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1.
BMJ Open ; 9(1): e023290, 2019 01 21.
Article En | MEDLINE | ID: mdl-30670511

OBJECTIVE: To characterise the costs, including for environmental surveillance (ES), of the Global Polio Laboratory Network (GPLN) that provides laboratory support to the Global Polio Eradication Initiative (GPEI). DESIGN AND PARTICIPANTS: We conducted a survey of the network across 92 countries of the 146 GPLN laboratories plus three non-GPLN laboratories that concentrate environmental samples to collect information about their activities, characteristics and costs during 2016. We estimate the total costs using regression of reported responses and complementing the findings with GPEI data. RESULTS: We received responses from 132 (89%) of the 149 laboratories, with variable response rates for individual questions. We estimate that processing samples of patients with acute flaccid paralysis leads to total costs of approximately $28 million per year (2016 US$) based on extrapolation from reported costs of $16 million, of which 61% were supported by internal (national) funds. Fifty-nine (45%) of the 132 responding laboratories reported supporting ES and we estimate an additional $5.3 million of recurring costs for ES activities performed by the laboratories. The reported costs do not include an estimated additional $10 million of annual global and regional costs to coordinate and support the GPLN. On average, the staff supported by funding for polio in the responding laboratories spent 30% of their time on non-polio activities. We estimate total costs for laboratory support of approximately $43 million (note that this estimate does not include any field or other non-laboratory costs of polio surveillance). CONCLUSIONS: Although countries contribute significantly to the GPLN financing, many laboratories currently depend on GPEI funds, and these laboratories also support the laboratory component of surveillance activities for other diseases. Sustaining critical global surveillance for polioviruses and transitioning support for other disease programmes will require continued significant funding after polio certification.


Global Health/economics , International Cooperation , Laboratories/economics , Poliomyelitis , Humans , Immunization Programs/economics , Poliomyelitis/diagnosis , Poliomyelitis/economics , Poliomyelitis/prevention & control , Poliovirus Vaccines/economics , Public Health/economics , Risk Management , Surveys and Questionnaires
2.
BMJ Open ; 9(1): e023938, 2019 01 15.
Article En | MEDLINE | ID: mdl-30647038

OBJECTIVE: To explore the extent to which undervaccinated subpopulations may influence the confidence about no circulation of wild poliovirus (WPV) after the last detected case. DESIGN AND PARTICIPANTS: We used a hypothetical model to examine the extent to which the existence of an undervaccinated subpopulation influences the confidence about no WPV circulation after the last detected case as a function of different characteristics of the subpopulation (eg, size, extent of isolation). We also used the hypothetical population model to inform the bounds on the maximum possible time required to reach high confidence about no circulation in a completely isolated and unvaccinated subpopulation starting either at the endemic equilibrium or with a single infection in an entirely susceptible population. RESULTS: It may take over 3 years to reach 95% confidence about no circulation for this hypothetical population despite high surveillance sensitivity and high vaccination coverage in the surrounding general population if: (1) ability to detect cases in the undervaccinated subpopulation remains exceedingly small, (2) the undervaccinated subpopulation remains small and highly isolated from the general population and (3) the coverage in the undervaccinated subpopulation remains very close to the minimum needed to eradicate. Fully-isolated hypothetical populations of 4000 people or less cannot sustain endemic transmission for more than 5 years, with at least 20 000 people required for a 50% chance of at least 5 years of sustained transmission in a population without seasonality that starts at the endemic equilibrium. Notably, however, the population size required for persistent transmission increases significantly for realistic populations that include some vaccination and seasonality and/or that do not begin at the endemic equilibrium. CONCLUSIONS: Significant trade-offs remain inherent in global polio certification decisions, which underscore the need for making and valuing investments to maximise population immunity and surveillance quality in all remaining possible WPV reservoirs.


Disease Eradication , Poliomyelitis/prevention & control , Poliomyelitis/transmission , Vaccination Coverage/statistics & numerical data , Developing Countries , Global Health , Humans , Models, Statistical , Poliomyelitis/immunology , Poliovirus/classification , Poliovirus/pathogenicity , Time Factors
3.
Risk Anal ; 39(2): 402-413, 2019 02.
Article En | MEDLINE | ID: mdl-30296340

