AMI -RAVREDA – USAID Project report, Colombia March 2009 Preliminary results on efficacy and Safety of Coartem ® on the treatment of Acute Uncomplicated Plasmodium falciparum Malaria Infections conducted at Malaria Clinic Georgetown, hospital Region 4 Guyana

This study was conducted in Subjects > 10 Kg of a body-weight with parasitological-confirmed, acute uncomplicated P. falciparum infections was assigned treatment with Coartem® (6-dose regimen, according to WHO recommendation. Clinical and parasitological` parameters was monitored over a 28-day follow-up period to evaluate the anti-malaria drug efficacy and safety

OBJECTIVES: (1) Assess the efficacy and safety of Co-artem® therapy for the treatment of acute uncomplicated P. falciparum infections in Georgetown Region 4; Guyana (2)Evaluate the impact of Co-artem® therapy on gametocytaemia

Study Team: Physician as a monitor, A Medex to obtain clinical histories and carry out examinations; Senior Field Workers to administer the study medications and provide patient instructions; 2 Laboratory Technicians (Malaria Microscopists) to take and examine the blood smears And a Computer Data Entry Personnel were participants as a study team. While all of the personnel will have prior experience with the protocol, at least one of them will serve as Study Site Supervisor. The entire study was constantly and closely monitored by the Investigators

During the period of the trial ( ) Total amount of 8477 smear taken – 1343 (15.84 %) P. falciparum, – 1369 (16.14 %), P. vivax – 62 Malariae (0.73 %), – 245 mix- infections (2.89 %) – and 5458 negatives (64.38%). A total of 695 patients were screened 90 patients were enrolled; 606 were not enrolled

Main reasons for non enrolment of patients into the Trial. Guyana

Main characteristics of the patients participating in the trial % between years old, Occupation 56 % miner and 14 % other activity; Gender :male 85.5 % and 15.5 % female, Ethnic group, 37 % Afro-Guyanese, 33 % Mixed, Region visited before the diagnosis 57 % from region 7, 13 % from region 10, 15 % from region 8.

Place of residence and Region visited before the diagnosis Region 7 Region 10 Region Visited RegionFrequencyPercent 144,40% ,40% 75763,30% 81516,70% 911,10% Total90100,00% Region 8 Region 1 Region 9 95 % Residence in R 4

Clinical presentation at initial diagnosis In vivo Study Guyana Initial Diagnosis(Thick)Frequency% ,20 % ,20 % ,20 % <- +/23 3,30 % Total90 100,0 0%

Bodypain BodypainFrequencyPercent No2123,33 Day 06774,44 Days 0-111,11 Days 111,11 Total90100 Fever FrequencyPercent No7381,10% Yes1718,90% Total90100,00% FdaysFrequencyPercent No7382,20% Day-01516,70% Days 0-121,10% Total90100,00% Frequency of Symptoms reported by the patients recruited, In vivo study,

Headache Headache DaysFrequencyPercent No2022,20% Day-06673,30% Days 0-133,30% Days -111,10% Total90100,00% Diarrea DaysFrequencyPercent No8493,30% Day-066,70% Total90100,00%

SUMMARY OF CLASSIFICATION #rPrevalence ETF LCF LPF ACPR Total analysis63 Withdrawal13 LOSS140.3 TOTAL90 (ETF): Early Therapeutic Failure (LCF ) Late Clinic Failure (LPF Late Parasitological Failure) ACPR) Adequate Clinical Response

DayNumber of patients FailuresLoss + Wth Success cumulative incidence Failure cumulative incidence Total52795 % CI Kaplan Meyer Analysis

Conclusions 2004 evaluation Coartem ® induced rapid clearance of parasites with 88.9% on day 2 and 100% on day 3. The 28-day cure rate was 100% (Adequate Clinical and Parasitological Response). The high dose regimen of arthemeter – lumefantrine was very well tolerated, with good compliance (1 patient loss to follow up). Further, 81.2% of malaria symptoms were present in the first 24 hours and 95.8% within the first 72 hours of treatment. Headache (12%), joint pain (20.8%), dizziness (18.7%) was the most frequent adverse effects occurring within the first 72 hours of treatment. Chills, vomiting and diarrhea show a very low frequency. The presence of gametocytes in peripheral blood were noted in 24 patients (33.8%) at time of enrollment, 24 (33.8%) on day 2; 20 (28.2%) on day 3; 18 (25.3%) on day 7; 12 (16.9%) on day 14; 8 (11.3%) on day 21 and 1 (1.4%) on day 28. [1] [1] First Coartem Invivo Analysis Study results.

Parasite Density Day# Patients%