Efficacy of artemether-lumefantrine and artesunate-amodiaquine for treating uncomplicated falciparum malaria in children

Background Artesunate-amodiaquine (ASAQ) has been usedas a firsdine treatment for uncomplicated faldparum malariain Indonesia since 2004. Its efficacy depends on amodiaquineresistance of the infecting parasites. Artemether-lumefantrine(AL) has been shown to be highly efficacious in treatinguncomplicated faldparum malaria in several countries. However,there have been few studies on these anti-malarial medicationsin Indonesia.Objective To compare the efficacy of AL to ASAQ for treatinguncomplicated faldparum malaria in children.Methods An open, randomized, controlled trial wasconducted in school-aged children in the Mandailing NatalRegency, North Sumatera Province, Indonesia, from Octoberto December 2010. A total of 280 pediatric, uncomplicatedfalciparum malaria patients were randomly assigned to receiveeither AL or ASAQ for 3 days. Participants were followed-up ondays 1,2,3,7, 14, 28 and 42 following the first medication dose.The outcomes noted were adequate clinical and parasitologicalresponse (ACPR), parasite reduction, parasite clearance time,fever clearance time and adverse events. Analysis was basedon intention-to-treat.Results In this study, ACPRs on day 42 were 86.4% and 90.7%for the ASAQ and AL groups, respectively (p=0.260). On days 7and 14, the AL group had higher cure rates than that of the ASAQgroup (P<0.05). Early treatment failure, late treatment failure andparasitological failure for both groups were similar. We also foundfaster parasite clearance time and higher parasite reduction in theAL group than in the ASAQ group. However, fever clearancetime was shorter in the ASAQ group. The incidence of adverseevents such as nausea, vomiting, malaise, and pruritus were similarbetween the two groups (P=0.441).Conclusion AL had higher efficacy than ASAQ for the treatment of uncomplicated falciparum malaria in children.[Paediatr rndones. 2012;52:260-6].

Download Full-text

Quinine Pharmacokinetic-Pharmacodynamic Relationships in Uncomplicated Falciparum Malaria

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.11.3458-3463.2003 ◽

2003 ◽

Vol 47 (11) ◽

pp. 3458-3463 ◽

Cited By ~ 39

Author(s):

S. Pukrittayakamee ◽

S. Wanwimolruk ◽

K. Stepniewska ◽

A. Jantra ◽

S. Huyakorn ◽

...

Keyword(s):

Falciparum Malaria ◽

Day Treatment ◽

Parasite Clearance ◽

Uncomplicated Falciparum Malaria ◽

Clearance Time ◽

Time Curve ◽

Parasite Clearance Time ◽

Fever Clearance Time ◽

Pharmacokinetic Properties ◽

The Mean

ABSTRACT The relationships between the pharmacokinetic properties of quinine during a 7-day treatment course and the therapeutic response were studied in 30 adult patients with uncomplicated falciparum malaria monitored for ≥28 days. All patients received a 7-day oral quinine regimen either alone (n = 22) or in combination with rifampin (n = 8). The median fever clearance time was 58.5 h, and the mean ± standard deviation parasite clearance time was 73 ± 24 h. After recovery, six patients had recrudescences of Plasmodium falciparum malaria and seven had delayed appearances of P. vivax infection between days 16 and 23. Between the patients with and without recrudescences, there were no significant differences either in fever clearance time or parasite clearance time or in the overall pharmacokinetics of quinine and 3-hydroxyquinine. Patients for whom the area under the concentration-time curve from 3 to 7 days for quinine in plasma was <20 μg · day/ml had a relative risk of 5.3 (95% confidence interval = 1.6 to 17.7) of having a subsequent recrudescence of infection (P = 0.016). Modeling of these data suggested an average minimum parasiticidal concentration of quinine in plasma of 3.4 μg/ml and an MIC of 0.7 μg/ml for uncomplicated falciparum malaria in Thailand. To ensure a cure, the minimum parasiticidal concentration must be exceeded during four asexual cycles (>6 days).