Since most poliovirus infections occur with no paralytic symptoms, the possibility of silent circulation complicates the confirmation of the end of poliovirus transmission. Based on empirical field experience and theoretical modeling results, the Global Polio Eradication Initiative identified three years without observing paralytic cases from wild polioviruses with good acute flaccid paralysis surveillance as an indication of sufficient confidence that poliovirus circulation stopped. The complexities of real populations and the imperfect nature of real surveillance systems subsequently demonstrated the importance of specific modeling for areas at high risk of undetected circulation, resulting in varying periods of time required to obtain the same level of confidence about no undetected circulation. Using a poliovirus transmission model that accounts for variability in transmissibility and neurovirulence for different poliovirus serotypes and characterizes country-specific factors (e.g., vaccination and surveillance activities, demographics) related to wild and vaccine-derived poliovirus transmission in Pakistan and Afghanistan, we consider the probability of undetected poliovirus circulation for those countries once apparent die-out occurs (i.e., in the absence of any epidemiological signals). We find that gaps in poliovirus surveillance or reaching elimination with borderline sufficient population immunity could significantly increase the time to reach high confidence about interruption of live poliovirus transmission, such that the path taken to achieve and maintain poliovirus elimination matters. Pakistan and Afghanistan will need to sustain high-quality surveillance for polioviruses after apparent interruption of transmission and recognize that as efforts to identify cases or circulating live polioviruses decrease, the risks of undetected circulation increase and significantly delay the global polio endgame.


Communicable Disease Control/methods , Disease Eradication/methods , Poliomyelitis/prevention & control , Poliovirus Vaccine, Oral/therapeutic use , Afghanistan/epidemiology , Global Health , Humans , Models, Theoretical , Pakistan/epidemiology , Poliovirus , Risk Assessment , Risk Management , Vaccination
4.
Risk Anal ; 39(2): 414-425, 2019 02.
Article En | MEDLINE | ID: mdl-30239023

Surveillance for poliovirus during the polio endgame remains uncertain. Building on prior modeling of the potential for undetected poliovirus transmission for conditions like those in Pakistan and Afghanistan, we use a hypothetical model to explore several key characteristics of the poliovirus environmental surveillance (ES) system (e.g., number and quality of sites, catchment sizes, and sampling frequency) and characterize their impacts on the time required to reach high (i.e., 95%) confidence about no circulation (CNC95%) following the last detected case of serotype 1 wild poliovirus. The nature and quality of the existing and future acute flaccid paralysis (AFP) surveillance and ES system significantly impact the estimated CNC95% for places like Pakistan and Afghanistan. The analysis illustrates the tradeoffs between number of sites, sampling frequency, and catchments sizes, and suggests diminishing returns of increasing these three factors beyond a point that depends on site quality and the location of sites. Limitations in data quality and the hypothetical nature of the model reduce the ability to assess the extent to which actual ES systems offer benefits that exceed their costs. Thus, although poliovirus ES may help to reduce the time required to reach high confidence about the absence of undetected circulation, the effect strongly depends on the ability to establish effective ES sites in high-risk areas. The costs and benefits of ES require further analysis.


Disease Eradication/methods , Poliomyelitis/prevention & control , Poliovirus/genetics , Afghanistan/epidemiology , Cost-Benefit Analysis , Humans , Pakistan/epidemiology , Population Surveillance , Probability , Risk Assessment , Serogroup , Sewage , Stochastic Processes
5.
Risk Anal ; 39(2): 389-401, 2019 02.
Article En | MEDLINE | ID: mdl-30239026

Only Pakistan and Afghanistan reported any polio cases caused by serotype 1 wild polioviruses (WPV1s) in 2017. With the dwindling cases in both countries and pressure to finish eradication with the least possible resources, a danger exists of inappropriate prioritization of efforts between the two countries and insufficient investment in the two countries to finish the job. We used an existing differential-equation-based poliovirus transmission and oral poliovirus (OPV) evolution model to simulate a proactive strategy to stop transmission, and different hypothetical reactive strategies that adapt the quality of supplemental immunization activities (SIAs) in response to observed polio cases in Pakistan and Afghanistan. To account for the delay in perception and adaptation, we related the coverage of the SIAs in high-risk, undervaccinated subpopulations to the perceived (i.e., smoothed) polio incidence. Continuation of the current frequency and quality of SIAs remains insufficient to eradicate WPV1 in Pakistan and Afghanistan. Proactive strategies that significantly improve and sustain SIA quality lead to WPV1 eradication and the prevention of circulating vaccine-derived poliovirus (cVDPV) outbreaks. Reactive vaccination efforts that adapt moderately quickly and independently to changes in polio incidence in each country may succeed in WPV1 interruption after several cycles of outbreaks, or may interrupt WPV1 transmission in one country but subsequently import WPV1 from the other country or enable the emergence of cVDPV outbreaks. Reactive vaccination efforts that adapt independently and either more rapidly or more slowly to changes in polio incidence in each country may similarly fail to interrupt WPV1 transmission and result in oscillations of the incidence. Reactive strategies that divert resources to the country of highest priority may lead to alternating large outbreaks. Achieving WPV1 eradication and subsequent successful OPV cessation in Pakistan and Afghanistan requires proactive and sustained efforts to improve vaccination intensity in under-vaccinated subpopulations while maintaining high population immunity elsewhere.


