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1.
MMWR Morb Mortal Wkly Rep ; 72(49): 1327-1330, 2023 Dec 08.
Article in English | MEDLINE | ID: mdl-38060431

ABSTRACT

Poliovirus can cause poliomyelitis and lifelong paralysis. Although wild poliovirus types 2 and 3 have been eradicated, wild poliovirus type 1 and vaccine-derived polioviruses are still circulating in multiple countries worldwide. In 2022, a case of paralytic polio caused by vaccine-derived poliovirus type 2 was identified in an unvaccinated young adult in New York. This case and subsequent detection of community transmission underscored the ongoing risk for importation of poliovirus into the United States and risk for poliomyelitis among unvaccinated persons. However, previous Advisory Committee on Immunization Practices (ACIP) recommendations for adult polio vaccination were limited to adults known to be at increased risk for exposure. During October 2022-June 2023, the ACIP Polio Vaccine Work Group reviewed data on poliovirus surveillance and epidemiology, safety and effectiveness of inactivated poliovirus vaccine (IPV), and other considerations outlined in the ACIP Evidence to Recommendations Framework. On June 21, 2023, ACIP voted to recommend that all U.S. adults aged ≥18 years who are known or suspected to be unvaccinated or incompletely vaccinated against polio complete a primary polio vaccination series with IPV. This report summarizes evidence considered for this recommendation and provides clinical guidance for the use of IPV in adults.


Subject(s)
Poliomyelitis , Poliovirus Vaccine, Inactivated , Poliovirus , Adolescent , Adult , Humans , Advisory Committees , Immunization , New York , Poliomyelitis/epidemiology , Poliomyelitis/prevention & control , Poliomyelitis/etiology , Poliovirus Vaccine, Inactivated/adverse effects , Poliovirus Vaccine, Oral/adverse effects , United States/epidemiology , Vaccination
2.
MMWR Morb Mortal Wkly Rep ; 72(19): 517-522, 2023 May 12.
Article in English | MEDLINE | ID: mdl-37167156

ABSTRACT

Since the World Health Assembly established the Global Polio Eradication Initiative (GPEI) in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been eradicated, and global WPV cases have decreased by more than 99.9%. Afghanistan and Pakistan remain the only countries where indigenous WPV type 1 (WPV1) transmission has not been interrupted. This report summarizes progress toward global polio eradication during January 1, 2021-March 31, 2023, and updates previous reports (1,2). In 2022, Afghanistan and Pakistan reported 22 WPV1 cases, compared with five in 2021; as of May 5, 2023, a single WPV1 case was reported in Pakistan in 2023. A WPV1 case was reported on the African continent for the first time since 2016, when officials in Malawi confirmed a WPV1 case in a child with paralysis onset in November 2021; neighboring Mozambique subsequently reported eight genetically linked cases. Outbreaks of polio caused by circulating vaccine-derived polioviruses (cVDPVs) can occur when oral poliovirus vaccine (OPV) strains circulate for a prolonged time in underimmunized populations, allowing reversion to neurovirulence (3). A total of 859 cVDPV cases occurred during 2022, an increase of 23% from 698 cases in 2021. cVDPVs were detected in areas where poliovirus transmission had long been eliminated (including in Canada, Israel, the United Kingdom, and the United States). In addition, cocirculation of multiple poliovirus types occurred in multiple countries globally (including Democratic Republic of the Congo [DRC], Israel, Malawi, Mozambique, Republic of the Congo, and Yemen). The 2022-2026 GPEI strategic plan targeted the goal of detecting the last cases of WPV1 and cVDPV in 2023 (4). The current global epidemiology of poliovirus transmission makes the likelihood of meeting this target date unlikely. The detections of poliovirus (WPV1 and cVDPVs) in areas where it had been previously eliminated underscore the threat of continued poliovirus spread to any area where there is insufficient vaccination to poliovirus (3). Mass vaccination and surveillance should be further enhanced in areas of transmission to interrupt poliovirus transmission and to end the global threat of paralytic polio in children.


