
areas. Chemoprophylaxis is available in many different forms. The drug of choice

is determined by the destination of the traveler and any medical conditions the
traveler may have that contraindicate the use of a specific drug.
Before traveling, people should consult their physician and the Malaria and
Traveler's Web site of the CDC to determine the most appropriate
chemoprophylaxis.[34] Travel Medicine clinics are also a useful source of
information and advice.
Investigational malaria vaccine
Interim phase 3 trial results have been reported for the malaria vaccine
RTS,S/AS01. The results included 6000 African children aged 5-17 months who
received the malaria vaccine or a comparator vaccine and were followed for 12
months. The incidence of malaria was 0.44 case per person-year in the
RTS,S/AS01 group, compared with 0.83 case per person-year in the comparator
vaccine group. The vaccine efficacy rate was calculated to be 55.8%.[35, 36]
Consultations
Consider consulting an infectious disease specialist for assistance with malaria
diagnosis, treatment, and disease management. The CDC is an excellent resource if
no local resources are available. To obtain the latest recommendations for malaria
prophylaxis and treatment from the CDC, call the CDC Malaria Hotline at (770)
488-7788 or (855) 856-4713 (M-F, 9 am-5 pm, Eastern time). For emergency
consultation after hours, call (770) 488-7100 and ask to talk with a CDC Malaria
Branch clinician.[37]
Pregnant patients with malaria are at increased risk of morbidity and mortality.[38]
In addition, nonimmune mothers and immune primigravidas may be at an
increased risk of low birth weight, fetal loss, and prematurity. Consult an expert in
malaria to determine the safest and most effective prophylaxis or treatment in a
pregnant woman
Medication Summary
The 4 major drug classes currently used to treat malaria include quinoline-related
compounds, antifolates, artemisinin derivatives, and antimicrobials. No single
drug that can eradicate all forms of the parasite's life cycle has been discovered or
manufactured yet. Therefore, 1 or more classes of drugs often are given at the
same time to combat malarial infection synergistically. Treatment regimens are

dependent on the geographic location of infection, the likely Plasmodium species,


and the severity of disease presentation.
Beware of counterfeit antimalarial drugs being taken by patients that may have
been purchased overseas or via the Internet. They may not contain any active
ingredients at all and may contain dangerous materials.
Antipyretics, such as acetaminophen or nonsteroidal anti-inflammatory drugs
(NSAIDs), are indicated to reduce the level of discomfort caused by the infection
and to reduce fever. NSAIDs should be used with caution if bleeding disorder or
hemolysis is suspected.
Antimalarials can cause significant prolongation of the QT interval, which can be
associated with an increased risk of potentially lethal ventricular dysrhythmias.
Patients receiving these drugs should be assessed for QT prolongation at baseline
and carefully monitored if this is present. Patients with normal QT intervals on
electrocardiogram (ECG) may not be at a significantly increased risk for druginduced dysrhythmia, but caution is advised, particularly if the patient is taking
multiple drug regimens or if he or she is on other drugs affecting the QT interval.
Methemoglobinemia is a complication that may be associated with high-dose
regimens of quinine or the derivatives chloroquine and primaquine.[23] A patient
presenting with cyanosis and a normal PaO2 on room air should be suspected of
having methemoglobinemia.
Antimalarials
Class Summary
These agents inhibit growth by concentrating within acid vesicles of the parasite,
increasing the internal pH of the organism. They also inhibit hemoglobin
utilization and parasite metabolism.
View full drug information
Chloroquine phosphate (Aralen)

Chloroquine phosphate is effective against P vivax, P ovale, P malariae, and drugsensitive P falciparum. It can be used for prophylaxis or treatment. This is the
prophylactic drug of choice for sensitive malaria.
View full drug information
Quinine (Qualaquin)

Quinine is used for malaria treatment only; it has no role in prophylaxis. It is used
with a second agent in drug-resistant P falciparum. For drug-resistant parasites, the
second agent is doxycycline, tetracycline, pyrimethamine sulfadoxine, or
clindamycin.
View full drug information
Quinidine gluconate

Quinidine gluconate is indicated for severe or complicated malaria and is used in


conjunction with doxycycline, tetracycline, or clindamycin. Quinidine gluconate
can be administered IV and is the only parenterally available quinine derivative in
the United States.
View full drug information
Doxycycline (Vibramycin, Adoxa, Doryx)

Doxycycline is used for malaria prophylaxis or treatment. When it is administered


for treatment of P falciparum malaria, this drug must be used as part of
combination therapy (eg, typically with quinine or quinidine).
View full drug information
Tetracycline

Tetracycline may specifically impair the progeny of apicoplast genes, resulting in


their abnormal cell division. Loss of apicoplast function in progeny of treated
parasites leads to slow, but potent, antimalarial effect.
Clindamycin (Cleocin HCl, Cleocin Phosphate)

Clindamycin is part of combination therapy for drug-resistant malaria (eg, typically


with quinine or quinidine). It is a good second agent in pregnant patients.
Mefloquine

Mefloquine acts as a blood schizonticide. It may act by raising intravesicular pH


within the parasite's acid vesicles. Mefloquine is structurally similar to quinine. It
is used for the prophylaxis or treatment of drug-resistant malaria. It may cause
adverse neuropsychiatric reactions and should not be prescribed for prophylaxis
in patients with active or recent history of depression, generalized anxiety disorder,
psychosis, or schizophrenia or other major psychiatric disorders.
View full drug information
Atovaquone and proguanil (Malarone)

Atovaquone may inhibit metabolic enzymes, which in turn inhibits the growth of
microorganisms.
Used for pediatric patients, this combination should be administered for
uncomplicated P falciparum; can also be used in combination with chloroquine.
This agent is approved in the United States for the prophylaxis and treatment of
mild chloroquine-resistant malaria. It may be a good prophylactic option for
patients who are visiting areas with chloroquine-resistant malaria and who cannot
tolerate mefloquine. Each tab combines 250 mg of atovaquone and 100 mg of
proguanil hydrochloride. The dosage for children is based on body weight; in
children 40 kg (88 lb) or less, a lower-dose pediatric tablet (62.5 mg of atovaquone
and 25 mg of proguanil hydrochloride) is available.

View full drug information


Primaquine

Primaquine is not used to treat the erythrocytic stage of malaria. Administer the
drug for the hypnozoite stage of P vivax and P ovale to prevent relapse.
View full drug information
Artemether and lumefantrine (Coartem)

This drug combination is indicated for the treatment of acute, uncomplicated P


falciparum malaria. It contains a fixed ratio of 20 mg artemether and 120 mg
lumefantrine (1:6 parts). Both components inhibit nucleic acid and protein
synthesis. Artemether is rapidly metabolized into the active metabolite
dihydroartemisinin (DHA), producing an endoperoxide moiety. Lumefantrine may
form a complex with hemin, which inhibits the formation of beta hematin.
View full drug information
Artesunate

Artesunate, a form of artemisinin that can be used intravenously, is available from


the CDC. It is not licensed for use in the United States but is available as part of an
investigational new drug protocol.

Vous aimerez peut-être aussi