MALARIA use of long-­lasting insecticidal nets, indoor residual spraying pro-
grams, rapid diagnostic testing, and access to artemisinin combi-
Nestor Sosa, MD; and Jose Antonio Suarez, MD
CURRENT DIAGNOSIS
• Malaria is endemic in tropical and subtropical areas of Africa,
Asia, Oceania, and Central and South America.
• Suspect malaria in returning travelers and recently arrived
immigrants from an endemic region with fever, accompanied
by headaches, chills, malaise and body aches.
• The microscopic examination of Giemsa-­stained thin and
thick peripheral blood smears is the standard diagnostic
method for malaria.
• Rapid diagnostic antigen detection and polymerase chain
reaction (PCR) testing can be used for initial diagnosis, but
species confirmation and level of parasitemia require micros-
copy.
CURRENT THERAPY
• Treatment selection should be based on Plasmodium species
involved, geographic area where the infection was acquired,
presence of resistance to antimalarial drugs, and disease
severity.
VIII  Infectious Diseases
• Intravenous (IV) artesunate (available from Centers for
Disease Control and Prevention [CDC])5 is the recommended
therapy for severe malaria. Alternative treatments are
artemether-­lumefantrine (Coartem)1, atovaquone-­proguanil
(Malarone)1 or quinine (Qualaquin)1 plus doxycycline1 or
clindamycin1.
• Uncomplicated malaria caused by chloroquine-­sensitive Plas-
modium species can be treated with chloroquine or hydroxy-
chloroquine (Plaquenil). Radical cure of Plasmodium vivax
and Plasmodium ovale1 requires subsequent therapy with
primaquine or tafenoquine (Krintafel).
• Artemisinin combination therapies (i.e., artemether-­
606 lumefantrine [Coartem]) are the primary regimens for uncom-
plicated malaria caused by chloroquine-­resistant P. falciparum
or P. vivax1.
5Investigationaldrug in the United States.
1Not FDA approved for this indication.
Ιntroduction
Malaria is an important parasitic disease caused by protozoa of
the genus Plasmodium (Phylum Apicomplexa) and transmitted
primarily by the bite of female Anopheles mosquitoes.
Malaria remains a formidable health problem, especially
in sub-­Saharan Africa, and other tropical regions in Southeast
Asia, Oceania, and Latin America. The World Health Organiza-
tion (WHO) estimates that in 2018, there were 228 million new
cases of malaria and 405,000 deaths worldwide. Two thirds of
all deaths occur in children under 5 years of age. The economic
losses from the disease, only in Africa, are estimated to reach
US$12 billion per year.
In recent years, a significant investment has been made in
malaria control and elimination efforts. According to the 2019
WHO World Malaria Report, an estimated US$ 2.7 billion was
invested by governments of malaria-endemic countries and inter-
national partners in 2018. The incidence rate of malaria declined
globally between 2010 and 2018 from 71 to 57 cases per 1000
population at risk; the number of countries with zero or less than
100 indigenous cases have also increased in the same period of
time. These advances in malaria control can be explained by the
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nation therapy (ACT). 
Epidemiology
Most cases of malaria occur in Africa, but cases are reported
in other tropical and subtropical regions of Southeast Asia (the
Greater Mekong Region), Oceania, India, and Central and South
America (Figure 1).
Five different species of Plasmodia have been associated with
the disease: four human malaria parasites, P. falciparum, P.
vivax, P. ovale, and P. malariae, and one simian plasmodia of
macaques monkeys, P. knowlesi, which affects humans in Borneo
and Peninsular Malaysia.
P. falciparum is responsible for the great majority of cases
overall, is the most prevalent in sub-­Saharan Africa, and it is
associated more frequently with the most severe and fatal forms
of the disease. P. vivax is the most prevalent species in Southeast
Asia and Central and South America; P. ovale circulates with a
very low incidence in Africa, Asia and Oceania; and P. malariae
is rare but has been reported worldwide.
The infection is transmitted primarily from person to person,
via the bite of the female mosquito of the genus Anopheles. More
than 30 different species of Anopheles have been associated with
malaria transmission worldwide. Environmental factors, like
relative humidity, elevation, and temperature, influence the trans-
mission of malaria in the endemic areas. Highest transmission
occurs during the wet or rainy season. Other less common modes
of transmission are mother to child (congenital malaria), blood
transfusions, needle sharing, and via solid organ transplants.
Most cases in nonendemic areas are reported in travelers and
immigrants arriving from areas with local malaria transmission.
Rarely, infected mosquitos can be accidentally transported in air-
planes and cause cases in and around airport terminals in non-­
endemic regions, the so-­ called “airport malaria.” In the United
States, the CDC report about 2000 imported malaria cases every
year and it is a nationally reportable disease. Travelers to sub-­
Saharan Africa have the greatest risk of acquiring the disease. Sixty-­
seven percent of the cases reported in the United States in 2015 were
caused by P. falciparum, 12% by P. vivax, 4% by P. ovale, 3% by
P. malariae, and less than 1% by more than one species.
One of the greatest challenges for the prevention and treatment
of malaria has been the development of drug resistance, especially
among P. falciparum, but also reported with P. vivax. The pat-
terns and geographical distribution of drug-resistant parasites is
complex. Resistance to malaria medication continues to be an
essential consideration when selecting drugs for treatment and
chemoprophylaxis.
Since the 1970s, chloroquine resistance in P. falciparum has
been confirmed in every continent where malaria is endemic,
sparing only Mexico, Central America west of the Panama
Canal, Haiti, the Dominican Republic, and a few Middle East-
ern countries. High-­grade chloroquine resistance in P. vivax has
been reported in Papua New Guinea, the Solomon Islands, India,
Myanmar, and Indonesia.
The emergence of resistance of P. falciparum to mefloquine
(Lariam) has been documented in Myanmar (Burma), Lao People’s
Democratic Republic (Laos), Thailand, Cambodia, China, and
Vietnam. Resistance to sulfadoxine/pyrimethamine (Fansidar)2
and atovaquone/proguanil (Malarone) has also been reported. The
resistance to these drugs has made ACT the treatment of choice
for most cases of P. falciparum malaria. Unfortunately, there have
been recent reports of clinical failures and resistance to artemisinin
derivatives from the five countries of Greater Mekong Subregions:
Cambodia, Laos, Myanmar, Thailand, and Vietnam. 
Parasite Life Cycle
The life cycle of the different species of Plasmodia are similar
(Figure 2). The sexual cycle occurs in the mosquito, and repeated
2 Not available in the United States.
 Malaria endemic Malaria endemic
country country
Non-malaria Non-malaria
endemic country endemic country