Subject(s)
Poliomyelitis , Poliovirus Vaccine, Oral , Poliovirus , Child , Humans , Disease Eradication , Disease Outbreaks , Global Health , Immunization Programs , Poliomyelitis/epidemiology , Poliomyelitis/prevention & control , Poliomyelitis/etiology , Poliovirus/genetics , Poliovirus Vaccine, Oral/adverse effects , Population Surveillance
3.
Curr Opin Neurol ; 36(3): 229-237, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37078665

ABSTRACT

PURPOSE OF REVIEW: Recent outbreaks of poliomyelitis in countries that have been free of cases for decades highlight the challenges of eradicating polio in a globalized interconnected world beset with a novel viral pandemic. We provide an epidemiological update, advancements in vaccines, and amendments in public health strategy of poliomyelitis in this review. RECENT FINDINGS: Last year, new cases of wild poliovirus type 1 (WPV1) were documented in regions previously documented to have eradicated WPV1 and reports of circulating vaccine-derived poliovirus type 2 (cVDPV2) and 3 (cVDPV3) in New York and Jerusalem made international headlines. Sequencing of wastewater samples from environmental surveillance revealed that the WPV1 strains were related to WPV1 lineages from endemic countries and the cVDPV2 strains from New York and Jerusalem were not only related to each other but also to environmental isolates found in London. The evidence of importation of WPV1 cases from endemic countries, and global transmission of cVDPVs justifies renewed efforts in routine vaccination programs and outbreak control measures that were interrupted by the COVID-19 pandemic. After the novel oral poliovirus vaccine type 2 (nOPV2) received emergency authorization for containment of cVDPV2 outbreaks in 2021, subsequent reduced incidence, transmission rates, and vaccine adverse events, alongside increased genetic stability of viral isolates substantiates the safety and efficacy of nOPV2. The nOPV1 and nOPV3 vaccines, against type 1 and 3 cVDPVs, and measures to increase accessibility and efficacy of inactivated poliovirus vaccine (IPV) are in development. SUMMARY: A revised strategy utilizing more genetically stable vaccine formulations, with uninterrupted vaccination programs and continued active surveillance optimizes the prospect of global poliomyelitis eradication.


Subject(s)
COVID-19 , Poliomyelitis , Poliovirus , Humans , Poliovirus/genetics , Pandemics , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/complications , Poliovirus Vaccine, Oral/adverse effects , Poliomyelitis/epidemiology , Poliomyelitis/prevention & control , Poliomyelitis/etiology , Disease Outbreaks
4.
Front Immunol ; 14: 1135834, 2023.
Article in English | MEDLINE | ID: mdl-36936936

ABSTRACT

The global polio eradication campaign has had remarkable success in reducing wild-type poliovirus infection, largely built upon the live attenuated Sabin oral poliovirus vaccine. Whilst rare, vaccine poliovirus strains may cause infection and subsequently revert to a neurovirulent type, termed vaccine-derived poliovirus (VDPV). Persistent, vaccine derived infection may occur in an immunocompromised host (iVDPV), where it is a recognised complication following receipt of the Sabin vaccine. This has significant implications for the global polio eradication campaign and there is currently no agreed global strategy to manage such patients.Here we describe a case of a 50-year-old man with common variable immune deficiency, persistently infected with a neurovirulent vaccine-derived type 2 poliovirus following vaccination in childhood. iVDPV infection had proven resistant to multiple prior attempts at treatment with human breast milk, ribavirin and oral administration of a normal human pooled immunoglobulin product. His iVDPV infection subsequently resolved after 12 days treatment with remdesivir, an adenosine analogue prodrug that is an inhibitor of viral RNA-dependent RNA polymerase, administered as treatment for a prolonged, moderate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. iVDPV from the patient, isolated prior to treatment, was subsequently demonstrated to be sensitive to remdesivir in vitro. Based on the observations made in this case, and the mechanistic rationale for use with iVDPV, there is strong justification for further clinical studies of remdesivir treatment as a potentially curative intervention in patients with iVDPV infection.


Subject(s)
COVID-19 , Immunologic Deficiency Syndromes , Poliomyelitis , Poliovirus Vaccine, Oral , Poliovirus , Female , Humans , Male , Middle Aged , COVID-19/complications , COVID-19 Drug Treatment , Poliomyelitis/drug therapy , Poliomyelitis/etiology , Poliomyelitis/prevention & control , Poliovirus Vaccine, Oral/adverse effects , SARS-CoV-2
5.
Geroscience ; 45(2): 707-717, 2023 04.
Article in English | MEDLINE | ID: mdl-36260265

