Effects of artesunate-mefloquine combination on incidence of Plasmodium falciparum malaria and mefloquine resistance in western Thailand: a prospective study

• Published in: The Lancet (British edition) Vol. 356; no. 9226; pp. 297 - 302
• Main Authors: Nosten, F, van Vugt, M, Price, R, Luxemburger, C, Thway, KL, Brockman, A, McGready, R, ter Kuile, F, Looareesuwan, S, White, NJ
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 22-07-2000; Lancet; Elsevier Limited
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - administration & dosage; Antimalarials - therapeutic use; Antiparasitic agents; Artemisinins; Artesunate; Biological and medical sciences; Cohort Studies; Disease transmission; Drug resistance; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Health care; Health risks; Human protozoal diseases; Humans; Incidence; Infectious diseases; Malaria; Malaria, Falciparum - drug therapy; Malaria, Falciparum - epidemiology; Male; Medical sciences; Mefloquine - administration & dosage; Mefloquine - therapeutic use; Minority & ethnic groups; Parasitic diseases; Pharmacology. Drug treatments; Plasmodium falciparum - drug effects; Population; Pregnancy; Pregnancy Complications, Parasitic - drug therapy; Pregnancy Complications, Parasitic - epidemiology; Prospective Studies; Protozoal diseases; Random Allocation; Sesquiterpenes - administration & dosage; Sesquiterpenes - therapeutic use; Thailand - epidemiology; Vector-borne diseases; Thailand; Asia; Human; Protozoa; Antimalarial; Apicomplexa; Protozoal disease; Mefloquine; Malaria; Parasitosis; Epidemiology; Incidence; Infection; Prospective; Plasmodium falciparum; Artesunate; Negative therapeutic reaction; Drugs; Public Health; Prospective Studies; Cultural Background; Health; Malaria > prevention and control; Research Methodology; Thailand; Diseases; Studies; Ethnic Groups; Treatment; Asia; Southeastern Asia; Population Characteristics; Population; Research Report; Developing Countries; Parasitic Diseases; Demographic Factors; Parasite Control
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(00)02505-8

Worsening drug resistance in Plasmodium falciparum malaria is a major threat to health in tropical countries. We did a prospective study of malaria incidence and treatment in an area of highly multidrug-resistant P falciparum malaria.
We assessed incidence of P falciparum malaria and the in-vivo responses to mefloquine treatment over 13 years in two large camps for displaced Karen people on the northwest border of Thailand. During this time, the standard mefloquine dose was first increased, and then combined artesunate and mefloquine was introduced as first-line treatment for uncomplicated P falciparum malaria.
Early detection and treatment controlled P falciparum malaria initially while mefloquine was effective (cure rate with mefloquine [15 mg/kg] and sulphadoxine-pyrimethamine in 1985, 98% [95% CI 97–100]), but as mefloquine resistance developed, the cure rate fell (71% [67–77] in 1990). A similar pattern was seen for high-dose (25 mg/kg) mefloquine monotherapy from 1990–94. Since the general deployment of the artesunate-mefloquine combination in 1994, the cure rate increased again to almost 100% from 1998 onwards, and there has been a sustained decline in the incidence of P falciparum malaria in the study area. In-vitro susceptibility of P falciparum to mefloquine has improved significantly (p=0·003).
In this area of low malaria transmission, early diagnosis and treatment with combined artesunate and mefloquine has reduced the incidence of P falciparum malaria and halted the progression of mefloquine resistance. We recommend that antimalarial drugs should be combined with artemisinin or a derivative to protect them against resistance.