TY - JOUR
T1 - Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria
AU - Carlsson, Anja M.
AU - Ngasala, Billy E.
AU - Dahlström, Sabina
AU - Membi, Christopher
AU - Veiga, Isabel M.
AU - Rombo, Lars
AU - Abdulla, Salim
AU - Premji, Zul
AU - Gil, J. Pedro
AU - Björkman, Anders
AU - Mårtensson, Andreas
N1 - Funding Information:
We sincerely thank all children, parents/guardians and staff members at Fukayosi Health Care Centre for their participation in the study. This study received financial support from the Swedish Development Cooperation Agency (SIDA-SAREC; SWE 2003-278), the R&D-Unit, Sörmland Count Council, Sweden (Project grant 82090), Golje’s Foundation, Irma and Arvid Larsson-Röst’s Foundation and Anders Otto Swärd’s Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
PY - 2011
Y1 - 2011
N2 - Background: This study aimed to explore Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment with artemisinin-based combination therapy in children with clinical malaria in a high transmission area in Africa. Methods. A total of 50 children aged 1-10 years with acute uncomplicated P. falciparum malaria in Bagamoyo District, Tanzania, were enrolled. Participants were hospitalized and received supervised standard treatment with artemether-lumefantrine according to body weight in six doses over 3 days. Blood samples were collected 11 times, i.e. at time of diagnosis (-2 h) and 0, 2, 4, 8, 16, 24, 36, 48, 60 and 72 h after initiation of treatment. Parasite population dynamics were assessed using nested polymerase chain reaction (PCR)-genotyping of merozoite surface protein (msp) 1 and 2. Results: PCR-analyses from nine sequential blood samples collected after initiation of treatment identified 20 and 21 additional genotypes in 15/50 (30%) and 14/50 (28%) children with msp1 and msp2, respectively, non-detectable in the pre-treatment samples (-2 and 0 h combined). Some 15/20 (75%) and 14/21 (67%) of these genotypes were identified within 24 h, whereas 17/20 (85%) and 19/21 (90%) within 48 h for msp1 and msp2, respectively. The genotype profile was diverse, and varied considerably over time both within and between patients, molecular markers and their respective families. Conclusion: PCR analyses from multiple blood samples collected during the early treatment phase revealed a complex picture of parasite sub-populations. This underlines the importance of interpreting PCR-outcomes with caution and suggests that the present use of PCR-adjustment from paired blood samples in anti-malarial drug trials may overestimate assessment of drug efficacy in high transmission areas in Africa. The study is registered at with identifier NCT00336375.
AB - Background: This study aimed to explore Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment with artemisinin-based combination therapy in children with clinical malaria in a high transmission area in Africa. Methods. A total of 50 children aged 1-10 years with acute uncomplicated P. falciparum malaria in Bagamoyo District, Tanzania, were enrolled. Participants were hospitalized and received supervised standard treatment with artemether-lumefantrine according to body weight in six doses over 3 days. Blood samples were collected 11 times, i.e. at time of diagnosis (-2 h) and 0, 2, 4, 8, 16, 24, 36, 48, 60 and 72 h after initiation of treatment. Parasite population dynamics were assessed using nested polymerase chain reaction (PCR)-genotyping of merozoite surface protein (msp) 1 and 2. Results: PCR-analyses from nine sequential blood samples collected after initiation of treatment identified 20 and 21 additional genotypes in 15/50 (30%) and 14/50 (28%) children with msp1 and msp2, respectively, non-detectable in the pre-treatment samples (-2 and 0 h combined). Some 15/20 (75%) and 14/21 (67%) of these genotypes were identified within 24 h, whereas 17/20 (85%) and 19/21 (90%) within 48 h for msp1 and msp2, respectively. The genotype profile was diverse, and varied considerably over time both within and between patients, molecular markers and their respective families. Conclusion: PCR analyses from multiple blood samples collected during the early treatment phase revealed a complex picture of parasite sub-populations. This underlines the importance of interpreting PCR-outcomes with caution and suggests that the present use of PCR-adjustment from paired blood samples in anti-malarial drug trials may overestimate assessment of drug efficacy in high transmission areas in Africa. The study is registered at with identifier NCT00336375.
KW - Anti-malarial drug trials
KW - Artemether-lumefantrine
KW - Malaria
KW - PCR
KW - Parasite population dynamics
KW - Plasmodium falciparum
UR - http://www.scopus.com/inward/record.url?scp=83655183190&partnerID=8YFLogxK
U2 - 10.1186/1475-2875-10-380
DO - 10.1186/1475-2875-10-380
M3 - Article
C2 - 22185672
AN - SCOPUS:83655183190
SN - 1475-2875
VL - 10
JO - Malaria Journal
JF - Malaria Journal
M1 - 380
ER -
