Background Vaccine-derived polioviruses (VDPVs), strains of poliovirus mutated from the oral polio vaccine, pose a challenge to global polio eradication. Immunodeficiency-related vaccine-derived polioviruses (iVDPVs) are a type of VDPV which may serve as sources of poliovirus reintroduction after the eradication of wild-type poliovirus. This review is a comprehensive update of confirmed iVDPV cases published in the scientific literature from 1962 to 2012, and describes clinically relevant trends in reported iVDPV cases worldwide. Methods We conducted a systematic review of published iVDPV case reports from January 1960 to November 2012 from four databases. We included cases in which the patient had a primary immunodeficiency, and the vaccine virus isolated from the patient either met the sequencing definition of VDPV (>1% divergence for serotypes 1 and 3 and >0.6% for serotype 2) and/or was previously reported as an iVDPV by the World Health Organization. Results We identified 68 iVDPV cases in 49 manuscripts reported from 25 countries and the Palestinian territories. 62% of case patients were male, 78% presented clinically with acute flaccid paralysis, and 65% were iVDPV2. 57% of cases occurred in patients with predominantly antibody immunodeficiencies, and the overall all-cause mortality rate was greater than 60%. The median age at case detection was 1.4 years [IQR: 0.8, 4.5] and the median duration of shedding was 1.3 years [IQR: 0.7, 2.2]. We identified a poliovirus genome VP1 region mutation rate of 0.72% per year and a higher median percent divergence for iVDPV1 cases. More cases were reported from high income countries, which also had a larger age variation and different distribution of immunodeficiencies compared to upper and lower middle-income countries. Conclusion Our study describes the incidence and characteristics of global iVDPV cases reported in the literature in the past five decades. It also highlights the regional and economic disparities of reported iVDPV cases.
New are R&D Staff at Oak Ridge National Laboratory. This manuscript has been authored by UT-Battelle, LLC, under contract DE-AC05-00OR22725 with the US Department of Energy (DOE). The US government retains and the publisher, by accepting the article for publication, acknowledges that the US government retains a nonexclusive, paidup, irrevocable, worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for US government purposes. DOE will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan).
US background ozone (O 3) includes O 3 produced from anthropogenic O 3 precursors emitted outside of the USA, from global methane, and from any natural sources. Using a suite of sensitivity simulations in the GEOS-Chem global chemistry transport model, we estimate the influence from individual background sources versus US anthropogenic sources on total surface O 3 over 10 continental US regions from 2004 to 2012. Evaluation with observations reveals model biases of +0-19 ppb in seasonal mean maximum daily 8 h average (MDA8) O 3 , highest in summer over the eastern USA. Simulated high-O 3 events cluster too late in the season. We link these model biases to excessive regional O 3 production (e.g., US anthropogenic, biogenic volatile organic compounds (BVOCs), and soil NO x , emissions), or coincident missing sinks. On the 10 highest observed O 3 days during summer (O 3 _top10obs_JJA), US anthropogenic emissions enhance O 3 by 5-11 ppb and by less than 2 ppb in the eastern versus western USA. The O 3 enhancement from BVOC emissions during summer is 1-7 ppb higher on O 3 _top10obs_JJA days than on average days, while intercontinental pollution is up to 2 ppb higher on average versus on O 3 _top10obs_JJA days. During the summers of 2004-2012, monthly regional mean US background O 3 MDA8 levels vary by up to 15 ppb from year to year. Observed and simulated summertime total surface O 3 levels on O 3 _top10obs_JJA days decline by 3 ppb (averaged over all regions) from 2004-2006 to 2010-2012, reflecting rising US background (+2 ppb) and declining US anthropogenic O 3 emissions (−6 ppb) in the model. The model attributes interannual variability in US background O 3 on O 3 _top10obs days to natural sources, not international pollution transport. We find that a 3-year averaging period is not long enough to eliminate interannual variability in background O 3 on the highest observed O 3 days.
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