Final frontiers of the polio eradication endgame.

PURPOSE OF REVIEW: Focusing on the key developments since January 2019, this review aims to inform policymakers and clinical practitioners on the latest on evolving global polio epidemiology and scientific advancements to guide strategies for eradication. RECENT FINDINGS: An upsurge in wild poliovirus type 1 cases in Pakistan and Afghanistan and an expansion of type 2 circulating vaccine-derived poliovirus transmission in multiple countries threaten the remarkable progress made over past several decades by the global eradication program. These challenges have also spurred innovation on multiple fronts, including earlier detection, enhanced environmental surveillance and safer and more affordable vaccine options. SUMMARY: A concerted effort to adapt program strategies to address context-specific challenges and continued focus on innovations to enhance detection and response capabilities will be the key to achieve and sustain eradication of all types of polioviruses.

Vaccine hesitancy and (fake) news: Quasi-experimental evidence from Italy.

The spread of fake news and misinformation on social media is blamed as a primary cause of vaccine hesitancy, which is one of the major threats to global health, according to the World Health Organization. This paper studies the effect of the diffusion of misinformation on immunization rates in Italy by exploiting a quasi-experiment that occurred in 2012, when the Court of Rimini officially recognized a causal link between the measles-mumps-rubella vaccine and autism and awarded injury compensation. To this end, we exploit the virality of misinformation following the 2012 Italian court's ruling, along with the intensity of exposure to nontraditional media driven by regional infrastructural differences in Internet broadband coverage. Using a Difference-in-Differences regression on regional panel data, we show that the spread of this news resulted in a decrease in child immunization rates for all types of vaccines.

Finding inhabited settlements and tracking vaccination progress: the application of satellite imagery analysis to guide the immunization response to confirmation of previously-undetected, ongoing endemic wild poliovirus transmission in Borno State, Nigeria.

BACKGROUND: Four wild polio-virus cases were reported in Borno State, Nigeria 2016, 1 year after Nigeria had been removed from the list of polio endemic countries by the World Health Organization. Resulting from Nigeria's decade long conflict with Boko Haram, health officials had been unable to access as much as 60% of the settlements in Borno, hindering vaccination and surveillance efforts. This lack of accessibility made it difficult for the government to assess the current population distribution within Borno. This study aimed to use high resolution, visible band satellite imagery to assess the habitation of inaccessible villages in Borno State. METHODS: Using high resolution (31-50 cm) imagery from DigitalGlobe, analysts evaluated the habitation status of settlements in Borno State identified by Nigeria's Vaccination Tracking System. The analysts looked at imagery of each settlement and, using vegetation (overgrowth vs. cleared) as a proxy for human habitation, classified settlements into three categories: inhabited, partially abandoned, and abandoned. Analysts also classified the intact percentage of each settlement starting at 0% (totally destroyed since last assessment) and increasing in 25% intervals through 100% (completely intact but not expanded) up to 200+% (more than doubled in size) by looking for destroyed buildings. These assessments were then used to adjust previously established population estimates for each settlement. These new population distributions were compared to vaccination efforts to determine the number of children under 5 unreached by vaccination teams. RESULTS: Of the 11,927 settlements assessed 3203 were assessed as abandoned (1892 of those completely destroyed), 662 as partially abandoned, and 8062 as fully inhabited as of December of 2017. Comparing the derived population estimates from the new assessments to previous assessment and the activities of vaccination teams shows that an estimated 180,155 of the 337,411 under five children who were unreached in 2016 were reached in 2017 (70.5% through vaccination efforts in previously inaccessible areas, 29.5% through displacement to accessible areas). CONCLUSIONS: This study's methodology provides important planning and situation awareness information to health workers in Borno, Nigeria, and may serve as a model for future data gathering efforts in inaccessible regions.

Progress of polio eradication and containment requirements after eradication.

Wild poliovirus (WPV) is nearing eradication, and only three countries have never interrupted WPV transmission (Pakistan, Afghanistan, and Nigeria). WPV2 was last detected in 1999, and it was declared eradicated in 2015. WPV3 has not been detected since 2012. Since 2016, WPV1 has been detected in only two countries (Afghanistan and Pakistan), with only 22 cases reported in 2017 and 12 cases reported in 2018 (as of July 10). Because of WPV2 eradication and the risk of emergence of type 2 vaccine-derived polioviruses from continued use of trivalent oral polio vaccine (OPV), trivalent OPV was replaced by bivalent OPV (types 1 and 3) in a globally coordinated effort in 2016. WPV2 eradication and trivalent OPV cessation also mean that breach of containment in a facility working with type 2 poliovirus is now a major risk to reseed type 2 circulation in the community. As a result, the World Health Organization has developed a "Global Action Plan to minimize poliovirus facility-associated risk after type-specific eradication of wild polioviruses and sequential cessation of oral polio vaccine use." Because poliovirus has long been used as a standard for qualification of intravenous immunoglobulin, disinfectant products, and sanitation methods, poliovirus containment has implications far beyond poliovirus laboratories.

