Outbreak Of Poliomyelitis Research Articles

Immunogenicity and Safety of Inactivated Sabin-Strain Polio Vaccine “PoliovacSin”: Clinical Trials Phase I and II

Global polio eradication requires both safe and effective vaccines, and safe production processes. Sabin oral poliomyelitis vaccine (OPV) strains can evolve to virulent viruses and result in poliomyelitis outbreaks, and conventional inactivated poliomyelitis vaccine (Salk-IPV) production includes accumulation of large stocks of neurovirulent wild polioviruses. Therefore, IPV based on attenuated OPV strains seems a viable option. To increase the global supply of affordable inactivated vaccine in the still not-polio free world we developed an IPV made from the Sabin strains–PoliovacSin. Clinical trials included participants 18–60 years of age. A phase I single-center, randomized, double-blind placebo-controlled clinical trial included 60 participants, who received one dose of PoliovacSin or Placebo. A phase II multicenter, randomized, double-blind, comparative clinical trial included 200 participants, who received one dose of PoliovacSin or Imovax Polio. All vaccinations were well tolerated, and PoliovacSin had a comparable safety profile to the Placebo or the reference Imovax Polio preparations. A significant increase in neutralizing antibody levels to polioviruses types 1–3 (Sabin and wild) was observed in PoliovacSin and Imovax Polio vaccinated groups. Therefore, clinical trials confirmed good tolerability, low reactogenicity, and high safety profile of the PoliovacSin and its pronounced immunogenic properties. The preparation was approved for clinical trials involving infants.

Vaccine-Derived Polioviruses, Central African Republic, 2019.

Since May 2019, the Central African Republic has experienced a poliomyelitis outbreak caused by type 2 vaccine-derived polioviruses (VDPV-2s). The outbreak affected Bangui, the capital city, and 10 districts across the country. The outbreak resulted from several independent emergence events of VDPV-2s featuring recombinant genomes with complex mosaic genomes. The low number of mutations (<20) in the viral capsid protein 1–encoding region compared with the vaccine strain suggests that VDPV-2 had been circulating for a relatively short time (probably <3 years) before being isolated. Environmental surveillance, which relies on a limited number of sampling sites in the Central African Republic and does not cover the whole country, failed to detect the circulation of VDPV-2s before some had induced poliomyelitis in children.

Successfulimplementationof modern critical care in the low-resources country Bosnia and Herzegovina : Single-center experience.

BackgroundCritical care medicine is a relatively young discipline, developed in the mid-1950s in response to the outbreak of poliomyelitis. The mass application of mechanical ventilation and its subsequent technical advancement helped manage large numbers of patients with respiratory failure. This branch of medicine evolved much faster in high-income (HIC) than low- and middle-income countries (LMIC). Seventy years later, mankind’s encounter with coronavirus disease 2019 (COVID-19) represents another major challenge for critical care medicine especially in LMIC countries where over two thirds of the world population live.MethodsSystematic analysis of written documents related to the establishment of the first multidisciplinary medical intensive care unit (MICU) in Bosnia and Herzegovina and its development to the present day.ResultsWe describe the experience of setting up a modern critical care program under LMIC constraints as a promising way forward to meet the increased worldwide demand for critical care. Successful development is contingent on formal education and continued mentorship from HIC, establishment of a multidisciplinary team, the support from local health care authorities, development of a formal subspecialty training, academic faculty development, and research. Novel technologies including tele-education provide additional opportunities for rapid development and dissemination of critical care medicine programs in LMIC.ConclusionCritical care medicine is a critical public health need in HIC and LMIC alike. The challenges associated with the coronavirus pandemic should serve as a wakeup call for rapid development of critical care programs around the world.

Update on Vaccine-Derived Poliovirus Outbreaks - Worldwide, January 2018-June 2019.

