Inactivated Poliovirus Vaccine: Recent Developments and the Tortuous Path to Global Acceptance.

Inactivated poliovirus vaccine (IPV), available since 1955, became the first vaccine to be used to protect against poliomyelitis. While the immunogenicity of IPV to prevent paralytic poliomyelitis continues to be irrefutable, its requirement for strong containment (due to large quantities of live virus used in the manufacturing process), perceived lack of ability to induce intestinal mucosal immunity, high cost and increased complexity to administer compared to oral polio vaccine (OPV), have limited its use in the global efforts to eradicate poliomyelitis. In order to harvest the full potential of IPV, a program of work has been carried out by the Global Polio Eradication Initiative (GPEI) over the past two decades that has focused on: (1) increasing the scientific knowledge base of IPV; (2) translating new insights and evidence into programmatic action; (3) expanding the IPV manufacturing infrastructure for global demand; and (4) continuing to pursue an ambitious research program to develop more immunogenic and safer-to-produce vaccines. While the knowledge base of IPV continues to expand, further research and product development are necessary to ensure that the program priorities are met (e.g., non-infectious production through virus-like particles, non-transmissible vaccine inducing humoral and intestinal mucosal immunity and new methods for house-to-house administration through micro-needle patches and jet injectors), the discussions have largely moved from whether to how to use this vaccine most effectively. In this review, we summarize recent developments on expanding the science base of IPV and provide insight into policy development and the expansion of IPV manufacturing and production, and finally we provide an update on the current priorities.

The Last Mile in Polio Eradication: Program Challenges and Perseverance.

As the Global Polio Eradication Initiative (GPEI) strategizes towards the final steps of eradication, routine immunization schedules evolve, and high-quality vaccination campaigns and surveillance systems remain essential. New tools are consistently being developed, such as the novel oral poliovirus vaccine to combat outbreaks more sustainably, as well as non-infectiously manufactured vaccines such as virus-like particle vaccines to eliminate the risk of resurgence of polio on the eve of a polio-free world. As the GPEI inches towards eradication, re-strategizing in the face of evolving challenges and preparing for unknown risks in the post-certification era are critical.

Immunodeficiency-Related Vaccine-Derived Poliovirus (iVDPV) Excretion in an Infant with Severe Combined Immune Deficiency with Spillover to a Parent.

In order to maintain the polio eradication status, it has become evident that the surveillance of cases with acute flaccid paralysis and of environmental samples must be urgently supplemented with the surveillance of poliovirus excretions among individuals with inborn errors of immunity (IEI). All children with IEI were screened for the excretion of poliovirus during a collaborative study conducted by the ICMR-National Institute of Virology, Mumbai Unit, ICMR-National Institute of Immunohaematology, and World Health Organization, India. A seven-month -old male baby who presented with persistent pneumonia and lymphopenia was found to have severe combined immune deficiency (SCID) due to a missense variant in the RAG1 gene. He had received OPV at birth and at 20 weeks. Four stool samples collected at 4 weekly intervals yielded iVDPV type 1. The child's father, an asymptomatic 32-year-old male, was also found to be excreting iVDPV. A haploidentical hematopoietic stem cell transplant was performed, but the child succumbed due to severe myocarditis and pneumonia three weeks later. We report a rare case of transmission of iVDPV from an individual with IEI to a healthy household contact, demonstrating the threat of the spread of iVDPV from persons with IEI and the necessity to develop effective antivirals.

Factors predicting contralateral nodal spread in papillary carcinoma of thyroid

Background: Lymph node metastasis (LNM) is evident in about 20–50% of cases at presentation in papillary carcinoma thyroid (PTC). There are no clear recommendations for the need and extent of lateral and central compartment dissection in PTC. Methods: A total of 83 patients who underwent total thyroidectomy and bilateral selective neck dissection for diagnosed PTC from September 2011 to October 2017 were retrospectively analyzed. Results: Tumor site was bilobar or involving isthmus in 40 patients. Contralateral LNM was seen in 42 patients. Both radiological (median size 2.6 cm, P = 0.051) and pathological (median size 3.65 cm, P = 0.015) size of tumor, tumor involving isthmus or bilateral lobes (P = 0.006), and lymphovascular invasion (LVI) (P = 0.026) had significant correlation with contralateral LNM. Conclusion: Size and site of tumor, ipsilateral lateral compartment nodes involvement, and LVI status of tumor significantly increases the probability of contralateral LNM in patients of PTC.

Immunogenicity of Reduced-Dose Monovalent Type 2 Oral Poliovirus Vaccine in Mocuba, Mozambique

The global polio eradication initiative (gpei) has made steady progress toward the eradication target since its inception in 1988 [1]. the number of paralytic cases due to wild poliovirus has declined worldwide by >99.9%, and 2 of the 3 wild poliovirus serotypes have been declared eradicated by an independent global certification commission: serotype 2 in 2015 and serotype 3 in 2019 [2, 3]. the gpei has implemented the endgame strategic plan 2013­2018 to accelerate the eradication of wild poliovirus type 1 from its last endemic zones in pakistan and afghanistan. [4]. in addition, the plan called for the sequential removal of the sabin strains from the oral poliovirus vaccine (opv) and the concomitant addition of ≥1 dose of inactivated poliovirus vaccine (ipv) in routine national immunization programs. the removal was needed because the continuing use of live viral vaccines is incompatible with eradication, since these viruses can mutate and recombine, thus reacquiring the neurovirulence and transmission characteristics of wild poliovirus [5]. the burden of paralytic disease caused by vaccine-related polioviruses would not be accepted as the world approaches eradication of wild poliovirus. for example, sabin type 2 was responsible for approximately 40% of the vaccine-associated paralytic poliomyelitis burden and caused 91% of circulating vaccine-derived poliovirus (cvdpv) cases between 2000 and 2016...