Download Full-text

Artesunate-amodiaquine versus artesunatesulfadoxine- pyrimethamine for uncomplicated falciparum malaria in children

Paediatrica Indonesiana ◽

10.14238/pi54.1.2014.46-51 ◽

2014 ◽

Vol 54 (1) ◽

pp. 46

Author(s):

Novie H. Rampengan ◽

Jane Metusala ◽

Ronald Chandra ◽

Praevilia Salendu

Keyword(s):

Hospital Stay ◽

Falciparum Malaria ◽

Treatment Efficacy ◽

Medical Records ◽

Length Of Hospital Stay ◽

Parasite Clearance ◽

Uncomplicated Falciparum Malaria ◽

Clearance Time ◽

Combination Therapies ◽

Fever Clearance Time

Background Malaria is a major cause of morbidity and mortalityin children, especially in developing countries. Art emisinincombination therapy (ACT) has higher rates of parasite clearanceand inhibition of anti-malarial drugs resistance than non-ACT.Hence, we compared the efficacies of artesunate-amodiaquine(AS-AQ) versus artesunate-sulfadoxine pyrimethamine (AS-SP)combination therapies in children with uncomplicated falciparummalaria.Objective To compare the fever clearance time, parasite clearancetime, and length of hospital stay in uncomplicated falciparummalaria patients treated with AS-AQ and AS-SP.Methods We reviewed the medical records of children aged 1- 14years with uncomplicated falciparum malaria admitted to Prof.Dr. R. D. Kandou Hospital between January 2002 - June 2010.Treatment efficacy was evaluated by fever clearance time, parasiteclearan ce time, and length of hospital stay. The differencesof treatment efficacy between the two groups of therapy werean alyzed by independent T test.Results We identified 185 children with uncomplicatedfalciparum malaria, 104 cases were treated with AS-AQ whilethe other 81 received AS-SP. Parasite clearance time was shorterin AS-AQ group than in AS-SP group at 1.38 (SD 0.69) versus1.91 (SD 0.93) days, respectively (95%CI of differences 0.3 0 to0. 76, P<0.05) . The length of hospital stay was shorterin AS-AQgroup than in the AS-SP group, at 5.01 (SD 1.22) versus 6.04(SD 0.98) days, respectively (95%CI of differences 0. 71 to 1.35,P < 0.05). However, there was no statistically significant differencein fever clearance time between the groups.Conclusion AS-AQ combination therapy reduces parasiteclearance time and length of hospital stay compared to AS-SP46 • Paediatrlndones, Vol. 54, No. 1, January 2014combination therapy in children with uncomplicated falciparummalaria.

Download Full-text

Comparative efficacy of chloroquine and pyrimethamine-sulfadoxine versus artemether and pyrimethamine-sulfadoxine in the treatment of uncomplicated falciparum malaria in children

Paediatrica Indonesiana ◽

10.14238/pi44.6.2004.228-33 ◽

2016 ◽

Vol 44 (6) ◽

pp. 228

Author(s):

Femmy Tambajong ◽

Tonny H Rampengan

Keyword(s):

