The potential impact of expanding target age groups for polio immunization campaigns

Background: Global efforts to eradicate wild polioviruses (WPVs) continue to face challenges due to uninterrupted endemic WPV transmission in three countries and importation-related outbreaks into previously polio-free countries. We explore the potential role of including older children and adults in supplemental immunization activities (SIAs) to more rapidly increase population immunity and prevent or stop transmission. Methods: We use a differential equation-based dynamic poliovirus transmission model to analyze the epidemiological impact and vaccine resource implications of expanding target age groups in SIAs. We explore the use of older age groups in SIAs for three situations: alternative responses to the 2010 outbreak in Tajikistan, retrospective examination of elimination in two high-risk states in northern India, and prospective and retrospective strategies to accelerate elimination in endemic northwestern Nigeria. Our model recognizes the ability of individuals with waned mucosal immunity (i.e., immunity from a historical live poliovirus infection) to become re-infected and contribute to transmission to a limited extent. Results: SIAs involving expanded age groups reduce overall caseloads, decrease transmission, and generally lead to a small reduction in the time to achieve WPV elimination. Analysis of preventive expanded age group SIAs in Tajikistan or prior to type-specific surges in incidence in high-risk areas of India and Nigeria showed the greatest potential benefits of expanded age groups. Analysis of expanded age group SIAs in outbreak situations or to accelerate the interruption of endemic transmission showed relatively less benefit, largely due to the circulation of WPV reaching individuals sooner or more effectively than the SIAs. The India and Nigeria results depend strongly on how well SIAs involving expanded age groups reach relatively isolated subpopulations that sustain clusters of susceptible children, which we assume play a key role in persistent endemic WPV transmission in these areas. Conclusions: This study suggests the need to carefully consider the epidemiological situation in the context of decisions to use expanded age group SIAs. Subpopulations of susceptible individuals may independently sustain transmission, which will reduce the overall benefits associated with using expanded age group SIAs to increase population immunity to a sufficiently high level to stop transmission and reduce the incidence of paralytic cases

Modeling undetected live poliovirus circulation after apparent interruption of transmission: implications for surveillance and vaccination

Background: Most poliovirus infections occur with no symptoms and this leads to the possibility of silent circulation, which complicates the confirmation of global goals to permanently end poliovirus transmission. Previous simple models based on hypothetical populations assumed perfect detection of symptomatic cases and suggested the need to observe no paralytic cases from wild polioviruses (WPVs) for approximately 3-4 years to achieve 95% confidence about eradication, but the complexities in real populations and the imperfect nature of surveillance require consideration. Methods: We revisit the probability of undetected poliovirus circulation using a more comprehensive model that reflects the conditions in a number of places with different characteristics related to WPV transmission, and we model the actual environmental WPV detection that occurred in Israel in 2013. We consider the analogous potential for undetected transmission of circulating vaccine-derived polioviruses. The model explicitly accounts for the impact of different vaccination activities before and after the last detected case of paralytic polio, different levels of surveillance, variability in transmissibility and neurovirulence among serotypes, and the possibility of asymptomatic participation in transmission by previously-vaccinated or infected individuals. Results: We find that prolonged circulation in the absence of cases and thus undetectable by case-based surveillance may occur if vaccination keeps population immunity close to but not over the threshold required for the interruption of transmission, as may occur in northwestern Nigeria for serotype 2 circulating vaccine-derived poliovirus in the event of insufficient tOPV use. Participation of IPV-vaccinated individuals in asymptomatic fecal-oral transmission may also contribute to extended transmission undetectable by case-based surveillance, as occurred in Israel. We also find that gaps or quality issues in surveillance could significantly reduce confidence about actual disruption. Maintaining high population immunity and high-quality surveillance for several years after the last detected polio cases will remain critical elements of the polio end game. Conclusions: Countries will need to maintain vigilance in their surveillance for polioviruses and recognize that their risks of undetected circulation may differ as a function of their efforts to manage population immunity and to identify cases or circulating live polioviruses

The potential impact of expanding target age groups for polio immunization campaigns