ABSTRACT

For more than 20 years, the World Health Organization Western Pacific Region (WPR) has been polio-free. However, two current challenges are still polio-related. First, around half of poliomyelitis elderly survivors suffer late poliomyelitis sequelae with a substantial impact on daily activities and quality of life, experiencing varying degrees of residual weakness as they age. The post-polio syndrome as well as accelerated aging may be involved. Second, after the worldwide Sabin oral poliovirus (OPV) vaccination, the recent reappearance of strains of vaccine-derived poliovirus (VDPV) circulating in the environment is worrisome and able to persistent person-to-person transmission. Such VDPV strains exhibit atypical genetic characteristics and reversed neurovirulence that can cause paralysis similarly to wild poliovirus, posing a significant obstacle to the elimination of polio. Immunization is essential for preventing paralysis in those who are exposed to the poliovirus. Stress the necessity of maintaining high vaccination rates because declining immunity increases the likelihood of reemergence. If mankind wants to eradicate polio in the near future, measures to raise immunization rates and living conditions in poorer nations are needed, along with strict observation. New oral polio vaccine candidates offer a promissory tool for this goal.


Subject(s)
Poliomyelitis , Poliovirus Vaccine, Oral , Poliovirus , Aged , Humans , Paralysis/complications , Poliomyelitis/epidemiology , Poliomyelitis/prevention & control , Poliomyelitis/etiology , Poliovirus/genetics , Poliovirus Vaccine, Oral/adverse effects , Quality of Life
6.
Int J Pediatr Otorhinolaryngol ; 162: 111290, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36067711

ABSTRACT

OBJECTIVE: This paper serves to review the historical progression of clinical, epidemiological and immunological evidence on the relationship between tonsillectomy and poliomyelitis and its influence on clinical medicine. METHODS: A literature review was conducted using terms relating to poliomyelitis, tonsillectomy, and immunology. Primary sources published between 1900 and 2000 were reviewed, analyzed and evaluated based on their historical, clinical, epidemiological, scientific and immunological pertinence towards the relationship between tonsillectomy, and poliomyelitis during epidemics. RESULTS: The first study proposing a relationship between poliomyelitis and tonsillectomy was a case report published in 1910 by Phillip Sheppard. In response, other physicians began conducting clinical and epidemiological studies investigating the relationship between recent tonsillectomy and poliomyelitis in children. While the results of many of these studies demonstrated an increased morbidity and mortality rate associated with poliomyelitis in children who underwent recent tonsillectomy, other studies claimed there was no connection. Opposing study results and diverging physician views on this relationship left the medical community divided on whether to recommend against elective tonsillectomies during poliomyelitis outbreaks. The relationship between tonsillectomy and poliomyelitis was established after many years of clinical and epidemiological studies. Further scientific and immunological investigations revealed the causal nature of this relationship.


Subject(s)
Adenoids , Poliomyelitis , Tonsillectomy , Child , Elective Surgical Procedures/adverse effects , Humans , Palatine Tonsil , Poliomyelitis/epidemiology , Poliomyelitis/etiology , Tonsillectomy/adverse effects
7.
Vaccine ; 40(40): 5835-5841, 2022 Sep 22.
Article in English | MEDLINE | ID: mdl-36064670

ABSTRACT

BACKGROUND: To meet the demand for effective and affordable inactivated polio vaccines (IPVs), a reduced dose, aluminium hydroxide (Al(OH)3)-adjuvanted IPV vaccine was developed (IPV-Al, Picovax®) and evaluated in clinical trials. The present trial is an extension of two previous trials (a primary and a booster trial). The aim was to evaluate the persistence of seroprotective antibodies (poliovirus type-specific antibody titre ≥ 8) in 4-year-old children who previously received IPV-Al as primary and booster vaccine doses and to determine the potential booster response and safety profile of an additional dose of IPV-Al. METHODS: Children participating in the two previous trials were invited to receive one additional dose of IPV-Al at 4 years of age (2.5 years after the booster dose) and to have their blood samples collected to measure the pre- and post-vaccination antibody titres. Systemic adverse events (AEs) and local reactogenicity were recorded. RESULTS: At study entry, the seroprotection rates were 89.2%, 100% and 91.1% against poliovirus type 1, 2 and 3, respectively. The additional vaccination with IPV-Al boosted the level of poliovirus type 1, 2 and 3 antibodies to above the seroprotection threshold for all but one subject, i.e., 99.4% for type 1 and 100% for types 2 and 3. The additional dose induced a robust booster response of a 26.3-, 13.9- and 30.9-fold increase in titre for poliovirus types 1, 2 and 3, respectively. The vaccine was well tolerated, with only mild and transient AEs reported. CONCLUSIONS: The present trial demonstrated that the primary vaccination with an aluminium-adjuvanted reduced dose IPV induced a persistent immune memory as evidenced by the robust anamnestic response when the subjects were re-exposed to the antigen 2.5 years after the last dose. Thus, the IPV-Al is an efficient and safe addition to increase the availability of inactivated polio vaccines globally. (ClinicalTrials.gov reg no. NCT04448132).


