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    MALARIA IN CHILDREN

    PREVENTION AND TREATMENT

    Chairuddin P.Lubis

    Department o f Chi ld Health

    Medical School, Universi ty of Sumatera Utara

    Medan, Ind onesia

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    BACKGROUND

    Malaria is the worldsmost important parasitic infection (1)

    and remains a major global public heath concern (2)

    A long with tuberculosis and HIV infection, malaria forms a

    disease triad that accounts for almost half of all infectious

    disease mortality(3)

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    (1)

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    Malaria Rapid Diagnostic Tests (RDTs)

    (3)

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    Prevention of Malaria3,11

    1. Protection against Mosquito Bites

    2. Using an insect repellent

    3. Prophilactic Agents

    The risk for acquiring malaria varies according to

    geographic area, altitude, season, time of day, specific

    setting (urban versus rural), duration of stay in an

    endemic area, type of accomodation, and compliancewith preventive measure.

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    (6)

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    TREATMENT

    Just i f icat ion:The first guidel ine on d iagnos is and management of

    malar ia in chi ldren was formulated by Infect iou s Diseases Chapter of

    IAP in 2005. In subsequent year WHO proposed artem isin in b asedcombinat ion therapy in al l cases of uncompl icated falciparum malar ia.

    The number of falciparum malar ia as wel l as mult idrug resistant

    fa lciparum malar ia cases are constant ly on the r ise. So there was need

    to revise the exist ing guid eline.

    Process:The f irs t recommendat ions on the diagnos is and

    management of m alar ia in ch i ldren were form ulated in 2005. The same

    pro toco l was revised on 12 Octob er 2007 in NIMHANS, Bangalore in

    the l ight of var ious recommendations of WHO, where al l the members

    of the Task Force Comm ittee on Malar ia in Chi ld ren were present.

    Object ive: To revise and upd ate treatment guid el ines fo r m alar ia with

    special reference to artemisin in based combinat ion th erapy.Recommendat ions:The need for Ar temis in in based combination

    therapy (ACT) is emphasized in chlo roqu ine resistant falciparum

    malar ia. Monotherapy w ith artesunate wi l l fur th er increase the

    resistance. Once malar ia treatment is ini t iated it sh ou ld be com pleted.

    In severe malar ia the maintenance dose o f artesunate is revised.

    (7)

    (7)

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    Drug sensitivity Recommended treatment

    P. vivax and *Chloroquine 10 mg base/kg stat followed

    by 5mg/kg at 6, 24 and 48 hours.

    chloroquine sensitive OR

    P. falciparum Chloroquine 10mg base/kg stat followed by

    10mg/kg at 24 hours and 5mg/kg at 48

    hours (total dose 25mg base/kg).

    * In case of vivax malaria, to preventrelapse, primaquine should be given in a

    dose of 0.25 mg/kg once daily for 14

    days. In case of falciparum malaria, a

    single dose of primaquine (0.75mg/kg) is

    given for gametocytocidal action.

    TABLE Ia RECOMMENDED TREATMENT IN CHLOROQUINESENSITIVE MALARIA

    (7)

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    Chloroquine should not be given on an empty stomach and in

    high fever. Bring down the temperature first. If vomiting occurs

    within 45 minutes of a dose of chloroquine, that particular dose

    is to be repeated after taking care of vomiting by usingantiemetic (domperidone/ondansetron).

    According to National Anti Malarial Program, a 5 days course

    of primaquine is advocated because of risk of toxicity and

    operational feasibility. Whereas other authorities advocate 14days course of primaquine due to lack of evidence to support

    shorter courses(7). As primaquine can cause hemolytic anemia

    in children with G6PD deficiency, they should be preferably

    screened for the same prior to starting treatment. As infants

    are relatively G6PD deficient, it is not recommended in this age

    group and children with 14 days regime should be under close

    supervision to detect any complication. In cases of borderline

    G6PD deficiency, once weekly dose of primaquine 0.60.8

    mg/kg is given for 6 weeks.