A B
Figure 1  Malaria-­endemic countries in the (A) Western and (B) Eastern Hemispheres. Transmission occurs across most of Africa, Central and South
America, and Southern and Southeast Asia, as well as parts of the Caribbean, Eastern Europe, and the South Pacific. Countries are shaded completely
even if the area of endemicity is only in a small area of the country. (Adapted from Centers for Disease Control and Prevention: CDC Health Informa-
tion for International Travel 2016, New York, 2016, Oxford University Press. Public Domain.)

asexual cycles in the human host. The human infection starts
when between 10 and 100 sporozoites—present in the salivary
glands of the female Anopheles mosquito—enter the human host
when the insect takes a blood meal. These sporozoites migrate
from the dermis, invade the hepatocytes, and differentiate into
hepatic schizonts that produce merozoites that later are liberated
and invade circulating erythrocytes. P. vivax and P. ovale pref­
Several genetic polymorphisms seem to confer resistance to
severe P. falciparum infection. Its relative increased prevalence
in areas that are endemic for malaria demonstrates the natural
selection forces of this disease over the human genome. Hemo-
globin gene alterations like sickle cell disorders, thalassemia,
hemoglobin C, hemoglobin E, and hemoglobin F, and blood
cell enzyme deficiencies like glucose-­6-­phospate dehydrogenase

erentially invade younger erythrocytes (reticulocytes); P. falci-
parum invades all types of erythrocytes.
Differences in the duration of these exo-­ erythrocytic cycles
explain the variations in the incubation period of the different
species of malaria. P. knowlesi incubation period is from 9 to
12 days and P. falciparum is often 9 to 14 days, while P. vivax
ranges from 12 to 17 days and P. ovale from 16 to 18 days. P.
malariae is the most variable with ranges from 18 to 40 or more
days.
The erythrocytic cycles of invasion and growth take approxi-
mately 24 hours in P. knowlesi; 48 hours in P. falciparum, P.
ovale and P. vivax; and 72 hours in P. malariae. These differences
explain the periodicity of the fever paroxysm seen with the dif-
ferent parasites.
Once in the red blood cells, the merozoites develop into ring
forms, and mature into trophozoites and schizonts and finally
merozoites that rupture the cells and invade other erythrocytes,
repeating and amplifying this erythrocytic asexual phase.
Some of the trophozoites in the red cells mature into gameto-
cytes—the form that, when taken up by the mosquitoes, start the
sexual cycle. The sexual cycle takes approximately 1 to 2 weeks
within the mosquito. The gametocytes cross-­fertilize in the mos-
quito midgut and become diploid zygotes that form an ookinete
and finally close to 1000 sporozoites that migrate to the salivary
glands and can infect another human host.
In P. vivax and P. ovale infection, parasites may remain latent
in the liver as hypnozoites and reactivate after months, or even
years, causing relapses of the disease.  fever in P. malariae). In primary infections, this periodicity may
Malaria Immunity
Acquired immunity to malaria is not sterilizing, but it protects
against symptomatic and severe disease. It increases with age,
number of episodes of the infection, and time spent living in the
endemic area.
Malaria
and certain blood group antigens (Duffy negative and ABO type
O), have been associated with relative protection to infection or
severe malaria.
Malaria is uncommon in neonates. The presence of fetal hemo-
globin (hemoglobin F) and maternal antibodies may, in part,
explain this observation.  607
Clinical Manifestations
The incubation period ranges from 9 to 40 days and it is influ-
enced by the specific parasite species involved, the immune sta-
tus of the host, the administration of chemoprophylaxis, and the
infecting dose of sporozoites.
After a vague prodromal period of 2 to 3 days, malaria
classically manifests as an acute febrile illness with episodes
of paroxysms characterized by chills (classically described
as “teeth chattering, bed shaking chills”), rigor, high tem-
perature (T ≥40°C) and profuse sweating, usually followed
by fatigue and sleep. Other common symptoms include
headache, weakness, insomnia, arthralgia, myalgia, and,
less frequently, diarrhea, abdominal pain, or respiratory
symptoms.
Individuals with prior immunity and children may pres-
ent only with fever and headache; infants and very young
children may present with irritability and a decrease in food
intake.
The malaria paroxysms may recur every 24 (P. knowlesi), 48
(tertian fever in P. vivax and P. falciparum), or 72 hours (quartan
take several days to become apparent. The patient may be rela-
tively asymptomatic between these paroxysms.
On physical exam the patients may exhibit pallor, hepato-
splenomegaly and, in severe cases, jaundice, altered mental status,
and convulsions. Rash, pulmonary manifestation and lymphade-
nopathy are rare. 

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 1
MOSQUITO STAGES Mosquito takes a blood meal HUMAN LIVER STAGES
(injects sporozoites)
11 2
Oocyst Infected
10 Release of liver cell
Ookinete sporozoites

A
Exo-erythrocytic Cycle
C
Sporogonic Cycle
Liver cell 3
9 Schizont
Microgamete 4
entering 12 Ruptured
macrogamete Ruptured schizont
oocyst

6
Ruptured
Exflagellated Macrogametocyte schizont 5
microgametocyte

8
Mosquito takes
a blood meal B
(ingests gametocytes) Erythrocytic Cycle

P. vivax Schizont
P. ovale
VIII  Infectious Diseases

P. falciparum P. malariae
Immature
trophozoite
Mature (ring stage)
trophozoite

HUMAN BLOOD STAGES

7 7
Gametocytes Gametocytes
608 Figure 2  The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-­infected female Anopheles mosquito inoculates sporozoites
into the human host (1). Sporozoites infect liver cells (2) and mature into schizonts (3), which rupture and release merozoites (4). (In Plasmodium vivax
and Plasmodium ovale, a dormant stage [hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks to years later.)
After initial replication in the liver via exoerythrocytic cycle or tissue schizogony (A), the parasites undergo asexual multiplication in erythrocytes via
erythrocytic cycle or blood schizogony (B). Merozoites infect red blood cells (5). The ring stage trophozoites mature into schizonts, which rupture,
releasing merozoites (6). Some parasites differentiate into sexual erythrocytic stages (gametocytes) (7). Blood stage parasites are responsible for the
clinical manifestations of the disease. The gametocytes—male (microgametocytes) and female (macrogametocytes)—are ingested by an Anopheles mos-
quito during a blood meal (8). The parasites’ multiplication in the mosquito is known as the sporogonic cycle (C). While in the mosquito’s stomach,
the microgametes penetrate the macrogametes, generating zygotes (9). The zygotes in turn become motile and elongated (ookinetes) (10), and invade
the midgut wall of the mosquito, where they develop into oocysts (11). The oocysts grow, rupture, and release sporozoites (12), which make their way
to the mosquito’s salivary glands. Inoculation of the sporozoites (1) into a new human host perpetuates the malaria life cycle.

