Malaria falciparum , artesunate ja kiniini

Artesunate ja Kiniini vertailussa vaikean falciparum malarian hoidossa.


The Lancet, Volume 376, Issue 9753, Pages 1647 - 1657, 13 November 2010
doi:10.1016/S0140-6736(10)61924-1Cite or Link Using DOI
Published Online: 08 November 2010

Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial
Original Text
Arjen M Dondorp MD l, Caterina I Fanello PhD l et al.



Vaikea malaria on lasten päätappajia ja Sub-saharan alueella pääsyy lasten sairaalahoitoihin.

Severe malaria is a major cause of childhood death and often the main reason for paediatric hospital admission in sub-Saharan Africa.

KINIINI on ensisijainen lääke, mutta on lisääntyvää näyttöä ARTESUNATE- lääkkeen tehosta, johon liittyisi vähempää mortaliteettiakin.

Quinine is still the established treatment of choice, although evidence from Asia suggests that artesunate is associated with a lower mortality.

Tutkijaryhkmä vertaili näitä lääkkeitä afrikkalaisten lasten vaikean malarian hoitoaineina.

We compared parenteral treatment with either artesunate or quinine in African children with severe malaria.

• Yhdeksässä maassa, 11 keskuksessa tehtiin tutkimuksia.

Alle 15 vuotiaat falciparummalariaan sairastuneet sisällytettiin tutkjimukseen. Toisille annettiin parenteraalisesti artesunaattia ja toisille kiniiniä.

This open-label, randomised trial was undertaken in 11 centres in nine African countries. Children (<15> Randomisation was in blocks of 20, with study numbers corresponding to treatment allocations kept inside opaque sealed paper envelopes. The trial was open label at each site, and none of the investigators or trialists, apart from for the trial statistician, had access to the summaries of treatment allocations. The primary outcome measure was in-hospital mortality, analysed by intention to treat. This trial is registered, number ISRCTN50258054.

• 5424 lasta hoidettiin. Artesunate lääkettä sai 2712 ja kiniiniä 2713.

5425 children were enrolled; 2712 were assigned to artesunate and 2713 to quinine.

• 230 ( 8.5% artesunateryhmästä kuoli. 297(10.9 kiniiniryhmästä kuoli).

All patients were analysed for the primary outcome. 230 (8·5%) patients assigned to artesunate treatment died compared with 297 (10·9%) assigned to quinine treatment (odds ratio [OR] stratified for study site 0·75, 95% CI 0·63—0·90; relative reduction 22·5%, 95% CI 8·1—36·9; p=0·0022).

• Neurologisten jälkitautien insidenssi ei eronnut ryhmien kesken. mutta kooman kehittymisessä oli eroa( 3.5% ja 5.1%), kouristuksia (8.3 % ja 10.1%), kooma-asteikossa tapahtuvaa huononemista ( 6.1% ja 7.7%) . Siis artesunate- lääkkeella merkitsevästi vähemmän negatiivisia neurologisia oireita.

Incidence of neurological sequelae did not differ significantly between groups, but the development of coma (65/1832 [3·5%] with artesunate vs 91/1768 [5·1%] with quinine; OR 0·69 95% CI 0·49—0·95; p=0·0231), convulsions (224/2712 [8·3%] vs 273/2713 [10·1%]; OR 0·80, 0·66—0·97; p=0·0199), and deterioration of the coma score (166/2712 [6·1%] vs 208/2713 [7·7%]; OR 0·78, 0·64—0·97; p=0·0245) were all significantly less frequent in artesunate recipients than in quinine recipients.

• Hoidonjälkeinen hypoglykemia oli myöskin harvinaisempaa artesunate-ryhmässä ( 1.8 % ja 2.8%)

Post-treatment hypoglycaemia was also less frequent in patients assigned to artesunate than in those assigned to quinine (48/2712 [1·8%] vs 75/2713 [2·8%]; OR 0·63, 0·43—0·91; p=0·0134).

• Artesunate oli myöskin hyvin siedetty eikä sillä ollut vakavia lääkesivuvaikutuksia.

Artesunate was well tolerated, with no serious drug-related adverse effects.

• Tulosten tulkinta

Interpretation

Artesunate- lääkitys vähentää kuolleisuutta afrikkalaislasten vaikeassa malariassa. Artesunate ja kiniini vertailtuna osoittaa vahvasti, että parenteraalisella artesunaatilla voitaisiin korvata kiniini vaikean malarian ensimmäisenä lääkkeenä kautta maailman.

Artesunate substantially reduces mortality in African children with severe malaria. These data, together with a meta-analysis of all trials comparing artesunate and quinine, strongly suggest that parenteral artesunate should replace quinine as the treatment of choice for severe falciparum malaria worldwide.
Funding
The Wellcome Trust.

Artesunate- hakusana on Wikipediassa ja anti-malariaristiretki( Crusade) lähteestä saa enemmän tietoa ja otan siitä sitaatitn seuraavaan artikkeliin.

Tästä saa lisää hakusanoja:

Artesunate is an antimalarial agent. It is a water-soluble hemisuccinate derivative of dihydroartemisinin.
Artemisinin is a sesquiterpene lactone isolated from Artemisia annua, a herb that has traditionally been used in China for the treatment of malaria.
Artesunate and its active metabolite dihydroartemisinin are potent blood schizonticides, active against the ring stage of the parasite.
Artesunate is ideal for the treatment of severe malaria, including cerebral malaria.
It is also active against chloroquine and mefloquine resistant strains of P. falciparum.
The injectableIt is unstable in neutral solution and is therefore only available for injections as artesunic acid. formulation must be prepared immediately before use in 5% (w/v) sodium bicarbonate solution to produce the salt sodium artesunate.