See the published version of this preprint at BMC Infectious Diseases.
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 article
Molly Deutsch-Feldman
University of North Carolina at Chapel Hill
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6191-930X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys. Methods: We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time. Results: The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady. Conclusions: This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance.
Keywords
malaria, drug resistance, spatial-temporal modeling
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
Loading...
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 BMC Infectious Diseases.
No community comments so far
Submission checks complete
On 06 Nov, 2019
Editorial decision: Accept
On 28 Sep, 2019
Editor assigned
On 27 Sep, 2019
Editor invited
On 26 Sep, 2019
No comments provided
Editorial decision: Minor revision
On 24 Sep, 2019
Editor assigned
On 29 Aug, 2019
Submission checks complete
On 28 Aug, 2019
Editor invited
On 28 Aug, 2019
Version 1
Posted 29 Aug, 2019
No comments provided
Editorial decision: Minor revision
On 19 Aug, 2019
Review #3 received
Received 04 Aug, 2019
Review #1 received
Received 23 Jul, 2019
Review #2 received
Received 16 Jul, 2019
Reviewer #3 agreed
On 15 Jul, 2019
Reviewer #2 agreed
On 11 Jul, 2019
Reviewer #1 agreed
On 10 Jul, 2019
Editor assigned
On 09 Jul, 2019
Reviewers invited
Invitations sent on 09 Jul, 2019
Submission checks complete
On 09 Jul, 2019
Editor invited
On 09 Jul, 2019
First submitted
On 28 Jun, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Infectious Diseases
Learn more about our company.
See the published version of this preprint at BMC Infectious Diseases.
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 article
Molly Deutsch-Feldman
University of North Carolina at Chapel Hill
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6191-930X
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 BMC Infectious Diseases.
No community comments so far
Submission checks complete
On 06 Nov, 2019
Editorial decision: Accept
On 28 Sep, 2019
Editor assigned
On 27 Sep, 2019
Editor invited
On 26 Sep, 2019
No comments provided
Editorial decision: Minor revision
On 24 Sep, 2019
Editor assigned
On 29 Aug, 2019
Submission checks complete
On 28 Aug, 2019
Editor invited
On 28 Aug, 2019
Version 1
Posted 29 Aug, 2019
No comments provided
Editorial decision: Minor revision
On 19 Aug, 2019
Review #3 received
Received 04 Aug, 2019
Review #1 received
Received 23 Jul, 2019
Review #2 received
Received 16 Jul, 2019
Reviewer #3 agreed
On 15 Jul, 2019
Reviewer #2 agreed
On 11 Jul, 2019
Reviewer #1 agreed
On 10 Jul, 2019
Editor assigned
On 09 Jul, 2019
Reviewers invited
Invitations sent on 09 Jul, 2019
Submission checks complete
On 09 Jul, 2019
Editor invited
On 09 Jul, 2019
First submitted
On 28 Jun, 2019
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 BMC Infectious Diseases.
Background: Drug resistant malaria is a growing concern in the Democratic Republic of the Congo (DRC), where previous studies indicate that parasites resistant to sulfadoxine/pyrimethamine or chloroquine are spatially clustered. This study explores longitudinal changes in spatial patterns to understand how resistant malaria may be spreading within the DRC, using samples from nation-wide population-representative surveys. Methods: We selected 552 children with PCR-detectable Plasmodium falciparum infection and identified known variants in the pfdhps and pfcrt genes associated with resistance. We compared the proportion of mutant parasites in 2013 to those previously reported from adults in 2007, and identified risk factors for carrying a resistant allele using multivariate mixed-effects modeling. Finally, we fit a spatial-temporal model to the observed data, providing smooth allele frequency estimates over space and time. Results: The proportion of co-occurring pfdhps K540E/A581G mutations increased by 16% between 2007 and 2013. The spatial-temporal model suggests that the spatial range of the pfdhps double mutants expanded over time, while the prevalence and range of pfcrt mutations remained steady. Conclusions: This study uses population-representative samples to describe the changing landscape of SP resistance within the DRC, and the persistence of chloroquine resistance. Vigilant molecular surveillance is critical for controlling the spread of resistance.
Figure 1
Figure 2
Figure 3
Loading...