Poliomyelitis/prevention & control , Poliovirus Vaccine, Oral/therapeutic use , Adolescent , Adult , Afghanistan/epidemiology , Child , Child, Preschool , Disease Eradication , Disease Outbreaks , Humans , Immunization Programs , Incidence , Infant , Infant, Newborn , Pakistan/epidemiology , Poliovirus , Population Surveillance , Program Evaluation , Risk Assessment , Treatment Outcome , Vaccination , Young Adult
6.
Expert Rev Vaccines ; 17(8): 739-751, 2018 08.
Article En | MEDLINE | ID: mdl-30056767

INTRODUCTION: Ending all cases of poliomyelitis requires successful cessation of all oral poliovirus vaccine (OPV), but the Global Polio Eradication Initiative (GPEI) partners should consider the possibility of an OPV restart. AREAS COVERED: We review the risks of continued live poliovirus transmission after OPV cessation and characterize events that led to OPV restart in a global model that focused on identifying optimal strategies for OPV cessation and the polio endgame. Numerous different types of events that occurred since the globally coordinated cessation of serotype 2-containing OPV in 2016 highlight the possibility of continued outbreaks after homotypic OPV cessation. Modeling suggests a high risk of uncontrolled outbreaks once more than around 5,000 homotypic polio cases occur after cessation of an OPV serotype, at which point restarting OPV would become necessary to protect most populations. Current efforts to sunset the GPEI and transition its responsibilities to national governments poses risks that may limit the ability to implement management strategies needed to minimize the probability of an OPV restart. EXPERT COMMENTARY: OPV restart remains a real possibility, but risk management choices made by the GPEI partners and national governments can reduce the risks of this low-probability but high-consequence event.


Disease Eradication/methods , Poliomyelitis/prevention & control , Poliovirus Vaccine, Oral/administration & dosage , Disease Outbreaks/prevention & control , Global Health , Humans , Poliomyelitis/epidemiology , Poliovirus/immunology , Risk Management/methods , Serogroup , Vaccination/methods
7.
BMC Infect Dis ; 18(1): 165, 2018 04 10.
Article En | MEDLINE | ID: mdl-29631539

BACKGROUND: Oral polio vaccine (OPV) containing attenuated serotype 2 polioviruses was globally withdrawn in 2016, and bivalent OPV (bOPV) containing attenuated serotype 1 and 3 polioviruses needs to be withdrawn after the certification of eradication of all wild polioviruses to eliminate future risks from vaccine-derived polioviruses (VDPVs). To minimize risks from VDPVs, the planning and implementation of bOPV withdrawal should build on the experience with withdrawing OPV containing serotype 2 polioviruses while taking into account similarities and differences between the three poliovirus serotypes. METHODS: We explored the risks from (i) a failure to synchronize OPV cessation and (ii) unauthorized post-cessation OPV use for serotypes 1 and 3 in the context of globally-coordinated future bOPV cessation and compared the results to similar analyses for serotype 2 OPV cessation. RESULTS: While the risks associated with a failure to synchronize cessation and unauthorized post-cessation OPV use appear to be substantially lower for serotype 3 polioviruses than for serotype 2 polioviruses, the risks for serotype 1 appear similar to those for serotype 2. Increasing population immunity to serotype 1 and 3 poliovirus transmission using pre-cessation bOPV supplemental immunization activities and inactivated poliovirus vaccine in routine immunization reduces the risks of circulating VDPVs associated with non-synchronized cessation or unauthorized OPV use. CONCLUSIONS: The Global Polio Eradication Initiative should synchronize global bOPV cessation during a similar window of time as occurred for the global cessation of OPV containing serotype 2 polioviruses and should rigorously verify the absence of bOPV in immunization systems after its cessation.


Poliomyelitis/prevention & control , Poliovirus Vaccine, Oral/immunology , Humans , Poliomyelitis/pathology , Poliovirus/genetics , Poliovirus/immunology , Poliovirus Vaccine, Inactivated/immunology , Risk Management , Serogroup , Vaccination , Withholding Treatment
8.
Risk Anal ; 38(8): 1701-1717, 2018 08.
Article En | MEDLINE | ID: mdl-29314143