Vaccine-derived poliovirus surveillance in China during 2001-2013: the potential challenge for maintaining polio free status.

BACKGROUND: The goal of polio eradication is to complete elimination and containment of all wild, vaccine-related and Sabin polioviruses. Vaccine-derived poliovirus (VDPV) surveillance in China from 2001-2013 is summarized in this report, which has important implications for the global polio eradication initiative. METHODS: Acute flaccid paralysis (AFP) cases and their contacts with VDPVs isolated from fecal specimens were identified in our AFP surveillance system or by field investigation. Epidemiological and laboratory information for these children were analyzed and the reasons for the VDPV outbreak was explored. RESULTS: VDPVs were isolated from a total of 49 children in more than two-thirds of Chinese provinces from 2001-2013, including 15 VDPV cases, 15 non-polio AFP cases and 19 contacts of AFP cases or healthy subjects. A total of 3 circulating VDPVs (cVDPVs) outbreaks were reported in China, resulting in 6 cVDPVs cases who had not been vaccinated with oral attenuated poliomyelitis vaccine. Among the 4 immunodeficiency-associated VDPVs (iVDPVs) cases, the longest duration of virus excretion was about 20 months. In addition, one imported VDPV case from Myanmar was detected in Yunnan Province. CONCLUSIONS: Until all wild, vaccine-related and Sabin polioviruses are eradicated in the world, high quality routine immunization and sensitive AFP surveillance should be maintained, focusing efforts on underserved populations in high risk areas.

So close: remaining challenges to eradicating polio.

The Global Polio Eradication Initiative, launched in 1988, is close to achieving its goal. In 2015, reported cases of wild poliovirus were limited to just two countries - Afghanistan and Pakistan. Africa has been polio-free for more than 18 months. Remaining barriers to global eradication include insecurity in areas such as Northwest Pakistan and Eastern and Southern Afghanistan, where polio cases continue to be reported. Hostility to vaccination is either based on extreme ideologies, such as in Pakistan, vaccination fatigue by parents whose children have received more than 15 doses, and misunderstandings about the vaccine's safety and effectiveness such as in Ukraine. A further challenge is continued circulation of vaccine-derived poliovirus in populations with low immunity, with 28 cases reported in 2015 in countries as diverse as Madagascar, Ukraine, Laos, and Myanmar. This paper summarizes the current epidemiology of wild and vaccine-derived poliovirus, and describes the remaining challenges to eradication and innovative approaches being taken to overcome them.

Lessons learnt to keep Europe polio-free: a review of outbreaks in the European Union, European Economic Area, and candidate countries, 1973 to 2013.

Between 1973 and 2013, 12 outbreaks of paralytic poliomyelitis with a cumulative total of 660 cases were reported in the European Union, European Economic Area and candidate countries. Outbreaks lasted seven to 90 weeks (median: 24 weeks) and were identified through the diagnosis of cases of acute flaccid paralysis, for which infection with wild poliovirus was subsequently identified. In two countries, environmental surveillance was in place before the outbreaks, but did not detect any wild strain before the occurrence of clinical cases. This surveillance nonetheless provided useful information to monitor the outbreaks and their geographical spread. Outbreaks were predominantly caused by poliovirus type 1 and typically involved unvaccinated or inadequately vaccinated groups within highly immunised communities. Oral polio vaccine was primarily used to respond to the outbreaks with catch-up campaigns implemented either nationwide or in restricted geographical areas or age groups. The introduction of supplementary immunisation contained the outbreaks. In 2002, the European region of the World Health Organization was declared polio-free and it has maintained this status since. However, as long as there are non-vaccinated or under-vaccinated groups in European countries and poliomyelitis is not eradicated, countries remain continuously at risk of reintroduction and establishment of the virus. Continued efforts to reach these groups are needed in order to ensure a uniform and high vaccination coverage.

