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close this bookGuidelines for the Treatment of Malaria (WHO; 2006; 266 pages) View the PDF document
View the documentGlossary
View the documentAbbreviations
open this folder and view contents1. Introduction
View the document2. The clinical disease
open this folder and view contents3. Treatment objectives
open this folder and view contents4. Diagnosis of malaria
open this folder and view contents5. Resistance to antimalarial medicines9
open this folder and view contents6. Antimalarial treatment policy
open this folder and view contents7. Treatment of uncomplicated P. Falciparum malaria10
close this folder8. Treatment of severe falciparum malaria14
View the document8.1 Definition
View the document8.2 Treatment objectives
View the document8.3 Clinical assessment
View the document8.4 Specific antimalarial treatment
View the document8.5 Practical aspects of treatment
View the document8.6 Follow-on treatment
View the document8.7 Pre-referral treatment options16
View the document8.8 Adjunctive treatment
View the document8.9 Continuing supportive care
View the document8.10 Additional aspects of clinical management
View the document8.11 Treatment during pregnancy
View the document8.12 Management in epidemic situations
View the document8.13 Hyperparasitaemia18
open this folder and view contents9. Treatment of malaria caused by P. vivax, P. ovale or P. malariae19
View the document10. Mixed malaria infections
open this folder and view contents11. Complex emergencies and epidemics
open this folder and view contentsAnnexes

8.7 Pre-referral treatment options16

16 Further infromation is provided in Annex 9.8 can be instituted. If, however, referral is impossible, rectal treatment should be continued until the patient can tolerate oral medication, at which point a full course of the recommended ACT for uncomplicated malaria in the locality can be administered.

The risk of death from severe malaria is greatest in the first 24 h, yet in most malaria endemic countries, the transit time between referral and arrival at appropriate health facilities is usually prolonged thus delaying the commencement of appropriate antimalarial treatment, during which time the patient may deteriorate or die. It is recommended that patients are treated with the first dose of one of the recommended treatments by the parenteral route if possible or by the intra-rectal route before referral (unless the referral time is very short). This could be intramuscular artemether, artesunate or quinine, or a rectal formulation of artemisinin or artesunate.

Summary of recommendations on pre-referral treatment for severe falciparum malaria



The following may be given:


- artesunate or artemisinin by rectal administration

T, E


- artesunate or artemether i.m.



- quinine i.m.

O, E

8.7.1 Pre-referral and continued treatment with rectal artemisinins

The administration of an artemisinin by the rectal route as pre-referral treatment is feasible even at the community level.

There is insufficient evidence to show whether rectal artesunate is as good as intravenous or intramuscular options in the management of severe malaria. The recommendation, therefore, is to use artesunate or artemisinin suppositories only as pre-referral treatment and to refer the patient to a facility where complete parenteral treatment with artesunate, quinine or artemether

8.7.2 Dosing for antimalarials given by suppository

Artemisinin derivatives

Artemisinin suppositories are not widely available. Doses used have been variable and empiric: 10-40 mg/kg bw (at 0, 4 or 12, 24, 48 and 72 h). Some studies have given a maintenance dose of one- to two-thirds of the initial dose. Artesunate suppositories* are given in a dose of 10 mg/kg bw daily. The individual suppositories contain either 50, 100 or 400 mg of artesunate. Recommendations for artesunate suppositories for pre-referral treatment of severe malaria are provided in Tables 5 and 6.

Initial (pre-referral) treatment with rectal artesunate

The appropriate single dose of artesunate given by suppository should be administered rectally as soon as the presumptive diagnosis of severe malaria is made. In the event that an artesunate suppository is expelled from the rectum within 30 min of insertion, a second suppository should be inserted and, especially in young children, the buttocks should be held together, for 10 min to ensure retention of the rectal dose of artesunate.

For adults: one or more artesunate suppositories inserted in the rectum, dose as indicated in Table 5. The dose should be given once and followed as soon as possible by definitive therapy for malaria.

Table 5. Dosage* for initial (pre-referral) treatment in adult patients (aged ≥16 years)

Weight (kg)

Artesunate dose

Regimen (single dose)


10 mg/kg bw

Use appropriate no. of 100-mg rectal suppositories (see Table 6)


400 mg

One 400-mg suppository


800 mg

Two 400-mg suppositories


1200 mg

Three 400-mg suppositories


* It should be noted that the clinical trial data with rectal artesunate relate to a single suppository formulation and presentation17which has well characterized absorption kinetics and so cannot necessarily be extrapolated to other rectal formulations of artesunate.

17 This product is being developed by the UNDP/UNICEF/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.

For children: one or more artesunate suppositories inserted in the rectum as indicated in Table 6. The dose should be given once and followed as soon as possible by definitive therapy for malaria.

Table 6. Dosage for initial (pre-referral) treatment in children (aged 2-15 years) and weighing at least 5 kg

Weight (kg)


Artesunate dose (mg)

Regimen (single dose)


0-12 months


One 50-mg suppository


13-42 months


One 100-mg suppository


43-60 months


Two 100-mg suppositories


6-13 years


Three 100-mg suppositories


>14 years


One 400-mg suppository


The intrarectal dose used in treatment trials in Africa was either 12 mg/kg bw quinine base every 12 h without a loading dose, or 8 mg/kg bw every 8 h, also without a loading dose. The retention and absorption of quinine is dependent on pH. Results with gluconate salts (pH 4.5) cannot be extrapolated to more acidic solutions (such as the dihydrochloride salt, pH 2).

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