Search

Background: Recent efforts in malaria control have resulted in great gains in reducing the burden of Plasmodium falciparum, but P. vivax has been more refractory. Its ability to form dormant liver stages confounds control and elimination efforts. To compare the efficacy and safety of primaquine regimens for radical cure, we undertook a randomized controlled trial in Ethiopia.Methods and Findings: Patients with normal glucose-6-phosphate dehydrogenase status with symptomatic P. vivax mono-infection were enrolled and randomly assigned to receive either chloroquine (CQ) or artemether-lumefantrine (AL), alone or in combination with 14 d of semi-supervised primaquine (PQ) (3.5 mg/kg total). A total of 398 patients (n = 104 in the CQ arm, n = 100 in the AL arm, n = 102 in the CQ+PQ arm, and n = 92 in the AL+PQ arm) were followed for 1 y, and recurrent episodes were treated with the same treatment allocated at enrolment. The primary endpoints were the risk of P. vivax recurrence at day 28 and at day 42. The risk of recurrent P. vivax infection at day 28 was 4.0% (95% CI 1.5%-10.4%) after CQ treatment and 0% (95% CI 0%-4.0%) after CQ+PQ. The corresponding risks were 12.0% (95% CI 6.8%-20.6%) following AL alone and 2.3% (95% CI 0.6%-9.0%) following AL+PQ. On day 42, the risk was 18.7% (95% CI 12.2%-28.0%) after CQ, 1.2% (95% CI 0.2%-8.0%) after CQ+PQ, 29.9% (95% CI 21.6%-40.5%) after AL, and 5.9% (95% CI 2.4%-13.5%) after AL+PQ (overall p < 0.001). In those not prescribed PQ, the risk of recurrence by day 42 appeared greater following AL treatment than CQ treatment (HR = 1.8 [95% CI 1.0-3.2]; p = 0.059). At the end of follow-up, the incidence rate of P. vivax was 2.2 episodes/person-year for patients treated with CQ compared to 0.4 for patients treated with CQ+PQ (rate ratio: 5.1 [95% CI 2.9-9.1]; p < 0.001) and 2.3 episodes/person-year for AL compared to 0.5 for AL+PQ (rate ratio: 6.4 [95% CI 3.6-11.3]; p < 0.001). There was no difference in the occurrence of adverse events between treatment arms. The main limitations of the study were the early termination of the trial and the omission of haemoglobin measurement after day 42, resulting in an inability to estimate the cumulative risk of anaemia.Conclusions: Despite evidence of CQ-resistant P. vivax, the risk of recurrence in this study was greater following treatment with AL unless it was combined with a supervised course of PQ. PQ combined with either CQ or AL was well tolerated and reduced recurrence of vivax malaria by 5-fold at 1 y.Trial Registration: ClinicalTrials.gov NCT01680406. [ABSTRACT FROM AUTHOR]

Malaria, particularly due to Plasmodium falciparum, remains a major public health threat in Ethiopia. Artemether-lumefantine (AL) has been the first-line antimalarial drug against uncomplicated P. falciparum malaria in the country since 2004. Regular monitoring of antimalarial drugs is recommended by the World Health Organization (WHO) to help early detection of drug resistant strains of the parasite and contain their rapid spread. The objective of this study was to assess the therapeutic efficacy of AL in a high-transmission setting in Ethiopia. The study site was Setit Humera, northwest Ethiopia. Single-arm prospective study of a 28-day follow-up was conducted from October 2014 to January 2015 according to the revised WHO 2009 drug efficacy study protocol. Study end-points were classified into primary end-point and secondary end-point. While the primary end-point was the day-28 adequate clinical and parasitological response the secondary end-points were clinical and parasitological evaluations (parasite, fever and gametocyte clearance rate, incidence of drug adverse events) and the relative increment in hemoglobin (Hb) level from baseline to day (D) 14 and D28. A total of 92 patients were enrolled and 79 had completed the 28-day follow-up period. The overall cure rate was 98.8% with 95% confidence interval of 0.915–0.998 without polymerase chain reaction correction. The parasite clearance rate was high with fast resolution of clinical symptoms; 100% of the study participants cleared parasitaemia and fever on D3. Gametocyte carriage was reduced from 7% on D0 to 1% on D3 and complete clearance was achieved on D14. Mean Hb concentration significantly increased on D28 compared to that on D14. There was no serious adverse event. AL was efficacious and safe in a high-transmission setting for treatment of uncomplicated falciparum malaria. [ABSTRACT FROM AUTHOR]