Subject(s)
Poliomyelitis , Poliovirus , Adjuvants, Immunologic , Aluminum , Antibodies, Viral , Child, Preschool , Humans , Immunization, Secondary/adverse effects , Infant , Poliomyelitis/etiology , Poliomyelitis/prevention & control , Poliovirus Vaccine, Inactivated
9.
MMWR Morb Mortal Wkly Rep ; 71(24): 786-790, 2022 Jun 17.
Article in English | MEDLINE | ID: mdl-35709073

ABSTRACT

The emergence and international spread of neurovirulent circulating vaccine-derived polioviruses (cVDPVs) across multiple countries in Africa and Asia in recent years pose a major challenge to the goal of eradicating all forms of polioviruses. Approximately 90% of all cVDPV outbreaks are caused by the type 2 strain of the Sabin vaccine, an oral live, attenuated vaccine; cVDPV outbreaks typically occur in areas of persistently low immunization coverage (1). A novel type 2 oral poliovirus vaccine (nOPV2), produced by genetic modification of the type 2 Sabin vaccine virus genome (2), was developed and evaluated through phase I and phase II clinical trials during 2017-2019. nOPV2 was demonstrated to be safe and well-tolerated, have noninferior immunogenicity, and have superior genetic stability compared with Sabin monovalent type 2 (as measured by preservation of the primary attenuation site [domain V in the 5' noncoding region] and significantly lower neurovirulence of fecally shed vaccine virus in transgenic mice) (3-5). These findings indicate that nOPV2 could be an important tool in reducing the risk for generating vaccine-derived polioviruses (VDPVs) and the risk for vaccine-associated paralytic poliomyelitis cases. Based on the favorable preclinical and clinical data, and the public health emergency of international concern generated by ongoing endemic wild poliovirus transmission and cVDPV type 2 outbreaks, the World Health Organization authorized nOPV2 for use under the Emergency Use Listing (EUL) pathway in November 2020, allowing for its first use for outbreak response in March 2021 (6). As required by the EUL process, among other EUL obligations, an extensive plan was developed and deployed for obtaining and monitoring nOPV2 isolates detected during acute flaccid paralysis (AFP) surveillance, environmental surveillance, adverse events after immunization surveillance, and targeted surveillance for adverse events of special interest (i.e., prespecified events that have the potential to be causally associated with the vaccine product), during outbreak response, as well as through planned field studies. Under this monitoring framework, data generated from whole-genome sequencing of nOPV2 isolates, alongside other virologic data for isolates from AFP and environmental surveillance systems, are reviewed by the genetic characterization subgroup of an nOPV working group of the Global Polio Eradication Initiative. Global nOPV2 genomic surveillance during March-October 2021 confirmed genetic stability of the primary attenuating site. Sequence data generated through this unprecedented global effort confirm the genetic stability of nOPV2 relative to Sabin 2 and suggest that nOPV2 will be an important tool in the eradication of poliomyelitis. nOPV2 surveillance should continue for the duration of the EUL.


Subject(s)
Poliomyelitis , Poliovirus Vaccine, Oral , Poliovirus , Animals , Central Nervous System Viral Diseases/prevention & control , Disease Outbreaks/prevention & control , Humans , Mice , Myelitis/prevention & control , Neuromuscular Diseases/prevention & control , Poliomyelitis/epidemiology , Poliomyelitis/etiology , Poliomyelitis/prevention & control , Poliovirus/genetics , Poliovirus Vaccine, Oral/adverse effects , Poliovirus Vaccine, Oral/genetics , Vaccines, Attenuated/adverse effects , Vaccines, Attenuated/genetics
11.
Hum Vaccin Immunother ; 18(1): 2021711, 2022 12 31.
Article in English | MEDLINE | ID: mdl-35108152

