Comparing drug interaction frequencies of various hepatitis C treatment regimens among monoinfected patients.

INTRODUCTION AND OBJECTIVES: Four regimens are recommended for treating hepatitis C (HCV) genotype 1 infection. Study aims were to (1) compare frequencies of contraindicated drug interactions (XDDIs) when each HCV regimen is added to medication profiles of HCV-monoinfected patients, (2) quantify the proportion of patients with XDDIs to all four regimens and (3) determine covariates independently associated with having a XDDI to all four regimens. MATERIALS AND METHODS: A cross-sectional study was performed within Upstate New York Veterans Healthcare Administration. INCLUSION CRITERIA: (1) age ≥18 years, (2) HCV monoinfection and (3) available medication list. Data extracted were: demographics, comorbidities, and medication list. Primary outcome was XDDIs involving patient's home medications and each HCV regimen. University of Liverpool drug interaction website was used to define XDDIs. Two-way comparisons of regimens were performed using McNemar's test where p<0.0083 was considered statistically significant. Multivariate regression analyses were performed to determine predictors. RESULTS: Of the 4047 subjects, mean±standard deviation age was 59.8±7.6. Median (interquartile range) number of medications used was 7 [4-11]. Frequencies of XDDIs after the addition of each regimen ranged from 2.8% to 17.8% and were mostly statistically different from one another. There were 95 (2.3%) patients with XDDIs to all four regimens. Predictors of having XDDIs to all four regimens were ≥6 medications and HCV infection ≥10 years. CONCLUSION: The frequencies of XDDIs varied between HCV regimens. Number of medications and duration of HCV infection were predictors of having XDDIs to all four regimens.

Comparative oesophageal cancer risk assessment of hot beverage consumption (coffee, mate and tea): the margin of exposure of PAH vs very hot temperatures.

BACKGROUND: Consumption of very hot (> 65 °C) beverages is probably associated with increased risk of oesophageal cancer. First associations were reported for yerba mate and it was initially believed that high content of polycyclic aromatic hydrocarbons (PAH) might explain the risk. Later research on other beverage groups such as tea and coffee, which are also consumed very hot, found associations with increased risk of oesophageal cancer as well. The risk may therefore not be inherent in any compound contained in mate, but due to temperature. The aim of this study was to quantitatively assess the risk of PAH in comparison with the risk of the temperature effect using the margin of exposure (MOE) methodology. METHODS: The human dietary benzo[a]pyrene (BaP) and PAH4 (sum of benzo[a]pyrene, benzo[a]anthracene, chrysene, and benzo[b]fluoranthene) exposure through consumption of coffee, mate, and tea was estimated. The oesophageal cancer risk assessment for both PAH and temperature was conducted using the MOE approach. RESULTS: Considering differences in the transfer of the PAH from the leaves of mate and tea or from the ground coffee to the infusion, and considering the different preparation methods, exposures may vary considerably. The average individual exposure in µg/kg bw/day arising from consumption of 1 cup (0.2 L) of infusion was highest for mate (2.85E-04 BaP and 7.22E-04 PAH4). The average per capita exposure in µg/kg bw/day was as follows: coffee (4.21E-04 BaP, 4.15E-03 PAH4), mate (4.26E-03 BaP, 2.45E-02 PAH4), and tea (8.03E-04 BaP, 4.98E-03 PAH4). For all individual and population-based exposure scenarios, the average MOE for BaP and PAH4 was > 100,000 independent of beverage type. MOE values in this magnitude are considered as a very low risk. On the contrary, the MOE for the temperature effect was estimated as < 1 for very hot drinking temperatures, corroborating epidemiological observations about a probable oesophageal cancer risk caused by this behaviour. CONCLUSIONS: The temperature effect but not PAH exposure may pose an oesophageal cancer risk. Consumer education on risks associated with consumption of 'very hot' beverages and policy measures to threshold serving temperatures should be discussed.

A dietary strategy for the management of artemether-lumefantrine-induced cardiovascular and renal toxicity.