Severe or Complicated Malaria common in children; multiorgan system involvement is more

Nonimmune individuals such as children or travelers to endemic
areas or pregnant females may develop more severe manifesta-
tions of malaria. Complicated malaria, more commonly associ-
ated with P. falciparum infection, has been recently reported with
P. knowlesi and P. vivax. The most important clinical and labora-
tory findings of complicated malaria are listed in Table 1. In para-
sitemic patients, the presence of any of the clinical or laboratory
features of severe malaria represents a medical emergency, and
hospitalization, admission into critical care units, and rapid ini-
tiation of specific treatment are important. Even in patients with
less severe disease, because of the ability of P. falciparum infec-
tion to progress in just a few hours to severe and life-­threatening
complications, it is advisable to hospitalize all nonimmune indi-
viduals during their initial period of treatment.
The clinical presentation of complicated malaria may be differ­
ent in children and adults. Cerebral malaria (see later) is more
frequent in adults. Important clues in the physical exam are pros-
tration, deep breathing, a decreased level of consciousness, slow
capillary filling, signs of congestive heart failure, hepatospleno-
megaly, pallor, and decreased urine output. Mortality rates of
complicated or severe malaria range between 15% and 22% in
adults, and between 8.5% and 10.9% in children. 
Cerebral Malaria
Parasite sequestration in the cerebral microvasculature is asso-
ciated with a variable and potentially lethal constellation of
symptoms that include a decreased level of consciousness, coma,
generalized seizures and/or focal neurologic deficits. Histopath-
ologic findings frequently exhibit the presence of sequestered
parasites, ring hemorrhages, perivascular leukocyte infiltrates,
and immune-­ histochemical evidence of endothelial activation.
In children with cerebral malaria, intracranial pressure is usually

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TABLE 1  Features of Complicated or Severe Malaria
FINDING DESCRIPTION
Cerebral malaria Diminished consciousness, Blantyre Coma
Score of ≤2 in children, Glasgow Coma
Scale <9 in adults or seizures
Respiratory distress/ Radiographic evidence, hypoxemia
pulmonary edema
Hyperparasitemia >2% or >100,000/μL in low transmission
settings; or >5% or >250,00 in high
transmission settings
Severe anemia <5g Hgb or <15% hematocrit
Hypoglycemia <2.2 mmol/L or 40 mg/dL
Jaundice/icterus Clinically evident
Renal failure Creatinine >265 mmol/L
Hemoglobinuria
Metabolic acidosis or HCO3 <15 mmol/L or lactate >5 mmol/L
hyperlactatemia
Shock SBP <70 mm Hg in adults; SBP <50 mm
Hg in children
Abnormal spontaneous bleeding
HCO3, Bicarbonate; SBP, systolic blood pressure.
increased. Among those who survive, neurologic recovery can be
rapid and complete, but sequelae have been reported in up to
15% of children with cerebral malaria. In patients with malaria
that present with neurologic manifestations, it is important to
exclude other conditions like meningitis, hypoglycemia, and
other causes of encephalopathy. Fundoscopic examination may
be useful, revealing retinal hemorrhages and white exudates sug-
gestive of malarial retinopathy.  microscopy is not immediately available. RDTs are immuno-
Respiratory Failure/Respiratory Distress Syndrome
Noncardiogenic pulmonary edema is a complication of severe P.
falciparum malaria, seen more frequently in adults than children.
Sequestration of infected erythrocyte in the lungs is thought to be
associated with the production of cytokines, increased vascular per-
meability, pulmonary edema, dyspnea, hypoxia and progression to
acute lung injury, and respiratory distress syndrome. Patients may
become hypoxemic and require mechanical ventilation.  Even when RDTs are positive, direct microscopy is indicated
Acute Kidney Injury
Although mild proteinuria and oliguria can be present in uncom-
plicated malaria, acute renal failure—secondary to decreased
renal perfusion, intravascular hemolysis, hemoglobinuria, acute
tubular necrosis, and anuria—is a complication of severe malaria.
Renal replacement therapy and general support through the criti-
cal period is associated with complete recovery of renal function
in the majority of patients.  Serologic tests, like indirect fluorescent antibody (IFA), are not
Malaria During Pregnancy
Malaria during pregnancy, especially in nonimmune primigravi-
das, is associated with increased morbidity and mortality. The
relative immunosuppression of pregnancy and parasite accumu-
lation in the placenta related to its affinity with abundant chon-
droitin sulfate A (CSA) seem to be contributing factors for this
phenomenon. Complications such as premature delivery, intra-
uterine growth retardation, low neonatal birth weight, increased
newborn mortality, and maternal hypoglycemia and pulmonary
edema have been reported. Placental malaria during subsequent
pregnancies tends to be less severe than in the first pregnancy due
to the development of immunity to CSA-binding parasites.  especially in patients with iron deficiency or thalassemia. The
Non-­Falciparum Malaria
P. vivax and P. ovale are usually not associated with severe dis-
ease, but acute lung injury and splenic rupture may occur. Severe
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cases of P. vivax have been reported in Papua New Guinea and
Indonesia, with complications like severe anemia, cerebral malaria
and respiratory distress. Relapses of P. vivax and P. ovale due to
reactivation of the hypnozoites months or years after the initial
infection is another characteristic of these two Plasmodium.
P. malariae, the etiology of quartan fever, is associated with
very low parasitemia, chronic indolent infection, but nephrotic
syndrome has been reported in young children in endemic areas.
In P. knowlesi, clinical presentation is similar to uncomplicated
P. falciparum malaria, but approximately 10% of the cases may
present with daily fever spikes, hyperparasitemia, metabolic aci-
dosis, hepatic and renal dysfunction, respiratory distress, severe
anemia and refractory hypotension. 
Laboratory Diagnosis
The microscopic examination of Giemsa-­ stained thin and thick
peripheral blood smears is the standard diagnostic method for
malaria. Thick smears concentrate red cell layers by lysing the eryth-
rocytes and are used to screen a relatively large amount of blood.
Thin smears are used to determine the Plasmodium species based on
the morphology and characteristics of the circulating forms.
P. falciparum infections are characterized by the presence of
thin ring forms, frequently positioned at the red cell membrane,
multiple infected cells, banana-­ shaped gametocytes, and the
absence of trophozoites and schizonts that are sequestered in
the microvasculature. The smears of P. vivax and P. ovale have
thicker rings, ameboid trophozoites, schizonts and round game-
tocytes. Erythrocyte enlargement and Schüffner dots are common
in P. vivax and P. ovale but absent in other malaria species. P.
malariae has characteristic band forms and P. knowlesi rings are
similar to P. falciparum, but its mature forms and gametocytes
are indistinguishable from P. malariae.
In addition to direct microscopy, other diagnostic methods,
such as rapid diagnostic antigen detection (RDT), PCR, and
serology are used in different settings.
RDTs are increasingly useful, especially in situations where
Malaria
chromatographic tests that detect Plasmodium antigens, like P.
falciparum histidine-­ rich protein 2 (PfHRP2) or pan-­ malarial
Plasmodium aldolase (PMA). Some of these tests are specific for
P. falciparum or P. vivax, whereas others detect antigens com-
mon to several Plasmodium.
The reported sensitivities and specificity of most RDTs are high, 609
frequently around 95% and 99%, respectively. In patients with low
parasitemia (less than 100 parasites/μL), the sensitivity decreases.
to confirm the diagnosis to the species level (based on morphol-
ogy) and to estimate the level of parasitemia. Most RDTs are not
useful to evaluate treatment response because they may remain
positive for several weeks after successful treatment.
PCR detects segments of the parasite DNA using amplification.
It is very specific and may be useful in very low parasitemia, but it
is not yet readily available in most clinical settings where malaria
patients are diagnosed.
useful for routine diagnosis of acute cases of malaria. Antibody
positivity may take several days or weeks to develop. Serology
is useful to screen blood donors in transfusion-related cases, as
part of the evaluation of tropical splenomegaly syndrome (TSS)
to detect infection when parasitemia is below the level of detec-
tion for microscopy or RDTs, and for the testing of treated and
cured malaria patients.
Other nonspecific clinical laboratory abnormalities frequently
detected in patients with malaria are anemia, with decreased
hemoglobin and hematocrit, increased lactic dehydrogenase
(LDH) levels, and decreased haptoglobin levels. The anemia is
normocytic normochromic, but microcytosis is not infrequent—
white cell count may be increased, decreased or normal. Platelet
counts may be decreased or normal. Mild hyponatremia may be
present secondary to inappropriate secretion of antidiuretic hor-
mone, vomiting or urinary losses.
 TABLE 2  Antimalarial Drugs: Activity and Side Effects
DRUG (TRADE NAME) ACTIVITY INDICATION SIDE EFFECTS COMMENTS
Chloroquine (Aralen) Blood schizonts (all Treatment of choice for GI symptoms, headache, Safe in children and
Hydroxychloroquine Plasmodia) and chloroquine susceptible dizziness, insomnia, visual pregnant patients
(Plaquenil) gametocytes (P. Plasmodium changes, ototoxicity,
ovale, malariae, retinopathy, and peripheral
vivax, knowlesi) neuropathy
Atovaquone/Proguanil Blood and tissue Chemoprophylaxis Headache, cough, and GI upset, Safe in children >5 kg of
(Malarone) schizonts and treatment of dizziness, mucosal ulcerations, body weight
uncomplicated malaria increased LFTs Contraindicated in severe
outside endemic renal dysfunction
areas (in combination
with artesunate1 or
primaquine1)*
Artemisinin Blood schizonts and Treatment of choice for GI symptoms, dizziness, Contraindicated in the first
Derivatives**: gametocytes uncomplicated and severe headache, neutropenia, trimester of pregnancy
artemether, P. falciparum malaria1 in elevated LFTs
artesunate, endemic areas
dihydroartemisin
Quinine sulfate Blood schizonts of all Uncomplicated or severe Tinnitus, hearing impairment Can be used in the first
(Qualaquin) Plasmodium species, malaria when ACTs are or loss, nausea, headache, trimester of pregnancy
and Quinidine gametocytes of P. not available or cannot be dizziness, dysphoria, visual
gluconate*** vivax, P. ovale, and used (early pregnancy)1 changes, QT prolongation,
P. malariae angina, hypotension,
vertigo, vomiting, diarrhea,
hypoglycemia
Tetracyclines: Blood schizonts of all Chemoprophylaxis of P. GI symptoms, dry mouth, Contraindicated in
Doxycycline Plasmodium species falciparum. Treatment of stomatitis, photodermatitis, children <8 years and
VIII  Infectious Diseases