ABSTRACT

OBJECTIVES: The aim of this study is to describe the reporting rate of adverse events following immunization (AEFI) with pentavalent vaccine: diphtheria-pertussis-tetanus-poliomyelitis-Haemophilus influenzae type b (DPT-IPV/Hib), and to determine whether the reporting rate of AEFI following DPT-IPV/Hib was higher than the average level of the other vaccines. METHODS: Review and describe the AEFI reported to national adverse event following immunization surveillance system (NAEFISS) in Zhejiang province from 2015 to 2020. Reporting rates of AEFI were calculated by age, city, severity of AEFI, categories of AEFI, and reaction categories. The data mining algorithm used in this study was reporting odds ratio (ROR). A value of ROR­1.96SE >1 (standard error [SE]) was considered as positive signal. RESULTS: NAEFISS received 5726 AEFI reports following DTP-IPV/Hib, with a reporting rate of 20.01/10000 doses. Of the reported AEFI, 202 were serious vaccine product-related reactions, including two cases of anaphylactic shock, five cases of Guillain Barre Syndrome (GBS) and two cases of acute disseminated encephalomyelitis. The reporting rate of fever/redness/induration was the highest among all the clinical diagnosis (14.97/10000 doses). The positive signals were obtained for allergic rash (ROR-1.96SE: 1.36), febrile convulsion (ROR-1.96SE: 1.32) and GBS (ROR-1.96SE: 1.16). CONCLUSION: The present findings bolstered that the DTP-IPV/Hib administered as the four-dose schedule was generally well tolerated in Chinese infants as we did not identify any new/unexpected safety concern from the NAEFISS during a six-year timespan.


Subject(s)
Haemophilus Vaccines , Haemophilus influenzae type b , Poliomyelitis , Diphtheria-Tetanus-Pertussis Vaccine , Hepatitis B Vaccines , Humans , Immunization/adverse effects , Immunization Schedule , Infant , Poliomyelitis/etiology , Poliovirus Vaccine, Inactivated/adverse effects , Vaccination , Vaccines, Combined
12.
MMWR Morb Mortal Wkly Rep ; 70(49): 1691-1699, 2021 Dec 10.
Article in English | MEDLINE | ID: mdl-34882653

ABSTRACT

As of May 1, 2016, use of oral poliovirus vaccine (OPV) type 2 for routine and supplementary immunization activities ceased after a synchronized global switch from trivalent OPV (tOPV; containing Sabin strain types 1, 2, and 3) to bivalent OPV (bOPV; containing Sabin strain types 1 and 3) subsequent to the certified eradication of wild type poliovirus (WPV) type 2 in 2015 (1-3). Circulating vaccine-derived poliovirus (cVDPV) outbreaks* occur when transmission of Sabin strain poliovirus is prolonged in underimmunized populations, allowing viral genetic reversion to neurovirulence, resulting in cases of paralytic polio (1-3). Since the switch, monovalent OPV type 2 (mOPV2, containing Sabin strain type 2) has been used for response to cVDPV type 2 (cVDPV2) outbreaks; tOPV is used if cVDPV2 co-circulates with WPV type 1, and bOPV is used for cVDPV type 1 (cVDPV1) or type 3 (cVDPV3) outbreaks (1-4). In November 2020, the World Health Organization (WHO) Emergency Use Listing procedure authorized limited use of type 2 novel OPV (nOPV2), a vaccine modified to be more genetically stable than the Sabin strain, for cVDPV2 outbreak response (3,5). In October 2021, the Strategic Advisory Group of Experts on Immunization (WHO's principal advisory group) permitted wider use of nOPV2; however, current nOPV2 supply is limited (6). This report updates that of July 2019-February 2020 to describe global cVDPV outbreaks during January 2020-June 2021 (as of November 9, 2021)† (3). During this period, there were 44 cVDPV outbreaks of the three serotypes affecting 37 countries. The number of cVDPV2 cases increased from 366 in 2019 to 1,078 in 2020 (7). A goal of the Global Polio Eradication Initiative's (GPEI) 2022-2026 Strategic Plan is to better address the challenges to early CVDPV2 outbreak detection and initiate prompt and high coverage outbreak responses with available type 2 OPV to interrupt transmission by the end of 2023 (8).