Certification of global eradication of indigenous wild poliovirus type 2 occurred in 2015 and of type 3 in 2019. Since the launch of the Global Polio Eradication Initiative (GPEI) in 1988 and broad use of live, attenuated oral poliovirus vaccine (OPV), the number of wild poliovirus cases has declined >99.99% (1). Genetically divergent vaccine-derived poliovirus* (VDPV) strains can emerge during vaccine use and spread in underimmunized populations, becoming circulating VDPV (cVDPV) strains, and resulting in outbreaks of paralytic poliomyelitis.† In April 2016, all oral polio vaccination switched from trivalent OPV (tOPV; containing vaccine virus types 1, 2, and 3) to bivalent OPV (bOPV; containing types 1 and 3) (2). Monovalent type 2 OPV (mOPV2) is used in response campaigns to control type 2 cVDPV (cVDPV2) outbreaks. This report presents data on cVDPV outbreaks detected during January 2018-June 2019 (as of September 30, 2019). Compared with January 2017-June 2018 (3), the number of reported cVDPV outbreaks more than tripled, from nine to 29; 25 (86%) of the outbreaks were caused by cVDPV2. The increase in the number of outbreaks in 2019 resulted from VDPV2 both inside and outside of mOPV2 response areas. GPEI is planning future use of a novel type 2 OPV, stabilized to decrease the likelihood of reversion to neurovirulence. However, all countries must maintain high population immunity to decrease the risk for cVDPV emergence. Cessation of all OPV use after certification of polio eradication will eliminate the risk for VDPV emergence.

Evaluation of antigenic differences between wild and Sabin vaccine strains of poliovirus using the pseudovirus neutralization test

In the endgame of global polio eradication, serosurveillance is essential to monitor each country’s vulnerability to poliomyelitis outbreaks. Previously, we developed pseudovirus poliovirus (PV) neutralization test (pPNT) with type 1, 2, and 3 PV pseudovirus (PVpv), which possess a luciferase-encoding PV replicon in the capsids of wild-type strains (PVpv[WT]), showing that pPNT with type 2 and 3 PVpv(WT) but not type 1 shows high correlation with the conventional PV neutralization test (cPNT) performed with vaccine strains. Here, we analyse the antigenicity of PVpv(WT) and PVpv with capsid proteins of Sabin vaccine strains (PVpv[Sabin]) in human serum. Type 2 and 3 PVpv(WT) and PVpv(Sabin) show similar antigenicity in the analysed set of human sera in contrast to type 1 PVpv. The levels of PVpv(Sabin) infection (%), including about 70% of PVpv infection (%) measured in the presence of human serum diluted to the cPNT titre, serve as the optimal threshold values for pPNT (5% for type 1 and 2, 10% for type 3) to show high correlation with cPNT results. Our results suggest that pPNT with PVpv(Sabin) could serve as an alternative to cPNT and provide a rationale for pPNT threshold values.

Poliomyelitis outbreak in Papua New Guinea: health system and health security implications for PNG and Australia.

Poliomyelitis outbreak in Papua New Guinea: health system and health security implications for PNG and Australia.

Imported outbreak of poliomyelitis in Sudan 2004-2005: a teaching case-study

Imported outbreak of poliomyelitis in Sudan 2004-2005: a teaching case-study

60 años de la aprobación del título de Fisioterapia y de la primera escuela de Fisioterapia reconocida, la de Salus Infirmorum en el centro infantil

Se acaban de cumplir 60 años de la aprobación de la especialidad de Fisioterapia para los Ayudantes Técnicos Sanitarios, así como la creación de las primeras escuelas de Fisioterapia. El presente artículo justificará cómo el conjunto de brotes epidémicos de poliomielitis en España, influyeron de forma decisiva en el nacimiento de profesiones sanitarias como la Fisioterapia. Por otro lado, se reconstruirá el proceso de institucionalización, nacimiento y desarrollo en sus primeros años de la Escuela de Fisioterapia Salus Infirmorum, la primera en ser aprobada por el Ministerio de Educación. Salus Infirmorum, con la creación del centro infantil “Casa del Niño” consiguió aunar la formación de fisioterapeutas y el tratamiento de niños con problemas motóricos como consecuencia de la poliomielitis. En el centro se atendió a más de 680 niños y se formaron en ella 373 enfermeras fisioterapeutas, siendo reconocido como Obra de interés social, por la Comisaría de Asistencia Social del Ministerio de Educación Nacional, en orden 6 de junio de 1958.

