lumefantrine and Fever

Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5-25 kg. A total of 544 patients with uncomplicated P. falciparum malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis. Analysis of day 28 cure rate based on the intention-to-treat and evaluable populations yielded corrected cure rates for the six-dose regimen of 93% and 96% compared with 61% and 76%, respectively, for the four-dose regimen (P < 0.0001 for both comparisons). Similarly high cure rates were achieved with the six-dose regimen in non-immune infants weighing as little as 5 kg. The six- and four-dose regimens were equally well tolerated. The main finding of this analysis is that the six-dose regimen of coartemether is safe and more efficacious than the four-dose regimen in children.

Topics: Animals; Antimalarials; Artemether; Artemisinins; Body Weight; Child; Child, Preschool; Clinical Trials as Topic; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Ethanolamines; Female; Fever; Fluorenes; Humans; Infant; Life Cycle Stages; Lumefantrine; Malaria, Falciparum; Male; Time Factors

The safety and efficacy of the two most widely used fixed-dose artemisinin-based combination therapies (ACT), artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are well established for single episodes of uncomplicated Plasmodium falciparum malaria, but the effects of repeated, long-term use are not well documented. We conducted a 2-year randomized, open-label, longitudinal, phase IV clinical trial comparing the efficacy and safety of fixed-dose ASAQ and AL for repeated treatment of uncomplicated malaria in children under 5 years at Nagongera Health Centre, Uganda. Participants were randomized to ASAQ or AL and all subsequent malaria episodes were treated with the same regimen. 413 children were enrolled and experienced a total of 6027 malaria episodes (mean 15; range, 1-26). For the first malaria episode, the PCR-corrected-cure rate for ASAQ (97.5%) was non-inferior to that for AL (97.0%; 95% CI [-0.028; 0.037]). PCR-corrected cure rates for subsequent malaria episodes that had over 100 cases (episodes 2-18), ranged from 88.1% to 98.9% per episode, with no clear difference between the treatment arms. Parasites were completely cleared by day 3 for all malaria episodes and gametocyte carriage was less than 1% by day 21. Fever clearance was faster in the ASAQ group for the first episode. Treatment compliance for subsequent episodes (only first dose administration observed) was close to 100%. Adverse events though common were similar between treatment arms and mostly related to the disease. Serious adverse events were uncommon, comparable between treatment arms and resolved spontaneously. Anemia and neutropenia occurred in <0.5% of cases per episode, abnormal liver function tests occurred in 0.3% to 1.4% of cases. Both regimens were safe and effective for repeated treatment of malaria.. Current Controlled Trials NCT00699920.

Topics: Amodiaquine; Antimalarials; Artemether; Artemisinins; Child, Preschool; Data Collection; Drug Combinations; Ethanolamines; Female; Fever; Fluorenes; Hemoglobins; Humans; Infant; Insecticide-Treated Bednets; Lumefantrine; Malaria, Falciparum; Male; Parasite Load; Patient Compliance; Safety; Splenomegaly; Treatment Outcome; Uganda

To establish efficacy and safety of artesunate/lumefantrine fixed-dose combination (FDC) in comparison with artemether/lumefantrine FDC in treatment of uncomplicated Plasmodium falciparum malaria.. Confirmed cases of uncomplicated P. falciparum malaria were randomly assigned to receive artesunate (100 mg)/lumefantrine (480 mg) (ASLF FDC) or artemether (80 mg)/lumefantrine (480 mg) (AMLF FDC) tablets for 3 days. Patients were followed up on Day 7, 14, 21 and 28.. Of the 158 enrolled patients, 144 completed the study. Seventy-three patients (94.8%) from the ASLF group and 71 patients (94.7%) from the AMLF group showed parasite clearance within 48 h. The mean parasite clearance time was 25.40 ± 14.82 h in the ASLF group and 24 ± 13.32 h in the AMLF group (P = 0.542). All patients showed gametocyte clearance by Day 7 and remained gametocyte free till Day 28. Sixty-five patients (84.4%) from the ASLF group and 56 patients (74.7%) from the AMLF group were afebrile within 24 h. The mean fever clearance time was 17.38 ± 12.33 h in the ASLF group and 17.2 ± 12.01 h in the AMLF group (P = 0.929). There was one early treatment failure in the AMLF group as per WHO criteria. Improvement in haemoglobin and haematocrit was comparable in both the treatment groups. In the ASLF group, of the 25 (32.47%) patients anaemic at baseline, only seven (9.09%) reported anaemia on Day 28, while in the AMLF group, of the 14 (18.67%) patients anaemic at baseline, only four (5.33%) reported anaemia on Day 28. Both study medications were well tolerated.. Artesunate (100 mg)/lumefantrine (480 mg) fixed-dose combination could add one more option to currently available artemisinin combinations in treatment of uncomplicated P. falciparum malaria.