BACKGROUND: Unsweetened natural cocoa has antimalarial properties. Unsweetened natural cocoa powder (UNCP), obtained as a result of the removal of cocoa butter from a cocoa bean protects against malaria episodes. Cocoa powder, which is prepared after removal of the cocoa butter, contains about 1.9 % theobromine and 0.21 % caffeine. Concomitant consumption of cocoa and artemether/lumefantrine (A/L) is a common practice in Ghana, West Africa. This study seeks to determine the elemental composition of UNCP and its protective effect on the heart and kidney against (A/L) administration. METHODS: Energy dispersive x-ray fluorescence spectroscopy was used to detect the quality and quantity of the elemental composition in UNCP. Thereafter, 30 nonmalarious male guinea pigs were divided into five groups of six animals each. One group was administered with 75 mg/kg body weight A/L only and another group distilled water (control group). The rest received 300 mg/kg, 900 mg/kg and 1500 mg/kg body weight UNCP for 14 days orally and A/L for the last 3 days (ie day 11 to day 14). Biochemical and histopathological examinations were carried out after euthanisation of the animals. RESULTS: A total of thirty-eight (38) micro and macro elements were detected with the ED-XRF. Macro elements like sodium (Na), magnesium (Mg), aluminium (Al), phosphorus (P), chlorine (Cl), potassium (K), calcium (Ca), manganese (Mn) and iron (Fe) and micro elements like chromium (Cr), copper (Cu), zinc (Zn), arsenic (As), and lead (Pb) were identified and evaluated. Biochemical analysis revealed increases in HDL levels (p>0.05) while there were decreases in LDL levels (p>0.05), creatine kinase and AST levels (P<0.05) in animals that received UNCP compared to A/L only administered group. Urea levels reduced significantly by 53 % (p<0.05) in group that received 1500 mg/kg UNCP. Histopathological examinations of the heart and kidney buttressed the protective effects of cocoa administration. CONCLUSION: The percentage of recommended daily allowance of UNCP for chromium is 3750 % for men and 5250 % for women while % RDA for copper corresponds to 103.6 % in both sexes. UNCP proved to possess cardioprotective and renoprotective potential during artemether-lumefantrine administration.

Seeking treatment for uncomplicated malaria: experiences from the Kintampo districts of Ghana.

BACKGROUND: Malaria accounts for many deaths and illnesses, mostly among young children and pregnant women in sub-Saharan Africa. An integrated approach is recommended to ensure effective malaria control. Socio-cultural factors continue to serve as determinants of malaria health-seeking behaviour. An INDEPTH effectiveness and safety study platform was established to unearth issues around the use of licensed and nationally recommended anti-malarials in real life settings. This study reports on treatment-seeking behaviour for uncomplicated malaria among community members. METHODS: A qualitative study was conducted in the dry and rainy seasons in purposively selected communities in Kintampo north and south districts. This was based on distances to a health facility, ethnicity and availability of medicines at the sale outlets. Twenty-four focus group discussions were conducted among adult men, women care-takers of children less than 5 years and pregnant women. Ten INDEPTH interviews were also conducted among operators of medicine sale outlets and managers of health facilities. Fifty-one illnesses narrative interviews were conducted among adult men, women, women caretakers of children less than 5 years and pregnant women. Transcripts were transferred into Nvivo 8 software for data management and analysis. RESULTS: The artemisinin-based combinations that were commonly known and used were artesunate-amodiaquine and artemether-lumefantrine. Use of herbal preparation to treat diseases including uncomplicated malaria is rife in the communities. Drug stores were not the main source of artemisinin-based combination sales at time of the study. Monotherapies, pain killers and other medicines were purchased from these shops for malaria treatment. Dizziness, general body weakness and sleepiness were noted among respondents who used artemisinin-based combination therapy (ACT) in the past. CONCLUSION: There is no clear cut trajectory for management of uncomplicated malaria in the study area. Different approaches are adopted when treating malaria. There is need for community education to influence behaviour on the management of malaria to achieve real gains from ACT use.

Quality and safety of integrated community case management of malaria using rapid diagnostic tests and pneumonia by community health workers.

