Malaria

NON-SEVERE, UNCOMPLICATED MALARIA

Refer to the MOH National Malaria Control Program Revised Guidelines for the Treatment of Malaria in Malawi, 5^th edition, 2020, for full details of malaria management.

CLINICAL FEATURES

SIGNS AND SYMPTOMS

Fever or recent history of fever in pregnant women or children under the age of five years and fever or history of fever plus one other symptom or sign suggestive of malaria in over five children and adults

INVESTIGATIONS

All suspected uncomplicated malaria cases at all levels of the health care delivery system should be tested using malaria rapid diagnostic tests (mRDTs) or by microscopic examination of blood film wherever possible.
Testing (film or mRDT).
Repeat diagnostic test (film or mRDT) if:
- the first test was positive and there is persistent fever or worsening condition despite suitable antimalarial treatment.

TREATMENT

The first test was negative and antimalarial treatment was not given, but the patient's fever persists or condition deteriorates
In the event that both mRDT and microscopy are not available, REFER TO THE FACILITY WHERE THE TESTS CAN BE DONE: BUT IF SUSPECTING SEVERE MALARIA, GIVE PRE-REFERAL TREATMENT, INJECTABLE ARTESUNATE. Don’t treat on the basis of presumptive diagnosis

First-Line Treatment

Give Lumefantrine 120mg/Artemether 20mg (LA) even to pregnant women in 1st trimester
Lumefantrine-artemether comes in two formulations:
- Non-dispersible LA [LA(ND)] for older children weighing 20kgs or more including adults and
- Dispersible LA [LA(D)] for children weighing less than 20kg

Note: If LA(D) is not available, LA(ND) can be used to treat children weighing less than 25kg

Dosage Schedule for dispersible (D) and non- dispersible (ND) Lumefantrine-Artemether (LA- 120mg/20mg tablets).

Body weight in Kg (age in years)	No. of tablets at approximate timing of dosing
	Day 1		Day 2		Day 3
	Start dose	After 8 hrs	AM	PM	AM	PM
LA(D) ≤14.9 kg (<3)	1	1	1	1	1	1
LA(D) 15-24.9kg (>38)	2	2	2	2	2	2
LA(ND) 25-34.9kg (>9-14)	3	3	3	3	3	3
LA(ND) ≥35 kg (>14)	4	4	4	4	4	4

First dose should be given as DOT. If vomiting occurs within 30 minutes, repeat the dose
Dose is given according to body weight
If possible, each dose should be taken with milk, which improves the absorption of lumefantrine component of the combination
If fever persists beyond 72 hours, do malaria microscopy, and if the result is positive, give second line treatment in patients with contractions or intolerance to LA give second line treatment.

Second-Line Treatment

Give Artesunate 4 mg/kg/day and Amodiaquine 10 mg/kg/day 24 hourly for 3 days.

Dosage schedule for fixed combination dose of artesunate-amodiaquine

Body Weight (Kg)	Age	Daily Dose for 3 Days Artesunate-Amodiaquine	Preparation Strength per tablet
5.0- 8.9	2-11 months	1 tablet	25 mg/67.5 mg
9.0-17.9	1-5years	1 tablet	50mg/135mg
18.0-35.9	6-13 years	1 tablet	100 mg/270 mg
>36	14 years old and above	2 tablets	100mg/270mg

Note:

Treatment failure to first line treatment (LA) should be suspected if symptoms persist or the patient clinically deteriorates three to 14 days after initiation of LA drug therapy
Side effects: Transient rise in transaminases and transient reduction in white blood cell count. The dosing schedule is indicated in Table 1.4 below

SEVERE MALARIAClinical Features

Most severe malaria occurs in children under 5 years of age. Severe malaria is a medical emergency and as such treatment should begin immediately, whether the patient presents at the community, health center, or hospital level. Suspect severe malaria if a patient has one or more of the following conditions (mostly seen in combination):

Clinical manifestations and some laboratory findings

Clinical manifestations

Some laboratory findings

· Impaired level of consciousness (cerebral malaria)

· Respiratory distress (acidotic breathing)

· Repetitive convulsions

· Circulatory collapse

· Pulmonary Oedema

· Prostration

· Excessive or Persistent vomiting

· Extreme pallor Shock (weak pulse, cold extremities)

· Jaundice (yellowish coloration of eyes)

· Little or no urine output (think about acute kidney injury) or very dark coloured urine.

· Spontaneous bleeding (mouth, nose, skin, eyes)

· Hypovolaemia

· Severe anaemia: (Hb<5 g/dl) (i.e. Hb <5 g/dl or Hct < 15 %)

· Hypoglycaemia: (<2.2 mmol/l or <40 mg/dl)

· Hyperlactataemia (lactic acidosis) (blood lactate >4 mmol/l)

· Electrolyte imbalance (hyponatraemia)

· Acute kidney injury (serum creatinine >265 µmol/l)

· Haemoglobinuria

Although most children with malaria have a (history of) fever, this may be variable in patients who have progressed to severe malaria
Examine children with suspected severe malaria for other conditions (e.g. pneumonia, meningitis) as a possible cause of their symptoms and, if found, manage appropriately

Note:

Patients with hyperparasitaemia: 4+ (40,000 - 400,000/µl or ring stage >5% of RBCs) who do not have any of these indicators of severe (disease) malaria should be admitted for observation. Treat with first-line antimalarial (LA).