Due to security, access, and programmatic challenges in areas of Pakistan and Afghanistan, both countries continue to sustain indigenous wild poliovirus (WPV) transmission and threaten the success of global polio eradication and oral poliovirus vaccine (OPV) cessation. We fitted an existing differential-equation-based poliovirus transmission and OPV evolution model to Pakistan and Afghanistan using four subpopulations to characterize the well-vaccinated and undervaccinated subpopulations in each country. We explored retrospective and prospective scenarios for using inactivated poliovirus vaccine (IPV) in routine immunization or supplemental immunization activities (SIAs). The undervaccinated subpopulations sustain the circulation of serotype 1 WPV and serotype 2 circulating vaccine-derived poliovirus. We find a moderate impact of past IPV use on polio incidence and population immunity to transmission mainly due to (1) the boosting effect of IPV for individuals with preexisting immunity from a live poliovirus infection and (2) the effect of IPV-only on oropharyngeal transmission for individuals without preexisting immunity from a live poliovirus infection. Future IPV use may similarly yield moderate benefits, particularly if access to undervaccinated subpopulations dramatically improves. However, OPV provides a much greater impact on transmission and the incremental benefit of IPV in addition to OPV remains limited. This study suggests that despite the moderate effect of using IPV in SIAs, using OPV in SIAs remains the most effective means to stop transmission, while limited IPV resources should prioritize IPV use in routine immunization.


Poliomyelitis/prevention & control , Poliomyelitis/transmission , Afghanistan , Disease Eradication , Humans , Models, Biological , Pakistan , Poliomyelitis/immunology , Poliovirus/classification , Poliovirus/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Oral/administration & dosage , Prospective Studies , Retrospective Studies , Risk Assessment , Risk Management , Serotyping , Vaccination/methods
9.
Future Virol ; 13(9): 617-628, 2018 Aug 10.
Article En | MEDLINE | ID: mdl-33598044

AIM: Assess risks related to breaches of poliovirus containment. METHOD: Using a dynamic transmission model, we explore the variability among different populations in the vulnerability to poliovirus containment breaches as population immunity to transmission declines after oral poliovirus vaccine (OPV) cessation. RESULTS: Although using OPV instead of wild poliovirus (WPV) seed strains for inactivated poliovirus vaccine (IPV) production offers some expected risk reintroduction of live polioviruses from IPV manufacturing facilities, OPV seed strain releases may become a significant threat within 5-10 years of OPV cessation in areas most conducive to fecal-oral poliovirus transmission, regardless of IPV use. CONCLUSIONS: Efforts to quantify the risks demonstrate the challenges associated with understanding and managing relatively low-probability and high-consequence containment failure events.

10.
Infect Dis Model ; 3: 107-117, 2018.
Article En | MEDLINE | ID: mdl-30839913

BACKGROUND: Silent circulation of polioviruses complicates the polio endgame and motivates analyses that explore the probability of undetected circulation for different scenarios. A recent analysis suggested a relatively high probability of unusually long silent circulation of polioviruses in small populations (defined as 10,000 people or smaller). METHODS: We independently replicated the simple, hypothetical model by Vallejo et al. (2017) and repeated their analyses to explore the model behavior, interpretation of the results, and implications of simplifying assumptions. RESULTS: We found a similar trend of increasing times between detected cases with increasing basic reproduction number (R0) and population size. However, we found substantially lower estimates of the probability of at least 3 years between successive polio cases than they reported, which appear more consistent with the prior literature. While small and isolated populations may sustain prolonged silent circulation, our reanalysis suggests that the existing rule of thumb of less than a 5% chance of 3 or more years of undetected circulation with perfect surveillance holds for most conditions of the model used by Vallejo et al. and most realistic conditions. CONCLUSIONS: Avoiding gaps in surveillance remains critical to declaring wild poliovirus elimination with high confidence as soon as possible after the last detected poliovirus, but concern about transmission in small populations with adequate surveillance should not significantly change the criteria for the certification of wild polioviruses.

11.
J Infect Dis ; 216(suppl_1): S176-S182, 2017 07 01.
Article En | MEDLINE | ID: mdl-28838194

Background: Recent detections of circulating serotype 2 vaccine-derived poliovirus in northern Nigeria (Borno and Sokoto states) and Pakistan (Balochistan Province) and serotype 1 wild poliovirus in Pakistan, Afghanistan, and Nigeria (Borno) represent public health emergencies that require aggressive response. Methods: We demonstrate the importance of undervaccinated subpopulations, using an existing dynamic poliovirus transmission and oral poliovirus vaccine evolution model. We review the lessons learned during the polio endgame about the role of subpopulations in sustaining transmission, and we explore the implications of subpopulations for other vaccine-preventable disease eradication efforts. Results: Relatively isolated subpopulations benefit little from high surrounding population immunity to transmission and will sustain transmission as long as they do not attain high vaccination coverage. Failing to reach such subpopulations with high coverage represents the root cause of polio eradication delays. Achieving and maintaining eradication requires addressing the weakest links, which includes immunizing populations in insecure areas and/or with disrupted or poor-performing health systems and managing the risks of individuals with primary immunodeficiencies who can excrete vaccine-derived poliovirus long-term. Conclusions: Eradication efforts for vaccine-preventable diseases need to create performance expectations for countries to immunize all people living within their borders and maintain high coverage with appropriate interventions.Keywords. Polio; eradication; transmission; heterogeneity.