OBJECTIVES: To assess the quality and safety of having community health workers (CHWs) in rural Zambia use rapid diagnostic tests (RDTs) and provide integrated management of malaria and pneumonia. DESIGN/METHODS: In the context of a cluster-randomized controlled trial of two models for community-based management of malaria and/or non-severe pneumonia in children under 5 years old, CHWs in the intervention arm were trained to use RDTs, follow a simple algorithm for classification and treat malaria with artemether-lumefantrine (AL) and pneumonia with amoxicillin. CHW records were reviewed to assess the ability of the CHWs to appropriately classify and treat malaria and pneumonia, and account for supplies. Patients were also followed up to assess treatment safety. RESULTS: During the 12-month study, the CHWs evaluated 1017 children with fever and/or fast/difficult breathing and performed 975 RDTs. Malaria and/or pneumonia were appropriately classified 94-100% of the time. Treatment based on disease classification was correct in 94-100% of episodes. Supply management was excellent with over 98% of RDTs, amoxicillin, and AL properly accounted for. The use of RDTs, amoxicillin, and AL was associated with few minor adverse events. Most febrile children (90%) with negative RDT results recovered after being treated with an antipyretic alone. CONCLUSIONS: Volunteer CHWs in rural Zambia are capable of providing integrated management of malaria and pneumonia to children safely and at high quality.

Efficacy and tolerability of four antimalarial combinations in the treatment of uncomplicated Plasmodium falciparum malaria in Senegal.

BACKGROUND: In view of the high level of chloroquine resistance in many countries, WHO has recommended the use of combination therapy with artemisinin derivatives in the treatment of uncomplicated malaria due to Plasmodium falciparum. Four antimalarial drug combinations, artesunate plus amodiaquine (Arsucam), artesunate plus mefloquine (Artequin), artemether plus lumefantrine (Coartem; four doses and six doses), and amodiaquine plus sulphadoxine-pyrimethamine, were studied in five health districts in Senegal. METHODS: This is a descriptive, analytical, open, randomized study to evaluate the efficacy and tolerability of these four antimalarial combinations in the treatment of uncomplicated falciparum malaria using the 2002 WHO protocol. RESULTS: All drug combinations demonstrated good efficacy. On day 28, all combinations resulted in an excellent clinical and parasitological response rate of 100% after correction for PCR results, except for the four-dose artemether-lumefantrine regimen (96.4%). Follow-up of approximately 10% of each treatment group on day 42 demonstrated an efficacy of 100%.The combinations were well tolerated clinically and biologically. No unexpected side-effect was observed and all side-effects disappeared at the end of treatment. No serious side-effect requiring premature termination of treatment was observed. CONCLUSION: The four combinations are effective and well-tolerated.

A randomized trial of artesunate-sulfamethoxypyrazine-pyrimethamine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Mali.

The choice of artemisinin-based combination that is being adopted for malaria treatment in sub-Saharan Africa may depend on several factors, including cost, efficacy, side effects, and simplicity of administration. We tested the hypothesis that artesunate-sulfamethoxypyrazine-pyrimethamine is as efficacious as the four-dose regimen of artemether-lumefantrine for treatment of Plasmodium falciparum malaria. The study was carried out during two transmission seasons (2003 and 2004) in Sotuba, Mali. Participants at least 6 months of age with uncomplicated P. falciparum malaria were randomly assigned to receive artesunate-sulfamethoxypyrazine-pyrimethamine or artemether-lumefantrine. Treatment efficacy was assessed using the World Health Organization 28-day protocol. A total of 606 (303 in each arm) patients were enrolled. The cure rate was higher for artesunate-sulfamethoxypyrazine-pyrimethamine than for artemether-lumefantrine (98.7% versus 89.6%; P < 0.0001). After correction for cases of re-infection, the cure rates were 100% and 99.0%, respectively (P = 0.08). No serious adverse events occurred. Artesunate-sulfamethoxypyrazine-pyrimethamine is well-tolerated and effective against P. falciparum malaria. It showed an additional benefit of preventing new infections.

Efficacy and safety of the six-dose regimen of artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in adolescents and adults: a pooled analysis of individual patient data from randomized clinical trials.

To demonstrate the superiority of the six-dose over the four-dose regimen of artemether-lumefantrine (co-artemether, Coartem) in patients >12 years, data from 11 randomized clinical trials were pooled and analyzed. A total of 1368 patients with uncomplicated Plasmodium falciparum malaria (six-dose: 598; four-dose: 770) were included in the analysis, together with 717 patients treated with comparators. Analysis of the 28-day cure rate based on the ITT and evaluable populations yielded corrected cure rates for the six-dose regimen of 87% and 97% compared with 74% and 87%, respectively, with the four-dose regimen (P<0.0001, for both comparisons). For mefloquine/artesunate, the most frequently used comparator, cure rates were 87% and 99%, respectively. The six-dose regimen was well tolerated and not markedly different to the four-dose regimen. The main finding of our analysis is that the six-dose regimen of co-artemether is more effective than the four-dose regimen in adolescents and adults without compromising safety.

