08 Malaria Treatment

MalariaTreatment

Timely Treatment is Necessary Malaria can be effectively treated if suspected and recognized

early and appropriate medical intervention is made within a timely manner.

Time to symptom onset from initial exposure can vary, ranging as early as 7 days following a mosquito bite to several months or greater following departure from an endemic region.

The diagnosis of malaria is a medical emergency since time to definitive treatment is a critical factor in determining clinical outcome.

Drugs Used for Treatment of Malaria

Confirmed Diagnosis of Malaria All clinically suspected malaria cases require laboratory

examination and confirmation. Only in case where laboratory confirmation is not possible

start treatment immediately. Parasitological confirmation is done by thin-thick blood smear

microscopy examination or by dipstick (Rapid Diagnostic Test [RDT]).

Differential diagnosis for uncomplicated malaria Consider other febrile illnesses, such as: Upper respiratory tract infection (Pharyngitis, tonsillitis,

ear infection), pneumonia , measles, dengue, influenza, enteric fever.

Remember that the patient may be sufferingfrom more than one illness.

Uncomplicated malaria treatmentP. falciparum malaria The treatment of uncomplicated P. falciparum malaria is

undertaken after diagnosis of malaria by light microscopy or Dipstick.

Patients with positive thin-thick blood smears or dipstick for P. falciparum malaria is treated by blisters of Coartem® (artemether 20mg/lumefantrine 120mg). See Table 1 for details of prescription.

Table 1 : Dosage and administration Coartem (Artemether 20 mg/Lumefantrine 120 mg) for uncomplicated malaria falciparum

Age group Weight group Blistercolor (Day 1) (Day 2) (Day 3)

4 months to 5yrs 5 to 14 kg Yellow

1 tb R, 1 tb R, 1 tb R,

1 tb Z 1 tb Z 1 tb Z

6 to 11y 15 to 24 kg Blue2 tb R, 2 tb R, 2 tb R,

2 tb Z 2 tb Z 2 tb Z

12 to 14y 25 to 34 kg Orange3 tb R, 3 tb R, 3 tb R,

3 tb Z 3 tb Z 3 tb Z

> 14y > 34 Green4 tb R, 4 tb R, 4 tb R,

4 tb Z 4 tb Z 4 tb Z

Source: Guideline for the treatment of malaria, WHO; 2006

Coartem® Dosage Schedule

Source: WHO, 2007

Important notes (1) 1. It is obligatory to give Coartem® to patient whose dipstick test or

blood slide is positive for P. falciparum and to the patient who has mixed infections P. falciparum and P .vivax.

2. Give the correct dosage of Coartem® from the appropriate blister according to the patient’s weight or age.

3. Children under 5 kg or below 4 months should not be given Coartem instead treat with the following regimen (see table 2).

Table 2. Dosage and administration Plasmodium falciparum for young infant

Age Group Weight group Artesunate or *Quinine

0 - 4 months <5 kg

** IM first dose Artesunate 1.2 mg/kg or IM Arthemeter 1.6 mg/kg)

***Oral Artesunate 2mg/kg/day day 2 to day 7

Oral Quinine 10 mg/TID for

4 days then 15-20 mg/kg TID for 4 days

Source: Malaria in Children, Department of tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University.

** Preferably Artesunate/Artemether IM on day 1 if available *** When Artesunate/Artemether IM is unavailable, give oral Artesunate from day 1 to day 7* Treat the young infant with Quinine when oral Artesunate is not available

Important notes (2)

4. In case parasitological diagnostic facilities are not available paracetamol could be given to relieve pain and fever and referred to health facilities where parasitological diagnosis will be carried out.

5. Only in exceptional case when there is problem with thereferring patient in other health facility coartem® could be administered. (The health facility manager should write explanatory note why giving coartem® without parasitological diagnosis).

Important notes (3)6. Watch all patients swallowing the first dose of coartem® and observe for

1 hour after the intake. In the event of vomiting within one hour of administration, a repeat dose should be taken.

7. Inform patient that, the coartem® tablets are in the blister and after breaking should be taken immediately, as after 24 hours coartem® tablets exposed to air totally inactivated and can not be used for treatment of malaria.

8. Each blister of coartem® has expiry date and should not be used after the expiry date.

Important notes (4)9. For small children, paracetamol and coartem® can be crushed,

diluted in water and then put either directly into the mouth using a syringe or given with a spoon.