(Vibramycin), chloroquine-­resistant P. Candida vaginitis, anal pregnant patients

tetracycline
Clindamycin (Cleocin)
Mefloquine (Lariam)
610
Primaquine sulfate
falciparum and P. vivax1
in combination with
quinine
Blood schizonts of all Severe1 or uncomplicated
Plasmodium species malaria1 in combination
with artemisinin
derivatives or quinine
Blood schizonts of all Chemoprophylaxis of all
Plasmodium species Plasmodium species.1
Treatment of P. falciparum
malarias part of ACTs
Exo-­erythrocytic forms Chemoprophylaxis P. vivax
(hypnozoites), endemic areas1
gametocytes Treatment of P. vivax and
P. ovale hypnozoites1
(prevention of relapses or
radical cure)
pruritus
GI symptoms (including Not to be used as
Clostridium difficile colitis), monotherapy
rash
GI symptoms, neuropsychiatric Violent behavior reported
symptoms like anxiety, with prolonged use
irritability, paranoia, Safe during pregnancy
depression, hallucinations and
depression
GI symptoms, severe hemolytic Level of G6PD should
anemia in G6PD-deficient be checked before
patients primaquine use

*Not recommended in endemic areas due to resistance to atovaquone.

**Used in combination with other agents, artemisinin-­based combination therapy (ACT) is considered the treatment of choice for P. falciparum malaria in endemic areas.
(Available ACT: artemether + lumefantrine (Coartem) (only FDA-­approved treatment), artesunate + amodiaquine (Coarsucam)2, artesunate + mefloquine (Artequin)2,
artesunate + sulfadoxine-­pyrimethamine (Arsuamoon2/Fansidar2), and dihydroartemisinin + piperaquine (Eurartesim)2
***Quinidine gluconate IV formulation is the only FDA approved treatment for severe malaria in the United States, but it is no longer available. Cardiac monitoring is
recommended during treatment with this drug.
G6PD, Glucose 6 phosphate dehydrogenase; GI, gastrointestinal; LFTs liver function tests.
1Not FDA approved for this indication.
2Not available in the United States.