BACKGROUND: Global efforts to eradicate wild polioviruses (WPVs) continue to face challenges due to uninterrupted endemic WPV transmission in three countries and importation-related outbreaks into previously polio-free countries. We explore the potential role of including older children and adults in supplemental immunization activities (SIAs) to more rapidly increase population immunity and prevent or stop transmission. METHODS: We use a differential equation-based dynamic poliovirus transmission model to analyze the epidemiological impact and vaccine resource implications of expanding target age groups in SIAs. We explore the use of older age groups in SIAs for three situations: alternative responses to the 2010 outbreak in Tajikistan, retrospective examination of elimination in two high-risk states in northern India, and prospective and retrospective strategies to accelerate elimination in endemic northwestern Nigeria. Our model recognizes the ability of individuals with waned mucosal immunity (i.e., immunity from a historical live poliovirus infection) to become re-infected and contribute to transmission to a limited extent. RESULTS: SIAs involving expanded age groups reduce overall caseloads, decrease transmission, and generally lead to a small reduction in the time to achieve WPV elimination. Analysis of preventive expanded age group SIAs in Tajikistan or prior to type-specific surges in incidence in high-risk areas of India and Nigeria showed the greatest potential benefits of expanded age groups. Analysis of expanded age group SIAs in outbreak situations or to accelerate the interruption of endemic transmission showed relatively less benefit, largely due to the circulation of WPV reaching individuals sooner or more effectively than the SIAs. The India and Nigeria results depend strongly on how well SIAs involving expanded age groups reach relatively isolated subpopulations that sustain clusters of susceptible children, which we assume play a key role in persistent endemic WPV transmission in these areas. CONCLUSIONS: This study suggests the need to carefully consider the epidemiological situation in the context of decisions to use expanded age group SIAs. Subpopulations of susceptible individuals may independently sustain transmission, which will reduce the overall benefits associated with using expanded age group SIAs to increase population immunity to a sufficiently high level to stop transmission and reduce the incidence of paralytic cases

Logistical challenges and assumptions for modeling the failure of global cessation of oral poliovirus vaccine (OPV)

Introduction: The inability to successfully stop all use of oral poliovirus vaccine (OPV) as part of the polio endgame and/or the possibilities of reintroduction of live polioviruses after successful OPV cessation may imply the need to restart OPV production and use, either temporarily or permanently. Areas covered: Complementing prior work that explored the risks of potential OPV restart, we discuss the logistical challenges and implications of restarting OPV in the future, and we develop appropriate assumptions for modeling the possibility of OPV restart. The complexity of phased cessation of the three OPV serotypes implies different potential combinations of OPV use long term. We explore the complexity of polio vaccine choices and key unresolved policy questions that may impact continuing and future use of OPV and/or inactivated poliovirus vaccine (IPV). We then characterize the assumptions required to quantitatively model OPV restart in prospective global-integrated economic policy models for the polio endgame. Expert commentary: Depending on the timing, restarting production of OPV would imply some likely delays associated with ramp-up, re-licensing, and other logistics that would impact the availability and costs of restarting the use of OPV in national immunization programs after globally coordinated cessation of one or more OPV serotypes

Modeling Strategies To Increase Population Immunity And Prevent Poliovirus Transmission In 2 High-Risk Areas In Northern India

Methods: We used a differential equation-based model to characterize the dynamics of poliovirus transmission and various opportunities to increase and maintain high population immunity to poliovirus transmission for 2 high-risk areas in northern India. We explored options that India probably considered before 2011, to demonstrate the impact of strategies to accelerate WPV elimination and sustain high population immunity. We also characterized the impact of current and potential future vaccination strategies and explored the potential trade-offs associated with the various strategies

Managing Population Immunity To Reduce Or Eliminate The Risks Of Circulation Following The Importation Of Polioviruses

Poliovirus importations into polio-free countries represent a major concern during the final phases of global eradication of wild polioviruses (WPVs). We extend dynamic transmission models to demonstrate the dynamics of population immunity out through 2020 for three countries that only used inactivated poliovirus vaccine (IPV) for routine immunization: the US, Israel, and The Netherlands. For each country, we explore the vulnerability to re-established transmission following an importation for each poliovirus serotype, including the impact of immunization choices following the serotype 1 WPV importation that occurred in 2013 in Israel. As population immunity declines below the threshold required to prevent transmission, countries become at risk for re-established transmission. Although importations represent stochastic events that countries cannot fully control because people cross borders and polioviruses mainly cause asymptomatic infections, countries can ensure that any importations die out. Our results suggest that the general US population will remain above the threshold for transmission through 2020. In contrast, Israel became vulnerable to re-established transmission of importations of live polioviruses by the late 2000s. In Israel, the recent WPV importation and outbreak response use of bivalent oral poliovirus vaccine (bOPV) eliminated the vulnerability to an importation of poliovirus serotypes 1 and 3 for several years, but not serotype 2. The Netherlands experienced a serotype 1 WPV outbreak in 1992-1993 and became vulnerable to re-established transmission in religious communities with low vaccine acceptance around the year 2000, although the general population remains well-protected from widespread transmission. All countries should invest in active management of population immunity to avoid the potential circulation of imported live polioviruses. IPV-using countries may wish to consider prevention opportunities and/or ensure preparedness for response. Countries currently using a sequential IPV/OPV schedule should continue to use all licensed OPV serotypes until global OPV cessation to minimize vulnerability to circulation of imported polioviruses

Characterizing Poliovirus Transmission And Evolution: Insights From Modeling Experiences With Wild And Vaccine-Related Polioviruses