Background: Artemether-lumefantrine (AL) has been used as a first-line treatment for uncomplicated Plasmodium falciparum malaria in Ethiopia since 2004. Antimalarial drug resistance is one of the major obstacles for malaria control and curtails the lifespan of several drugs. Thus, continued monitoring of the efficacy of AL is of great public health importance in malaria endemic areas. Objective: This study aimed to investigate the therapeutic efficacy and safety of AL for the treatment of uncomplicated P. falciparum malaria in the Dembia district, northwest Ethiopia. Methods: A prospective study was conducted from April 2015 to February 2016 at Kola Diba Health Center (KHC) in the Dembia district to determine the therapeutic efficacy and safety of AL for the treatment of uncomplicated P. falciparum monoinfection. Patients were treated with the six-dose regimen of AL over 3 days and followed up for 28 days as per the World Health Organization protocol. Results: Of the total 80 patients enrolled in the AL efficacy study, 75 patients completed the 28 days follow-up. None of the participants reported major adverse events. No early treatment failure or late clinical failure were observed during the study, but there were 6 (8.0%) late parasitological failures. The uncorrected per protocol cure rate of AL was 92.0 (95% CI: 85.7-98.3). Treatment with AL cleared parasitemia and fever in .95% of the patients by day 3. Conclusion: This study showed that AL is well tolerated and remains efficacious for treatment of uncomplicated P. falciparum malaria in northwest Ethiopia. However, the observed late parasitological failures in this study are of a concern and warrant continued monitoring of drug efficacy as per the World Health Organization recommendations. [ABSTRACT FROM AUTHOR]

Background: Resistance to anti-malarials is a major challenge for effective malaria control in sub-Saharan Africa. This triggered a need for routine monitoring of the efficacy of the antimalarial drugs every two years in all malaria endemic countries. Chloroquine remained the drug of choice for the treatment of vivax malaria in Ethiopia. Though, a strong scientific evidence of chloroquine resistance to P.vivax that could have brought change of treatment regimen is yet to be established in Ethiopia, continuous and regular monitoring of drug’s efficacy is critical for establishing rational anti-malarial drug policies. This study therefore, assessed the therapeutic efficacy of Chloroquine (CQ) for the treatment of Plasmodium vivax infections in Northwestern Ethiopia. Methods: An observational, 28- day therapeutic clinical efficacy study was conducted from August to December, 2014, in Northwest Ethiopia. Patients confirmed to have monoinfection of vivax malaria, aged above 6 months were included. All subjects were treated with standard chloroquine dose of 25 mg/kg for three (3) days. Parasitological and clinical outcomes of treated patients were then evaluated on days 1, 2, 3, 7, 14, 21, and 28 during the entire 28-day follow-up period. A portable spectrophotometer (HemoCue Hb 301 System, Sweden) was used to estimate hemoglobin concentration. Results: A total of 69 subjects had completed follow up. Some 57/69 (82.6%) had fever at enrolment and the rest 12 patients 48 hours before enrollment. Out of total, 65/69 (94.2%) and 66/69 (95.6%) of the study subjects were free of fever by day 1 and day 2 respectively but fever was cleared in all subjects by day 3. At base line the mean asexual parasitemia was 3540 parasites/μL of blood. Parasite carriage on day 3 was 3%. The overall cure rate (an adequate and clinical parasitological response) was very high (97%) [(95% CI = 93.1–99.4)]. The time to parasite, fever and gametocyte clearance as expressed in mean (SD) was 35 (3), 25 (4.6), 28 (3.2) hours respectively. Mean hemoglobin was significantly increased (P<0.001) from 12.2 (7–15) g/dl at day 0 to 13.3 (10–16) g/dl on day 28. Conclusions: In view of our findings, CQ remains efficacious for the treatment of vivax malaria in the study area. However, there is a need to monitor CQR regularly using molecular and or biochemical tools for better evaluation of treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: As per the WHO recommendation, the development of resistance by P. falciparum to most artemisinin combination therapies (ACTs) triggered the need for routine monitoring of the efficacy of the drugs every two years in all malaria endemic countries. Hence, this study was carried out to assess the therapeutic efficacy of Artemether-Lumefantrine (Coartem®) in treating the uncomplicated falciparum malaria, after 9 years of its introduction in the Metehara, Eastern Ethiopia. Method: This is part of the therapeutic efficacy studies by the Federal Ministry of Health Ethiopia, which were conducted in regionally representative sentinel sites in the country from October 2014 to January 2015. Based on the study criteria set by WHO, febrile and malaria suspected outpatients in the health center were consecutively recruited to study. A standard six-dose regimen of AL was administered over three days and followed up for measuring therapeutic responses over 28 days. Data entry and analysis was done by using the WHO designed Excel spreadsheet and SPSS version 20 for Windows. Statistical significant was considered for P-value less than 0.05. Result: Of the 91 patients enrolled, the day-28 analysis showed 83 adequate clinical and parasitological responses (ACPRs). Per protocol analysis, PCR-uncorrected & corrected cure rates of Coartem® among the study participants were 97.6% (95%CI: 93.6–99.5) and 98.8% (CI: 93.5–100%), respectively. No parasite detected on day 3 and onwards. Fever clearance was above 91% on day-3. Mean hemoglobin was significantly increased (P<0.000) from 12.39 g/dl at day 0 to 13.45 g/dl on day 28. No serious adverse drug reactions were observed among the study participants. Conclusion: This study showed high efficacy of AL in the study area, which suggests the continuation of AL as first line drug for the treatment of uncomplicated P. falciparum malaria in the study area. This study recommends further studies on drug toxicity, particularly on repeated cough and oral ulceration. [ABSTRACT FROM AUTHOR]