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Background: Since 2014, seasonal malaria chemoprevention (SMC) with amodiaquine-sulfadoxine-pyrimethamine (AQ-SP) has been implemented on a large scale during the high malaria transmission season in Burkina Faso. This paper reports the prevalence of microscopic and submicroscopic malaria infection at the outset and after the first round of SMC in children under five years old in Bama, Burkina Faso, as well as host and parasite factors involved in mediating the efficacy and tolerability of SMC.
Methods: Two sequential cross-sectional surveys were conducted in late July and August 2017 during the first month of SMC in a rural area in southwest Burkina Faso. Blood smears and dried blood spots were collected from 106 and 93 children under five, respectively, at the start of SMC and again three weeks later. Malaria infection was detected by microscopy and by PCR from dried blood spots. For all children, day 7 plasma concentrations of desethylamodiaquine (DEAQ) were measured and CYP2C8 genetic variants influencing AQ metabolism were genotyped. Samples were additionally genotyped for pfcrt K76T and pfmdr1 N86Y, molecular markers associated with reduced amodiaquine susceptibility.
Results: 2.8% (3/106) of children were positive for Plasmodium falciparum infection by microscopy and 13.2% (14/106) by nested PCR within 2 days of SMC administration. Three weeks after SMC administration, in the same households, 4.3% (4/93) of samples were positive by microscopy and 14.0% (13/93) by PCR (p=0.0007). CYP2C8*2, associated with impaired amodiaquine metabolism, was common with an allelic frequency of 17.1% (95%CI=10.0-24.2). Day 7 concentration of DEAQ ranged from 0.48 to 362.80 ng/mL with a median concentration of 56.34 ng/mL. Pfmdr1 N86 predominated at both time points, whilst a non-significant trend towards a higher prevalence of pfcrt 76T was seen at week 3.
Conclusion: This study showed a moderate prevalence of low-level malaria parasitaemia in children 3 weeks following SMC during the first month of administration. Day 7 concentrations of the active DEAQ metabolite varied widely, likely reflecting variability in adherence and possibly metabolism. These findings highlight factors that may contribute to the effectiveness of SMC in children in a high transmission setting.
Keywords
Seasonal malaria chemoprevention, Plasmodium falciparum, microscopic and submicroscopic, Burkina Faso
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View the published article at Malaria Journal.
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Posted 22 Jun, 2020
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Editorial decision: Accept
On 25 Jun, 2020
Editor assigned
On 20 Jun, 2020
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On 19 Jun, 2020
Editor invited
On 19 Jun, 2020
No comments provided
Editorial decision: Minor Revision
On 16 Jun, 2020
Editor assigned
On 15 Jun, 2020
Submission checks complete
On 14 Jun, 2020
Editor invited
On 14 Jun, 2020
No comments provided
Editorial decision: Minor Revision
On 16 May, 2020
Review #1 received
Received 14 May, 2020
Review #2 received
Received 14 May, 2020
Reviewer #3 agreed
On 11 May, 2020
Reviewer #1 agreed
On 04 May, 2020
Reviewer #2 agreed
On 04 May, 2020
Reviewers invited
Invitations sent on 03 May, 2020
Editor assigned
On 18 Apr, 2020
First submitted
On 17 Apr, 2020
Submission checks complete
On 17 Apr, 2020
Editor invited
On 17 Apr, 2020
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See the published version of this preprint at Malaria Journal.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Malaria Journal.
Version 3
Posted 22 Jun, 2020
No community comments so far
Editorial decision: Accept
On 25 Jun, 2020
Editor assigned
On 20 Jun, 2020
Submission checks complete
On 19 Jun, 2020
Editor invited
On 19 Jun, 2020
No comments provided
Editorial decision: Minor Revision
On 16 Jun, 2020
Editor assigned
On 15 Jun, 2020
Submission checks complete
On 14 Jun, 2020
Editor invited
On 14 Jun, 2020
No comments provided
Editorial decision: Minor Revision
On 16 May, 2020
Review #1 received
Received 14 May, 2020
Review #2 received
Received 14 May, 2020
Reviewer #3 agreed
On 11 May, 2020
Reviewer #1 agreed
On 04 May, 2020
Reviewer #2 agreed
On 04 May, 2020
Reviewers invited
Invitations sent on 03 May, 2020
Editor assigned
On 18 Apr, 2020
First submitted
On 17 Apr, 2020
Submission checks complete
On 17 Apr, 2020
Editor invited
On 17 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Infectious Diseases
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Malaria Journal.
Background: Since 2014, seasonal malaria chemoprevention (SMC) with amodiaquine-sulfadoxine-pyrimethamine (AQ-SP) has been implemented on a large scale during the high malaria transmission season in Burkina Faso. This paper reports the prevalence of microscopic and submicroscopic malaria infection at the outset and after the first round of SMC in children under five years old in Bama, Burkina Faso, as well as host and parasite factors involved in mediating the efficacy and tolerability of SMC.
Methods: Two sequential cross-sectional surveys were conducted in late July and August 2017 during the first month of SMC in a rural area in southwest Burkina Faso. Blood smears and dried blood spots were collected from 106 and 93 children under five, respectively, at the start of SMC and again three weeks later. Malaria infection was detected by microscopy and by PCR from dried blood spots. For all children, day 7 plasma concentrations of desethylamodiaquine (DEAQ) were measured and CYP2C8 genetic variants influencing AQ metabolism were genotyped. Samples were additionally genotyped for pfcrt K76T and pfmdr1 N86Y, molecular markers associated with reduced amodiaquine susceptibility.
Results: 2.8% (3/106) of children were positive for Plasmodium falciparum infection by microscopy and 13.2% (14/106) by nested PCR within 2 days of SMC administration. Three weeks after SMC administration, in the same households, 4.3% (4/93) of samples were positive by microscopy and 14.0% (13/93) by PCR (p=0.0007). CYP2C8*2, associated with impaired amodiaquine metabolism, was common with an allelic frequency of 17.1% (95%CI=10.0-24.2). Day 7 concentration of DEAQ ranged from 0.48 to 362.80 ng/mL with a median concentration of 56.34 ng/mL. Pfmdr1 N86 predominated at both time points, whilst a non-significant trend towards a higher prevalence of pfcrt 76T was seen at week 3.
Conclusion: This study showed a moderate prevalence of low-level malaria parasitaemia in children 3 weeks following SMC during the first month of administration. Day 7 concentrations of the active DEAQ metabolite varied widely, likely reflecting variability in adherence and possibly metabolism. These findings highlight factors that may contribute to the effectiveness of SMC in children in a high transmission setting.
Figure 1
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