10. Any patient who seeks re-treatment for malaria within 2 weeks of taking full dose of any other antimalarial should be treated with coartem®.

Uncomplicated malaria treatmentP. vivax malaria Resistance of P. vivax to chloroquine has not been found

in Timor-Leste and Chloroquine is the drug of choice Chloroquine is safe and has few side effects. For the radical treatment of P. vivax in addition to

chloroquine, primaquine is recommended 0.5mg/kg per day for 14 days (primaquine should always be taken with food).

Chloroquine can be given to pregnant women and children.

Primaquine is not recommended for the children under one year and pregnant women.

• Details of treatment see table 4a.

Other oral combinations for treatment: Artesunate + amodiaquine, target dose of 4 mg/kg/day artesunate and 10

mg/kg/day amodiaquine, once a day for 3 days Artesunate + mefloquine, target dose of 4 mg/kg/day artesunate given once a day

for 3 days and 25 mg/kg of mefloquine either split over 2 days as 15 mg/kg and 10 mg/kg or over 3 days as 8.3 mg/kg/day once a day for 3 days.

Artesunate + sulfadoxine-pyrimethamine, target dose of 4 mg/kg/day artesunate given once a day for 3 days and a single administration of 25/1.25 mg/kg sulfadoxine-pyrimethamine on day 1, with a therapeutic dose range of 2–10 mg/kg/day artesunate and 25–70/1.25–3.5 mg/kg sulfadoxine-pyrimethamine

Artesunate + tetracycline or doxycycline or clindamycin, artesunate (2 mg/kg once a day) plus tetracycline (4 mg/kg four times a day) or doxycycline (3.5 mg/kg once a day) or clindamycin (10 mg/kg twice a day); to be given for 7 days.

Table 4a. Dosage and administration of Chloroquine and Primaquine for malaria vivax.

Age Group * Weight group (Kg)

CHLOROQUINE(150 mg base) 10 mg/kg on the

first two days. 5 mg/kg on day 3

PRIMAQUINE(15 mg base) 0.5 mg/kg bw

Give for 3 daysStart concurrently with CQ and give daily for 14 daysDay 1 Day 2 Day 3

4 months up to 12 months 4 - <10 ½ ½ ¼ -

13 months up to 5 years 10 - <19 1 1 ½ ¼

6 - 7 years 19 - < 24 1½ 1½ 1 ½

8 - 11 years 24 - <35 2½ 2½ 1 ¾

12 - 14 years 35 - < 50 3 3 2 1½

15 + 50 or more 4 4 2 2

P. vivax malaria

Young infant less than 5kg or below 4 months should be treated with Chloroquine alone for three days consecutive (Table 4b).

Table 4b. Dosage and administration of Chloroquine for malaria vivax in young infant

Age Group

Weight group

Chloroquine

Day 1 Day 2 Day 3

0 - 4 months <5 kg 10 mg/kg 5 mg/kg 5 mg/kg

P. falciparum and P. vivax (mixed infections)

The type of malaria where both infections occurs in patient requires treatment by

Coartem®.

Notes:Negative dipstick or thin-thick blood smear: If the Pf dipstick is negative and the clinical signs are typical for malaria, treat with

Chloroquine (it could be a case of P. vivax infection). If the Pf dipstick is negative and the clinical signs don’t suggest malaria, do not treat like malaria;

look for another illness. If the blood slide is negative, look for another illness. If symptoms persist, ask for another dipstick or blood slide. If dipstick and/or thin-thick blood smear are not available:

Treat the patient based on the clinical signs and symptoms. Treat as if the patient has P. falciparum.

Never treat a patient with FANSIDAR alone or oral arthemeter alo ne! NO MONOTHERAPY

Follow-up of uncomplicated malaria: If symptoms persist after treatment with coartem® or if the patient comes back

before the 14th day after treatment. Treatment failure within 14 days of receiving coartem® is extremely rare and is

more likely to be an inadequate absorption of the drug(s) than resistance of the parasites. It is important to determine from the patient’s history whether he or she vomited during the previous treatment or did not complete the full course.