Topics: Adolescent; Adult; Aged; Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Artesunate; Double-Blind Method; Drug Combinations; Ethanolamines; Female; Fever; Fluorenes; Humans; India; Lumefantrine; Malaria, Falciparum; Male; Middle Aged; Parasite Load; Plasmodium falciparum; Time Factors; Treatment Outcome; Young Adult

Access to prompt and effective treatment is the cornerstone for malaria control. Population Services International in collaboration with the Ministry of Health launched a malaria behaviour change communication intervention in Nyanza province, Kenya. The initiative aimed to improve: symptom recognition and prompt access to government health facilities for febrile children; effective treatment with the recommended first-line drug artemether-lumefantrine (AL) in public health facilities and adherence to the AL regimen.. Pre- and post-intervention cross-sectional household surveys were used to evaluate the impact of the intervention on prompt and correct use of AL for febrile children below five years of age. The primary outcome was the proportion of children below five years of age with fever in the last 14 days accessing AL within 48 hours of fever onset.. There was an increase from 62.8% pre-intervention to 79.4% post-intervention (95% CI: 11.1, 22.1) in caregivers who reported seeking formal treatment promptly (on the same day, or next day) for their febrile children. However, there was a decrease in the use of government health facilities in the post-intervention period. There was a small increase in the proportion of children accessing AL within 48 hours of fever onset [18.4% vs 23.5% (0.1-10.0)].. The findings of this evaluation demonstrate that interventions that target only one sector may have a limited impact on improvements in prompt and effective treatment where multiple sources of treatments are sought for febrile illness. Additionally, the context in which an intervention is implemented is likely to influence the process and outcomes.

Topics: Antimalarials; Artemether; Artemisinins; Awareness; Caregivers; Child, Preschool; Community Health Services; Community Participation; Cross-Sectional Studies; Ethanolamines; Family Characteristics; Female; Fever; Fluorenes; Humans; Infant; Infant, Newborn; Kenya; Lumefantrine; Malaria; Male; Patient Acceptance of Health Care

The World Health Organization aims at universal access to effective antimalarial treatment by the year 2015. Consequently, an enormous financial resource has been invested on Artemisinin Combination Therapy (ACT) subsidy. In Tanzania, strategies to increase access of artemether-lumufantrine (ALu) rural areas, where the burden is highest, includes subsidy to the Faith-based Organisations (FBO) facilities and accredited drug dispensing outlets (ADDOs). This study was done to assess the extent to which children suffering from malaria access ALu from the private sector in rural areas. A total of 1,235 under fives randomly selected from 12 rural villages were followed up at home on weekly basis for six months in Kilosa district in 2008. Using a structured questionnaire, caretakers were interviewed about the child's history of fever in the past 7 days; type of treatment given and the source. Baseline data were obtained on demographic characteristics, caretakers' knowledge about malaria and social economic indicators of the household. Of the 1,235 children followed-up, 740 care-seeking visits were recorded, of which, 264 (35.7%) were made at government health facilities and nearly a quarter (24.1%; 178/740) at ordinary shops that sell general merchandize including rice and sugar. Only 22% of the caretakers sought care from FBO and ADDOs. While 686 (86.6%) of the episodes were treated with antimalarials, only 319 (43%) received ALu, the recommended antimalarial. Majority (83%) of the visits made at government facilities were prescribed with ALu compared to less than half who went to FBO facilities (40.0%) and ADDOs (25.0%). In conclusion, this study has shown that less than a quarter of fever episodes suspected to be malaria in rural areas were made at FBO facilities and ADDOs, of which, less than half were treated with ALu. This shows that ALu subsidy to formal private sector does not adequately reach children in rural areas, where the malaria burden is highest. This cast some doubts if the target of universal access to effective antimalarial, by 2015, will be reached. There is need to consider enlisting the services of community health workers in the efforts to improve access to ALu in rural areas. Further research is needed to explore providers' / dispensers' preference for non-recommended antimalarials in the private sector and caretakers' preference for ordinary shops.