Subject(s)
Disease Outbreaks/statistics & numerical data , Global Health/statistics & numerical data , Poliomyelitis/epidemiology , Poliovirus Vaccine, Oral/adverse effects , Poliovirus/isolation & purification , Humans , Poliomyelitis/etiology , Poliomyelitis/prevention & control , Poliovirus/classification , Poliovirus Vaccine, Oral/administration & dosage , Serotyping
13.
Sci Rep ; 10(1): 7918, 2020 05 13.
Article in English | MEDLINE | ID: mdl-32404926

ABSTRACT

Antecedent viral infection may contribute to increased susceptibility to several neurological diseases, such as multiple sclerosis and Parkinson's disease. Variation in clinical presentations of these diseases is often associated with gender, genetic background, or a combination of these and other factors. The complicated etiologies of these virally influenced diseases are difficult to study in conventional laboratory mouse models, which display a very limited number of phenotypes. We have used the genetically and phenotypically diverse Collaborative Cross mouse panel to examine complex neurological phenotypes after viral infection. Female and male mice from 18 CC strains were evaluated using a multifaceted phenotyping pipeline to define their unique disease profiles following infection with Theiler's Murine Encephalomyelitis Virus, a neurotropic virus. We identified 4 distinct disease progression profiles based on limb-specific paresis and paralysis, tremors and seizures, and other clinical signs, along with separate gait profiles. We found that mice of the same strain had more similar profiles compared to those of different strains, and also identified strains and phenotypic parameters in which sex played a significant role in profile differences. These results demonstrate the value of using CC mice for studying complex disease subtypes influenced by sex and genetic background. Our findings will be useful for developing novel mouse models of virally induced neurological diseases with heterogenous presentation, an important step for designing personalized, precise treatments.


Subject(s)
Crosses, Genetic , Genetic Association Studies , H-2 Antigens/genetics , Phenotype , Animals , Cluster Analysis , Encephalitis/etiology , Female , Gait , Male , Mice , Poliomyelitis/etiology , Seizures/etiology , Sex Factors , Species Specificity , Theilovirus/physiology , Viral Load
14.
J Virol ; 94(14)2020 07 01.
Article in English | MEDLINE | ID: mdl-32404525

ABSTRACT

Mouse hepatitis virus (MHV) is a murine betacoronavirus (m-CoV) that causes a wide range of diseases in mice and rats, including hepatitis, enteritis, respiratory diseases, and encephalomyelitis in the central nervous system (CNS). MHV infection in mice provides an efficient cause-effect experimental model to understand the mechanisms of direct virus-induced neural-cell damage leading to demyelination and axonal loss, which are pathological features of multiple sclerosis (MS), the most common disabling neurological disease in young adults. Infiltration of T lymphocytes, activation of microglia, and their interplay are the primary pathophysiological events leading to disruption of the myelin sheath in MS. However, there is emerging evidence supporting gray matter involvement and degeneration in MS. The investigation of T cell function in the pathogenesis of deep gray matter damage is necessary. Here, we employed RSA59 (an isogenic recombinant strain of MHV-A59)-induced experimental neuroinflammation model to compare the disease in CD4-/- mice with that in CD4+/+ mice at days 5, 10, 15, and 30 postinfection (p.i.). Viral titer estimation, nucleocapsid gene amplification, and viral antinucleocapsid staining confirmed enhanced replication of the virions in the absence of functional CD4+ T cells in the brain. Histopathological analyses showed elevated susceptibility of CD4-/- mice to axonal degeneration in the CNS, with augmented progression of acute poliomyelitis and dorsal root ganglionic inflammation rarely observed in CD4+/+ mice. Depletion of CD4+ T cells showed unique pathological bulbar vacuolation in the brain parenchyma of infected mice with persistent CD11b+ microglia/macrophages in the inflamed regions on day 30 p.i. In summary, the current study suggests that CD4+ T cells are critical for controlling acute-stage poliomyelitis (gray matter inflammation), chronic axonal degeneration, and inflammatory demyelination due to loss of protective antiviral host immunity.IMPORTANCE The current trend in CNS disease biology is to attempt to understand the neural-cell-immune interaction to investigate the underlying mechanism of neuroinflammation, rather than focusing on peripheral immune activation. Most studies in MS are targeted toward understanding the involvement of CNS white matter. However, the importance of gray matter damage has become critical in understanding the long-term progressive neurological disorder. Our study highlights the importance of CD4+ T cells in safeguarding neurons against axonal blebbing and poliomyelitis from murine betacoronavirus-induced neuroinflammation. Current knowledge of the mechanisms that lead to gray matter damage in MS is limited, because the most widely used animal model, experimental autoimmune encephalomyelitis (EAE), does not present this aspect of the disease. Our results, therefore, add to the existing limited knowledge in the field. We also show that the microglia, though important for the initiation of neuroinflammation, cannot establish a protective host immune response without the help of CD4+ T cells.