[Polio vaccination and stool screening in German reception centers for asylum seekers, November 2013-January 2014 : What was implemented?]. / Polioimpfung und Stuhlscreening in deutschen Erstaufnahmeeinrichtungen für Asylsuchende, November 2013-Januar 2014 : Was wurde umgesetzt?

BACKGROUND: Following the polio outbreak in Syria and the rising number of Syrian asylum seekers in Germany in 2013, the Robert Koch Institute recommended - within the context of existing vaccination recommendations for asylum seekers - on 01/11/2013 to prioritize polio vaccination of Syrian asylum seekers and stool screening in a target group of Syrian asylum seekers aged less than three years. OBJECTIVES: The article evaluates the implementation of this recommendation in German asylum seeker reception centres (RC) to gain further knowledge on the vaccination practices in RCs and to identify opportunities for improving future recommendations. METHODS: The electronic questionnaire was sent by email to all German RCs, asking for general information on the RC, existing vaccination efforts, the main obstacles for implementation of the recommendations, the number of incoming and vaccinated asylum seekers, and asylum seekers screened for poliovirus in the period from 01/11/2013 to 31/01/2014. The RCs rated the feasibility of the recommendation and the provided multilingual information material. RESULTS AND CONCLUSION: All of the 20 identified RCs responded. During the study period, 33.874 asylum seekers arrived in the RCs. Of those with available information about possession of a vaccination record, on average 1.6 % did have one. All RCs offered timely vaccination to Syrian asylum seekers younger than three years. In this target group, eight RC achieved vaccination coverages of ≥ 80 %. Stool screening coverage was ≥ 80 % in five of 19 RCs. Eleven RCs rated the recommendation as very well/well implementable. Staff shortages and language barriers were mentioned as the main implementation obstacles. Similar future recommendations for asylum seekers in RCs should be accompanied by informational material in additional languages. Staff shortages hampering implementation could be overcome through collaborations with non-governmental organizations.

Regression in polio eradication in Pakistan: A national tragedy.

Polio is one out of 200 infections results to lasting paralysis, usually in the legs. The year 2014 has been the saddest year for the Pakistan when the World was about to eliminate Polio from all over the World. In year 1994 Pakistan took the initiative to eliminate Polio from the country. The efforts were going well until 2005, when Pakistan was on the wedge to overcome the Disease. The hopes were high that soon Pakistan will become a polio-virus-free country, but the drone strikes in FATA and the rise of different militant groups as a reaction of the drone attacks in FATA made it difficult for the health workers to continue their vaccination campaigns in these areas. However various factors ruined the efforts made to eradicate Polio. In Pakistan, polio is widespread to three sections. These are Karachi, Quetta block (Quetta, Pishin and Killah Abdullah district) and FATA and Peshawar district. Numerous things are accountable for polio flourishing in these regions. These comprise near to the ground socioeconomic rank of the families, not having the knowledge concerning hazard caused by polio and disinformation by limited significant people concerning how polio vaccines fabricate damage. In 2014, only 3 countries in the world remain polio-endemic: Nigeria, Pakistan and Afghanistan. From year 2012-2014 the number of registered Polio cases is on rise contrary to rest of the other two Polio-endemic countries. In spite of the extensive work done by Polio workers the number of Polio cases has broken the 16 year record. The situation is getting worse because it can also be threatening to the rest of the World.

A New Method for Estimating the Coverage of Mass Vaccination Campaigns Against Poliomyelitis From Surveillance Data.

Mass vaccination campaigns with the oral poliovirus vaccine targeting children aged <5 years are a critical component of the global poliomyelitis eradication effort. Monitoring the coverage of these campaigns is essential to allow corrective action, but current approaches are limited by their cross-sectional nature, nonrandom sampling, reporting biases, and accessibility issues. We describe a new Bayesian framework using data augmentation and Markov chain Monte Carlo methods to estimate variation in vaccination coverage from children's vaccination histories investigated during surveillance for acute flaccid paralysis. We tested the method using simulated data with at least 200 cases and were able to detect undervaccinated groups if they exceeded 10% of all children and temporal changes in coverage of ±10% with greater than 90% sensitivity. Application of the method to data from Pakistan for 2010-2011 identified undervaccinated groups within the Balochistan/Federally Administered Tribal Areas and Khyber Pakhtunkhwa regions, as well as temporal changes in coverage. The sizes of these groups are consistent with the multiple challenges faced by the program in these regions as a result of conflict and insecurity. Application of this new method to routinely collected data can be a useful tool for identifying poorly performing areas and assisting in eradication efforts.

[History of development of the live poliomyelitis vaccine from Sabin attenuated strains in 1959 and idea of poliomyelitis eradication].