Disease Outbreaks/prevention & control , Global Health , Poliomyelitis , Poliovirus , Adolescent , Child , Child, Preschool , Health Services Accessibility , Humans , Immunization , Infant , Infant, Newborn , Models, Biological , Models, Statistical , Poliomyelitis/immunology , Poliomyelitis/prevention & control , Poliomyelitis/transmission , Poliomyelitis/virology , Poliovirus/immunology , Poliovirus/pathogenicity , Poliovirus Vaccine, Oral
12.
J Infect Dis ; 216(suppl_1): S168-S175, 2017 07 01.
Article En | MEDLINE | ID: mdl-28838198

Background: Comparing model expectations with the experience of oral poliovirus vaccine (OPV) containing serotype 2 (OPV2) cessation can inform risk management for the expected cessation of OPV containing serotypes 1 and 3 (OPV13). Methods: We compare the expected post-OPV2-cessation OPV2-related viruses from models with the evidence available approximately 6 months after OPV2 cessation. We also model the trade-offs of use vs nonuse of monovalent OPV (mOPV) for outbreak response considering all 3 serotypes. Results: Although too early to tell definitively, the observed die-out of OPV2-related viruses in populations that attained sufficiently intense trivalent OPV (tOPV) use prior to OPV2 cessation appears consistent with model expectations. As expected, populations that did not intensify tOPV use prior to OPV2 cessation show continued circulation of serotype 2 vaccine-derived polioviruses (VDPVs). Failure to aggressively use mOPV to respond to circulating VDPVs results in a high risk of uncontrolled outbreaks that would require restarting OPV. Conclusions: Ensuring a successful endgame requires more aggressive OPV cessation risk management than has occurred to date for OPV2 cessation. This includes maintaining high population immunity to transmission up until OPV13 cessation, meeting all prerequisites for OPV cessation, and ensuring sufficient vaccine supply to prevent and respond to outbreaks.


Disease Outbreaks/prevention & control , Global Health , Poliomyelitis , Poliovirus Vaccine, Oral , Poliovirus/immunology , Humans , Models, Biological , Models, Statistical , Poliomyelitis/epidemiology , Poliomyelitis/prevention & control , Poliomyelitis/virology , Poliovirus Vaccine, Oral/administration & dosage , Poliovirus Vaccine, Oral/adverse effects , Poliovirus Vaccine, Oral/therapeutic use , Risk , Serogroup
13.
Food Environ Virol ; 9(4): 361-382, 2017 12.
Article En | MEDLINE | ID: mdl-28687986

Poliovirus surveillance plays a critical role in achieving and certifying eradication and will play a key role in the polio endgame. Environmental surveillance can provide an opportunity to detect circulating polioviruses prior to the observation of any acute flaccid paralysis cases. We completed a systematic review of peer-reviewed publications on environmental surveillance for polio including the search terms "environmental surveillance" or "sewage," and "polio," "poliovirus," or "poliomyelitis," and compared characteristics of the resulting studies. The review included 146 studies representing 101 environmental surveillance activities from 48 countries published between 1975 and 2016. Studies reported taking samples from sewage treatment facilities, surface waters, and various other environmental sources, although they generally did not present sufficient details to thoroughly evaluate the sewage systems and catchment areas. When reported, catchment areas varied from 50 to over 7.3 million people (median of 500,000 for the 25% of activities that reported catchment areas, notably with 60% of the studies not reporting this information and 16% reporting insufficient information to estimate the catchment area population size). While numerous studies reported the ability of environmental surveillance to detect polioviruses in the absence of clinical cases, the review revealed very limited information about the costs and limited information to support quantitative population effectiveness of conducting environmental surveillance. This review motivates future studies to better characterize poliovirus environmental surveillance systems and the potential value of information that they may provide in the polio endgame.