Artemether-lumefantrine (four-dose regimen) for treating uncomplicated falciparum malaria.

BACKGROUND: The World Health Organization recommends artemether-lumefantrine, an expensive drug, as a treatment for uncomplicated malaria. We sought evidence of the superiority of the four-dose regimen over existing treatments. OBJECTIVES: To evaluate the four-dose regimen of artemether-lumefantrine for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (October 2005), CENTRAL (The Cochrane Library 2005, Issue 3), MEDLINE (1966 to October 2005), EMBASE (1988 to October 2005), LILACS (1982 to October 2005), conference proceedings, and reference lists of articles. We also contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA: Randomized controlled trials comparing four doses of artemether-lumefantrine with standard treatment regimens (single drug or combination), or six doses of artemether-lumefantrine, for treating uncomplicated falciparum malaria. DATA COLLECTION AND ANALYSIS: Two authors independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data, including adverse events. Total failure by day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. MAIN RESULTS: Seven trials (2057 participants) tested a four-dose regimen. More people tended to fail treatment with artemether-lumefantrine than with other drugs, including sulfadoxine-pyrimethamine (247 participants, 1 trial), halofantrine (86 participants, 1 trial), and mefloquine (233 participants, 1 trial; difference statistically significant for mefloquine). When compared with chloroquine, artemether-lumefantrine was better in two trials (378 participants), but over 50% of the participants treated with chloroquine had total failure by day 28. Fewer people failed treatment with the six-dose regimen compared to the four-dose regimen (RR 7.71, 95% CI 2.99 to 19.88; 306 participants, 1 trial). AUTHORS' CONCLUSIONS: The four-dose regimen of artemether-lumefantrine seems to be less effective than regimens against which it has been tested. The six-dose regimen is superior to four-dose regimen.

The efficacies of artesunate-sulfadoxine-pyrimethamine and artemether-lumefantrine in the treatment of uncomplicated, Plasmodium falciparum malaria, in an area of low transmission in central Sudan.

In an efficacy trial of artemisinin-based combination treatments (ACT) in central Sudan, cases of uncomplicated, Plasmodium falciparum malaria were given artesunate-sulfadoxine-pyrimethamine (ASP) or artemether-lumefantrine (AL) as first-line treatment. On enrolment, the 71 patients given ASP were similar to the 72 given AL, apart from having generally lower parasitaemias (geometric mean counts of 4893 nu. 10,215 asexual parasites/microl) and having a lower mean age (15 nu. 23 years). Each patient was treated on days 0, 1 and 2, and all 137 who completed follow-up without further, unscheduled treatment were found aparasitaemic and afebrile from day 2 until the last follow-up, on day 28. No moderate or severe adverse side-effects, clinical failures or parasitological failures were observed among these 137 patients. ACT therefore appear both efficacious and safe for the treatment of uncomplicated malaria in central Sudan.

A randomized trial of artemether-lumefantrine versus mefloquine-artesunate for the treatment of uncomplicated multi-drug resistant Plasmodium falciparum on the western border of Thailand.

BACKGROUND: The use of antimalarial drug combinations with artemisinin derivatives is recommended to overcome drug resistance in Plasmodium falciparum. The fixed combination of oral artemether-lumefantrine, an artemisinin combination therapy (ACT) is highly effective and well tolerated. It is the only registered fixed combination containing an artemisinin. The trial presented here was conducted to monitor the efficacy of the six-dose regimen of artemether-lumefantrine (ALN) in an area of multi-drug resistance, along the Thai-Myanmar border. METHODS: The trial was an open-label, two-arm, randomized study comparing artemether-lumefantrine and mefloquine-artesunate for the treatment of uncomplicated falciparum malaria with 42 days of follow up. Parasite genotyping by polymerase chain reaction (PCR) was used to distinguish recrudescent from newly acquired P. falciparum infections. The PCR adjusted cure rates were evaluated by survival analysis. RESULTS: In 2001-2002 a total of 490 patients with slide confirmed uncomplicated P. falciparum malaria were randomly assigned to receive artemether-lumefantrine (n = 245) or artesunate and mefloquine (n = 245) and were followed for 42 days. All patients had rapid initial clinical and parasitological responses. In both groups, the PCR adjusted cure rates by day 42 were high: 98.8% (95% CI 96.4, 99.6%) for artemether-lumefantrine and 96.3% (95% CI 93.1, 98.0%) for artesunate-mefloquine. Both regimens were very well tolerated with no serious adverse events observed attributable to either combination. CONCLUSION: Overall, this study confirms that these two artemisinin-based combinations remain highly effective and result in equivalent therapeutic responses in the treatment of highly drug-resistant falciparum malaria.