If severe malaria is diagnosed in an out- patient, refer the child for hospitalization (see below)

PRE-REFERRAL TREATMENT AT COMMUNITY LEVEL

Refer any patient with severe malaria to the nearest hospital

TREATMENT

Give Rectal Artesunate at 10 mg/kg body weight in a single dose, followed as soon as possible by definitive therapy for severe malaria at a hospital
In the event that Artesunate Suppository is expelled from the rectum within 30 minutes of insertion, a second suppository should be inserted
If referral is not possible within 12 hours, a second dose of Rectal Artesunate should be administered at 12 hours after the initial dose, then once in every 24 hours until patient is transferred to a hospital

Initial (pre-referral) Dosage of Artesunate Suppositories for patients aged >6 yrs

Weight	Artesunate Dose	Regimen (Single Dose)
<40	10 mg/kg	Use appropriate no. of 50 mg rectal suppositories
40 -59	400 mg	Two suppositories of 200 mg each
60 - 80	800 mg	Four suppositories of 200 mg each
>80	1200 mg	Six suppositories of 200 mg each

Note:

For children, hold the buttocks together for 10 minutes to ensure retention of the rectal dose
Treatment with Rectal Artesunate is suboptimal, and every effort should be made to refer the patient as soon as possible
The table below shows the recommended pre-referral doses of Artesunate Suppositories for children aged <6 years
- As in adult patients, if referral is not possible within 12 hours, a second dose of Rectal Artesunate should be administered at 12 hours after the initial dose

Thereafter the dose may be repeated every 24 hours. Refer to the malaria treatment guidelines for RA insertion procedure

Initial (pre-referral) Dosage of Artesunate Suppositories for Children Aged 2months -15 Years (and weighing at least 5 kg)

Weight	Age	Artesunate Dose (mg)	Regimen (Single Dose)
5 - 8.9	2 – 12 months	50	One 50 mg suppository
9 - 19	13 – 42 months	100	Two 50 mg suppositories
20 - 29	43 – 60 months	200	One 200 mg suppository
30 - 39	6 years	200	One 200 mg suppository

Note: Do not give rectal Artesunate to patients above 6 years of age

PRE-REFERRAL TREATMENT AT HEALTH CENTRE LEVEL

Give Artesunate 3 mg/kg in children <20kg and 2.4 mg/kg (0.12 ml/kg) >20kg and adults IM
Artesunate should be given by intramuscular injection into the upper- outer quarter of anterior thigh and should not be injected into the buttocks
To administer IM Artesunate, weigh the patient and determine the number of vials needed for treatment as per the table below:

Number of Required Vials of Parenteral Artesunate by Body Weight

Weight	60mg Vials required
5 kg - 25 kg	1
26 kg - 50 kg	2
51 kg - 75 kg	3
76 kg - 100 kg	4

Each 60 mg vial of injectable Artesunate must be reconstituted with 1 ml of Sodium Bicarbonate
Dilute the Artesunate-Bicarbonate mixture with 2 ml of 5% Dextrose Solution or Normal Saline (0.9% Sodium Chloride) to produce a 20 mg/ml solution. Never use water for injection
Withdraw the appropriate volume in a syringe ([2.4 mg x body weight in kg]/20 mg/ml) for intramuscular injection, rounding to the next whole number in milliliters
Administration of pre-referral IM Artesunate should be followed as soon as possible by definitive therapy for malaria at a hospital
If referral is not possible within 12 hours, a second dose of IM Artesunate should be administered at 12 hours after the initial dose
If referral is still not possible after 24 hours, a third dose of IM Artesunate should be given

Alternatively

If IM Artesunate is unavailable or contraindicated, treat with high dose Quinine IM, administered in the thigh not the buttock
Give IM Quinine 10 mg (0.2 ml) per kg body weight
If the volume to be injected exceeds 3 ml, give half into each thigh. An example of body weights and dosing (ml) for IM quinine is given in the table below.

Dosage of Parenteral Quinine per body weight

Body Weight	Quinine (ml)	Number of Injection sites
Under 5 kg	1.0 ml	1
5.1 - 7.5 kg	1.5 ml	1
7.6 - 10.0 kg	2.0 ml	1
10.1 - 12.5 kg	2.5 ml	1
12.6 - 15.0 kg	3.0 ml	1
15.1 - 17.5 kg	3.5 ml	2
17.6 - 20.0 kg	4.0 ml	2
20.1 - 22.5 kg	4.5 ml	2
22.6 - 25.0 kg	5.0 ml	2
25.1 - 27.5 kg	5.5 ml	2
27.6 - 30.0 kg	6.0 ml	2

Administration of pre-referral IM Quinine should be followed as soon as possible by definitive therapy for malaria at a hospital
If referral is not possible within 12 hours, a second dose of IM quinine should be administered 12 hours after the initial dose
If referral is still not possible after 24 hours, a third dose of IM Quinine should be given
- Give 0.4ml/kg of this solution as the first
- (loading) dose - this is 20mg/kg
- Subsequent (12-hourly) doses should each be 0.2ml/kg (10mg/kg)
- The dose of Quinine for an adult at anyone time should not exceed 1,200mg

Note: Injectable artesunate or quinine should be for patients unable to take oral drugs.

Where there is no scale, weight of the child can be estimated as follows:
For children of 3months to 12months old
Weight (Kg) = Age (months) + 9/2
For children of 1 year to 6years old
Weight (Kg) = [Age (in years) x 2) + 8

If IM Artesunate and IM Quinine are unavailable

Give Rectal Artesunate