Falciparum Malaria ◽

Randomized Study ◽

Combined Treatment ◽

Parasite Clearance ◽

New Drugs ◽

Uncomplicated Falciparum Malaria ◽

Clearance Time ◽

Cure Rate ◽

Fever Clearance Time ◽

Single Blind

Background Large amount of data show that chloroquine andpyrimethamine-sulfadoxine (PS) as standard drugs for falciparummalaria cause resistance; for that reason new drugs or combina-tion drugs are urgently needed. Artemether is one of the newdrugs. It has been studied extensively in China and SoutheastAsia during the past 10 years. The effectiveness of this drug inclearing parasites has been thoroughly documented.Objective The objective of this study was to investigate theefficacy of the combination of chloroquine and PS compared toartemether and PS in the treatment of uncomplicated falciparummalaria.Methods We did a single-blind randomized study on 60 childrenwith uncomplicated falciparum malaria. Thirty children weretreated with chloroquine (10 mg/kg for 2 days, then 5 mg/kg inthe 3 rd day) and PS (pyrimethamine 1-1.5 mg/kg single dose onthe 1 st day) and the other 30 children were treated with artemether(4 mg/kg/day for 3 days) and PS. All patients were admitted tohospital for at least 7 days.Results Fever clearance time was significantly shorter in the groupthat received artemether and PS compared to that in the chloro-quine-and-PS group (42 hours vs. 75 hours 50 minutes, p<0.0001).Parasite clearance time was significantly different between thegroup that received artemether and PS and the chloroquine-and-PS group (2.5 days vs. 3.1 days, p=0.04). The cure rate in thechloroquine-and-PS group was 28/30 and that of the artemether-and-PS group was 30/30. Nausea and vomiting were found in 1patient treated with chloroquine and PS.Conclusion The combined treatment of artemether and PS waswell tolerated. No adverse reactions attributable to the treatmentwere noted

Download Full-text

Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria

The Lancet ◽

10.1016/s0140-6736(05)63604-5 ◽

1997 ◽

Vol 350 (9093) ◽

pp. 1776

Author(s):

Peter G Kremsner ◽

Christian H Brandts ◽

Maryse Ndjave ◽

Wolfgang Graninger

Keyword(s):

Plasmodium Falciparum ◽

Falciparum Malaria ◽

Plasmodium Falciparum Malaria ◽

Parasite Clearance ◽

Clearance Time ◽

Parasite Clearance Time

Download Full-text

Therapeutic Efficacy of Artemether-Lumefantrine (Coartem®) for the Treatment of Uncomplicated Falciparum Malaria in Africa: A Systematic Review

Journal of Parasitology Research ◽

10.1155/2020/7371681 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Awoke Derbie ◽

Daniel Mekonnen ◽

Meseret Adugna ◽

Biruk Yeshitela ◽

Yimtubezinash Woldeamanuel ◽

...

Keyword(s):

Falciparum Malaria ◽

Meta Analysis ◽

Grey Literature ◽

Age Groups ◽

Parasite Clearance ◽

Uncomplicated Falciparum Malaria ◽

Drug Of Choice ◽

Development Of Resistance ◽

Late Treatment ◽

Comprehensive Search

Background. Africa still bears the largest burden of malaria as the majority of infections in the continent are caused by P. falciparum. Artemether-lumefantrine (AL, Coartem®) is the most widely used artemisinin-based combination therapy (ACT), for treating uncomplicated falciparum malaria globally. However, the development of resistance to antimalarial drugs is a major challenge for malaria control. In this review, the efficacy of AL for the treatment of uncomplicated falciparum malaria in Africa was evaluated. Methods. Articles published between January 2015 and July 2019 were systematically searched using comprehensive search strings from PubMed/Medline, SCOPUS, and grey literature from Google Scholar. Interventional studies that followed patients for at least 28 days were included. Two reviewers independently assessed study eligibility, extracted data, and assessed risk of bias. All the included articles were measured to be good quality. While computing the efficacy of AL, polymerase chain reaction (PCR)–corrected cure rate (adequate clinical and parasitological response, ACPR) at day 28 was considered as the main endpoint. Meta-analysis was computed using STATA v 15 to calculate the pooled ACPR. Results. In this review, 39 articles that reported the treatment outcome of 8,320 patients were included. After 28 days of follow-up, the pooled PCR uncorrected and corrected APCR was at 87% (95% CI: 85-90%) and 97.0% (95% CI: 96-98%), respectively. Moreover, the proportion of early treatment failure (ETF) was almost 0%, while most of the included articles reported <8% late treatment failures. The reinfection and recrudescence rate was less than 10% and 2.6%, respectively, within 28 days. We noted rapid fever and parasite clearance in which greater than 93% and 94% patients were parasite and fever free at day three following AL treatment. Conclusions. This review discovered that despite more than a decade since its introduction, Coartem® remains effective and thus could continue to be the drug of choice for the treatment of uncomplicated falciparum malaria for all age groups in Africa. However, the risk of new emerging resistance for this combination warrants regular monitoring of its efficacy across the continent.

