|
Treatment of P. falciparum malaria depends on the severity of infection, status of the host and drug
sensitivity pattern in the locality. In view of the potential seriousness of the
infection and
synergistic toxicity of antimalarial drugs, the drugs should be properly chosen right at
the start of the treatment; changing the drugs or adding of drugs half-way through the
treatment only complicates the issue and adds to the adverse effects of treatment.
Go to
Treatment of P. vivax
/ P. ovale / P. malariae |
Treatment of Severe Malaria
Uncomplicated malaria is defined as symptomatic malaria without
signs of severity or evidence of vital organ dysfunction.[1] Uncomplicated P.
falciparum infection should be treated according the sensitivity
of the parasite at the area of acquiring the infection. To counter the threat of resistance of P. falciparum
to monotherapies, and to improve treatment outcome, combinations of antimalarials
are now recommended by WHO for the treatment of falciparum malaria.[1] Two or more blood schizontocidal
drugs with independent modes of action and thus unrelated
biochemical targets in the parasite are used and at present Artemisinin Combinations
(ACTs) are the recommended treatments for uncomplicated falciparum
malaria.[1]
Artemisinin-based combination therapy (ACT)
Artemisinin and its derivatives (artesunate, artemether,
artemotil, dihydroartemisinin) produce rapid clearance of parasitaemia and rapid
resolution of symptoms. They reduce parasite numbers by a factor of
approximately 10 000 in each asexual cycle, which is more than other current
antimalarials (which reduce parasite numbers 100- to 1000-fold per cycle).
Artemisinin and its derivatives are eliminated rapidly. When given in
combination with rapidly eliminated compounds (tetracyclines, clindamycin), a
7-day course of treatment with an artemisinin compound is required; but when
given in combination with slowly eliminated antimalarials, shorter courses of
treatment (3 days) are effective.[1]
Non-artemisinin based combinations (non-ACTs) include sulfadoxine–pyrimethamine with chloroquine
(SP+CQ) or amodiaquine (SP+AQ). However, the prevailing high levels
of resistance have compromised the efficacy of these combinations. There is
no convincing evidence that SP+CQ provides any additional benefit
over SP, so this combination is not recommended.[1]
The choice of ACT in a country or region is based on the
level of resistance of the partner medicine in the combination. In areas of multidrug resistance (South-East Asia), artesunate
+mefloquine or artemether-lumefantrine is recommended, while in Africa, artemether-lumefantrine, artesunate + amodiaquine
or artesunate + sulfadoxine-pyrimethamine can be used. Amodiaquine + sulfadoxine-pyrimethamine may be considered as an
interim option in situations where ACTs cannot be made available.[1]
|
The National Vector Borne Disease Control Programme (NVBDCP) of India recommends
Chloroquine (10mg/kg stat, followed by 5mg/kg every 12 hours for 3 doses) and
Primaquine (0.75mg/kg as single dose on the first day; not to be given in pregnancy) as the first
line treatment. In areas with resistance to chloroquine, NVBDCP recommends
Artesunate + sulfadoxine–pyrimethamine and in such cases, primaquine need not be
given.[2] At present AS+SP combination is being implemented in 117 districts (i.e 50
high endemic districts of States namely Andhra Pradesh, Chhatisgarh, Jharkhand,
Madhya Pradesh & Orissa + 67 in North Eastern States), in addition to 253 PHCs
of 46 districts included on the basis of chloroquine resistance status and its
surrounding cluster of Blocks.[3] [See
list of PHCs] |
Artesunate + Sulfadoxine–pyrimethamine
This is currently available as separate scored tablets
containing 50 mg of artesunate, and tablets containing 500 mg of sulfadoxine and
25 mg of pyrimethamine. The total recommended treatment is 4 mg/kg bw of artesunate given once a day for
3 days and a single administration of sulfadoxine+pyrimethamine (25/1.25 mg
base/kg bw) on day 1. This combination is sufficiently efficacious only where
28-day cure rates with sulfadoxine–pyrimethamine alone exceed 80%.[1]
|
Dosing of Artesunate + Sulfadoxine–Pyrimethamine (WHO, 2006)[1] |
| Age |
Dose of Artesunate (50mg)Tablet |
Dose of SP (500/25) |
|
5-11 months |
HALF tablet once daily for 3 days |
HALF tablet on first day |
|
≥1-6 |
ONE
tablet once daily for 3 days |
ONE
tablet on first day |
|
≥7-13 |
TWO
tablets once daily for 3 days |
TWO
tablets on first day |
| >13 |
FOUR
tablets once daily for 3 days |
THREE
tablets on first day |
|
Under the NVBDCP, Artesunate + Sulfadoxine–pyrimethamine
kits are available for free at
all the PHCs where this has been recommended. |
Artesunate + Amodiaquine
This is currently available as separate scored tablets
containing 50 mg of artesunate and 153 mg base of amodiaquine, respectively.
