MALARIA TREATMENT PROTOCOL Third edition June 2007 Ministry of Health Republic Democratic of Timor- Leste

UNCOMPLICATED MALARIA Uncomplicated malaria definition: Fever and any of the following:  Headache,  Body and joint pains  Feeling cold and sometimes shivering  Loss of appetite and sometimes abdominal pains  Diarrhoea, nausea and vomiting.  Spleenomegaly

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 illnesses, such as:  Upper respiratory tract infection (Pharyngitis, tonsillitis, ear infection), pneumonia, measles, dengue, influenza, typhoid fever. Remember that the patient may be suffering from more than one illness.

Uncomplicated malaria treatment P. falciparum malaria  The treatment of uncomplicated P. falciparum malaria is undertaken after diagnosis of malaria by light microscopy or Dipstick.  Patients with positive think-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 groupWeight group Blister color (Day 1)(Day 2)(Day 3) 4 months to 5yrs 5 to 14 kgYellow 1 tb , 1 tb  6 to 11y15 to 24 kgBlue 2 tb , 2 tb  12 to 14y25 to 34 kgOrange 3 tb , 3 tb  > 14y> 34Green 4 tb , 4 tb  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 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 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 the referring 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 treatment P. 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.

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 days Start concurrently with CQ and give daily for 14 days Day 1Day 2Day 3 4 months up to 12 months 4 - <10½½¼- 13 months up to 5 years 10 - <1911½¼ years19 - < 241½ 1½ years24 - <352½ 1¾ years35 - < ½ or more4422

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 1Day 2Day months <5 kg10 mg/kg5 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:  If there is no possibility of dipstick or slide results, treat the patient based on the clinical signs and symptoms. Treat as if the patient has P. falciparum.

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 lactated woman or child less than 8 years:  Quinine (10mg salt /kg bw three times a day) + clindamycin (10mg/kg bw twice a day) for 7days. For small children, (quinine and clindamycin) crush tablets and mix with water and sugar.

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).

SEVERE MALARIA Severe or complicated malaria definition: Fever and any of the following:  Impaired consciousness  Anxiety, palpitation and sweating  Convulsions or fits with this fever  Fast or difficult breathing  Vomiting every feed / unable to feed  Pale hands, tongue and inner parts of the eyelid  Generalized body weakness  Dehydration  Jaundice  Severe malnutrition  Dark urine or no urine

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!

 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.

Confirmed 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, typhoid fever, tuberculosis, hypoglycemia.

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®.  Arteether (150 mg): 3.2 mg/kg bw IM on the first day, followed by 1.6 mg/kg bw for the next 4 days. Once the patient can tolerate oral therapy, may switch 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.

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 two 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 mg/kg after 4 days or add tetracycline 5 mg/kg twice a day for children above 7 years.

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)..