Subject(s)
Axons/immunology , Axons/metabolism , CD4 Antigens/deficiency , Coronavirus Infections/immunology , Coronavirus Infections/virology , Murine hepatitis virus/physiology , Poliomyelitis/etiology , Animals , Axons/pathology , Brain/immunology , Brain/metabolism , Brain/pathology , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Coronavirus Infections/pathology , Cytokines/metabolism , Disease Models, Animal , Disease Susceptibility/immunology , Ganglia, Spinal/immunology , Ganglia, Spinal/metabolism , Ganglia, Spinal/pathology , Immunohistochemistry , Inflammation Mediators/metabolism , Mice
15.
MMWR Morb Mortal Wkly Rep ; 69(16): 489-495, 2020 Apr 24.
Article in English | MEDLINE | ID: mdl-32324719

ABSTRACT

Circulating vaccine-derived polioviruses (cVDPVs) can emerge in areas with low poliovirus immunity and cause outbreaks* of paralytic polio (1-5). Among the three types of wild poliovirus, type 2 was declared eradicated in 2015 (1,2). The use of trivalent oral poliovirus vaccine (tOPV; types 1, 2, and 3 Sabin strains) ceased in April 2016 via a 1-month-long, global synchronized switch to bivalent OPV (bOPV; types 1 and 3 Sabin strains) in immunization activities (1-4). Monovalent type 2 OPV (mOPV2; type 2 Sabin strain) is available for cVDPV type 2 (cVDPV2) outbreak response immunization (1-5). The number and geographic breadth of post-switch cVDPV2 outbreaks have exceeded forecasts that trended toward zero outbreaks 4 years after the switch and assumed rapid and effective control of any that occurred (4). New cVDPV2 outbreaks have been seeded by mOPV2 use, by both suboptimal mOPV2 coverage within response zones and recently mOPV2-vaccinated children or contacts traveling outside of response zones, where children born after the global switch are fully susceptible to poliovirus type 2 transmission (2-4). In addition, new emergences can develop by inadvertent exposure to Sabin OPV2-containing vaccine (i.e., residual response mOPV2 or tOPV) (4). This report updates the January 2018-June 2019 report with information on global cVDPV outbreaks during July 2019-February 2020 (as of March 25, 2020)† (2). Among 33 cVDPV outbreaks reported during July 2019-February 2020, 31 (94%) were cVDPV2; 18 (58%) of these followed new emergences. In mid-2020, the Global Polio Eradication Initiative (GPEI) plans to introduce a genetically stabilized, novel OPV type 2 (nOPV2) that has a lower risk for generating VDPV2 than does Sabin mOPV2; if nOPV2 is successful in limiting new VDPV2 emergences, GPEI foresees the replacement of Sabin mOPV2 with nOPV2 for cVDPV2 outbreak responses during 2021 (2,4,6).


Subject(s)
Disease Outbreaks/statistics & numerical data , Global Health/statistics & numerical data , Poliomyelitis/epidemiology , Poliovirus Vaccine, Oral/adverse effects , Poliovirus/isolation & purification , Humans , Poliomyelitis/etiology , Poliomyelitis/prevention & control , Poliovirus/classification , Poliovirus Vaccine, Oral/administration & dosage , Serotyping
16.
PLoS Med ; 17(3): e1003070, 2020 03.
Article in English | MEDLINE | ID: mdl-32231366

ABSTRACT

BACKGROUND: We performed a cross-sectional survey in April-May 2018 among Rohingya in Cox's Bazar, Bangladesh, to assess polio immunity and inform vaccination strategies. METHODS AND FINDINGS: Rohingya children aged 1-6 years (younger group) and 7-14 years (older group) were selected using multi-stage cluster sampling in makeshift settlements and simple random sampling in Nayapara registered camp. Surveyors asked parents/caregivers if the child received any oral poliovirus vaccine (OPV) in Myanmar and, for younger children, if the child received vaccine in any of the 5 campaigns delivering bivalent OPV (serotypes 1 and 3) conducted during September 2017-April 2018 in Cox's Bazar. Dried blood spot (DBS) specimens were tested for neutralizing antibodies to poliovirus types 1, 2, and 3 in 580 younger and 297 older children. Titers ≥ 1:8 were considered protective. Among 632 children (335 aged 1-6 years, 297 aged 7-14 years) enrolled in the study in makeshift settlements, 51% were male and 89% had arrived after August 9, 2017. Among 245 children (all aged 1-6 years) enrolled in the study in Nayapara, 54% were male and 10% had arrived after August 9, 2017. Among younger children, 74% in makeshift settlements and 92% in Nayapara received >3 bivalent OPV doses in campaigns. Type 1 seroprevalence was 85% (95% CI 80%-89%) among younger children and 91% (95% CI 86%-95%) among older children in makeshift settlements, and 92% (88%-95%) among younger children in Nayapara. Type 2 seroprevalence was lower among younger children than older children in makeshift settlements (74% [95% CI 68%-79%] versus 97% [95% CI 94%-99%], p < 0.001), and was 69% (95% CI 63%-74%) among younger children in Nayapara. Type 3 seroprevalence was below 75% for both age groups and areas. The limitations of this study are unknown routine immunization history and poor retention of vaccination cards. CONCLUSIONS: Younger Rohingya children had immunity gaps to all 3 polio serotypes and should be targeted by future campaigns and catch-up routine immunization. DBS collection can enhance the reliability of assessments of outbreak risk and vaccination strategy impact in emergency settings.


