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Multiscale model for forecasting Sabin 2 vaccine virus household and community transmission.

ABSTRACT: Since the global withdrawal of Sabin 2 oral poliovirus vaccine (OPV) from routine immunization, the Global Polio Eradication Initiative (GPEI) has reported multiple circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks. Here, we generated an agent-based, mechanistic model designed to assess OPV-related vaccine virus transmission risk in populations with heterogeneous immunity, demography, and social mixing patterns. To showcase the utility of our model, we present a simulation of mOPV2-related Sabin 2 transmission in rural Matlab, Bangladesh based on stool samples collected from infants and their household contacts during an mOPV2 clinical trial. Sabin 2 transmission following the mOPV2 clinical trial was replicated by specifying multiple, heterogeneous contact rates based on household and community membership. Once calibrated, the model generated Matlab-specific insights regarding poliovirus transmission following an accidental point importation or mass vaccination event. We also show that assuming homogeneous contact rates (mass action), as is common of poliovirus forecast models, does not accurately represent the clinical trial and risks overestimating forecasted poliovirus outbreak probability. Our study identifies household and community structure as an important source of transmission heterogeneity when assessing OPV-related transmission risk and provides a calibratable framework for expanding these analyses to other populations. Trial Registration: ClinicalTrials.gov This trial is registered with clinicaltrials.gov, NCT02477046.

SUBMITTER: Famulare M

PROVIDER: S-EPMC8726461 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Multiscale model for forecasting Sabin 2 vaccine virus household and community transmission.

Famulare Michael M Wong Wesley W Haque Rashidul R Platts-Mills James A JA Saha Parimalendu P Aziz Asma B AB Ahmed Tahmina T Islam Md Ohedul MO Uddin Md Jashim MJ Bandyopadhyay Ananda S AS Yunus Mohammed M Zaman Khalequ K Taniuchi Mami M

PLoS computational biology 20211221 12

Since the global withdrawal of Sabin 2 oral poliovirus vaccine (OPV) from routine immunization, the Global Polio Eradication Initiative (GPEI) has reported multiple circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks. Here, we generated an agent-based, mechanistic model designed to assess OPV-related vaccine virus transmission risk in populations with heterogeneous immunity, demography, and social mixing patterns. To showcase the utility of our model, we present a simulation of mOPV ...[more]

PMID: 34932560

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Project description:The oral poliovirus vaccines (OPVs) are one of the most effective disease eradication tools in public health. However, the OPV strains are genetically unstable and can cause outbreaks of circulating, vaccine-derived Type 2 poliovirus (cVDPV2) that are clinically indistinguishable from wild poliovirus (WPV) outbreaks. Here, we developed a Sabin 2 reversion model that simulates the reversion of Sabin 2 to reacquire a WPV-like phenotype based on the clinical differences in shedding duration and infectiousness between individuals vaccinated with Sabin 2 and those infected with WPV. Genetic reversion is informed by a canonical reversion pathway defined by three gatekeeper mutations (A481G, U2909C, and U398C) and the accumulation of deleterious nonsynonymous mutations. Our model captures essential aspects of both phenotypic and molecular evolution and simulates transmission using a multiscale transmission model that consolidates the relationships among immunity, susceptibility, and transmission risk. Despite rapid Sabin 2 attenuation reversal, we show that the emergence of a revertant virus does not guarantee a cVDPV2 outbreak. When simulating outbreaks in Matlab, Bangladesh, we found that cVDPV2 outbreaks are most likely in areas with low population-level immunity and poor sanitation. In Matlab, our model predicted that declining immunity against Type 2 poliovirus following the cessation of routine OPV vaccination was not enough to promote cVDPV2 emergence. However, cVDPV2 emergencedepended on the average viral exposure dose per contact, which was modeled as a combination of the viral concentration per fecal gram and the average fecal-oral dose per contact. These results suggest that cVDPV2 emergence risk can be mitigated by reducing the amount of infectious fecal material individuals are exposed to. Thus, a combined strategy of assessing and improving sanitation levels in conjunction with high-coverage vaccination campaigns could limit the future cVDPV2 emergence.

Project description:UnlabelledFour cases of acute flaccid paralysis caused by slightly evolved (Sabin-like) vaccine polioviruses of serotype 2 were registered in July to August 2010 in an orphanage of Biysk (Altai Region, Russia). The Biysk cluster of vaccine-associated paralytic poliomyelitis (VAPP) had several uncommon, if not unique, features. (i) Until this outbreak, Sabin-like viruses (in distinction to more markedly evolved vaccine-derived polioviruses [VDPVs]) were reported to cause only sporadic cases of VAPP. Consequently, VAPP cases were not considered to require outbreak-type responses. However, the Biysk outbreak completely blurred the borderline between Sabin-like viruses and VDPVs in epidemiological terms. (ii) The outbreak demonstrated a very high disease/infection ratio, apparently exceeding even that reported for wild polioviruses. The viral genome structures did not provide any substantial hints as to the underlying reason(s) for such pathogenicity. (iii) The replacement of intestinal poliovirus lineages by other Sabin-like lineages during short intervals after the disease onsets was observed in two patients. Again, the sequences of the respective genomes provided no clues to explain these events. (iv) The polioviruses isolated from the patients and their contacts demonstrated a striking heterogeneity as well as rapid and uneven evolution of the whole genomes and their parts, apparently due to extensive interpersonal contacts in a relatively small closed community, multiple bottlenecking, and recombination. Altogether, the results demonstrate several new aspects of pathogenicity, epidemiology, and evolution of vaccine-related polioviruses and underscore several serious gaps in understanding these problems.ImportanceThe oral poliovirus vaccine largely contributed to the nearly complete disappearance of poliovirus-caused poliomyelitis. Being generally safe, it can, in some cases, result in a paralytic disease. Two types of such outcomes are distinguished: those caused by slightly diverged (Sabin-like) viruses on the one hand and those caused by significantly diverged VDPVs on the other. This classification is based on the number of mutations in the viral genome region encoding a viral structural protein. Until now, only sporadic poliomyelitis cases due to Sabin-like polioviruses had been described, and in distinction from the VDPV-triggered outbreaks, they did not require broad-scale epidemiological responses. Here, an unusual outbreak of poliomyelitis caused by a Sabin-like virus is reported, which had an exceptionally high disease/infection ratio. This outbreak blurred the borderline between Sabin-like polioviruses and VDPVs both in pathogenicity and in the kind of responses required, as well as underscoring important gaps in understanding the pathogenicity, epidemiology, and evolution of vaccine-derived polioviruses.

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Dataset Information

Multiscale model for forecasting Sabin 2 vaccine virus household and community transmission.

Publications

Multiscale model for forecasting Sabin 2 vaccine virus household and community transmission.

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