Poliomyelitis in modern conditions: achievements and prospects

The creation in the middle of the 20th century vaccines against poliomyelitis (PM) – inactivated vaccine (IPV) and live oral vaccine from Sabin strains (OPV) with various properties, advantages and disadvantages, but highly effective, made it possible to implement the idea of elimination of PM. Since 1988, the WHO Global Program of PM eradication has achieved remarkable success: the incidence of PM caused by wild poliovirus (PV) has been reduced by 10 thousand times, the number of endemic countries has been reduced to 3, the circulation of wild PV has been discontinued in 4 regions of the world the wild type 2 of PV has been eradicated, and wild type 3 of PV has not been detected for almost 5 years. Under conditions of a decrease in the incidence of PM caused by wild PV, the known negative properties of trivalent OPV made its further use problematic. These negative properties are: 1) the ability to cause post-vaccination complications and 2) the genetic instability of Sabin strains, especially PV of type 2, and their ability under certain conditions (primarily in conditions of low collective immunity to PV) to quickly restore neurovirulence, transforming into circulating vaccinederived PV (VDPV), capable of causing incidents and outbreaks of PM. In order to reduce the risk associated primarily with type 2 PV, WHO proposed a global switch to the use of bivalent OPV from types 1 and 3, completed in 2016. In 2019, WHO plans to complete eradication of type 1 and 3 PVs, and in 2022 completely abandon the OPV. The precondition for the safety of such tactics is the maintenance of high collective immunity to PM. There are several threats to the security of this strategy. PVs can “silently” circulate in the human population for a long time without clinical manifestations of PM, which, with inadequate epidemiological surveillance can lead to the return of PM. The reintroduction of both wild PV and Sabin strains can occur from institutions that preserve / work with PV. The source of VDPV can be people with primary immunodeficiencies, which continuously excrete PV. It is necessary to maintain surveillance over the PM, expand additional types of surveillance for the PV, strict containment of all PVs. The only way to maintain collective immunity is immunization with trivalent IPV. The current global shortage of IPV poses a significant threat to the world’s epidemiological well-being. The solution to the problem is the development of a new generation of safe and effective vaccines, improving the ways of introducing IPV, developing antiviral drugs.

Strategic Response to an Outbreak of Circulating Vaccine-Derived Poliovirus Type 2 - Syria, 2017-2018.

Since the 1988 inception of the Global Polio Eradication Initiative (GPEI), progress toward interruption of wild poliovirus (WPV) transmission has occurred mostly through extensive use of oral poliovirus vaccine (OPV) in mass vaccination campaigns and through routine immunization services (1,2). However, because OPV contains live, attenuated virus, it carries the rare risk for reversion to neurovirulence. In areas with very low OPV coverage, prolonged transmission of vaccine-associated viruses can lead to the emergence of vaccine-derived polioviruses (VDPVs), which can cause outbreaks of paralytic poliomyelitis. Although WPV type 2 has not been detected since 1999, and was declared eradicated in 2015,* most VDPV outbreaks have been attributable to VDPV serotype 2 (VDPV2) (3,4). After the synchronized global switch from trivalent OPV (tOPV) (containing vaccine virus types 1, 2, and 3) to bivalent OPV (bOPV) (types 1 and 3) in April 2016 (5), GPEI regards any VDPV2 emergence as a public health emergency (6,7). During May-June 2017, VDPV2 was isolated from stool specimens from two children with acute flaccid paralysis (AFP) in Deir-ez-Zor governorate, Syria. The first isolate differed from Sabin vaccine virus by 22 nucleotides in the VP1 coding region (903 nucleotides). Genetic sequence analysis linked the two cases, confirming an outbreak of circulating VDPV2 (cVDPV2). Poliovirus surveillance activities were intensified, and three rounds of vaccination campaigns, aimed at children aged <5 years, were conducted using monovalent OPV type 2 (mOPV2). During the outbreak, 74 cVDPV2 cases were identified; the most recent occurred in September 2017. Evidence indicates that enhanced surveillance measures coupled with vaccination activities using mOPV2 have interrupted cVDPV2 transmission in Syria.