Environmental Monitoring/economics , Poliomyelitis/virology , Poliovirus/isolation & purification , Environmental Monitoring/methods , Fresh Water/virology , Humans , Poliomyelitis/economics , Poliomyelitis/prevention & control , Poliovirus/classification , Poliovirus/genetics , Sewage/virology
14.
Vaccine ; 35(31): 3823-3833, 2017 07 05.
Article En | MEDLINE | ID: mdl-28606811

Recognizing that infectious agents readily cross international borders, the International Health Regulations Emergency Committee issues Temporary Recommendations (TRs) that include vaccination of travelers from countries affected by public health emergencies, including serotype 1 wild polioviruses (WPV1s). This analysis estimates the costs and benefits of TRs implemented by countries with reported WPV1 during 2014-2016 while accounting for numerous uncertainties. We estimate the TR costs based on programmatic data and prior economic analyses and TR benefits by simulating potential WPV1 outbreaks in the absence of the TRs using the rate and extent of WPV1 importation outbreaks per reported WPV1 case during 2004-2013 and the number of reported WPV1 cases that occurred in countries with active TRs. The benefits of TRs outweigh the costs in 77% of model iterations, resulting in expected incremental net economic benefits of $210 million. Inclusion of indirect costs increases the costs by 13%, the expected savings from prevented outbreaks by 4%, and the expected incremental net benefits by 3%. Despite the considerable costs of implementing TRs, this study provides health and economic justification for these investments in the context of managing a disease in advanced stages of its global eradication.


Cost-Benefit Analysis , Medication Reconciliation/economics , Poliomyelitis/prevention & control , Travel-Related Illness , Global Health , Humans
15.
Expert Rev Vaccines ; 16(6): 577-586, 2017 06.
Article En | MEDLINE | ID: mdl-28437234

INTRODUCTION: Managing the polio endgame requires access to sufficient quantities of poliovirus vaccines. After oral poliovirus vaccine (OPV) cessation, outbreaks may occur that require outbreak response using monovalent OPV (mOPV) and/or inactivated poliovirus vaccine. Areas covered: We review the experience and challenges with managing vaccine supplies in the context of the polio endgame. Building on models that explored polio endgame risks and the potential mOPV needs to stop outbreaks from live poliovirus reintroductions, we conceptually explore the potential demands for finished and bulk mOPV doses from a stockpile in the context of limited shelf-life of finished vaccine and time delays to convert bulk to finished vaccine. Our analysis suggests that the required size of the mOPV stockpile varies by serotype, with the highest expected needs for serotype 1 mOPV. Based on realizations of poliovirus risks after OPV cessation, the stockpile required to eliminate the chance of a stock-out appears considerably larger than the currently planned mOPV stockpiles. Expert commentary: The total required stockpile size depends on the acceptable probability of a stock-out, and increases with longer times to finish bulk doses and shorter shelf-lives of finished doses. Successful polio endgame management will require careful attention to poliovirus vaccine supplies.


Disease Eradication , Poliomyelitis/prevention & control , Poliovirus Vaccines/immunology , Poliovirus Vaccines/supply & distribution , Vaccination/methods , Humans , Poliovirus Vaccines/administration & dosage
16.
MDM Policy Pract ; 2(1): 2381468317697002, 2017.
Article En | MEDLINE | ID: mdl-30288417

Background: After stopping serotype 2-containing oral poliovirus vaccine use, serotype 2 poliovirus outbreaks may still occur and require outbreak response supplemental immunization activities (oSIAs). Current oSIA plans include the use of both serotype 2 monovalent oral poliovirus vaccine (mOPV2) and inactivated poliovirus vaccine (IPV). Methods: We used an existing model to compare the effectiveness of mOPV2 oSIAs with or without IPV in response to a hypothetical postcessation serotype 2 outbreak in northwest Nigeria. We considered strategies that co-administer IPV with mOPV2, use IPV only for older age groups, or use only IPV during at least one oSIA. We considered the cost and supply implications and estimated from a societal perspective the incremental cost-effectiveness and incremental net benefits of adding IPV to oSIAs in the context of this hypothetical outbreak in 2017. Results: Adding IPV to the first or second oSIA resulted in a 4% to 6% reduction in expected polio cases compared to exclusive mOPV2 oSIAs. We found the greatest benefit of IPV use if added preemptively as a ring around the initial oSIA target population, and negligible benefit if added to later oSIAs or older age groups. We saw an increase in expected polio cases if IPV replaced mOPV2 during an oSIA. None of the oSIA strategies that included IPV for this outbreak represented a cost-effective or net beneficial intervention compared to reliance on mOPV2 only. Conclusions: While adding IPV to oSIAs results in marginal improvements in performance, the poor cost-effectiveness and current limited IPV supply make it economically unattractive for high-risk settings in which IPV does not significantly affect transmission.