Subject(s)
Poliomyelitis/epidemiology , Poliovirus Vaccine, Oral/administration & dosage , Refugees/statistics & numerical data , Vaccination/statistics & numerical data , Adolescent , Bangladesh/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Male , Myanmar/ethnology , Poliomyelitis/etiology , Poliomyelitis/prevention & control , Prevalence , Seroepidemiologic Studies
17.
Science ; 368(6489): 401-405, 2020 04 24.
Article in English | MEDLINE | ID: mdl-32193361

ABSTRACT

Although there have been no cases of serotype 2 wild poliovirus for more than 20 years, transmission of serotype 2 vaccine-derived poliovirus (VDPV2) and associated paralytic cases in several continents represent a threat to eradication. The withdrawal of the serotype 2 component of oral poliovirus vaccine (OPV2) was implemented in April 2016 to stop VDPV2 emergence and secure eradication of all serotype 2 poliovirus. Globally, children born after this date have limited immunity to prevent transmission. Using a statistical model, we estimated the emergence date and source of VDPV2s detected between May 2016 and November 2019. Outbreak response campaigns with monovalent OPV2 are the only available method to induce immunity to prevent transmission. Yet our analysis shows that using monovalent OPV2 is generating more paralytic VDPV2 outbreaks with the potential for establishing endemic transmission. A novel OPV2, for which two candidates are currently in clinical trials, is urgently required, together with a contingency strategy if this vaccine does not materialize or perform as anticipated.


Subject(s)
Disease Eradication/methods , Disease Outbreaks/prevention & control , Global Health , Poliomyelitis/epidemiology , Poliomyelitis/etiology , Poliovirus Vaccine, Oral/adverse effects , Poliovirus/immunology , Humans , Poliomyelitis/prevention & control , Poliomyelitis/transmission , Withholding Treatment
18.
Sci Rep ; 10(1): 5058, 2020 03 19.
Article in English | MEDLINE | ID: mdl-32193487

ABSTRACT

Recently, significant attention has been devoted to vaccine-derived poliovirus (VDPV) surveillance due to its severe consequences. Prediction of the outbreak incidence of VDPF requires an accurate analysis of the alarming data. The overarching aim to this study is to develop a novel hybrid machine learning approach to identify the key parameters that dominate the outbreak incidence of VDPV. The proposed method is based on the integration of random vector functional link (RVFL) networks with a robust optimization algorithm called whale optimization algorithm (WOA). WOA is applied to improve the accuracy of the RVFL network by finding the suitable parameter configurations for the algorithm. The classification performance of the WOA-RVFL method is successfully validated using a number of datasets from the UCI machine learning repository. Thereafter, the method is implemented to track the VDPV outbreak incidences recently occurred in several provinces in Lao People's Democratic Republic. The results demonstrate the accuracy and efficiency of the WOA-RVFL algorithm in detecting the VDPV outbreak incidences, as well as its superior performance to the traditional RVFL method.


Subject(s)
Epidemiological Monitoring , Machine Learning , Poliomyelitis/epidemiology , Poliomyelitis/etiology , Poliovirus Vaccines/adverse effects , Poliovirus , Algorithms , Disease Outbreaks , Forecasting , Humans , Incidence , Laos/epidemiology , Paraplegia/epidemiology , Paraplegia/etiology , Paraplegia/prevention & control , Poliomyelitis/immunology , Poliomyelitis/virology
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