In severe cases of malaria, hyperbilirubinemia, metabolic (lac-
tic) acidosis, increased creatinine, albuminuria and hemoglobin-
uria may be present. Hypoglycemia may occur in patients with
malaria. Contributing factors to hypoglycemia are impaired
hepatic neoglucogenesis, decreased oral intake, and increased
glucose consumption due to the hypermetabolic state and hyper-
insulinemia—secondary to drugs like quinine or quinidine.
In African children with malaria, secondary bacterial infection,
including bacteremia, is not uncommon.  preventing the sexual stage in the mosquito. See Table 2 for the
Antimalarial Drugs
There are multiple drugs used in the treatment and prevention
of malaria. Their indication depends on the species involved,
availability of the medication, presence of drug resistance and
severity of the disease. Some of the drugs have activity against
the erythrocytic phase or asexual forms and are referred to as
blood schizonticides. Other antimalarial substances kill tissue or
exoerythrocytic parasites in the liver and are called tissue schizon-
ticides. Tissue schizonticides prevent disease relapses in patients
with P. vivax and P. malariae. Finally, other drugs demonstrate
activity against gametocytes and decrease disease transmission,
name, activity and side effects of the most commonly used anti-
malarial drugs.
Chloroquine (Aralen) and hydroxychloroquine (Plaquenil)
are two of the oldest antimalarial drugs. They are considered

