Clinical trial NCT01998295: Parasite Clearance Time and Time to Recurrent Infection Following Treatment With Artemether/Lumefantrine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Instantaneous Clearance
Keywords: Clearance time
Recurrence time
Artemether/lumefantrine
P. falciparum
Uncomplicated malaria
Children
Lead sponsor: Muhimbili University of Health and Allied Sciences
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
First posted: 2013-11-28
Enrollment: 45
Sex: ALL
Minimum age (years): 6
Maximum age (years): 120
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Time to parasite clearance
timeFrame: 72 hours
Secondary outcomes:
measure: Time to recurrent infection
timeFrame: 42 days
Other outcomes:
measure: Time to parasite clearance
timeFrame: 7 days
measure: Time to alleles clearance
timeFrame: 168 hours
Locations:
city: Dar es Salaam
country: Tanzania
facility: Muhimbili University of Health and Allied Sciences
Study officials:
affiliation: Karolinska Institutet
name: Andreas Martensson, PhD
role: STUDY_DIRECTOR
References:
citation: Mwaiswelo R, Ngasala B, Jovel I, Xu W, Larsson E, Malmberg M, Gil JP, Premji Z, Mmbando BP, Martensson A. Prevalence of and Risk Factors Associated with Polymerase Chain Reaction-Determined Plasmodium falciparum Positivity on Day 3 after Initiation of Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Bagamoyo District, Tanzania. Am J Trop Med Hyg. 2019 May;100(5):1179-1186. doi: 10.4269/ajtmh.18-0729.