Time taken to detect and respond to polio outbreaks in Africa and the potential impact of direct molecular detection and nanopore sequencing
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Supporting information
Supporting information
Author(s)
Type
Journal Article
Abstract
Background
Detection of poliovirus outbreaks relies on a complex laboratory algorithm of cell-culture, PCR and sequencing to distinguish wild-type and vaccine-derived polioviruses (VDPV) from Sabin-like strains. We investigated the potential for direct molecular detection and nanopore sequencing (DDNS) to accelerate poliovirus detection.
Methods
We analysed laboratory data for time required to analyse and sequence serotype-2 VDPV (VDPV2) in stool collected from children with acute flaccid paralysis in Africa (May 2016-February 2020). Impact of delayed detection on VDPV2 outbreak size was assessed through negative binomial regression.
Results
VDPV2 confirmation in 525 stools required a median of 49 days from paralysis onset (10th-90th percentile: 29-74), comprising collection and transport (median: 16 days), cell-culture (7 days), intratypic differentiation RT-qPCR (3 days) and sequencing (including shipping if required) (15 days). New VDPV2 outbreaks were confirmed a median of 35 days (27-60) after paralysis onset, which we estimate could be reduced to 16 days by DDNS (9-37). Because longer delays in confirmation and response were positively associated with more cases (p<0.001), we estimate that DDNS could reduce the number of VDPV2 cases before a response by 28% (95% CrI 12-42%).
Conclusions
DDNS could accelerate poliovirus outbreak response, reducing their size and the cost of eradication.
Detection of poliovirus outbreaks relies on a complex laboratory algorithm of cell-culture, PCR and sequencing to distinguish wild-type and vaccine-derived polioviruses (VDPV) from Sabin-like strains. We investigated the potential for direct molecular detection and nanopore sequencing (DDNS) to accelerate poliovirus detection.
Methods
We analysed laboratory data for time required to analyse and sequence serotype-2 VDPV (VDPV2) in stool collected from children with acute flaccid paralysis in Africa (May 2016-February 2020). Impact of delayed detection on VDPV2 outbreak size was assessed through negative binomial regression.
Results
VDPV2 confirmation in 525 stools required a median of 49 days from paralysis onset (10th-90th percentile: 29-74), comprising collection and transport (median: 16 days), cell-culture (7 days), intratypic differentiation RT-qPCR (3 days) and sequencing (including shipping if required) (15 days). New VDPV2 outbreaks were confirmed a median of 35 days (27-60) after paralysis onset, which we estimate could be reduced to 16 days by DDNS (9-37). Because longer delays in confirmation and response were positively associated with more cases (p<0.001), we estimate that DDNS could reduce the number of VDPV2 cases before a response by 28% (95% CrI 12-42%).
Conclusions
DDNS could accelerate poliovirus outbreak response, reducing their size and the cost of eradication.
Date Issued
2022-08-01
Date Acceptance
2021-10-05
Citation
Journal of Infectious Diseases, 2022, 226 (3), pp.453-462
ISSN
0022-1899
Publisher
Oxford University Press
Start Page
453
End Page
462
Journal / Book Title
Journal of Infectious Diseases
Volume
226
Issue
3
Copyright Statement
© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Bill & Melinda Gates Foundation
Bill & Melinda Gates Foundation
World Health Organization
Bill & Melinda Gates Foundation
Medical Research Council (MRC)
Identifier
https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab518/6384638
Grant Number
OPP1207299
OPP1171890
2020/1014353-0
INV-024477
MR/R015600/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Immunology
Infectious Diseases
Microbiology
poliovirus
direct detection
VDPV
outbreak
stool
AFP
nanopore
surveillance
REAL-TIME
CULTURE
PCR
AFP
VDPV
direct detection
nanopore
outbreak
poliovirus
stool
surveillance
Africa
Child
Disease Outbreaks
Humans
Nanopore Sequencing
Paralysis
Poliomyelitis
Poliovirus
Poliovirus Vaccine, Oral
Humans
Poliovirus
Poliomyelitis
Paralysis
Poliovirus Vaccine, Oral
Disease Outbreaks
Child
Africa
Nanopore Sequencing
Microbiology
06 Biological Sciences
11 Medical and Health Sciences
Publication Status
Published
Date Publish Online
2021-10-08