Outbreak of poliomyelitis in a previously Polio-Free State in Nigeria, 2013

Introduction: globally, Nigeria is one of the three polio endemic countries. Taraba State reported two confirmed wild polio virus type 1 (WPV 1) cases between April - May 2013. The cases were in settlements 2 - 3 kilometers apart. The state last reported WPV 1 in 2008. We conducted an outbreak investigation of Poliomyelitis to determine the factor(s) that contributed to the re-emergence of WPV 1 and to assess the extent of spread of the cases.

China's Belt and Road Initiative from a global health perspective.

China's Belt and Road Initiative from a global health perspective.

An assessment of the geographical risks of wild and vaccine-derived poliomyelitis outbreaks in Africa and Asia

BackgroundThe international spread of wild poliomyelitis outbreaks continues to threaten eradication of poliomyelitis and in 2014 a public health emergency of international concern was declared. Here we describe a risk scoring system that has been used to assess country-level risks of wild poliomyelitis outbreaks, to inform prioritisation of mass vaccination planning, and describe the change in risk from 2014 to 2016. The methods were also used to assess the risk of emergence of vaccine-derived poliomyelitis outbreaks.MethodsPotential explanatory variables were tested against the reported outbreaks of wild poliomyelitis since 2003 using multivariable regression analysis. The regression analysis was translated to a risk score and used to classify countries as Low, Medium, Medium High and High risk, based on the predictive ability of the score.ResultsIndicators of population immunity, population displacement and diarrhoeal disease were associated with an increased risk of both wild and vaccine-derived outbreaks. High migration from countries with wild cases was associated with wild outbreaks. High birth numbers were associated with an increased risk of vaccine-derived outbreaks.ConclusionsUse of the scoring system is a transparent and rapid approach to assess country risk of wild and vaccine-derived poliomyelitis outbreaks. Since 2008 there has been a steep reduction in the number of wild poliomyelitis outbreaks and the reduction in countries classified as High and Medium High risk has reflected this. The risk of vaccine-derived poliomyelitis outbreaks has varied geographically. These findings highlight that many countries remain susceptible to poliomyelitis outbreaks and maintenance or improvement in routine immunisation is vital.

ПОЛІОМІЄЛІТ: НОВІ ВИКЛИКИ НА ШЛЯХУ ДО ЕРАДИКАЦІЇ

Незважаючи на очевидний прогрес у здійсненні Глобальної ініціативи по ліквідації поліомієліту (з 1988 р. кількість випадків поліомієліту скоротилася більш ніж на 99,9 %, припинення циркуляції «диких» поліовірусів типів 1 і 3, зменшилася кількість ендемічних з поліомієліту країн від 125 до 3 і т. д.), ряд невирішених питань залишаються, що перешкоджає досягненню кінцевої мети (тривала циркуляця «дикого» штаму поліовірусу 1 типу, формування вакциноспоріднених вірусів (VDPVs) і пов’язаних з ними ризиків, випадки вакцинасоційованого паралітичного поліомієліту (VAPP), прогалини в програмах імунізації деяких країн). У 2015 р. в Україні був спалах поліомієліту, спричинений циркулюючим вірусом VDPV1 (cVDPV1). Це сталося на тлі зниження планової вакцинації проти поліомієліту (наприклад, в 2014 р. – 44,7 %, за 7 міс. 2015 р. – 17,3 %). Це сприяло накопиченню неімунного прошарку серед дітей і формуванню VDPVs. У відповідь на спалах поліомієліту було проведено три раунди імунізації ОПВ. Проте їх рівні були недостатніми (відповідно 64,4, 71,7 і 80,7 % порівняно з необхідними 95 %). У той же час, результати спостереження показали високу ймовірність припинення циркуляції вірусу VDPV1.