Co-formulated tablets are under development. The total recommended treatment is
4 mg/kg bw of artesunate and 10 mg base/kg bw of amodiaquine given once a day
for 3 days. This combination is sufficiently efficacious only where 28-day cure
rates with amodiaquine monotherapy exceed 80%.[1]
|
Dosing of Artesunate + Amodiaquine (WHO, 2006)[1] |
|
Age |
Dose |
| 5-11 months |
HALF tablet of each once daily for 3 days |
| ≥1-6 |
ONE
tablet of each once daily for 3 days |
|
≥7-13 |
TWO
tablets of each once daily for 3 days |
|
>13 |
FOUR
tablets of each once daily for 3 days |
Artesunate +
Mefloquine
This is currently available as separate scored tablets
containing 50 mg of artesunate and 250 mg base of mefloquine, respectively.
Co-formulated tablets are under development but are not available at present.
The total recommended treatment is 4 mg/kg bw of artesunate given once a day for
3 days and 25 mg base/kg bw of mefloquine usually split over 2 or 3 days.[1]
|
Dosing of Artesunate + Mefloquine (WHO, 2006)[1] |
| Age |
Dose of Artesunate (50mg) Tablet |
Dose of Mefloquine (250mg) Tablet |
| 5-11 months |
HALF tablet once daily for 3 days |
HALF tablet on second day |
|
≥1-6 |
ONE
tablet once daily for 3 days |
ONE
tablet on second day |
|
≥7-13 |
TWO
tablets once daily for 3 days |
TWO
tablets on second day, ONE tablet on third day |
| >13 |
FOUR
tablets once daily for 3 days |
FOUR
tablets on first day, TWO tablets on third day |
Mefloquine is associated with an increased incidence of nausea,
vomiting, dizziness, dysphoria and sleep disturbance in clinical trials, but
these are seldom debilitating and in general has been well tolerated.[1]
Artemether-lumefantrine
This is currently available as co-formulated tablets containing
20 mg of artemether and 120 mg of lumefantrine. The total recommended treatment
is a 6-dose regimen of artemether-lumefantrine twice a day for 3 days.[1]
|
Dosing of Artesunate + Lumefantrine (WHO, 2006)[1] |
|
Weight |
Age |
Dose |
| 5-14 |
<3 |
1 tablet stat, after 8-12 hours, then twice a day for four
doses |
| 15-24 |
≥3-8 |
2 tablet
stat, after 8-12 hours, then twice a day for four doses |
| 25-34 |
≥9-14 |
3 tablet
stat, after 8-12 hours, then twice a day for four doses |
| >35 |
>14 |
4 tablet
stat, after 8-12 hours, then twice a day for four doses |
Fat-containing food (like milk or butter) enhances the absorption of this ACT
and is therefore recommended, particularly on the second and third days of
treatment.
|
While the WHO
recommends Artemether-lumefantrine in areas of multidrug resistance such as
South-East Asia, the NVBDCP does not recommend this ACT for use anywhere in
India.[1,2] Therefore, this ACT, now widely marketed in India by the private
pharma, need not be used to treat malaria in India. |
Treatment in Pregnancy:
The antimalarials considered safe in the first trimester of pregnancy are quinine, chloroquine, proguanil,
pyrimethamine and sulfadoxine–pyrimethamine. Of these, quinine remains the most
effective and can be used in all trimesters of pregnancy including the first trimester.[1]
There is increasing experience with artemisinin derivatives in
the second and third trimesters and there have
been no adverse effects on the mother or fetus. Therefore, artemisinin
derivatives can be used to treat uncomplicated falciparum malaria in the second
and third trimesters of pregnancy, but should not be the first choice in the first
trimester. However, if nothing other than ACTs are immediately available to treat in the first trimester,
it should be used without delay. The choice of combination partner,
however, can be
difficult. Mefloquine has been associated with an increased risk of stillbirth. Sulfadoxine–pyrimethamine is safe but may be ineffective in many areas
because of increasing resistance. Clindamycin is also safe, but both
medicines (clindamycin and the artemisinin partner) must be given for 7 days.