Topics: Antimalarials; Artemether; Artemisinins; Child; Child, Preschool; Drug Combinations; Ethanolamines; Female; Fever; Fluorenes; Health Services Accessibility; Humans; Infant; Infant, Newborn; Lumefantrine; Malaria; Male; Private Sector; Rural Population; Surveys and Questionnaires; Tanzania

To examine access to, timing and use of artemisinin-based combination therapy among rural Kenyan febrile children before and following the introduction of artemether-lumefantrine (AL) as first-line antimalarial drug policy.. In August 2006, a cohort was established within 72 rural clusters in four sentinel districts to monitor the period prevalence of fever and treatment in children aged 0-4 years through four repeat cross-sectional surveys (one prior to introduction of AL and three post-AL introduction: January-June 2007). Mothers/guardians of children were asked about fever in the last 14 days and related treatment actions including the timing, drugs used, dosing and adherence supported by visual aids of commonly available drug products.. A total of 2526 child-observations were recorded during the four survey rounds. The period prevalence of fever was between 20% and 26% with little variation between survey rounds. The overall proportion of children with fever receiving antimalarial drugs for their fever was 31 % (95% CI, 26-36%) and the proportion of febrile children receiving antimalarial drugs within 48 h was 23.3% (95% CI, 18.6-28.0%). The proportion of febrile children who received first-line recommended AL within 48 h was 10.2% (95% CI, 7.0-13.4%), compared to only 4.6% (95% CI, 3.8-5.4%) of children receiving sulphadoxine-pyrimethamine first-line therapy in 2001.. Although Kenya was less than a year into the new policy implementation and AL is restricted to the public formal sector, access to antimalarial drugs among children within 48 h and to the first-line therapy has improved. But it remains well below national and international targets. The continued use of amodiaquine and artemisinin monotherapies constrains effective implementation of artemisinin-based combination therapy policy in Kenya.

Topics: Anti-Infective Agents; Antimalarials; Artemether; Artemisinins; Child, Preschool; Cohort Studies; Cross-Sectional Studies; Drug Therapy, Combination; Ethanolamines; Fever; Fluorenes; Health Policy; Humans; Infant; Infant, Newborn; Kenya; Lumefantrine; Rural Health

A recent observational study undertaken at 17 health facilities with microscopy in Kenya revealed that potential benefits of malaria microscopy are not realized because of irrational clinical practices and the low accuracy of routine microscopy. Using these data, we modelled financial and clinical implications of revised clinical practices and improved accuracy of malaria microscopy among adult outpatients under the artemether-lumefantrine (AL) treatment policy for uncomplicated malaria in Kenya.. The cost of AL, antibiotics and malaria microscopy and the expected number of malaria diagnosis errors were estimated per 1,000 adult outpatients presenting at a facility with microscopy under three scenarios: (1) current clinical practice and accuracy of microscopy (option A), (2) revised clinical practice with current accuracy of microscopy (option B) and (3) revised clinical practice with improved accuracy of microscopy (option C). Revised clinical practice was defined as performing a blood slide for all febrile adults and prescribing antimalarial treatment only for positive results. Improved accuracy of routine microscopy was defined as 90% sensitivity and specificity. In the sensitivity analysis, the implications of changes in the cost of drugs and malaria microscopy and changes in background malaria prevalence were examined for each option.. The costs of AL, antibiotics and malaria microscopy decreased from 2,154 dollars under option A to 1,254 dollars under option B and 892 dollars under option C. Of the cost savings from option C, 72% was from changes in clinical practice, while 28% was from improvements in the accuracy of microscopy. Compared with 638 malaria overdiagnosis errors per 1,000 adults under option A, 375 and 548 fewer overdiagnosis errors were estimated, respectively, under options B and C. At the same time, the number of missed malaria diagnoses remained generally low under all options. Sensitivity analysis showed that both options B and C are robust to a wide range of assumptions on the costs of drugs, costs of blood slides and malaria prevalence.. Even with the imperfect microscopy conditions at Kenyan facilities, implementation of revised clinical practice (option B) would substantially reduce the costs and errors from malaria overdiagnosis. Additional interventions to improve the accuracy of microscopy (option C) can achieve further benefits; however, improved microscopy in the absence of revised clinical practice is unlikely to generate significant cost savings. Revision of guidelines to state explicitly age-specific indications for the use and interpretation of malaria microscopy is urgently needed. Further prospective studies are required to evaluate the effectiveness and costs of interventions to improve clinical practice and the accuracy of malaria microscopy.

