Parasite Clearance Time and Time to Recurrent Infection Following Treatment With Artemether/Lumefantrine

Study Overview
=================
Brief Summary
-----------------
Plasmodium falciparum resistance against artemisinins has been confirmed in South-East Asia and it is expressed phenotypically as a slow rate of parasite clearance. Nonetheless, it is not known whether the problem exist in Tanzania. This study assessed parasite clearance time and time to recurrent infection following treatment with Artemether/Lumefantrine (AL) among children with uncomplicated malaria.

Detailed Description
-----------------
Artemether/Lumefantrine (AL) has been in wide scale use in Tanzania since 2007 as first line treatment for uncomplicated falciparum malaria. Nonetheless, reports of confirmed resistance against Artemisinin derivatives expressed phenotypically as prolonged parasite clearance have emerged from South-East Asia (SEA), signifying reduced parasites susceptibility to the otherwise rapidly acting artemisinins. Prolonged clearance is associated with an increase in day 28 treatment failure, gametocytes carriage and transmission of resistance. Nonetheless, no detailed study has been done in East Africa to assess parasite clearance time following treatment with Artemisinin based combination therapies (ACTs). In order to evaluate time to parasite clearance following treatment with AL, we conducted a detailed clinical trial with twenty blood sampling time points prior, during and after treatment. Detailed sampling allowed us to assess parasite clearance, and selection of Plasmodium falciparum multidrug resistance (Pfmdr) 1 N86Y and Plasmodium falciparum chloroquine resistance transporter (Pfcrt) K76T genes between different time points and its association with parasite clearance and recurrence. Furthermore, as a sensitive tool and an ideal early warning system, nested polymerase chain reaction (PCR) was used to assess parasite clearance and compare it with microscopic findings.

Official Title
-----------------
Parasite Clearance Time and Time to Recurrent Infection Following Treatment With Artemether/Lumefantrine Among Children With Uncomplicated P. Falciparum Malaria Five Years After Wide Scale Use of the Drug in Tanzania

Conditions
-----------------
Instantaneous Clearance

Intervention / Treatment
-----------------
* Drug: Artemether/lumefantrine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 6-120 months Presence of asexual P. falciparum parasitaemia of 2000-200 000/μL No general danger signs or severe malaria present Hemoglobin ≥5 g/dL History of fever within 24 hours or axillary temperature ≥ 37.5 degree Celsius No other cause of fever is detectable No severe malnutrition Guardian/patient has consented Exclusion Criteria: general danger signs or signs of severe falciparum malaria severe malnutrition febrile condition due to diseases other than malaria regular medication which might interfere with antimalarial pharmacokinetics contraindications to any medicine being used

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 120 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Artemether/lumefantrine<br>Artemether/lumefantrine tablets, 6 doses, for 3 days Dosage: tablet for body weight between 5-14.9 Kilograms. tablets for body weight between 15-24.9 Kilograms. tablets for body weight between 25-34.9 Kilograms. | Drug: Artemether/lumefantrine<br>* Medication was given at 0, 8, 24, 36, 48 and 60 hours. Food was given to all patients prior to medication to ensure proper absorption of the drug.<br>* Other names: Coartem;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to parasite clearance | Time to parasite clearance was assessed by taking blood samples and examining it by light microscopy prior (0 hour) and during treatment at 4, 8, 12 hours and then 6 hourly until two consecutive negative blood slides. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recurrent infection | Time taken for parasites to reappear in the peripheral blood of the participant after initial treatment was assessed during the 42 days of follow up from blood samples taken on days 14, 21, 28 and 42. | 42 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Clearance time, Recurrence time, Artemether/lumefantrine, Uncomplicated malaria, Children, P. falciparum