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    TABLE Ib RECOMMENDED TREATMENT IN CHLOROQUINE

    RESISTANT P. FALCIPARUM

    Artesunate 4mg/kg of body weight once daily for 3 days anda single administration of SP as 25mg/kg of sulfadoxine and

    1.25 mg/kg of pyrimethamine on day 1or artesunate as above

    and mefloquine 25mg/kg of body weight in two (15 + 10)

    divided doses on day 2 and day 3.OR

    Co-formulated tablets containing 20 mg of artemether and 120

    mg of lumefantrine can be used as a six dose regimen twice a

    day for 3 days. For 5-14 kg body weight 1 tablet at diagnosis,again after 8 hours and then twice daily on day 2 and day 3.

    For 15 to 24 kg body weight same schedule with 2 tablets. For

    25-35 kg body weight and above same schedule with 3 and 4

    tablets, respectively.

    (7)

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    (i) Under the previous National Drug Policy, SP monotherapy

    in a single dose was used in areas of chloroquine

    resistance. Countries where SP was introduced following

    CQ resistance showed its rapid decline in efficacy withinfew years.

    (ii) Currently there are insufficient safety and tolerability data

    on mefloquine at its recommended dosage of 25 mg/kg

    body weight in children. Mefloquine shares cross resistancewith quinine which is still a effective drug in our country.

    Health planners of our country do not advocate use of

    menfloquine.

    (iii) Advantage of artemether lumefantrine combination is that

    lumefantrine is not available as monotherapy and has never

    been used by itself for the treatment of malaria.

    Lumefantrine absorption is enhanced by coadministration

    with fatty food like milk.

    TABLE I RECOMMENDED TREATMENT OF MULTIDRUG (7)

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    TABLE Ic: RECOMMENDED TREATMENT OF MULTIDRUG

    RESISTANT P. FALCIPARUM (BOTH TO CHLOROQUINE AND

    SULFADOXINEPYRIMETHAMINE)

    Quinine, 10mg salt/kg/dose 3 times daily for 7 days.+

    Tetracycline (above 8 years) 4mg/kg/dose 4 times daily for 7 days

    OR

    Doxycycline (above 8 years) 3.5mg/kg once a day for 7 days

    OR

    Clindamycin 20mg/kg/day in 2 divided doses for 7 days.In case of cinchonism,

    Quinine, 10mg salt/kg/dose 3 times daily for 3-5 days

    +

    Tetracycline (above 8 years) 4mg/kg/dose 4 times daily for 7 days

    OR

    Doxycycline (above 8 years) 3.5mg/kg once a day for 7 daysOR

    Clindamycin 20mg/kg/day in 2 divided doses for 7 days.

    A single dose of primaquine above 1 year age (0.75mg/kg) is given for

    gametocytocidal action.

    OR

    Artemether lumefantrine combination as in table 1b .

    (7)

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    (i) Doxycycline is preferred to tetracycline as it can be givenonce daily and does not accumulate in renal failure.

    (ii) One of the drawbacks of quinine therapy is its long course.

    Unsupervised and ambulatory setting may decrease

    patients compliance and many patients might not

    complete the full course of prescribed therapy.

    (iii) Fortunately children tolerate quinine better than adults.

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    TABLE Id RECOMMENDED TREATMENT IN FAILURE

    WITH ARTEMISININ COMBINATION THERAPY (ACT)

    Quinine + Tetracycline or Doxycycline or Clindamycin for 7 days as in Table Ic .

    (i) Treatment failure within 14 days of receiving an ACT isunusual. It should be confirmed parasitologically by

    blood slide examination. It is important to determine

    whether patient has vomited previous treatment or did

    not complete a full course.

    (ii) Failure after 14 days of treatment can be re-treated with

    first line ACT.

    (7)

    (7)

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    TABLE II DRUG AND DOSAGE OF ANTIMALARIALS IN

    COMPLICATED AND SEVERE MALARIA

    Drug Dosages(5,9)

    Quinine salt 20mg salt/kg (loading dose) diluted in 10mL of isotonic

    fluid/kg by infusion over 4 hours. Then 12 hours after

    the start of loading dose give a maintenance dose of

    10mg salt/kg over 2 hours. This maintenance dose

    should be repeated every 8 hours, calculated from beginning of previous infusion, until the patient can

    swallow, then quinine tablets, 10mg salt / kg 8 hourly to

    complete a 7 day course of treatment (including both

    parenteral and oral). Tetracycline or doxycycline or

    clindamycin is added to quinine as soon as the patientis able to swallow and should be continued for 7 days.