17.
Future Microbiol ; 11: 1549-1561, 2016 12.
Article En | MEDLINE | ID: mdl-27831742

AIM: To estimate the incremental net benefits (INBs) of a hypothetical ideal vaccine with all of the advantages and no disadvantages of existing oral and inactivated poliovirus vaccines compared with current vaccines available for future outbreak response. METHODS: INB estimates based on expected costs and polio cases from an existing global model of long-term poliovirus risk management. RESULTS: Excluding the development costs, an ideal poliovirus vaccine could offer expected INBs of US$1.6 billion. The ideal vaccine yields small benefits in most realizations of long-term risks, but great benefits in low-probability-high-consequence realizations. CONCLUSION: New poliovirus vaccines may offer valuable insurance against long-term poliovirus risks and new vaccine development efforts should continue as the world gathers more evidence about polio endgame risks.


Poliomyelitis/prevention & control , Poliovirus Vaccines/immunology , Poliovirus/immunology , Humans , Models, Theoretical , Poliomyelitis/economics , Poliomyelitis/immunology , Poliomyelitis/virology , Poliovirus/classification , Poliovirus/genetics , Poliovirus Vaccines/administration & dosage , Poliovirus Vaccines/economics , Risk Management , Vaccination/economics
18.
BMC Infect Dis ; 16: 237, 2016 06 01.
Article En | MEDLINE | ID: mdl-27246198

BACKGROUND: The endgame for polio eradication includes coordinated global cessation of oral poliovirus vaccine (OPV), starting with the cessation of vaccine containing OPV serotype 2 (OPV2) by switching all trivalent OPV (tOPV) to bivalent OPV (bOPV). The logistics associated with this global switch represent a significant undertaking, with some possibility of inadvertent tOPV use after the switch. METHODS: We used a previously developed poliovirus transmission and OPV evolution model to explore the relationships between the extent of inadvertent tOPV use, the time after the switch of the inadvertent tOPV use and corresponding population immunity to serotype 2 poliovirus transmission, and the ability of the inadvertently introduced viruses to cause a serotype 2 circulating vaccine-derived poliovirus (cVDPV2) outbreak in a hypothetical population. We then estimated the minimum time until inadvertent tOPV use in a supplemental immunization activity (SIA) or in routine immunization (RI) can lead to a cVDPV2 outbreak in realistic populations with properties like those of northern India, northern Pakistan and Afghanistan, northern Nigeria, and Ukraine. RESULTS: At low levels of inadvertent tOPV use, the minimum time after the switch for the inadvertent use to cause a cVDPV2 outbreak decreases sharply with increasing proportions of children inadvertently receiving tOPV. The minimum times until inadvertent tOPV use in an SIA or in RI can lead to a cVDPV2 outbreak varies widely among populations, with higher basic reproduction numbers, lower tOPV-induced population immunity to serotype 2 poliovirus transmission prior to the switch, and a lower proportion of transmission occurring via the oropharyngeal route all resulting in shorter times. In populations with the lowest expected immunity to serotype 2 poliovirus transmission after the switch, inadvertent tOPV use in an SIA leads to a cVDPV2 outbreak if it occurs as soon as 9 months after the switch with 0.5 % of children aged 0-4 years inadvertently receiving tOPV, and as short as 6 months after the switch with 10-20 % of children aged 0-1 years inadvertently receiving tOPV. In the same populations, inadvertent tOPV use in RI leads to a cVDPV2 outbreak if 0.5 % of OPV RI doses given use tOPV instead of bOPV for at least 20 months after the switch, with the minimum length of use dropping to at least 9 months if inadvertent tOPV use occurs in 50 % of OPV RI doses. CONCLUSIONS: Efforts to ensure timely and complete tOPV withdrawal at all levels, particularly from locations storing large amounts of tOPV, will help minimize risks associated with the tOPV-bOPV switch. Under-vaccinated populations with poor hygiene become at risk of a cVDPV2 outbreak in the event of inadvertent tOPV use the soonest after the tOPV-bOPV switch and therefore should represent priority areas to ensure tOPV withdrawal from all OPV stocks.


Disease Eradication/organization & administration , Global Health , Health Plan Implementation/organization & administration , Poliomyelitis/prevention & control , Poliovirus Vaccine, Oral/therapeutic use , Withholding Treatment , Child , Disease Eradication/methods , Disease Outbreaks/prevention & control , Health Plan Implementation/methods , Humans , Inappropriate Prescribing/prevention & control , Inappropriate Prescribing/statistics & numerical data , Infant , Models, Theoretical , Poliomyelitis/epidemiology , Poliomyelitis/virology , Poliovirus/immunology , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Inactivated/adverse effects , Poliovirus Vaccine, Oral/adverse effects , Risk Management , Serogroup , Vaccination
19.
BMC Infect Dis ; 16: 231, 2016 05 26.
Article En | MEDLINE | ID: mdl-27230071