In 1958 Poliomyelitis Institute in Moscow and Institute of Experimental Medicine in St. Petersburg received from A. Sabin the attenuated strains of poliomyelitis virus. The characteristics of the strains were thoroughly studied by A. A. Smorodintsev and coworkers. They found that the virulence of the strains fluctuated slightly in 10 consecutive passages through the intestine of the non-immune children. A part of the Sabin material was used by A. A. Smorodintsev and M. P. Chumakov in the beginning of 1959 for immunizing approximately 40000 children in Estonia, Lithuania, and Latvia. Epidemic poliomyelitis rate in these republics decreased from approximately 1000 cases yearly before vaccination to less than 20 in the third quarter of 1959. This was a convincing proof of the efficacy and safety of the vaccine from the attenuated Sabin strains. In 1959, according to A. Sabin's recommendation, a technology of live vaccine production was developed at the Poliomyelitis Institute, and several experimental lots of vaccine were prepared. In the second part of 1959, 13.5 million children in USSR were immunized. The epidemic poliomyelitis rate decreased 3-5 times in different regions without paralytic cases, which could be attributed to the vaccination. These results were the final proof of high efficiency and safety of live poliomyelitis vaccine from the attenuated Sabin strains. Based on these results, A. Sabin and M. P. Chumakov suggested in 1960 the idea of poliomyelitis eradication using mass immunization of children with live vaccine. 72 million persons up to 20 years old were vaccinated in USSR in 1960 with a 5 times drop in the paralytic rate. 50-year-long use of live vaccine results in poliomyelitis eradication in almost all countries worldwide. More than 10 million children were rescued from the death and palsy. Poliomyelitis eradication in a few countries where it still exists depends not on medical services but is defined by the attitude of their leaders to fight against poliomyelitis. In some developing countries the vaccination data are falsified, thereby threatening the polio epidemics reappearance and the virus spreading to other countries. Methods must be developed for detection and dealing with extremely rare persistent virus carriers. Because of all these constraints the outcome of poliomyelitis eradication at present is uncertain and vaccination must be continued. The world has become poliovaccine dependent.

Associations between vaccination and childhood cancers in Texas regions.

OBJECTIVES: To determine whether children born in Texas regions with higher vaccination coverage had reduced risk of childhood cancer. STUDY DESIGN: The Texas Cancer Registry identified 2800 cases diagnosed from 1995 to 2006 who were (1) born in Texas and (2) diagnosed at ages 2 to 17 years. The state birth certificate data were used to identify 11 200 age- and sex-matched control subjects. A multilevel mixed-effects regression model compared vaccination rates among cases and control subjects at the public health region and county level. RESULTS: Children born in counties with higher hepatitis B vaccine coverage had lower odds of all cancers combined (OR = 0.81, 95% CI: 0.67 to 0.98) and acute lymphoblastic leukemia (ALL) specifically (OR = 0.63, 95% CI: 0.46 to 0.88). A decreased odds for ALL also was associated at the county level with higher rates of the inactivated poliovirus vaccine (OR = 0.67, 95% CI: 0.49 to 0.92) and 4-3-1-3-3 vaccination series (OR = 0.62, 95% CI: 0.44 to 0.87). Children born in public health regions with higher coverage levels of the Haemophilus influenzae type b-conjugate vaccine had lower odds of ALL (OR: 0.58; 95% CI: 0.42 to 0.82). CONCLUSIONS: Some common childhood vaccines appear to be protective against ALL at the population level.

Vaccines for prophylaxis of viral infections in patients with hematological malignancies.