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blood schizonticides and also have gametocidal activity. They
can be used in the prevention and treatment of all Plasmo-
dium species in the absence of drug resistance, and are con-
sidered the treatment of choice for P. vivax, P. malariae, P.
ovale, and P. knowlesi. Unfortunately, chloroquine resistance
in P. falciparum is widespread and these drugs are no longer
recommended for prevention or treatment, except in limited
areas of Central America, the Caribbean, and the Middle
East.
The combination of atovaquone/proguanil (Malarone)
demonstrates activity against both tissue and blood schizonts
and is frequently used in malaria prophylaxis, or as part of
multidrug regimens with primaquine1 or artesunate5 for the
treatment of uncomplicated chloroquine-­ resistant malaria
in returning travelers outside endemic areas. The emergence
of resistance to the atovaquone component limits its use in
endemic areas.
Artemisinin derivatives, like artemether, artesunate5, and dihy-
droartemisinin2, have activity against blood schizonts and game-
tocytes. These substances are originally derived from the Chinese
medicinal plant quinghaosu (Artemisia annua) and are frequently
used in combination with other drugs. The available combina-
tions are artemether + lumefantrine (Coartem, FDA approved),
artesunate + amiodaquine (Coarsucam)2, artesunate + mefloquine
(Artequin)2, dihydroartemisinin + piperaquine (Eurartesim)2
or artesunate (Arsuamoon)2 + sulfadoxina + pyrimethamine
(Fansidar)2 and are collectively referred to as artemisinin combi-
nation therapy (ACT).
ACT is considered the first-line treatment of uncomplicated
P. falciparum malaria in endemic areas. The recent emergence
of P. falciparum resistant to ACT in Southeast Asia is compro-
mising the efficacy of these two drug combinations. A recent
study demonstrated improved efficacy of three-­drug regimen
(dihydroartemisinin + piperaquine + mefloquine) in areas with
artemisinin resistance. Artemisinin derivatives can be used in
children and pregnant woman but are contraindicated during
the first trimester of pregnancy. Oral monotherapy with arte-
misinin derivatives is strongly discouraged to prevent the devel-
opment of resistance.
Quinine sulfate (Qualaquin), one of the oldest antimalarial
drugs, derived from the bark of the Cinchona tree (Cinchona
calisaya), demonstrates activity against blood schizonts and
gametocytes of P. vivax, P. ovale, and P. malariae. It is used in
combination with other drugs in severe malaria1 and for uncom-
plicated chloroquine-­resistant malaria species during pregnancy.
Quinine has a narrow therapeutic index, and can produce car-
diac conduction disturbances (e.g., QT prolongation, angina) and
lead to cardiac arrest. Hyperinsulinemic hypoglycemia has been
observed in children, elderly patients and pregnant women. IV
preparations of quinine dihydrochloride and the antiarrhythmic
quinidine gluconate had been used as antimalarial drugs but are
no longer available in the United States.
The antibiotics, tetracycline and doxycycline (Vibramycin),
display activity against blood schizonts; the latter is frequently
used in travelers as prophylaxis for chloroquine and mefloquine
resistant P. falciparum malaria. Tetracyclines can be employed
in combination with quinine for the treatment of uncomplicated
P. falciparum malaria and chloroquine-­resistant P. vivax1. These
antibiotics should not be used as monotherapy against malaria,
and are contraindicated during pregnancy and for children
younger than 8 years.
Clindamycin (Cleocin) is another antibiotic that acts as a
blood schizonticide for all Plasmodium species. It is effective in
combination with quinine for the treatment of uncomplicated P.
falciparum malaria, and chloroquine resistant P. vivax when tet-
racyclines are contraindicated1.
1Not FDA approved for this indication.
2Not available in the United States.
5Investigational drug in the United States.
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Mefloquine (Lariam) is an antimalarial structurally related to
quinine. It has a long half-­life and has activity against blood
schizonts of all Plasmodium species. It is used in prophylaxis of
malaria but can be used as an alternative treatment of uncom-
plicated P. falciparum malaria, and in combination with prima-
quine1 (tissue schizonticide) in cases of chloroquine-­resistant P.
vivax infection. It is generally well tolerated, but central ner-
vous system and psychiatric side effects, like anxiety, depres-
sion, paranoia, hallucinations, and violent behavior, have been
reported.
Primaquine is active against tissue or exoerythrocytic forms
and gametocytes of malaria parasites. It is indicated in the radi-
cal cure of P. vivax and P. ovale1 eliminating the hypnozoites
and preventing relapses of the disease. Primaquine can be used
for prophylaxis in travelers to areas when greater than 90% of
the cases of malaria are caused by P. vivax1. In patients with
glucose-­6-­
phosphate dehydrogenase (G6PD) deficiency, pri-
maquine administration may cause acute hemolytic anemia.
The activity of the G6PD enzyme should be measured before
its usage. Primaquine is also contraindicated during pregnancy
and breastfeeding, unless the infant has been tested for G6PD
deficiency.
Tafenoquine (Arakoda, Krintafel), an FDC-­ approved anti-
malarial drug related to primaquine, is recommended for pro-
phylaxis of all Plasmodium species (Arakoda), and as a radical
cure of P. vivax infection combined with chloroquine only
(Krintafel). Like primaquine, tafenoquine should not be used
in people with G6PD deficiency, during pregnancy or while
breastfeeding.
Lumefantrine is an antimalarial drug used in combination
with artemether (as Coartem) in the treatment of uncomplicated
P. falciparum malaria. It is active against erythrocytic stages
of all Plasmodium species. Possible serious adverse effects
reported with this combination include QT prolongation, bul-
lous eruption, urticaria, splenomegaly hepatomegaly, hyper-
sensitivity reaction, and angioedema. Artemether-­lumefantrine
(Coartem) is assigned a pregnancy category C by the US
Malaria
Food and Drug Administration (FDA) and its use during preg-
nancy should only be considered when the benefits outweigh
the risks.
For the specific adult and pediatric dosing, clinical indication,
treatment duration, and primary and alternative antimalarial
regimens, see Table 3.  611
Treatment of Uncomplicated Malaria
The CDC provides advice to healthcare providers on the diagno-
sis and treatment of malaria and can be reached through the CDC
Malaria Hotline (770) 488-­7788 (or, toll free: [855] 856-­4713)
Monday–Friday, 9 am to 5 pm EST. Off-­hours, weekends, and
federal holidays, call (770) 488-­7100 and ask to have the malaria
clinician on-­call paged.
For P. falciparum or species not identified acquired in
areas with chloroquine resistance, there are four regimens:
Artemether-­lumefantrine (Coartem) is the preferred regimen;
alternatives are atovaquone-­ proguanil (Malarone), quinine
plus either doxycycline1, tetracycline1, or clindamycin1, and the
fourth regimen is mefloquine (Lariam). For cases of P. falci-
parum acquired in areas without chloroquine resistance, either
chloroquine or hydroxychloroquine can be used. Alternatively,
the same drugs used for chloroquine-­resistant P. falciparum can
be used.
Chloroquine or hydroxychloroquine can be used for most
cases of malaria caused by P. ovale and P. vivax, P. malariae,
and P. knowlesi. If these drugs are not available, artemether-­
lumefantrine (Coartem)1, atovaquone-­ proguanil (Malarone)1,
mefloquine (Lariam)1, or quinine1 plus either doxycycline1, tet-
racycline1, or clindamycin1 can be used. These regimens can be
used for infections where chloroquine-­resistant P. vivax has been
1Not FDA approved for this indication.
 TABLE 3  Antimalarial Regimens and Dosing by Clinical Diagnosis and Resistance
CLINICAL
DIAGNOSIS/PLASMODIUM
SPECIES/DRUG SUSCEPTIBILITY
Primary Regimens
Uncomplicated malaria/P.
falciparum/chloroquine-­
sensitive or uncomplicated
malaria/P. malariae or P.
knowlesi
Primary Regimens
Uncomplicated malaria/P.
falciparum or species not
identified
Chloroquine resistance or
unknown resistance
VIII  Infectious Diseases
Primary Regimens
612
Uncomplicated malaria/P.
vivax or P. ovale
chloroquine sensitive
Primary Regimens
Uncomplicated malaria/P.
vivax
In case of suspected
chloroquine-­resistant P.
vivax
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DRUG/PRESENTATION
Chloroquine phosphate 1
tab = 500 mg (salt) (300
mg of base)
Hydroxychloroquine
1 tab = 200 mg (salt)
(155 mg of base)
Artemether/lumefantrine
(Coartem)*
1 tab = 20 mg/120 mg
Atovaquone/proguanil
(Malarone)**
Adult tab = 250 mg/100 mg
Ped tab = 62.5 mg/25 mg
Quinine sulfate
(Qualaquine)
1 tab = 324 mg
plus one of the following:
doxycycline1 100 mg,***
tetracycline1 250 mg,***
or clindamycin1 450 mg
Alternative Regimens
Mefloquine****
1 tab = 250 mg
Chloroquine phosphate
or hydroxychloroquine
plus either primaquine1
phosphate
1 tab = 15 mg (base) or
tafenoquine1 (Arakoda): 1
tab = 100 mg
(Krintafel): 1 tab = 150 mg
1. Artemether-­lumefantrine
(Coartem)1 plus either
primaquine phosphate or
tafenoquine
2. Atovaquone-­proguanil
(Malarone)1 plus either
primaquine phosphate or
tafenoquine
3. Quinine sulfate1 plus
either doxycycline1 or
tetracycline1 plus either
primaquine phosphate or
tafenoquine
4. Mefloquine plus either
primaquine phosphate or
tafenoquine
PEDIATRIC DOSE#
10 mg base/kg PO then 5 mg base /kg PO
at 6, 24, 48 h. Total 25 mg base/kg
The patient should receive the initial dose,
followed by the second dose 8 h later,
then 1 dose bid for the following 2 days.
5–<15 kg: 1 tablet per dose
15–<25 kg: 2 tablets per dose
25–<35 kg: 3 tablets per dose
≥35 kg: 4 tablets per dose
5–<8 kg: 2 peds tabs PO qd × 3 days
8–<10 kg: 3 peds tabs PO qd × 3 days
10–<20 kg: 1 adult tab PO qd × 3 days
20–<30 kg: 2 adult tabs PO qd × 3 days
30–<40 kg: 3 adult tabs PO qd × 3 days
≥0 kg: 4 adult tabs PO qd × 3 days
Quinine sulfate: 10 mg/kg PO tid × 3
days (7 days if SE Asia) + Clindamycin:
20 mg/kg/day divided tid x 7 days
for children under 8 years of age or
Doxycycline: 2.2 mg/kg/bid × 7 days or
Tetracycline: 25 mg/kg/day PO divided
qid × 7 days
15 mg salt/kg (13.7 mg base) PO as initial
dose, then 10 mg salt/kg (9.1 mg base/
kg) PO given 6–12 h after initial dose
Total dose: 25 mg salt/kg
Chloroquine phosphate or
hydroxychloroquine same as above
Primaquine phosphate: 0.5 mg/kg base PO
qd × 14 days
or
Tafenoquine succinate: 300 mg PO × 1
dose (children ≥16 years old)
Artemether-­lumefantrine: see doses above
Primaquine phosphate: see doses above
Tafenoquine: see doses above
Atovaquone-­proguanil: see doses above
Primaquine phosphate or Tafenoquine: see
doses above
Quinine sulfate: see doses above for 3 days
Doxycycline or Tetracycline: see doses above
Clindamycin: see doses above
Primaquine phosphate: see doses above
Tafenoquine can be used instead of
primaquine in children ≥16 years: 300
mg PO × 1 dose
Mefloquine: see doses above
Primaquine phosphate: see doses above
Tafenoquine can be used instead of primaquine
in children ≥16 years: 300 mg PO × 1 dose
ADULT DOSE
1 g salt (600 mg base) PO, then
500 mg in 6 h, then 500 mg
daily × 2 days. Total dose 2500
mg
800 mg salt (620 mg base) PO,
then 400 mg daily × 2 days.
Total dose 2000 mg
4 tabs PO in a single dose, then 4
tabs after 8 h, then 4 tabs every
12 h × 2 days
4 adult tabs PO in a single dose
daily × 3 days
Quinine sulfate: 648 mg PO tid
× 3 days (7 days if SE Asia) +
Doxycycline: 100 mg PO bid ×
7 days or
Tetracycline: 250 mg PO qid × 7
days or Clindamycin: 20 mg/
kg/day PO divided tid × 7 days
750 mg (684 mg base) PO as
initial dose, then 500 mg PO
× 1 dose 6-­12 h later.^ Total
1250 mg
Chloroquine phosphate: same as
above
Primaquine phosphate: 30 mg
base = 2 tab PO qd × 14 days
or
Tafenoquine succinate: *****
300 mg PO × 1 dose
Artemether-­lumefantrine: see
doses above
Primaquine phosphate: see doses
above
Tafenoquine: see doses above
Atovaquone-­proguanil: see doses
above
Primaquine phosphate or
Tafenoquine: see doses above
Quinine sulfate: see doses above
for 3 days
Doxycycline or Tetracycline: see
doses above
Clindamycin: see doses above
Primaquine phosphate or
Tafenoquine: see doses above
Mefloquine: see doses above
Primaquine phosphate or
Tafenoquine: see doses above
 TABLE 3  Antimalarial Regimens and Dosing by Clinical Diagnosis and Resistance—cont’d
CLINICAL
DIAGNOSIS/PLASMODIUM
SPECIES/DRUG SUSCEPTIBILITY DRUG/PRESENTATION PEDIATRIC DOSE# ADULT DOSE
Severe malaria 1. Artesunate IV5110 Artesunate: <20 kg 3.0 mg/kg IV at 0, 12, Artesunate: 2.4 mg/kg IV at 0, 12,
mg/vial follow with a 24 h. Continue q24h if unable to take 24 h. Continue q24h if unable
complete oral course oral medication to take oral medication
of one of: artemether/ Atovaquane/proguanil × 3 days (see doses Atovaquane/proguanil × 3 days
lumefantrine1 atovaquane/ above) (see doses above)
proguanil1 quinine1 plus Artemether/lumefantrine × 3 days (see Artemether/lumefantrine × 3 days
doxycycline1 doses above) (see doses above)
Quinine sulfate: × 3 days (7 days if SE Asia) Quinine sulfate: × 3 days (7 days
plus Doxycycline: 2.2 mg/kg q12h × 7 if SE Asia) plus Doxycycline:
days 100 mg q12h × 7 days