BACKGROUND: The endgame for polio eradication involves coordinated global cessation of oral poliovirus vaccine (OPV) with cessation of serotype 2 OPV (OPV2 cessation) implemented in late April and early May 2016 and cessation of serotypes 1 and 3 OPV (OPV13 cessation) currently planned for after 2018. The logistics associated with globally switching all use of trivalent OPV (tOPV) to bivalent OPV (bOPV) represent a significant undertaking, which may cause some complications, including delays that lead to different timing of the switch across shared borders. METHODS: Building on an integrated global model for long-term poliovirus risk management, we consider the expected vulnerability of different populations to transmission of OPV2-related polioviruses as a function of time following the switch. We explore the relationship between the net reproduction number (Rn) of OPV2 at the time of the switch and the time until OPV2-related viruses imported from countries still using OPV2 can establish transmission. We also analyze some specific situations modeled after populations at high potential risk of circulating serotype 2 vaccine-derived poliovirus (cVDPV2) outbreaks in the event of a non-synchronous switch. RESULTS: Well-implemented tOPV immunization activities prior to the tOPV to bOPV switch (i.e., tOPV intensification sufficient to prevent the creation of indigenous cVDPV2 outbreaks) lead to sufficient population immunity to transmission to cause die-out of any imported OPV2-related viruses for over 6 months after the switch in all populations in the global model. Higher Rn of OPV2 at the time of the switch reduces the time until imported OPV2-related viruses can establish transmission and increases the time during which indigenous OPV2-related viruses circulate. Modeling specific connected populations suggests a relatively low vulnerability to importations of OPV2-related viruses that could establish transmission in the context of a non-synchronous switch from tOPV to bOPV, unless the gap between switch times becomes very long (>6 months) or a high risk of indigenous cVDPV2s already exists in the importing and/or the exporting population. CONCLUSIONS: Short national discrepancies in the timing of the tOPV to bOPV switch will likely not significantly increase cVDPV2 risks due to the insurance provided by tOPV intensification efforts, although the goal to coordinate national switches within the globally agreed April 17-May 1, 2016 time window minimized the risks associated with cross-border importations.


Poliomyelitis/prevention & control , Poliovirus Vaccine, Inactivated/administration & dosage , Poliovirus Vaccine, Oral/administration & dosage , Poliovirus/immunology , Disease Outbreaks/prevention & control , Global Health , Humans , Models, Theoretical , Risk Management , Serogroup
20.
BMC Infect Dis ; 16: 137, 2016 Mar 24.
Article En | MEDLINE | ID: mdl-27009272

BACKGROUND: Following successful eradication of wild polioviruses and planned globally-coordinated cessation of oral poliovirus vaccine (OPV), national and global health leaders may need to respond to outbreaks from reintroduced live polioviruses, particularly vaccine-derived polioviruses (VDPVs). Preparing outbreak response plans and assessing potential vaccine needs from an emergency stockpile require consideration of the different national risks and conditions as they change with time after OPV cessation. METHODS: We used an integrated global model to consider several key issues related to managing poliovirus risks and outbreak response, including the time interval during which monovalent OPV (mOPV) can be safely used following homotypic OPV cessation; the timing, quality, and quantity of rounds required to stop transmission; vaccine stockpile needs; and the impacts of vaccine choices and surveillance quality. We compare the base case scenario that assumes aggressive outbreak response and sufficient mOPV available from the stockpile for all outbreaks that occur in the model, with various scenarios that change the outbreak response strategies. RESULTS: Outbreak response after OPV cessation will require careful management, with some circumstances expected to require more and/or higher quality rounds to stop transmission than others. For outbreaks involving serotype 2, using trivalent OPV instead of mOPV2 following cessation of OPV serotype 2 but before cessation of OPV serotypes 1 and 3 would represent a good option if logistically feasible. Using mOPV for outbreak response can start new outbreaks if exported outside the outbreak population into populations with decreasing population immunity to transmission after OPV cessation, but failure to contain outbreaks resulting in exportation of the outbreak poliovirus may represent a greater risk. The possibility of mOPV use generating new long-term poliovirus excretors represents a real concern. Using the base case outbreak response assumptions, we expect over 25% probability of a shortage of stockpiled filled mOPV vaccine, which could jeopardize the achievement of global polio eradication. For the long term, responding to any poliovirus reintroductions may require a global IPV stockpile. Despite the risks, our model suggests that good risk management and response strategies can successfully control most potential outbreaks after OPV cessation. CONCLUSIONS: Health leaders should carefully consider the numerous outbreak response choices that affect the probability of successfully managing poliovirus risks after OPV cessation.


Poliomyelitis/prevention & control , Poliovirus Vaccine, Oral/supply & distribution , Disaster Planning , Disease Outbreaks/prevention & control , Humans , International Cooperation , Risk Management , Vaccination/methods
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