If patient is in health facility where microscope is available failure of treatment should be confirmed parasitologically and could be treated using the following regimen:

Follow-up of uncomplicated malaria:For adult: Quinine (10mg salt /kg bw three times a day) + doxycycline (3.0mg/kg bw once a day) for 7

days. Do not give doxycycline with milk or iron, which will reduce its absorption. If patient is in health facility where microscopy facility is not available patient should be

referred to the facility where microscope is available. If refer is not possible treatment should be given Quinine + Doxycycline. Please refer to Table 5 for details of the prescription.

Doxycycline should not be given to pregnant or lactating woman, or child aged up to 8 years.

For pregnant or lactating woman or child less than 8 years: Quinine (10mg salt /kg bw three times a day) for 7days. For small children, crush tablets and

mix with water and sugar (where reliable syrup is unavailable).

Antimalarial treatment failure in uncomplicated malaria: WHO definitions Early treatment failure

Development of danger signs or severe malaria on days 1-3 + parassitaemia;Parassitaemia day 2 higher than day 0 or; Parassitemia on day 3 + axillary temp

≥37.5oC or; parassitaemia day 3 of ≥25% of count on day1 Late treatment failure: Development of danger signs or severe malaria after

day 3 + parassitaemia Late clinical failure: parassitaemia + axillary temp ≥37.5oC on day 4-28 Late parasitological failure: parassitaemia on day 7-28 + fever Adequate clinical and parasitological response: absent

parassitaemia on day 28 irrespective of axillary temp

Note: For high transmission areas where parasitological

confirmation is not available, children <5 yrs of age is recommended to be treated with anti malarial drugs when symptomatic (especially fever without a focus).

Pre-referral treatment of severe malaria

A patient who is non responsive should be quickly assessed and managed. This includes assessment of the airway, breathing and circulation. The staff at the first level health facility should be able to maintain airway, provide assisted breathing and manage shock if required.

Pre-referral treatment for severe malaria the administration of Artesunate by the rectal route is recommended for all except pregnant women first trimester pregnancy. For the complete dosage and treatment.

Check blood sugar, if possible!

Pre-referral In case Artesunate suppository is not available IM quinine

injection 20mg/kg bw should be given. The Quinine injection dosage should be split and injections given in the anterior part of the thigh.

In case Artesunate suppository is not available, give also Quinine for children with severe malaria.

Confirm diagnosis of severe malaria: All clinically suspected severe malaria cases require

laboratory examination and confirmation. Only in case where laboratory confirmation is not possible

start treatment immediately. Parasitological confirmation is done by thin-thick blood smear microscopy examination or by dipstick (Rapid Diagnostic Test [RDT]).

Differential diagnosis for complicated malaria Consider other illnesses, such as: Measles, meningitis, tonsillitis, dengue, otitis media (ear

infection), influenza, pneumonia, enteric fever, tuberculosis, hypoglycemia.

Immediate Clinical Management of Severe MalariaComa (Cerebral malaria) Maintain airway Place pt on his/her side Exclude other causes of coma (e.g.

hypoglycaemia, bacterial meningitis) Avoid harmful treatment (e.g., steroids,

heparin, adrenaline) Intubate if necessary

Pulmonary Oedema Cardiac bed; O2

Diuretic; stop IV fluids In life threatening hypoxaemia:

intubation and (PEEP)/CPAPMetabolic acidosis Exclude/treat hypoglycaemia,

hypovolaemia and septicaemia If severe haemofiltration or

haemodialysis

Immediate Clinical Management of Severe MalariaConvulsions Maintain airway IV or rectal benzodiazepineHypoglycaemia (BG<2.2mmol/L or <40mg/dl) Correct and maintain with glucose infusionSevere Anaemia (HB<5g/dl or PCV<15%) Transfuse with screened whole bloodSpontaneous bleeding coagulopathy Transfuse with screened fresh whole blood

(FFP or cryoprecipitate if available) Give vitamin K injection

Shock Suspect septic shock Take blood for culture Parenteral antibiotics Correct haemodynamic disturbancesHyperparassitaemia (>10% of circulating RBCs parasitized in non-immune patients) Immediate parenteral antimalarialsAcute renal failure Exclude pre-renal causes Check fluid balance and urinary Na+

If established ARFhaemodialysis; if unavailable peritoneal dialysis

Stop IV fluids

Specific severe malaria treatment IV Quinine in DW5% (600mg vials): 10 mg/kg body weight (bw) IV

over 4 hours on admission (time=0), followed by 10mg/Kg at 8hours interval. Once the patient can tolerate oral therapy, treatment should be switched to a complete dosage of coartem® for three days as recommended in the national treatment guidelines for uncomplicated malaria .