With national and global health policymakers facing numerous complex decisions related to achieving and maintaining polio eradication, we expanded our previously developed dynamic poliovirus transmission model using information from an expert literature review process and including additional immunity states and the evolution of oral poliovirus vaccine (OPV). The model explicitly considers serotype differences and distinguishes fecal-oral and oropharyngeal transmission. We evaluated the model by simulating diverse historical experiences with polioviruses, including one country that eliminated wild poliovirus using both OPV and inactivated poliovirus vaccine (IPV) (USA), three importation outbreaks of wild poliovirus (Albania, the Netherlands, Tajikistan), one situation in which no circulating vaccine-derived polioviruses (cVDPVs) emerge despite annual OPV use and cessation (Cuba), three cVDPV outbreaks (Haiti, Madura Island in Indonesia, northern Nigeria), one area of current endemic circulation of all three serotypes (northern Nigeria), and one area with recent endemic circulation and subsequent elimination of multiple serotypes (northern India). We find that when sufficient information about the conditions exists, the model can reproduce the general behavior of poliovirus transmission and outbreaks while maintaining consistency in the generic model inputs. The assumption of spatially homogeneous mixing remains a significant limitation that affects the performance of the differential equation-based model when significant heterogeneities in immunity and mixing may exist. Further studies on OPV virus evolution and improved understanding of the mechanisms of mixing and transmission may help to better characterize poliovirus transmission in populations. Broad application of the model promises to offer insights in the context of global and national policy and economic models. © 2013 Society for Risk Analysis

Modeling Options To Manage Type 1 Wild Poliovirus Imported Into Israel In 2013

Background. After 25 years without poliomyelitis cases caused by circulating wild poliovirus (WPV) in Israel, sewage sampling detected WPV type 1 (WPV1) in April 2013, despite high vaccination coverage with only inactivated poliovirus vaccine (IPV) since 2005. Methods. We used a differential equation-based model to simulate the dynamics of poliovirus transmission and population immunity in Israel due to past exposure to WPV and use of oral poliovirus vaccine (OPV) in addition to IPV. We explored the influences of various immunization options to stop imported WPV1 circulation in Israel. Results. We successfully modeled the potential for WPVs to circulate without detected cases in Israel. Maintaining a sequential IPV/OPV schedule instead of switching to an IPV-only schedule in 2005 would have kept population immunity high enough in Israel to prevent WPV1 circulation. The Israeli response to WPV1 detection prevented paralytic cases; a more rapid response might have interrupted transmission more quickly. Conclusions. IPV-based protection alone might not provide sufficient population immunity to prevent poliovirus transmission after an importation. As countries transition to IPV in immunization schedules, they may need to actively manage population immunity and consider continued use of OPV, to avoid the potential circulation of imported live polioviruses before globally coordinated cessation of OPV use

Associations between pneumonia and residential distance to livestock farms over a five-year period in a large population-based study

In a recent study of electronic health records (EHR) of general practitioners in a livestock-dense area in The Netherlands in 2009, associations were found between residential distance to poultry farms and the occurrence of community-acquired pneumonia (CAP). In addition, in a recent cross-sectional study in 2494 adults in 2014/2015 an association between CAP and proximity to goat farms was observed. Here, we extended the 2009 EHR analyses across a wider period of time (2009-2013), a wider set of health effects, and a wider set of farm types as potential risk sources. A spatial (transmission) kernel model was used to investigate associations between proximity to farms and CAP diagnosis for the period from 2009 to 2013, obtained from EHR of in total 140,059 GP patients. Also, associations between proximity to farms and upper respiratory infections, inflammatory bowel disease, and (as a control disease) lower back pain were analysed. Farm types included as potential risk sources in these analyses were cattle, (dairy) goats, mink, poultry, sheep, and swine. The previously found association between CAP occurrence and proximity to poultry farms was confirmed across the full 5-year study period. In addition, we found an association between increased risk for pneumonia and proximity to (dairy) goat farms, again consistently across all years from 2009 to 2013. No consistent associations were found for any of the other farm types (cattle, mink, sheep and swine), nor for the other health effects considered. On average, the proximity to poultry farms corresponds to approximately 119 extra patients with CAP each year per 100,000 people in the research area, which accounts for approximately 7.2% extra cases. The population attributable risk percentage of CAP cases in the research area attributable to proximity to goat farms is approximately 5.4% over the years 2009-2013. The most probable explanation for the association of CAP with proximity to poultry farms is thought to be that particulate matter and its components are making people more susceptible to respiratory infections. The causes of the association with proximity to goat farms is still unclear. Although the 2007-2010 Q-fever epidemic in the area probably contributed Q-fever related pneumonia cases to the observed additional cases in 2009 and 2010, it cannot explain the association found in later years 2011-2013