Supervised versus unsupervised intake of six-dose artemether-lumefantrine for treatment of acute, uncomplicated Plasmodium falciparum malaria in Mbarara, Uganda: a randomised trial.

BACKGROUND: The six-dose regimen of artemether-lumefantrine is effective and is among combination therapies prioritised to replace antimalarials that no longer work in Africa. However, its effectiveness has not been assessed in the field, and could be compromised by poor adherence, incorrect timing of doses, and insufficient intake of fatty foods with every dose. Our aim, therefore, was to assess the effectiveness of artemether-lumefantrine prescribed under routine outpatient conditions, compared with its efficacy when given under supervision to inpatients with acute uncomplicated falciparum malaria. METHODS: We did a randomised trial to compare the efficacy, safety, and pharmacokinetics of artemether-lumefantrine when given in a supervised (all doses observed with fatty-food intake; n=313) or unsupervised (first dose supervised followed by outpatient treatment with nutritional advice; n=644) setting to patients of all ages (weight >10 kg) with acute, uncomplicated falciparum malaria in Mbarara, Uganda. Our primary endpoint was 28 day, PCR-adjusted, parasitological cure rate. Analysis was by intention to treat and evaluability analysis. FINDINGS: 38 patients were lost to follow-up and one withdrew consent. Day-28 cure rates were 97.7% (296 of 303) and 98.0% (603 of 615) in the supervised and unsupervised groups, respectively. We recorded 15 non-severe, drug-related adverse events, all of which resolved. INTERPRETATION: Artemether-lumefantrine has a high cure rate irrespective of whether given under supervision with food or under conditions of routine clinic practice. If used as first-line treatment, artemether-lumefantrine could make a substantial contribution to malaria control in Africa, though cost is an issue.

Therapeutic efficacy of artemether-lumefantrine and artesunate-mefloquine for treatment of uncomplicated Plasmodium falciparum malaria in Luang Namtha Province, Lao People's Democratic Republic.

The efficacy of the six-dose regimen of artemether-lumefantrine was compared with the combination of artesunate and mefloquine in a randomised, comparative trial in Luang Namtha Province, Northern Laos. Of 1033 screened patients, 201 were positive for Plasmodium falciparum; 108 patients of all age groups (2-66 years) with acute, uncomplicated P. falciparum malaria were enrolled in the study, 100 of whom were followed-up for 42 days. Fifty-three patients received artemether-lumefantrine and 55 received artesunante-mefloquine. Both drug combinations induced rapid clearance of parasites and malaria symptoms; there was no significant difference in the initial therapeutic response parameters. Both regimes were well tolerated. After 42 days, cure rates were 93.6% (95% CI = 82.5-98.7%; 44 of 47 patients) for artemether-lumefantrine and 100% (95% CI = 93.3-100.0%; 53 of 53 patients) for artesunate-mefloquine. The results show the excellent efficacy and tolerability of both artemether-lumefantrine and artesunate-mefloquine in Northern Laos.

[Efficacy of therapeutic combinations with artemisinin derivatives in the treatment of non complicated malaria in Burundi]. / Efficacité de combinaisons thérapeutiques avec des dérivés de l'artémisinine dans le traitement de l'accès palustre non-complique au Burundi.

