Effects of artemisinin derivatives on malaria transmissibility.
BACKGROUND
On the western border of Thailand the efficacy of mefloquine in the treatment of falciparum malaria has declined while gametocyte carriage rates have increased, which suggests increased transmissibility of these resistant infections. We compared the following antimalarial drugs in relation to subsequent Plasmodium falciparum gametocyte carriage: mefloquine, halofantrine, quinine, and the artemisinin derivatives.


METHODS
Between 1990 and 1995 we assessed gametocytaemia in a series of prospective studies of antimalarial drug treatment in 5193 adults and children with acute uncomplicated falciparum malaria in an area of malarious hill forest on the western border of Thailand. Weekly parasite counts from thick and thin blood films were done during the 4-week (1990-93) or 9-week (1993-95) follow-up period. Gametocyte positivity rates and person gametocyte week (PGW) rates were calculated to measure gametocyte carriage and transmission potential.


RESULTS
In primary P falciparum infections the gametocyte carriage rate was significantly higher after treatment with mefloquine than after treatment with the artemisinin derivatives (PGW 34.1 [95% CI 25.2-42.9] vs 3.9 [1.9-5.9] per 1000 person weeks; relative risk 8.0 [4.1-15.6]; p<0.0001). Recrudescent infections were associated with increased gametocyte carrier rates (relative risk 2.2 [1.6-3.0]; p<0.0001), but retreatment with artemisinin derivatives reduced subsequent gametocyte carriage 18.5 fold [3.5-98] compared with mefloquine retreatment and 6.8 fold (3.1-15.1) compared with quinine retreatment (p<0.001). The introduction of the artemisinin derivatives in routine treatment at this study site in mid 1994 was associated with a reduction in the subsequent incidence of falciparum malaria of 47 (25-69)%


CONCLUSIONS
Although environmental changes affect vector numbers, and hence malaria incidence, artemisinin derivatives were found to reduce the transmission potential of falciparum malaria. Widespread introduction of artemisinin derivatives in the treatment of falciparum malaria may prevent the spread of multidrug resistance.
Price
R N
RN
Shoklo Malaria Research Unit, Tak Province, Thailand.
Nosten
F
F
Luxemburger
C
C
ter Kuile
F O
FO
Paiphun
L
L
Chongsuphajaisiddhi
T
T
White
N J
NJ
D000293:Adolescent; D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins; D002648:Child; D002675:Child, Preschool; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D005260:Female; D005718:Gametogenesis / Q000187:drug effects; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000517:prevention & control* / Q000635:transmission; D008297:Male; D010349:Patient Compliance; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D012717:Sesquiterpenes / Q000627:therapeutic use*; D013785:Thailand / Q000453:epidemiology
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C031327:artemisinin