Therapy of uncomplicated falciparum malaria in Europe: MALTHER - a prospective observational multicentre study.
BACKGROUND
Malaria continues to be amongst the most frequent infectious diseases imported to Europe. Whilst European treatment guidelines are based on data from studies carried out in endemic areas, there is a paucity of original prospective treatment data. The objective was to summarize data on treatments to harmonize and optimize treatment for uncomplicated malaria in Europe.


METHODS
A prospective observational multicentre study was conducted, assessing tolerance and efficacy of treatment regimens for imported uncomplicated falciparum malaria in adults amongst European centres of tropical and travel medicine.


RESULTS
Between December 2003 and 2009, 504 patients were included in 16 centres from five European countries. Eighteen treatment regimens were reported, the top three being atovaquone-proguanil, mefloquine, and artemether-lumefantrine. Treatments significantly differed with respect to the occurrence of treatment changes (p = 0.005) and adverse events (p = 0.001), parasite and fever clearance times (p < 0.001), and hospitalization rates (p = 0.0066) and durations (p = 0.001). Four recrudescences and two progressions to severe disease were observed. Compared to other regimens, quinine alone was associated with more frequent switches to second line treatment, more adverse events and longer inpatient stays. Parasite and fever clearance times were shortest with artemether-mefloquine combination treatment. Vomiting was the most frequent cause of treatment change, occurring in 5.5% of all patients but 9% of the atovaquone-proguanil group.


CONCLUSIONS
This study highlights the heterogeneity of standards of care within Europe. A consensus discussion at European level is desirable to foster a standardized management of imported falciparum malaria.
Infectious and Tropical Diseases Department, Hôpital Avicenne-APHP and Université Paris 13, Bobigny, France.
Olivier
O
Bouchaud
Nikolai
N
Mühlberger
Philippe
P
Parola
Guido
G
Calleri
Alberto
A
Matteelli
Gabriele
G
Peyerl-Hoffmann
Frédéric
F
Méchaï
Philippe
P
Gautret
Jan
J
Clerinx
Peter G
PG
Kremsner
Tomas
T
Jelinek
Annette
A
Kaiser
Anna
A
Beltrame
Matthias L
ML
Schmid
Peter
P
Kern
Meike
M
Probst
Alessandro
A
Bartoloni
Thomas
T
Weinke
Martin P
MP
Grobusch
D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use; D053626:Atovaquone / Q000627:therapeutic use; D004338:Drug Combinations; D004358:Drug Therapy / Q000379:methods / Q000592:standards; D004983:Ethanolamines / Q000627:therapeutic use; D005060:Europe; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D015767:Mefloquine / Q000627:therapeutic use; D008875:Middle Aged; D002727:Proguanil / Q000627:therapeutic use; D011446:Prospective Studies; D055815:Young Adult
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; C109496:atovaquone, proguanil drug combination; D002727:Proguanil; D015767:Mefloquine; D053626:Atovaquone