Faced with the problem of resistance to chloroquine and sulfadoxine-pyrimethamine, the Ministry of Public Health of Burundi decided to study the efficacy of two artemisinin-based combinations, the fixed combination of artemether-lumefantrine and the combination of amodiaquine + artesunate. The efficacy of these combinations for the treatment of uncomplicated falciparum malaria was studied in two sites representative of the country, in Kigobe neighbourhood of Bujumbura, the capital city, and in Buhiga, a rural area. The study followed the standardized WHO protocol from October 2001 to November 2002. A total of 295 children under 5 years were included; 153 children were treated with artesunate and amodiaquine (77 at Buhiga and 76 at Kigobe), and 142 children with the combination of artemether-lumefantrine (64 at Buhiga and 78 at Kigobe). Among the 295 children, 290 were followed up to 14 days. In the group of 149 children treated with artesunate and amodiaquine, 142 (95.3%, 95% CI: 91.9-98.7%) presented with adequate clinical and parasitological response, five (3.3%) with late parasitological failure, one (0.7%) with late clinical failure and one (0.7%) with early treatment failure. Among the 141 children treated with artemether-lumefantrine, 140 (99.3%, 95% CI: 97.9-100%) presented with adequate clinical and parasitological response and one (0.7%) with late parasitological failure at Buhiga. Side-effects were comparable in both groups except for the vomiting. Vomiting was more frequent in the artesunate + amodiaquine on D1 and D2. Both treatments decreased the gametocyte carriage but without getting full clearance in all the patients. During a consensus workshop, the Ministry of Public Health agreed on the combination of artesunate and amodiaquine as the first line drug for the treatment of uncomplicated falciparum malaria in Burundi including epidemic outbreak.

Audiometric changes associated with the treatment of uncomplicated falciparum malaria with co-artemether.

Animal studies have demonstrated artemisinin brain stem toxicity with auditory centres being especially affected; there has, to date, been no evidence of such toxicity with oral artemisinins in humans. Subjects working at a construction site in Mozambique had audiometric assessments taken on joining and leaving the project. Subjects with uncomplicated malarias received co-artemether (artemether-lumefantrine) (n = 150) while age-, gender-, weight- and race-matched controls (n = 150) neither suffered malaria nor received antimalarial therapy. Hearing thresholds were measured at predefined frequencies in treated subjects and controls. Subjects receiving co-artemether had a significantly greater heating loss than controls at all frequencies except 250 Hz and 500 Hz (P values ranging from <0.001 to 0.04, Mann-Whitney U). Mean changes at the different frequencies in subjects ranged from -6.50 dB (95% CI -8.19 to -4.81) [at 1kHz frequency] to -0.07 dB (95% CI -2.19 to 2.05) [at 6 kHz frequency]. Mean changes in the control group ranged from -4.20 dB (95% CI -5.97 to -2.43) [at 1 kHz frequency] to +2.7 dB (95% CI -0.93 to 4.47) [at 6 kHz frequency]. Treatment of uncomplicated malaria with co-artemether is associated with hearing loss, possibly from synergy between potentially ototoxic agents in combination. The safety and neurotoxicity of artemesinins and other endoperoxides needs to be more fully evaluated.

A randomized, double-blind, parallel-group, comparative safety, and efficacy trial of oral co-artemether versus oral chloroquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in India.

In India, treatment of acute, uncomplicated Plasmodium falciparum malaria is becoming increasingly difficult due to resistance to chloroquine, thus there is a need for new antimalarial drugs. CGP 56697 (co-artemether), a new drug, is a combination of artemether and lumefantrine in a single oral formulation (one tablet = 20 mg of artemether plus 120 mg of lumefantrine). In a double-blind study, 179 patients with acute uncomplicated P. falciparum malaria were randomly assigned to receive either CGP (n = 89) given as a short course of 4 x 4 tablets over a 48-hr period or chloroquine (n = 90) given as four tablets (one tablet = 150 mg of chloroquine base) initially, followed by two tablets each at 6-8, 24, and 48 hr. Due to a death in the chloroquine group and a decrease in the chloroquine cure rate to < 50% (based on the blinded overall cure rate at that time), recruitment was terminated prematurely. CGP 56697 showed a superior 28-day cure rate (95.4% versus 19.7%; P < 0.001), time to parasite clearance (median = 36 versus 60 hr; P < 0.001), and resolution of fever (median = 18 versus 27 hr; P = 0.0456). This drug provides a safe, effective, and rapid therapy for the treatment of acute uncomplicated P. falciparum malaria.