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Artemether for severe malaria



Clinical bottom line: Artemether was equally as effective as quinine in the treatment of severe malaria; mortality rates were about 15%.

Artemether is the active component of the Chinese herb qinghao (Artemesia annua). Extracts of qinghao have been used in traditional Chinese herbal medicine to treat febrile illness. Uncontrolled studies have shown artemether to be effective for treating malaria.


Systematic review:

Pittler MH, Ernst E. Artemether for severe malaria: A meta-analysis of randomised clinical trials. Chronic Infectious Disease 1999; 28: 597-601.



Date review completed: January 1998

Number of trials included: Nine

Number of patients: (915 artemether; 904 quinine)

Control groups: quinine.

Main outcomes: mortality rate.

Inclusion criteria were randomised, comparative trial which assessed artemether and quinine for the treatment of severe malaria.

Medline, Embase, Biosis, CICSOM and the Cochrane Library were searched (to January 1998) for published reports. The reviewers' own files were searched for relevant studies. Bibliographies of retrieved trials and reviews were checked for additional citations and no language restrictions were made. Manufacturers of artemether and experts were contacted for published and unpublished trials. Data were extracted in a standardised, predefined manner by the two reviewers. Methodological quality was rated using a validated 5-point scale. A meta-analysis was conducted; mortality rate and odds ratios (with 95% confidence intervals) were calculated using a random effects model.


Findings:

Nine studies were included; all used the WHO definition of severe malaria. One study was double blind, the others were open. Various doses of intravenous or intramuscular artemether or quinine were assessed (Table 1).

 

Table 1

Dose

Intramuscular

Intravenous

Loading dose 3.2, 4 or 160 mg/Kg 20 mg/Kg
Followed by either: 2 mg/Kg every eight hours until the patient could drink 10 mg/Kg every eight hours until parasitemia was cleared
  1.6 mg/Kg/day until parasitemia was cleared or for 3-4 days 10 mg/Kg every eight hours until arousal
  80 mg/day for six days 10 mg/Kg every eight hours for 3 or 7 days

 

The results of the individual studies are shown in Figure 1.

 

 

 

Data from all nine studies were pooled in a meta-analysis. The pooled mortality rate was 15% (95% C.I. 12 to 17; 134/915 patients) with artemether and 18% (15 to 20; 159/904 patients) with quinine.

For cerebral malaria, the mortality rate was 19% (15 to 23) with both treatments (83/437 patients with artemether and 81/432 patients with quinine); odds ratio 0.76 (0.5 to 1.1).

For mixed malaria, the mortality rate was 11% (8 to 13) with artemether (51/478 patients) and 17% (13 to 20; 78/472 patients) with quinine. There was no significant difference between artemether and quinine for any analysis.


Adverse effects

Hypoglycemia, abdominal pain and pain at the injection site were reported with artemether. The reviewer's stated that adverse effects occurred less frequently with artemether than with quinine and were milder.

 

Comment

The lack of blinding in these studies is unlikely to be important because bias should not influence mortality. Patients were randomised to treatment groups, so selection bias should be minimised. The limitation of the meta-analysis is that the results were based on relatively small numbers of patients. The mortality rates reported with artemether were comparable to those reported with quinine. This suggests that artemether may provide a useful alternative for treating severe malaria in areas where resistance to quinine is a problem.


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Identifier

AT127 - 5874 ARTEMETHER FOR SEVERE MALARIA: Sep-2000