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Treatment:
General Approach | Treatment:
Uncomplicated Malaria | References
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you wish to share your clinical experience, please contact us at: nciddpdmalaria@cdc.gov
For
download: Treatment Guidelines Table
Treatment summary in tabular form (Updated
March 6, 2007)
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Treatment:
General Approach
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).
Once the diagnosis of malaria has been confirmed, appropriate antimalarial
treatment must be initiated immediately. Treatment should be guided by three
main factors: the infecting Plasmodium species, the clinical status
of the patient, and the drug susceptibility of the infecting parasites as
determined by the geographic area where the infection was acquired.
Determination
of the infecting Plasmodium species for treatment purposes is
important for three main reasons:
- P. falciparum infections can
cause rapidly progressive severe illness or death while the non-falciparum
( P. vivax,
P. ovale, or P. malariae) species rarely cause severe manifestations;
- P.
vivax and P. ovale infections require treatment for
the hypnozoite forms that remain dormant in the liver and can cause
a relapsing infection;
- and P. falciparum and P. vivax species
have different drug resistance patterns in differing geographic
regions. For P. falciparum infections,
the urgent initiation of appropriate therapy is especially critical.
The second factor affecting treatment is 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
(impaired consciousness/coma, severe normocytic anemia, renal failure,
pulmonary edema, acute respiratory distress syndrome, circulatory shock,
disseminated intravascular coagulation, spontaneous bleeding, acidosis,
hemoglobinuria, jaundice, repeated generalized convulsions, and/or parasitemia
of > 5%) are considered to have manifestations of more severe disease
and should be treated aggressively with parenteral antimalarial therapy.15
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. 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 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 onto the
CDC. CDC clinicians are on-call 24 hours to provide advice to clinicians
on the diagnosis and treatment of malaria and can be reached through
the Malaria Hotline 770-488-7788 Monday – Friday, 8:00 am to 4:30
pm. Off-hours, weekends, and federal holidays, call 770-488-7100 and
ask to have the malaria clinician on-call to be paged.
The three-page Treatment Guidelines table ( Download
PDF version formatted for print (67
KB/3 pages)) 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),
the antimalarial dose is expressed in base with the salt equivalency
noted in parenthesis.
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 followed by clearance).
Treatment:
Uncomplicated Malaria
P. falciparum or Species Not Identified
For 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 should 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).
As a 2nd line alternative for treatment, a hydroxychloroquine dose of 620 mg base (=800 mg salt) po can be given immediately, followed by 310 mg base (=400 mg salt) po at 6, 24, and 48 hours after the initial does for a total hydroxychloroquine dose of 1,550 mg base (=2,000 mg salt).
For P. falciparum infections acquired in areas with chloroquine-resistant
strains, three treatment options are available. The first two treatment
options are quinine sulfate plus doxycycline, tetracycline, or clindamycin; or atovaquone-proguanil
(Malarone). Both of these options are very efficacious. 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 infections acquired in Africa or South America. The third option,
mefloquine, is associated with a higher rate of severe neuropsychiatric
reactions when used at treatment doses. We recommend this third option
only when the quinine sulfate combination or atovaquone-proguanil
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. For children
less than eight years old, doxycycline and tetracycline are generally
not indicated; therefore, quinine (given alone for a full 7 days regardless
of where the infection was acquired or given in combination with clindamycin
as recommended above) and atovaquone-proguanil are recommended treatment
options for chloroquine-resistant P. falciparum infections;
mefloquine can be considered if these options are not available. In
rare instances, doxycycline or tetracycline can be used in combination
with quinine in children 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
subsequently diagnosed as being due to P. vivax or P.
ovale, additional treatment with primaquine should be administered
(see P. vivax and P. ovale, below).
P.
malariae
There has been no widespread evidence of chloroquine resistance in P.
malariae species; therefore, chloroquine remains the drug of
choice for all P. malariae infections. As a 2nd line alternative for treatment, hydroxychloroquine may be given instead.
P. vivax and P. ovale
Chloroquine (hydroxychloroquine as 2nd line alternative for treatment) remains the treatment of choice for all P. vivax and P. ovale
infections except for P. vivax infections acquired in Papua New Guinea or Indonesia.