Download Full-text

OC 8459 ASSESSMENT OF PARASITE CLEARANCE AFTER REPEATED TREATMENT WITH ARTESUNATE AMODIAQUINE, DIHYDROARTEMISININ-PIPERAQUINE, PYRONARIDINE-ARTESUNATE IN MALARIA PATIENTS IN BURKINA FASO

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.17 ◽

2019 ◽

Vol 4 (Suppl 3) ◽

pp. A7.2-A8

Author(s):

Issiaka Soulama ◽

Sodiomon B Sirima

Keyword(s):

Parasite Clearance ◽

Phase Iii ◽

Repeated Treatment ◽

Clearance Time ◽

Combination Therapies ◽

First Line ◽

Open Label ◽

Parasite Clearance Time ◽

Secondary Endpoints ◽

Cure Rates

BackgroundReports from Southeast Asia showed delayed parasite clearance after treatment with known artemisinin-based combination therapies (ACTs), the first-line treatment for malaria. We then carried out a study in the framework of the WANECAM clinical trial to assess comparatively the parasite clearance time and rate from P. falciparum malaria patients repeatedly treated with the artesunate-amodiaquine (ASAQ), dihydroartemisinin-piperaquine (DHA-PQ) and artesunate-pyronaridine (PYR).MethodsA randomised, phase III/IV comparative, multicentre, open-label, parallel 3-arms trial was conducted in Banfora Health District area comparing the efficacy of a three-day regimen of DHA-PQ, PYR with ASAQ for the treatment of children (above 6 months) and adults with uncomplicated falciparum malaria. From August 2012 to December 2013, each randomised patient was followed up for 42 days over a period of two years. Treatment was directly observed, and blood smear samples were collected twice daily (12 hour±2 hour) until parasite clearance.The endpoints of the present sub-study were parasite clearance rate and time. The secondary endpoints included PCR-corrected and uncorrected cure rates.ResultsOut of 2843 screened patients, 763 were recruited for parasite clearance endpoint analyses. The median parasite clearance time (PCT) was 24.1 hour (2-sided 95% CI, 24.0 to 24.2 hour), 23.9 hour (2-sided 95% CI, 23.8 to 24.0 hour) and 24.2 hour (2-sided 95% CI, 24.1 to 24.5 hour), in PYR and DHA-PQ, respectively. The PCR-corrected efficacy rates were estimated at 99.8%; 99.7%; 99.9%, at day 28% and 99.3%; 99.7%–99.9% in PYR, ASAQ and DHA-PQ, respectively.ConclusionThe parasite clearance times were comparable among the three ACT arms of treatment and their efficacy was comparable and higher than 99%. There was no delay in parasite clearance time (PCT ≥72 hour).

Download Full-text

Trimethoprim-sulfamethoxazole Versus Azithromycin for the Treatment of Undifferentiated Febrile Illness in Nepal: A Double-blind, Randomized, Placebo-controlled Trial

Clinical Infectious Diseases ◽

10.1093/cid/ciaa1489 ◽

2020 ◽

Cited By ~ 1

Author(s):

Abhishek Giri ◽

Abhilasha Karkey ◽

Sabina Dangol ◽

Amit Arjyal ◽

Sunil Pokharel ◽

...