BACKGROUND: Viral infections cause significant morbidity and mortality in patients with hematological malignancies. It remains uncertain whether viral vaccinations in these patients are supported by good evidence. OBJECTIVES: We aimed to determine the effectiveness and safety of viral vaccines in patients with hematological malignancies. SEARCH STRATEGY: We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL (June 2010), reference lists of relevant papers, abstracts from scientific meetings and contacted vaccine manufacturers. SELECTION CRITERIA: Randomized controlled trials (RCTs) evaluating viral vaccines in patients with hematological malignancies were included. DATA COLLECTION AND ANALYSIS: Relative risk (RR) was used for binary data and mean difference (MD) for continuous data. Primary outcome was incidence of infection. Secondary outcomes were mortality, incidence of complications and severe viral infection, hospitalization, immune response and adverse effects. Fixed-effect model was used in meta-analyses. MAIN RESULTS: Eight RCTs were included, with 305 patients in the intervention groups and 288 in the control groups. They evaluated heat-inactivated varicella zoster virus (VZV) vaccine (two trials), influenza vaccines (five trials) and inactivated poliovirus vaccine (IPV) (one trial). Seven trials had high and one trial had moderate risk of bias.VZV vaccine might reduce herpes zoster compared to no vaccine (RR 0.54, 95% CI 0.3 to 1.0, P=0.05), but not statistically significant. Vaccination also demonstrated efficacy in immune response but frequently caused local adverse effects. One trial reported severity score of zoster, which favored vaccination (MD 2.6, 95% CI 0.94 to 4.26, P=0.002).Two RCTs compared inactivated influenza vaccine with no vaccine and reported lower risk of lower respiratory infections (RR 0.39, 95% CI 0.19 to 0.78, P=0.008) and hospitalization (RR 0.17, 95% CI 0.09 to 0.31, P<0.00001) in vaccine recipients. However, vaccine recipients more frequently experienced irritability and local adverse effects. There was no significant difference in seroconversion between one and two doses of influenza vaccine (one trial), or between recombinant and standard influenza vaccine (one trial), or influenza vaccine given with or without re-induction chemotherapy (one trial).The IPV trial comparing vaccination starting at 6 versus 18 months after stem cell transplant (SCT) found no significant difference in seroconversion. AUTHORS' CONCLUSIONS: Inactivated VZV vaccine might reduce zoster severity in adult SCT recipients. Inactivated influenza vaccine might reduce respiratory infections and hospitalization in adults with multiple myeloma or children with leukemia or lymphoma. However, the quality of evidence is low. Local adverse effects occur frequently. Further high-quality RCTs are needed.

[Discovery of Foci of Type-2 Poliovirus Derived from Oral Polio Vaccine in Central African Republic in 2019]. / Découverte de Foyers de Poliovirus de Type-2 Dérivé du Vaccin Antipoliomyélitique Oral en République Centrafricaine en 2019.

Objective: In 2019, the Central African Republic identified foci of circulating vaccine-derived poliovirus 2 (PVDV2c). The objective of this work is to describe the vaccination status of children paralyzed by PVDV2c and their contacts and to assess the circulation of this strain in these contacts. Patients and method: The study population of this retrospective survey consists of children with acute flaccid paralysis (AFP) and their contacts. We included paralyzed children whose sequencing results showed the presence of PVDV2c. Results: A total of 21 children paralyzed by PVDVc and 64 contacts were enrolled in the survey. Fourteen out of 21 children who are paralyzed (66%) received at least one dose of bivalent oral polio vaccine (OPV) compared to 36 out of 64 contacts (57%, non-significant difference). Of the vaccinated patients, 7 had received less than three doses. For the injectable polio vaccine (IPV), vaccination coverage for both patients and contacts was 33%.The proportion of children who received both doses of OPV and IPV was 33% among patients and 25% in contacts. Contacts with VDPV2 were vaccinated with OPV and IPV, respectively 55 and 27%. VDPV2 and Sabin 2 were also found in contact stools, 34% and 9% respectively. Conclusion: The absence or inadequacy of IPV vaccination has a serious impact on children by the occurrence of virus derived from the vaccine responsible for life-old paralysis. Protecting children from poliomyelitis requires a combination of a good cold chain, multiple doses and adherence to the vaccine schedule.

Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations.

Clinical studies are ongoing to assess whether existing vaccines may afford protection against SARS-CoV-2 infection through trained immunity. In this exploratory study, we analyze immunization records from 137,037 individuals who received SARS-CoV-2 PCR tests. We find that polio, Haemophilus influenzae type-B (HIB), measles-mumps-rubella (MMR), Varicella, pneumococcal conjugate (PCV13), Geriatric Flu, and hepatitis A/hepatitis B (HepA-HepB) vaccines administered in the past 1, 2, and 5 years are associated with decreased SARS-CoV-2 infection rates, even after adjusting for geographic SARS-CoV-2 incidence and testing rates, demographics, comorbidities, and number of other vaccinations. Furthermore, age, race/ethnicity, and blood group stratified analyses reveal significantly lower SARS-CoV-2 rate among black individuals who have taken the PCV13 vaccine, with relative risk of 0.45 at the 5 year time horizon (n: 653, 95% CI (0.32, 0.64), p-value: 6.9e-05). Overall, this study identifies existing approved vaccines which can be promising candidates for pre-clinical research and Randomized Clinical Trials towards combating COVID-19.