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FOR DISEASE CONTROL AND PREVENTION
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TREATMENT GUIDELINES
Treatment of Malaria (Guidelines f
or Clinicians)
Treatment Table
The Treatment Table is available in PDF format at
http://www.cdc.gov/malaria/resources/pdf/treatmenttable.pdf
Reporting
We encourage clinicians to report all cases of laboratory
-confirmed malaria to help CDC's
surveillance efforts. Refer to our information on the
Malaria Case Surveillance Report Form
(http://www.cdc.gov
/malaria/report.html
).
Evaluation and Diagnosis
Because malaria cases are seen relatively rarely in North America, misdiagnosis by clinicians
and laboratorians has been a commonly documented problem in published reports.
However, malaria may be a common
illness in areas where it is transmitted and therefore
the diagnosis of malaria should routinely be considered for any febrile person who has
traveled to an area with known malaria transmission in the past several months preceding
symptom onset.
Symptoms of malaria are generally non
-specific and most commonly consist of fever,
malaise, weakness, gastrointestinal complaints (nausea, vomiting, diarrhea), neurologic
complaints (dizziness, confusion, disorientation, coma), headache, back pain, myalgia,
chill
s, and/or cough. The diagnosis of malaria should also be considered in any person with
fever of unknown origin regardless of travel history.
Patients suspected of having malaria infection should be urgently evaluated. Treatment for
malaria should not be
initiated until the diagnosis has been confirmed by laboratory
investigations. "Presumptive treatment" without the benefit of laboratory confirmation
should be reserved for extreme circumstances (strong clinical suspicion, severe disease,
impossibility of
obtaining prompt laboratory confirmation, usually by microscopy).
Laboratory diagnosis of malaria can be made
through microscopic examination of thick and
thin blood smears. Thick blood smears are more sensitive in detecting malaria parasites
because the blood is more concentrated allowing for a greater volume of blood to be
examined; however, thick smears are more difficult to read. Thin smears aid in parasite
species identification and quantification. Blood films need to be read immediately; off
-hours,
qualified personnel who can perform this function should be on-
call. A negative blood smear
makes the diagnosis
of malaria unlikely. However, because non
-immune individuals may be
symptomatic at very low parasite densities that initially may be undetectable by blood
smear, blood smears should be repeated every 12
–24 hours for a total of 3 sets. If all 3 are
negativ
e, the diagnosis of malaria has been essentially ruled out.
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After malaria parasites are detected on a blood smear, the parasite density should then be
estimated. The parasite density can be estimated by looking at a monolayer of red blood
cells (RBCs) on
the thin smear using the oil immersion objective at 100x. The slide should
be examined where the RBCs are more or less touching (approximately 400 RBCs per field).
The parasite density can then be estimated from the percentage of infected RBCs, after
count
ing 500 to 2000 RBCs.
In addition to microscopy, other laboratory diagnostic tests are available. Several antigen
detection tests (rapid diagnostic tests or RDTs) using a “dipstick” or cassette format exist,
but only one is approved for general diagnostic use in the United States. RDTs can more
rapidly determine that the patient is infected with malaria, but they cannot confirm the
species or the parasitemia. Laboratories that do not provide in
-house on
-the
-spot
microscopy services should maintain a stock of malaria RDTs so that they will be able to
perform malaria diagnostic testing when urgently needed.
Parasite nucleic acid detection using polymerase chain reaction (PCR) is more sensitive and
specific than microscopy but can be performed only in refe
rence laboratories and so results
are not often available quickly enough for routine diagnosis. However, PCR is a very useful
tool for confirmation of species and detecting of drug resistance mutations. CDC offers
malaria drug resistance testing for all ma
laria diagnosed in the United States free of charge.
Serologic tests, also performed in reference laboratories, can be used to assess past malaria
experience but not current infection by malaria parasites. Your state health department or
the CDC can be con
tacted for more information on utilizing one of these tests.