Keyword(s):

Treatment Failure ◽

Enteric Fever ◽

Controlled Trial ◽

Febrile Illness ◽

Blood Cultures ◽

Clearance Time ◽

Double Blind ◽

Fever Clearance Time ◽

Secondary Endpoints ◽

Fever Treatment

Abstract Background Azithromycin and trimethoprim-sulfamethoxazole (SXT) are widely used to treat undifferentiated febrile illness (UFI). We hypothesized that azithromycin is superior to SXT for UFI treatment, but the drugs are noninferior to each other for culture-confirmed enteric fever treatment. Methods We conducted a double-blind, randomized, placebo-controlled trial of azithromycin (20 mg/kg/day) or SXT (trimethoprim 10 mg/kg/day plus sulfamethoxazole 50 mg/kg/day) orally for 7 days for UFI treatment in Nepal. We enrolled patients >2 years and <65 years of age presenting to 2 Kathmandu hospitals with temperature ≥38.0°C for ≥4 days without localizing signs. The primary endpoint was fever clearance time (FCT); secondary endpoints were treatment failure and adverse events. Results From June 2016 to May 2019, we randomized 326 participants (163 in each arm); 87 (26.7%) had blood culture–confirmed enteric fever. In all participants, the median FCT was 2.7 days (95% confidence interval [CI], 2.6–3.3 days) in the SXT arm and 2.1 days (95% CI, 1.6–3.2 days) in the azithromycin arm (hazard ratio [HR], 1.25 [95% CI, .99–1.58]; P = .059). The HR of treatment failures by 28 days between azithromycin and SXT was 0.62 (95% CI, .37–1.05; P = .073). Planned subgroup analysis showed that azithromycin resulted in faster FCT in those with sterile blood cultures and fewer relapses in culture-confirmed enteric fever. Nausea, vomiting, constipation, and headache were more common in the SXT arm. Conclusions Despite similar FCT and treatment failure in the 2 arms, significantly fewer complications and relapses make azithromycin a better choice for empirical treatment of UFI in Nepal. Clinical Trials Registration NCT02773407.

Download Full-text

Comparison of artesunate and quinine in the treatment of severe Plasmodium falciparum malaria at Kassala hospital, Sudan

The Journal of Infection in Developing Countries ◽

10.3855/jidc.3813 ◽

2014 ◽

Vol 8 (05) ◽

pp. 611-615 ◽

Cited By ~ 9

Author(s):

Tajeldin M Abdallah ◽

Khalid A Elmardi ◽

Asama H Elhassan ◽

Mona B Omer ◽

Mousab S Elhag ◽

...

Keyword(s):

Severe Malaria ◽

Falciparum Malaria ◽

Plasmodium Falciparum Malaria ◽

Parasite Clearance ◽

Loading Dose ◽

Clearance Time ◽

Resolution Time ◽

Fever Clearance Time ◽

The Mean ◽

Eastern Sudan

Introduction: There is a need to investigate the treatment (artesunate and quinine) of severe malaria, as this will influence the outcome of morbidity and the mortality of the disease. Methodology: An open randomized trial conducted at Kassala, Sudan. Patients with severe P. falciparum malaria were randomly assigned to either intravenous artesunate at 2.4 mg/kg at 0, 12, and 24 hours, then daily, or intravenous quinine at a 20 mg/kg loading dose, then 10 mg/kg three times a day. Fever and parasite clearance and coma resolution time were compared between the two groups . Results: The two groups (47 in each group) were well matched in the clinical and biochemical characteristics. Hypotension, convulsions, severe anemia, hypoglycemia, cerebral malaria, and jaundice were the predominant manifestations of severe malaria. The mean (SD) of the fever clearance (10.8 [5.5] vs. 14.0 [8.1] hours, p = 0.028) and the parasite clearance time (16.5 [6.4] vs. 21.7 [11.3] hours, p = 0.007) were significantly shorter in the artesunate-treated patients. In comatose patients, there was no difference between the two groups in coma resolution time. Following quinine infusion, ten patients developed tinnitus (p < 0.001), and four had hypoglycemia (p = 0.033). Tinnitus and hypoglycemia were not detected in the artesunate group. One patient in the artesunate group died. Conclusions: Artesunate is more effective than quinine, in term of parasite and fever clearance time, in the treatment of P. falciparum malaria in eastern Sudan. The study found no difference between artesunate and quinine in coma resolution time.

Download Full-text