Preventing Vaccine-Derived Poliovirus Emergence during the Polio Endgame.

Reversion and spread of vaccine-derived poliovirus (VDPV) to cause outbreaks of poliomyelitis is a rare outcome resulting from immunisation with the live-attenuated oral poliovirus vaccines (OPVs). Global withdrawal of all three OPV serotypes is therefore a key objective of the polio endgame strategic plan, starting with serotype 2 (OPV2) in April 2016. Supplementary immunisation activities (SIAs) with trivalent OPV (tOPV) in advance of this date could mitigate the risks of OPV2 withdrawal by increasing serotype-2 immunity, but may also create new serotype-2 VDPV (VDPV2). Here, we examine the risk factors for VDPV2 emergence and implications for the strategy of tOPV SIAs prior to OPV2 withdrawal. We first developed mathematical models of VDPV2 emergence and spread. We found that in settings with low routine immunisation coverage, the implementation of a single SIA increases the risk of VDPV2 emergence. If routine coverage is 20%, at least 3 SIAs are needed to bring that risk close to zero, and if SIA coverage is low or there are persistently “missed” groups, the risk remains high despite the implementation of multiple SIAs. We then analysed data from Nigeria on the 29 VDPV2 emergences that occurred during 2004−2014. Districts reporting the first case of poliomyelitis associated with a VDPV2 emergence were compared to districts with no VDPV2 emergence in the same 6-month period using conditional logistic regression. In agreement with the model results, the odds of VDPV2 emergence decreased with higher routine immunisation coverage (odds ratio 0.67 for a 10% absolute increase in coverage [95% confidence interval 0.55−0.82]). We also found that the probability of a VDPV2 emergence resulting in poliomyelitis in >1 child was significantly higher in districts with low serotype-2 population immunity. Our results support a strategy of focused tOPV SIAs before OPV2 withdrawal in areas at risk of VDPV2 emergence and in sufficient number to raise population immunity above the threshold permitting VDPV2 circulation. A failure to implement this risk-based approach could mean these SIAs actually increase the risk of VDPV2 emergence and spread.

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.

Faster Detection of Poliomyelitis Outbreaks to Support Polio Eradication.

As the global eradication of poliomyelitis approaches the final stages, prompt detection of new outbreaks is critical to enable a fast and effective outbreak response. Surveillance relies on reporting of acute flaccid paralysis (AFP) cases and laboratory confirmation through isolation of poliovirus from stool. However, delayed sample collection and testing can delay outbreak detection. We investigated whether weekly testing for clusters of AFP by location and time, using the Kulldorff scan statistic, could provide an early warning for outbreaks in 20 countries. A mixed-effects regression model was used to predict background rates of nonpolio AFP at the district level. In Tajikistan and Congo, testing for AFP clusters would have resulted in an outbreak warning 39 and 11 days, respectively, before official confirmation of large outbreaks. This method has relatively high specificity and could be integrated into the current polio information system to support rapid outbreak response activities.

An Insight into Recombination with Enterovirus Species C and Nucleotide G-480 Reversion from the Viewpoint of Neurovirulence of Vaccine-Derived Polioviruses.

