<it>Plasmodium falciparum </it>population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria
<p>Abstract</p> <p>Background</p> <p>This study aimed to explore <it>Plasmodium falciparum </it>population dynamics during the early phase of anti-malarial drug treatment with artemisinin-based combination therapy in children with clinical malaria in a high...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-12-01
|
| Series: | Malaria Journal |
| Subjects: | |
| Online Access: | http://www.malariajournal.com/content/10/1/380 |
| _version_ | 1828738640899997696 |
|---|---|
| author | Carlsson Anja M Ngasala Billy E Dahlström Sabina Membi Christopher Veiga Isabel M Rombo Lars Abdulla Salim Premji Zul Gil J Björkman Anders Mårtensson Andreas |
| author_facet | Carlsson Anja M Ngasala Billy E Dahlström Sabina Membi Christopher Veiga Isabel M Rombo Lars Abdulla Salim Premji Zul Gil J Björkman Anders Mårtensson Andreas |
| author_sort | Carlsson Anja M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>This study aimed to explore <it>Plasmodium falciparum </it>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.</p> <p>Methods</p> <p>A total of 50 children aged 1-10 years with acute uncomplicated <it>P. falciparum </it>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 <it>merozoite surface protein (msp) 1 </it>and <it>2</it>.</p> <p>Results</p> <p>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 <it>msp1 </it>and <it>msp2</it>, 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 <it>msp1 </it>and <it>msp2</it>, respectively. The genotype profile was diverse, and varied considerably over time both within and between patients, molecular markers and their respective families.</p> <p>Conclusion</p> <p>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.</p> <p>The study is registered at <url>http://www.clinicaltrials.gov</url> with identifier NCT00336375.</p> |
| first_indexed | 2024-04-13T00:07:03Z |
| format | Article |
| id | doaj.art-99a3bb113f1d4528902f22a88880af9d |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-04-13T00:07:03Z |
| publishDate | 2011-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-99a3bb113f1d4528902f22a88880af9d2022-12-22T03:11:12ZengBMCMalaria Journal1475-28752011-12-0110138010.1186/1475-2875-10-380<it>Plasmodium falciparum </it>population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malariaCarlsson Anja MNgasala Billy EDahlström SabinaMembi ChristopherVeiga Isabel MRombo LarsAbdulla SalimPremji ZulGil JBjörkman AndersMårtensson Andreas<p>Abstract</p> <p>Background</p> <p>This study aimed to explore <it>Plasmodium falciparum </it>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.</p> <p>Methods</p> <p>A total of 50 children aged 1-10 years with acute uncomplicated <it>P. falciparum </it>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 <it>merozoite surface protein (msp) 1 </it>and <it>2</it>.</p> <p>Results</p> <p>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 <it>msp1 </it>and <it>msp2</it>, 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 <it>msp1 </it>and <it>msp2</it>, respectively. The genotype profile was diverse, and varied considerably over time both within and between patients, molecular markers and their respective families.</p> <p>Conclusion</p> <p>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.</p> <p>The study is registered at <url>http://www.clinicaltrials.gov</url> with identifier NCT00336375.</p>http://www.malariajournal.com/content/10/1/380<it>Plasmodium falciparum</it>MalariaPCRParasite population dynamicsArtemether-lumefantrineAnti-malarial drug trials |
| spellingShingle | Carlsson Anja M Ngasala Billy E Dahlström Sabina Membi Christopher Veiga Isabel M Rombo Lars Abdulla Salim Premji Zul Gil J Björkman Anders Mårtensson Andreas <it>Plasmodium falciparum </it>population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria Malaria Journal <it>Plasmodium falciparum</it> Malaria PCR Parasite population dynamics Artemether-lumefantrine Anti-malarial drug trials |
| title | <it>Plasmodium falciparum </it>population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria |
| title_full | <it>Plasmodium falciparum </it>population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria |
| title_fullStr | <it>Plasmodium falciparum </it>population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria |
| title_full_unstemmed | <it>Plasmodium falciparum </it>population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria |
| title_short | <it>Plasmodium falciparum </it>population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria |
| title_sort | it plasmodium falciparum it population dynamics during the early phase of anti malarial drug treatment in tanzanian children with acute uncomplicated malaria |
| topic | <it>Plasmodium falciparum</it> Malaria PCR Parasite population dynamics Artemether-lumefantrine Anti-malarial drug trials |
| url | http://www.malariajournal.com/content/10/1/380 |
| work_keys_str_mv | AT carlssonanjam itplasmodiumfalciparumitpopulationdynamicsduringtheearlyphaseofantimalarialdrugtreatmentintanzanianchildrenwithacuteuncomplicatedmalaria AT ngasalabillye itplasmodiumfalciparumitpopulationdynamicsduringtheearlyphaseofantimalarialdrugtreatmentintanzanianchildrenwithacuteuncomplicatedmalaria AT dahlstromsabina itplasmodiumfalciparumitpopulationdynamicsduringtheearlyphaseofantimalarialdrugtreatmentintanzanianchildrenwithacuteuncomplicatedmalaria AT membichristopher itplasmodiumfalciparumitpopulationdynamicsduringtheearlyphaseofantimalarialdrugtreatmentintanzanianchildrenwithacuteuncomplicatedmalaria AT veigaisabelm itplasmodiumfalciparumitpopulationdynamicsduringtheearlyphaseofantimalarialdrugtreatmentintanzanianchildrenwithacuteuncomplicatedmalaria AT rombolars itplasmodiumfalciparumitpopulationdynamicsduringtheearlyphaseofantimalarialdrugtreatmentintanzanianchildrenwithacuteuncomplicatedmalaria AT abdullasalim itplasmodiumfalciparumitpopulationdynamicsduringtheearlyphaseofantimalarialdrugtreatmentintanzanianchildrenwithacuteuncomplicatedmalaria AT premjizul itplasmodiumfalciparumitpopulationdynamicsduringtheearlyphaseofantimalarialdrugtreatmentintanzanianchildrenwithacuteuncomplicatedmalaria AT gilj itplasmodiumfalciparumitpopulationdynamicsduringtheearlyphaseofantimalarialdrugtreatmentintanzanianchildrenwithacuteuncomplicatedmalaria AT bjorkmananders itplasmodiumfalciparumitpopulationdynamicsduringtheearlyphaseofantimalarialdrugtreatmentintanzanianchildrenwithacuteuncomplicatedmalaria AT martenssonandreas itplasmodiumfalciparumitpopulationdynamicsduringtheearlyphaseofantimalarialdrugtreatmentintanzanianchildrenwithacuteuncomplicatedmalaria |