Reports have confirmed a high prevalence of chloroquine-resistant P. vivax in these
two specific areas. Rare case reports of chloroquine-resistant P. vivax have also been
documented in Burma (Myanmar), India, and South America. Persons acquiring P. vivax
infections from regions other than Papua New Guinea or Indonesia should initially be treated
with chloroquine. If the patient does not respond to chloroquine, treatment should be changed
to one of the two regimens recommended for chloroquine-resistant P. vivax infections,
and your state health department and the CDC should be notified (CDC Malaria Hotline: (770)
488-7788 Monday-Friday 8am to 4:30pm EST; (770) 488-7100 after hours, weekends and holidays).
Persons acquiring P. vivax infections in Papua New Guinea or Indonesia should initially
be treated with a regimen recommended for chloroquine-resistant P. vivax infections.
The two treatment regimens for chloroquine-resistant P. vivax infections are quinine
sulfate plus doxycycline or tetracycline, or mefloquine. These two treatment options are equally
recommended. There are no adequate, well-controlled studies to support the use of
atovaquone-proguanil to treat chloroquine-resistant P. vivax infections.
In addition to requiring blood stage treatment, infections with P.
vivax and P. ovale can relapse due to hypnozoites
that remain dormant in the liver. To eradicate the hypnozoites,
patients should be treated with a 14-day course of primaquine phosphate.
CDC has recently changed its recommendations for treating hypnozoites
by increasing the recommended primaquine phosphate dose to 30 mg
(base) by mouth daily for 14 days. Because primaquine can cause
hemolytic anemia in persons with glucose-6-phosphate-dehydrogenase
(G6PD) deficiency, persons must be screened for G6PD deficiency
prior to starting primaquine treatment. For persons with borderline
G6PD deficiency or as an alternate to the above regimen, primaquine
may be given at the dose of 45 mg (base) orally one time per week
for 8 weeks ; consultation with an expert in infectious disease
and/or tropical medicine is advised if this alternative regimen
is considered in G6PD-deficient persons. Primaquine must not be
used during pregnancy.
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 adult recommended adult dose. For children less
than eight years old, doxycycline and tetracycline are generally not
indicated; therefore, quinine (given alone for 7 days) or mefloquine
are recommended treatment options for chloroquine-resistant P. vivax infections.
In rare instances, doxycycline or tetracycline can be used in combination
with quinine in children less than 8 years old if other treatment options
are not available, are not being tolerated, and the benefit of adding
doxycycline or tetracycline is judged to outweigh the risk. Primaquine
should be given to pediatric patients only after they have been screened
for G6PD deficiency.
References
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at risk. Wkly Epidemiol Rec, 1997. 72(36):
p. 269-74.
- Breman, J.G., The ears of the hippopotamus: manifestations,
determinants, and estimates of the malaria burden. Am
J Trop Med Hyg, 2001. 64(1-2 Suppl): p.
1-11.
- Shah, S., et al., Malaria surveillance--United States,
2002. MMWR Surveill Summ, 2004. 53(1):
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- CDC, Congenital malaria as a result of Plasmodium malariae--North
Carolina, 2000. MMWR Morb Mortal Wkly Rep, 2002. 51(8):
p. 164-5.
- CDC, Probable transfusion-transmitted malaria--Houston,
Texas, 2003. MMWR Morb Mortal Wkly Rep, 2003. 52(44):
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Beach County, Florida, 2003. MMWR Morb Mortal Wkly Rep,
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- Greenberg, A.E. and H.O. Lobel, Mortality from Plasmodium
falciparum malaria in travelers from the United States, 1959
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- Moore, T.A., et al., Imported malaria in the 1990s.
A report of 59 cases from Houston, Tex. Arch Fam Med,
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- Kyriacou, D.N., et al., Emergency department presentation
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- Severe falciparum malaria. World Health Organization,
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- Miller, K.D., A.E. Greenberg, and C.C. Campbell, Treatment
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- Powell, V.I. and K. Grima, Exchange transfusion for
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- Luxemburger, C., et al., The epidemiology of severe
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Page last modified : March 6, 2007
Content source: Division of Parasitic Diseases
National Center for Zoonotic, Vector-Borne, and Enteric Diseases (ZVED)
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