A poliomyelitis outbreak caused by type 1 circulating vaccine-derived polioviruses (cVDPVs) was identified in China in 2004. Six independent cVDPVs (eight isolates) could be grouped into a single cluster with pathways of divergence different from a single cVDPV progenitor, which circulated and evolved into both a highly neurovirulent lineage and a less neurovirulent lineage. They were as neurovirulent as the wild type 1 Mahoney strain, recombination was absent, and their nucleotide 480-G was identical to that of the Sabin strain. The Guizhou/China cVDPV strains shared 4 amino acid replacements in the NAg sites: 3 located at the BC loop, which may underlie the aberrant results of the ELISA intratypic differentiation (ITD) test. The complete ORF tree diverged into two main branches from a common ancestral infection estimated to have occurred in about mid-September 2003, nine months before the appearance of the VDPV case, which indicated recently evolved VDPV. Further, recombination with species C enteroviruses may indicate the presence and density of these enteroviruses in the population and prolonged virus circulation in the community. The aforementioned cVDPVs has important implications in the global initiative to eradicate polio: high quality surveillance permitted earliest detection and response.

Twenty-Eight Years of Poliovirus Replication in an Immunodeficient Individual: Impact on the Global Polio Eradication Initiative.

There are currently huge efforts by the World Health Organization and partners to complete global polio eradication. With the significant decline in poliomyelitis cases due to wild poliovirus in recent years, rare cases related to the use of live-attenuated oral polio vaccine assume greater importance. Poliovirus strains in the oral vaccine are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These strains can transmit from person to person leading to poliomyelitis outbreaks and can replicate for long periods of time in immunodeficient individuals leading to paralysis or chronic infection, with currently no effective treatment to stop excretion from these patients. Here, we describe an individual who has been excreting type 2 vaccine-derived poliovirus for twenty eight years as estimated by the molecular clock established with VP1 capsid gene nucleotide sequences of serial isolates. This represents by far the longest period of excretion described from such a patient who is the only identified individual known to be excreting highly evolved vaccine-derived poliovirus at present. Using a range of in vivo and in vitro assays we show that the viruses are very virulent, antigenically drifted and excreted at high titre suggesting that such chronic excreters pose an obvious risk to the eradication programme. Our results in virus neutralization assays with human sera and immunisation-challenge experiments using transgenic mice expressing the human poliovirus receptor indicate that while maintaining high immunisation coverage will likely confer protection against paralytic disease caused by these viruses, significant changes in immunisation strategies might be required to effectively stop their occurrence and potential widespread transmission. Eventually, new stable live-attenuated polio vaccines with no risk of reversion might be required to respond to any poliovirus isolation in the post-eradication era.

A probable case of poliomyelitis imported to Malaysia

We report a previously well 10-month-old Somalian girl who acquired asymmetric lower limb weakness in July 2013 in Mogadishu, Banadir, before arriving in Malaysia at 12months of age. In May 2013, there was a wild poliomyelitis outbreak in that area, as reported by the World Health Organization. Laboratory investigation, including cerebrospinal fluid, was unremarkable, and electrophysiological studies showed active axonal denervation in the left lower limb. The whole spine T2-weighted MRI revealed non-enhancing hyperintensities of the bilateral anterior horn cells, predominantly on the left side at T11–12. The viral isolations from two stool specimens at her presentation to our centre, 2months after the onset of illness and 2weeks apart, were negative. Despite lacking the acute virological evidence of poliomyelitis, in view of the girl’s clinical, electrophysiological and classical spinal neuroradiological features, together with her temporal relationship with a World Health Organization reported wild poliomyelitis outbreak, we believe these findings are consistent with a diagnosis of imported poliomyelitis. A review at 30months of age showed persistent left lower limb monoplegia with little recovery. Our patient reiterates the importance of maintaining awareness of wild polio importation, and keeping abreast of the latest news of global poliomyelitis outbreaks when treating patients with flaccid paralysis, even if they arrive from non-endemic poliomyelitis areas.