Assess for evidence of neurological damage (visual, speech, hearing, and motor deficits) before discharge

Antimalarial treatment for cerebral malaria

Quinine Loading dose: Quinine dihydrochloride 20 mg salt/ kg bw

diluted in 10 ml/kg bw of 5% dextrose or dextrose saline administered by IV infusion over a period of four hours for both adult and children. In severe Childhood falciparum malaria, if patient received quinine or quinidine or mefloquine in 48 hrs before arrival, give 10 mg/kg over 2 hours.

Quinine Maintenance dose: Quinine dihydrochloride 10 mg salt/ kg body weight diluted in

10 ml/kg body weight of 5% dextrose or dextrose saline administered by IV infusion. In adults, the maintenance dose is infused over a period of four hours and repeated every eight hours. Similarly in children including congenital malaria, it is infused over a period of four hours and repeated every eight hours (calculated from the beginning of the previous infusion) until the patient can swallow. To complete the seven-day to eight-day treatment in children, give Quinine sulfate 10 mg/kg per oral three times in a day. Increase the dosage of Quinine sulfate to 15-20 mg/kg after 4 days or add tetracycline 5 mg/kg twice a day for children above 7 years.

Specific severe malaria treatment Artesunate (60 mg): 2.4 mg/kg body weight (bw) IV or IM on

admission (time=0), followed by 2.4 mg/kg at 12 and 24 hours, followed by once daily for seven days. Once the patient can tolerate oral therapy, treatment should be switched to a complete dosage of coartem® for three days as recommended in the national treatment guidelines for uncomplicated malaria .The congenital malaria is also treated with Artesunate, where 2.4 mg/kg is initially given through IV, followed by 1.2 mg/kg at 12 and 24 hr then every 24 hr for 3 -5 days.

Specific severe malaria treatment Artemether (80mg for adult and 40 mg for children and the newborn):

3.2 mg/kg bw IM on the first day followed by 1.6 mg/kg bw daily for seven days. Once the patient can tolerate oral therapy, treatment should be switched to a complete dosage of coartem®.

If Coartem® is not available, quinine should be administered in combination with tetracycline or doxycycline or clindamycin, to complete the seven-day treatment, except for pregnant women and children under eight years of age for whom tetracycline/doxycycline is contraindicated.

ANTIMALARIAL TREATMENT: UNCOMPLICATED FALCIPARUM MALARIA

OR MIXED INFECTIONDrugs Doses Duration (days)

Artemether (20) –lumefantrine (120)

<15 kg: 1 tab BID16-25 kg: 2 tabs BID26-35 kg: 3 tabs BID>35 kg: 4 tabs BID

3

Atovaquone (250) –proguanil (100)

20 mg/kg/day8 mg/kg/day

3

Quinine SO4 +Tetracycline orDoxycyclineClindamycin

10 mg/kg TID4 mg/kg QID2 mg/kg BID5 mg/kg TID

7

Artesunate +Mefloquine

4 mg/kg/day15 mg/kg10 mg/kg

32nd day of Rx3rd day of Rx

Notes Artemisinin derivatives are safe, effective, have a wider therapeutic window, can be

administered intramuscularly and should be considered a safer alternative to quinine. A loading dose of quinine should not be given (1) if the patient has received or suspected to have

received quinine, quinidine or mefloquine within the preceding 12 hours, and (2) facilities for controlled rate of flow of quinine infusion are not available. In order to improve treatment outcome of quinine add a course of oral tetracycline 4 mg/kg bw 4 times daily or doxycycline 3 mg/kg bw once daily except for children under 8 years of age and pregnant women, or clindamycin 10 mg/kg bw twice daily for 3-7 days.

If there is no clinical improvement after 48 hours of parenteral therapy, the maintenance dose of parenteral quinine should be reduced by one-third to a half (i.e., 5-7 mg/kg bw quinine dihydrochloride). .

ANTIMALARIAL TREATMENT: NON-FALCIPARUM MALARIA

Chloroquine 600 mg base at hour 0 followed by 300 mg base at hour 6, 2nd day, and 3rd day of treatment +Primaquine (for P. vivax and P. ovale only) 0.3-0.6 mg base/kg daily for 14 days