Treatment: General Approach
It is preferable that treatment for malaria should not be initiated until the diagnosis has
been established by laboratory investigations. "Presumptive treatment" w
ithout the benefit
of laboratory confirmation should be reserved for extreme circumstances (strong clinical
suspicion, severe disease, impossibility of obtaining prompt laboratory diagnosis).
Once the diagnosis of malaria has been made, appropriate antim
alarial treatment must be
initiated immediately. Treatment should be guided by three main factors:
• The infecting
Plasmodium
species
• The clinical status of the patient
• The drug susceptibility of the infecting parasites as determined by the geograph
ic area
where the infection was acquired and the previous use of antimalarial medicines
The infecting
Plasmodium
species
: Determination of the infecting
Plasmodium
species
for treatment purposes is important for three main reasons. Firstly,
P. falciparum
and
P.
knowlesi
infections can cause rapidly progressive severe illness or death while the other
species,
P. vivax, P. ovale,
or
P. malariae,
are less likely to cause severe manifestations.
Secondly,
P. vivax
and
P. ovale
infections also requ
ire treatment for the hypnozoite forms
that remain dormant in the liver and can cause a relapsing infection. Finally,
P. falciparum
and
P. vivax
species have different drug resistance patterns in differing geographic regions.
For
P. falciparum
and
P. knowl
esi
infections, the urgent initiation of appropriate therapy is
especially critical.
The clinical status of the patient
: Patients diagnosed with malaria are generally
categorized as having either uncomplicated or severe malaria. Patients diagnosed with
uncomplicated malaria can be effectively treated with oral antimalarials. However, patients
who have one or more of the following clinical criteria
are considered to have manifestations
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of more severe disease and should be treated aggressively with parenteral antimalarial
therapy:
impaired consciousness/coma, severe normocytic anemia [hemoglobin<7], renal
failure, acute respiratory distress syndrome, hypotension, disseminated intravascular
coagulation, spontaneous bleeding, acidosis, hemoglobinuria, jaundice
, repeated
generalized convulsions, and/or parasitemia of >5%.
The drug susceptibility of the infecting parasites
: Finally, knowledge of the geographic
area where the infection was acquired provides information on the likelihood of drug
resistance of the
infecting parasite and enables the treating clinician to choose an
appropriate drug or drug combination and treatment course. In addition, if a malaria
infection occurred despite use of a medicine for chemoprophylaxis, that medicine should not
be a part o
f the treatment regimen. If the diagnosis of malaria is suspected and cannot be
confirmed, or if the diagnosis of malaria is confirmed but species determination is not
possible, antimalarial treatment effective against chloroquine
-resistant
P. falciparum
must
be initiated immediately.
Malaria is a nationally notifiable disease and all cases should be reported to your state
health department, which are forwarded on
to CDC.
CDC clinicians are on
call 24 hours to provide advice to clinicians on the diagnos
is and
treatment of malaria and can be reached through the Malaria Hotline 770
-488
-7788 (or toll
free 855
-856
-4713) Monday
–Friday, 9am
–5pm. Off
-hours, weekends, and federal holidays,
call 770-
488
-7100 and ask to have the malaria clinician on
call to be pag
ed.
The three
-page Treatment Guidelines table
(http://www.cdc.gov/malaria/resources/pdf/treatmenttable.pdf
) can be used
as a guide for
treatment of malaria in the United States. The drug or drug combinations recommended for
treatment are listed in bold on the first line of each box in the adult and pediatric “drug and
dose” columns. Each drug and its recommended dose are then listed individually on the
lines below in the same box. It is important to note that the base/salt conversions for
antimalarials are a continual source of confusion and can contribute to treatment errors. In
this treatment table (where appropriate), th
e antimalarial dose is expressed in base with the
salt equivalency noted in parentheses.