    Dosage as in table 1c. If controlled IV infusion cannot

    be administered then quinine salt can be given in the

    same dosages by IM injection in the anterior thigh (not

    in buttock).

    (7)

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    The dose of quinine should be divided between two sites,

    half the dose in each anterior thigh. If possible IM quinine

    should be diluted in normal saline to a concentration of 60-

    100mg salt/ml. (Quinine is usually available as 300mg

    salt/ml). Tetracycline or doxycycline or clindamycin should

    be added as above.

    Artesunate 2.4 mg/kg IV then at 12 and 24 hours, then once a day for

    total 7 days. If the patient is able to swallow, then the daily

    dose can be given orally. Tetracycline or doxycycline or

    clindamycin is added to artesunate as soon as the patient

    can swallow and should be continued for 7 days. Dosage

    as in Tab le 1c.

    OR

    Artemether 3.2 mg/kg (loading dose) IM, followed by 1.6 mg/kg daily

    for 6 days. If the patient is able to swallow, then the dailydose can be given orally. Tetracycline or doxycycline or

    clindamycin is added to artemether as soon as the patient

    can swallow and should be continued for 7 days. Dosage

    as in Table 1c.

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    (i) Loading do se of quin ine shou ld not be used i f the pat ient has

    received quinin e, qu inid ine or mefloquine within th e preceding

    12 hours. Alternat ively, loading dos e can be admin istered as

    7mg salt/kg by IV infusion pump over 30 m inutes, fol lowedimm ediately by 10mg salt /kg d i luted in 10 ml isoto nic f lu id/kg

    by IV infus ion over 4 hours.

    (i i) Quin ine shou ld not b e given by bolus or push in ject ion.

    Infus ion rate shou ld no t exceed 5 mg salt /kg /hou r.

    (i i i) If there is no cl in ical imp rovement after 48 hou rs o f parenteral

    therapy, the maintenance dose of quin ine shou ld be reduc ed

    by one third to one half i.e., 5-7 mg salt/kg.

    (iv) Quin ine shou ld not b e given subcutaneously as th is may

    cause skin necrosis.

    (v) Previou s maintenance dose of parenteral artesun ate of 1.2

    mg/kg has been modif ied by WHO to 2.4 mg/kg.

    (v i) Artesunate, 60mg per ampoule is diss olved in 0.6mL o f 5%

    sodium bicarbonate di lu ted to 35 mL with 5% dextrose and

    given immediately by IV bolu s (push inject ion).

    (v i i) Artemether is disp ensed in 1 mL ampoule conta in ing 80mg of

    artemether in peanut o il .

    (6)

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    (6)

    (5)

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    (5)

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    (6)

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    (6)

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    Local cost and availability of antimalarial drugs.

    Area of malaria acquisition (i.e. drug resistance

    pattern of P. falciparum).

    Prior chemoprophylaxis.

    Known allergies.

    Concomitant illnesses other than malaria.

    Age and pregnancy.

    Likely patient compliance with therapy.

    Risk of re-exposure to malaria after treatment.

    Choice of regimen is based on:(7)

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    References

    1. White N. J. The treatment of malaria. The New England Journal of

    Medicine, September 12, 1996, pp. 800-6.2. Making a difference. The Wold Health Report 1999. Health Millions

    1999, 25(4), pp. 3-5.

    3. Wolf J. E. Treatment and prevention of malaria: an update. Hospital

    Physician, December 2002, pp. 15-22.

    4. Davis, T. M. E. Malaria Treatment. (15/04/2003). .

    5. Juckett, G. Malaria Prevention in Travelers. American Family Physicians

    (8/01/2001). .

    6. Bosman Andrea How to protect your self against malaria. GlobalMalaria Programme Geneva, 10 September 2008.

    7. Kundu Ritabtata Management of Malaria in Children : Updated 2008

    Infectious Diseases Chapter, Indian Academic of Pediatrics, Vol 45,

    September 17, 2008.

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    TERIMA

    KASIH