*Artemether-­lumefantrine: Take with food. Drug of choice in second/third trimester of pregnancy. Recommended by experts in the first trimester but not yet in the official
guidelines.
**Atovaquone-­proguanil: Take with food; repeat dose if patient vomits within 30 minutes; Not recommended in pregnancy.
***Doxycycline and tetracycline: Not recommended during pregnancy or in children less than 8 years old. Avoid concomitant intake of divalent cations and antacids.
American Academy of Pediatrics now permits less than 21 days for any acute infection for children of all ages.
****Mefloquine: Not effective against strains of P. falciparum from SE Asia.
*****Tafenoquine succinate: if G6PD normal.
#Pediatric dose should not be higher than adult dose.
1Not FDA approved for this indication.
5Investigational drug in the United States.
^This is an off-­label dose.

reported (Papua New Guinea, Indonesia, Burma, and certain
areas of Central and South America).
To eradicate P. vivax and P. ovale hypnozoites, patients
should also be treated with either tafenoquine (Krintafel)1 or
primaquine phosphate1. Tafenoquine can be used in patients 16
years of age or older and is given as a single dose. If primaquine
phosphate is used, CDC recommends a dose of 30 mg (base) by
mouth daily for 14 days. Due to reduced efficacy of primaquine
in patients over 70 kg, the total dose of primaquine should be
adjusted in these patients to 6 mg/kg. This total dose should be
developing fetus. The scheme will depend on drug susceptibility,
the region where infection was acquired, gestational age, severity
of the disease, and drug category.
For infections with chloroquine-sensitive P. falciparum, P.
vivax, P. ovale, and P. knowlesi, chloroquine or hydroxychlo-
roquine can be used during pregnancy. If resistance to chloro-
quine is suspected, quinine sulfate1 + clindamycin1 or mefloquine1
can be used for treatment during the first trimester of preg-
nancy. Artemether-­lumefantrine (Coartem)1 is the treatment of
choice during the second and third trimesters of pregnancy in

given in daily doses of 30 mg for the number of days needed
to complete the total dose. As mentioned before, quantitative
G6PD enzyme activity should be measured before the use of pri-
maquine or tafenoquine.  should receive chloroquine prophylaxis1 (300 mg [base] PO once
Treatment of Severe Malaria
Patients with severe malaria should be treated promptly. IV
artesunate5 is the treatment of choice regardless of the species
involved. Clinicians caring for patients with suspected severe
malaria should call CDC to obtain IV artesunate, as part of
an expanded-­ use investigational new drug (IND) protocol
(see CDC contact information earlier). Oral therapies should
be started while waiting for IV artesunate to arrive. The pre-
ferred antimalarial for interim oral treatment is artemether-­
lumefantrine (Coartem)1 because of its fast onset of action.
Other oral options include atovaquone-­proguanil (Malarone)1,
quinine1 plus doxycycline (Vibramycin)1, and mefloquine
(Lariam)1. Patients on treatment for severe malaria should have
one set of blood smears (thick and thin) performed every 12 to
24 hours until a negative result (no Plasmodium parasites are
detected) is reported.
After the course of IV artesunate is completed, if parasite den-
sity is ≤1% (assessed on a blood smear collected 4 hours after
the last dose of IV artesunate), and the patient can tolerate oral
treatment, a full treatment course with a follow-­up regimen must
be administered (see Table 3). 
Antimalarial Drugs in Pregnancy
Monitoring the safety of antimalarial drugs and understand-
ing their pharmacokinetics is particularly important in preg-
nancy—with the altered maternal physiology and the risks to the
Malaria
chloroquine-­resistant malaria infections.
Primaquine and tafenoquine should not be given during preg-
nancy. Pregnant patients with P. vivax and P. ovale infections
a week) for the duration of the pregnancy to prevent relapses.
After delivery, patients with normal G6PD activity should be 613
treated with primaquine or tafenoquine or continue with chlo-
roquine prophylaxis for a total of 1 year. For women who are
breastfeeding, infants should be tested for G6PD deficiency
and, if found to have normal activity, oral primaquine can be
given to the mother. Tafenoquine is not recommended during
breastfeeding. 
Treatment of Pediatric Patients
The majority of cases and deaths, especially in sub-­ Saharan
Africa, occur in young children. Prompt diagnosis and therapy
initiation is key to prevent complications, like cerebral malaria
in young children. Treatment regimens recommended are essen-
tially the same as in adults, with few differences. Weight-based
dose adjustments are necessary and pediatric doses should not
exceed those given to adults. Tetracycline and doxycycline should
be avoided in children younger than 8 years. Tafenoquine is not
indicated in those younger than 16 years of age. For complete
details on dosing and treatment duration in pediatric patients, see
Table 3. 
Prevention of Malaria
Prevention of malaria includes both chemoprophylaxis and mea-
sures taken to reduce the number of mosquito bites. Malaria
vaccines are still experimental or in early pilot implementation

1Not FDA approved for this indication.