Topics: Adolescent; Adult; Anti-Infective Agents; Antimalarials; Artemether; Artemisinins; Diagnostic Errors; Ethanolamines; Fever; Fluorenes; Health Care Costs; Humans; Kenya; Lumefantrine; Malaria; Microscopy; Models, Economic; Prevalence; Sensitivity and Specificity

Fever is the clinical hallmark of malaria disease. The Roll Back Malaria (RBM) movement promotes prompt, effective treatment of childhood fevers as a key component to achieving its optimistic mortality reduction goals by 2010. A neglected concern is how communities will access these new medicines promptly and the costs to poor households when they are located in rural areas distant to health services.. We assemble data developed between 2001 and 2002 in Kenya to describe treatment choices made by rural households to treat a child's fever and the related costs to households. Using a cost-of-illness approach, we estimate the expected cost of a childhood fever to Kenyan households in 2002. We develop two scenarios to explore how expected costs to households would change if more children were treated at a health care facility with an effective antimalarial within 48 hours of fever onset.. 30% of uncomplicated fevers were managed at home with modern medicines, 38% were taken to a health care facility (HCF), and 32% were managed at home without the use of modern medicines. Direct household cash expenditures were estimated at $0.44 per fever, while the total expected cost to households (cash and time) of an uncomplicated childhood fever is estimated to be $1.91. An estimated mean of 1.42 days of caretaker time devoted to each fever accounts for the majority of household costs of managing fevers. The aggregate cost to Kenyan households of managing uncomplicated childhood fevers was at least $96 million in 2002, equivalent to 1.00% of the Kenyan GDP. Fewer than 8% of all fevers were treated with an antimalarial drug within 24 hours of fever onset, while 17.5% were treated within 48 hours at a HCF. To achieve an increase from 17.5% to 33% of fevers treated with an antimalarial drug within 48 hours at a HCF (Scenario 1), children already being taken to a HCF would need to be taken earlier. Under this scenario, direct cash expenditures would not change, and total household costs would fall slightly to $1.86 because caretakers also save time with prompt treatment if the child has malaria.. The management of uncomplicated childhood fevers imposes substantial costs on Kenyan households. Achieving substantial improvements in the numbers of fevers treated within 48 hours at a HCF with an effective antimalarial drug (Scenario 1) will not impose additional costs on households. Achieving additional improvements in fevers treated promptly at a HCF (Scenario 2) will impose additional costs on some households roughly equal to average cash expenses for transportation to a HCF. Additional financing mechanisms that further reduce the costs of accessing care at a HCF and/or that make artemisinin-based combination therapies (ACTs) accessible for home management need to be developed and evaluated as a top priority.

Topics: Antimalarials; Artemisinins; Caregivers; Child, Preschool; Cost of Illness; Drug Therapy, Combination; Ethanolamines; Family Characteristics; Fever; Fluorenes; Health Care Surveys; Health Expenditures; Health Services Accessibility; Home Nursing; Humans; Infant; Kenya; Lactones; Lumefantrine; Malaria; Models, Econometric; Rural Health Services; Sesquiterpenes; Time Factors