After initiation of treatment, the patient's clinical and parasitologic status should be
monitored. In infections with
P. falciparum
or suspected chloroquine
-resistant
P. vivax
,
blood smears should be made to confirm adequate parasitologic response to treatment
(decrease in parasite density).
Treatment: Uncomplicated Malaria
P. falciparum
or Species Not Identified –
Acquired in Areas Without
Chloroquine Resistance
Fo r
P. falciparum
infections acquired in areas without chloroquine
-resistant strains, which
include Central America west of the Panama Canal, Haiti, the Dominican Republic, and most
of the Middle East, patients can be be
treated with oral chloroquine. A chloroquine dose of
600 mg base (=1,000 mg salt) should be given initially, followed by 300 mg base (=500 mg
salt) at 6, 24, and 48 hours after the initial dose for a total chloroquine dose of 1,500 mg
base (=2,500 mg salt)
. Alternatively, hydroxychloroquine may be used at a dose of 620 mg
base (=800 mg salt)
by mouth
given initially, followed by 310 mg base (=400 mg salt)
by
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mouth
at 6, 24, and 48 hours after the initial dose for a total hydroxychloroquine
dose of
1,550 mg base (=2,000 mg salt).
In addition, any of the regimens listed below for the treatment of chloroquine
-resistant
malaria may be used for the treatment of chloroquine
-sensitive malaria. Prompt initiation of
an effective regimen is vitally
important and so using any one of the effective regimens that
readily at hand would be the preferred strategy.
P. falciparum
or Species Not Identified –
Acquired in Areas With
Chloroquine Resistance
For
P. falciparum
infections acquired in areas with
chloroquine resistance, four treatment
options are available. The first two treatment options are atovaquone
-proguanil (Malarone)
or
artemether-
lumefantrine (Coartem). These are fixed dose combination medicines that
can be used for non
-pregnant adult and p
ediatric patients. Both of these options are very
efficacious. Quinine sulfate plus doxycycline, tetracycline, or clindamycin is the next
treatment option. For the quinine sulfate combination options, quinine sulfate plus either
doxycycline or tetracycline
is generally preferred to quinine sulfate plus clindamycin because
there are more data on the efficacy of quinine plus doxycycline or tetracycline. Quinine
treatment should continue for 7 days for infections acquired in Southeast Asia and for 3
days for i
nfections acquired in Africa or South America. The fourth option, mefloquine, is
associated with rare but potentially severe neuropsychiatric reactions when used at
treatment doses. We recommend this fourth option only when the other options cannot be
used
.
For pediatric patients, the treatment options are the same as for adults except the drug
dose is adjusted by patient weight. The pediatric dose should never exceed the
recommended adult dose. Pediatric dosing may be difficult due to unavailability of n
on -
capsule forms of quinine. If unable to provide pediatric doses of quinine, consider one of the
other three options.
If using a quinine
-based regimen for children less than eight years old, doxycycline and
tetracycline are generally not indicated; ther
efore, quinine can be given alone for a full 7
days regardless of where the infection was acquired or given in combination with
clindamycin as recommended above. In rare instances, doxycycline or tetracycline can be
used in combination with quinine in chil
dren less than eight years old if other treatment
options are not available or are not tolerated, and the benefit of adding doxycycline or
tetracycline is judged to outweigh the risk.
If infections initially attributed to "species not identified" are sub
sequently diagnosed as
being due to
P. vivax
or
P. ovale
, additional treatment with primaquine
or tafenoquine
should be administered (see
P. vivax
and
P. ovale
, below).
P. malariae
and
P. knowlesi
There has been no widespread evidence of chloroquine resistance in
P. malariae
and
P.
knowlesi
species; therefore, chloroquine (or hydroxychloroquine) may still be used for both
of these infections. In addition, any of the regimens listed above for the tre
atment of
chloroquine
-resistant malaria may be used for the treatment of
P. malariae
and
P. knowlesi
infections.
P. vivax
and
P. ovale