5Investigational
drug in the United States 1Not FDA approved for this indication

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 phases. They have been studied primarily in children in endemic
areas and are not universally recommended.
Travelers to endemic areas can reduce mosquito bites by
using N,N-­diethyl-­meta-­toluamide (DEET 10% to 50%) or 7%
picaridin-­containing insect repellents on exposed skin (applied
after sunscreen), wearing permethrin-­treated clothing, wearing
clothes and footwear that cover as much skin as possible, sleep-
ing under permethrin-­treated bed nets, staying in housing with
air-­conditioning and well-­screened areas cleared of mosquitoes,
and refraining from outdoor activity during peak Anopheles bit-
ing hours (from dusk to dawn).
Recommendations for chemoprophylaxis based on the country
being visited can be found on the CDC’s website at, https://www
.cdc.gov/malaria/travelers/country_table/a.html
Several considerations have to be taken into account for the
chemoprophylaxis in travelers to malarial areas. An individual-
ized risk benefit assessment should be conducted for every trav-
eler, considering not only the region or country to be visited but
also the itinerary and duration, specific cities or rural areas, types
of accommodations, season (rainy or dry), and type of travel
(adventure or business).
It is important to consider that no chemoprophylactic regimen
is 100% effective, and other measures to decrease mosquito bites,
as described previously, should be considered. If a person devel-
ops malaria while taking chemoprophylaxis, that particular drug
should not be used as part of the treatment regimen.
The recommended regimens according to the Plasmodium spe-
cies and its pattern of resistance are detailed in Table 4.

TABLE 4  Chemoprophylaxis of Malaria

LOCAL RESISTANCE PATTERN
Primary Regimens
Chloroquine sensitive Plasmodium
falciparum
VIII  Infectious Diseases
DRUG PEDIATRIC DOSE
1. Chloroquine phosphate 1 8.3 mg/kg (5 mg/kg of base) PO
tab = 500 mg (salt) (300 mg 1×/week up to 300 mg (base)
of base) max dose. Starting 1–2 weeks
before travel, during travel and
4 weeks post-­travel
ADULT DOSE
500 mg (300 mg base) PO per
week. Starting 1–2 weeks
before travel, during travel
and 4 weeks post-­travel

2. Atovaquone/proguanil
(Malarone)*1 adult tab =
250/100 mg
1 ped tab = 62.5/25 mg
Alternative Regimens
1. Tafenoquine**(Arakoda)
614 ≥16 years only
1 tab = 100 mg
2. Doxycycline 1 tab = 100
mg***
3. Mefloquine 1 tab = 250
mg****
Nonchloroquine resistant Plasmodium Primaquine phosphate1
vivax 1 tab = 15 mg (base)
5–8 kg ½ peds tab
9–10 kg ¾ peds tab
11–20 kg 1 peds tab
21–30 kg 2 peds tab
31–40 Kg 3 peds tab
>40 kg 1 adult tab
per day with food.
One day prior to, during and 7
days post travel
8–12 years: 2.2 mg/kg once/day
up to 100 mg/day. 1–2 days
before, during and for 4 weeks
post-­travel
Weekly dose by weight in kg
5–<10 kg: 31.25 mg (1/8 tablet)
10–<20 kg: 62.5 mg (1/4 tablet)
20–<30 kg: 125 mg (1/2 tablet)
30–45 kg: 187.5 mg (3/4 tablet)
>45 kg: 250 mg (1 tablet)
Start 1–2 weeks before travel and
continue 4 weeks after leaving
endemic area.
0.5 mg/kg base (0.8 mg/kg salt) up
to adult dose 30 mg base (52.6
mg salt) daily
Start 1–2 days prior, during, and 7
days after travel
One adult tab (250/100 mg) per
day with food.
One day prior to, during and 7
days post travel
Prior to malaria-­endemic area
(loading regimen): 200 mg
once daily × 3 days (starting
3 days before travel)
In endemic area (maintenance
regimen) 200 mg once
weekly (starting 7 days after
last loading regimen dose)
Post travel: 200 mg one-­time
dose (7 days after last
maintenance dose)
100 mg PO qd. 1–2 days pre-­
travel, during and 4 weeks
post travel
250 mg (228 mg base) 1 tab PO
once per week, 1–2 weeks
before, during and 4 weeks
after travel
30 mg base PO daily in non-­
pregnant, G6PD-­normal
travelers
Start 1–2 days prior, during,
and 7 days after travel

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 TABLE 4  Chemoprophylaxis of Malaria—cont’d
LOCAL RESISTANCE PATTERN DRUG
Primary Regimens
Chloroquine resistant Plasmodium 1. Atovaquone/proguanil*
falciparum 1 adult tab = 250/100 mg
1 ped tab = 62.5/25 mg
Alternative Regimens
1. Tafenoquine (Arakoda) 1
tab = 100 mg**
2. Doxycycline 1 tab = 100
mg***
3. Mefloquine 1 tab = 250
mg****
PEDIATRIC DOSE ADULT DOSE
5–8 kg ½ peds tab 1 adult tab/day with food 1–2
9–10 kg ¾ peds tab days prior to, during and for
11–20 kg 1 peds tab 7 days post travel in endemic
21–30 kg 2 peds tab area
31–40 kg 3 peds tab
>40 kg 1 adult tab
Daily with food 1–2 days prior to,
during and for 7 days post travel
in endemic area
Not approved for malaria Prior to malaria-­endemic area
prophylaxis in <18 years of age (loading regimen): 200 mg
once daily × 3 days (starting
3 days before travel)
In endemic area (maintenance
regimen) 200 mg once
weekly (starting 7 days after
last loading regimen dose)
Post travel: 200 mg one-­time
dose (7 days after last
maintenance dose)
8–12 years: 2.2 mg/kg once/day 100 mg PO qd. 1–2 days pre-­
up to 100 mg/day 1–2 days travel, during and 4 weeks
before, during and for 4 weeks post travel
post-­travel
Weekly dose by weight in kg 250 mg (228 mg base) 1 tab PO
<9 kg 5 mg/kg once per week, 2–3 weeks
15–19 kg ¼ adult dose before, during and 4 weeks

Measles (Rubeola)
20–30 kg ½ adult dose after travel
31–45 kg ¾ adult dose
>45 kg adult dose

*Atovaquone-­proguanil: preferred for short trips due to increase adherence.

**Tafenoquine: must have G6PD activity greater than 70% normal on a quantitative test. Preferred for longer trips due to few adverse effects.
***Doxycycline: the American Academy of Pediatrics now recommends that doxycycline can safely be administered for short durations (≤21 days) regardless of patient age;
this does not apply to malaria prophylaxis due to required duration of dosing.
****Mefloquine: start 3 weeks ahead, if feasible, to assess for intolerance. This is the current best option for pregnancy.
1Not FDA approved for this indication.

615

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