Primaquine and tetracyclines should not be used in pregnancy. Amodiaquine, chlorproguanil-dapsone, halofantrine, lumefantrine and piperaquine have not
been evaluated sufficiently to permit positive recommendations.[1] The NVDCP in
India does not recommend artemisinin compounds in any trimester of pregnancy.[2]
|
Recommendations for Treatment of Uncomplicated P. falciparum Malaria in
Pregnancy (WHO, 2006) [1] |
|
First trimester |
Quinine +
Clindamycin for 7 days. ACT should be used if it is the only effective treatment
available. |
|
Second and third trimesters |
ACT known to
be effective in the country/region or artesunate + clindamycin to be given for 7
days or quinine + clindamycin to be given for 7 days. |
Lactating women
Dapsone is
excreted in relatively large amounts in breast milk (14% of the adult dose), and
therefore should not be prescribed. Tetracyclines are also contraindicated
because of their effect on the infant’s bones and teeth.
For infants and young children, ACTs should be the first-line
treatment.
For travellers returning to non-endemic countries, WHO
recommends any of the following:
-
Atovaquone–proguanil (15/6 mg/kg; usual adult dose, 4 tablets
once a day for 3 days)
-
Artemether–lumefantrine (adult dose, 4 tablets twice a day for
3 days)
-
Quinine (10 mg salt/kg bw every 8 h) + doxycycline (3.5 mg/kg bw once a day) or clindamycin (10 mg/kg bw twice a day); all drugs to be given for 7 days
See
CDC
Guidelines for Treatment of
Malaria in the United States[4]
Patients with HIV infection who develop malaria should receive standard antimalarial
treatment regimens.
Patients who do not tolerate oral medications or who have high parasitemia can be managed as for
severe falciparum malaria
Fever can be treated with antipyretics and, if necessary, tepid
sponging. Care should be taken to ensure that the water is not too cool as,
paradoxically, this may raise the core temperature by inducing cutaneous
vasoconstriction. Paracetamol (acetaminophen) 15 mg/kg bw every 4 h is widely
used; it is safe and well tolerated given orally or as a suppository. Ibuprofen
(5 mg/kg bw) has been used successfully as an alternative. There has been some
concern that antipyretics might attenuate the host defence against malaria, as
their use is associated with delayed parasite clearance. However, this appears
to result from delaying cytoadherence, which is likely to be beneficial. There
is no reason to withhold antipyretics in malaria.[1]
Follow-up:
All cases of P. falciparum malaria, particularly in the
non-immune and high-risk population, should be monitored for complications.
In case of deterioration, treatment for
severe malaria should be instituted without any delay.
Follow-up MP
tests
In all cases of P. falciparum malaria,
follow-up MP tests should be done on the 6th and 28th days after
treatment. The 6th day smear is done to assess clearance of parasitemia and 28th
day smear is done to identify recrudescence.
6th day smear: If the parasite
is sensitive to the drugs that have been used, then the parasitemia should clear within 7
days. However, gametocytes may be found on the smear and this does not require any
treatment; if primaquine has not been given, it can be given now. Persistence of ring
forms of the parasite indicates incomplete clearance and hence drug resistance. These
cases should be re-treated accordingly with other anti malarial drugs.
RDTs
may show a positive test, but this does not call for re-treatment.
Failure within 14 days:
Treatment failure within 14 days of receiving an ACT is very unusual. It is
important to determine from the patient’s history whether he or she vomited
previous treatment or did not complete a full course. Cases of true treatment failures within
14 days should be treated with a second-line antimalarials.[1]
Failure after 14 days: Recurrence of fever and parasitaemia more than 2 weeks after
treatment is due to either recrudescence or new infection and should be
retreated with the first-line ACT. A repeat smear on the 28th day is
recommended to look for parasitemia.[1]
Second-line treatments recommended:[1]
-
Artesunate (2 mg/kg bw once a day) + tetracycline (4 mg/kg bw
four times a day) or doxycycline (3.5 mg/kg bw once a day) or
clindamycin (10 mg/kg bw twice a day) - Any of these combinations to be given for 7 days.
-
Quinine (10 mg salt/kg bw three times a day) + tetracycline or doxycycline or clindamycin. Any of these combinations to be
given for 7 days.
|
