Poliovirus returns to Pakistan: A rising concern.

Poliomyelitis is a completely preventable but deadly virus causing paralysis in children and in some cases, death. Pakistan is one of the only two countries where polio is still prevalent despite relentless vaccination drives. In the past two months, four cases of polio have been documented in children no older than two years, condemning them to a life of disability. This commentary explores the reasons for the recent spike in polio cases and what measures can be taken to limit the spread of the disease, especially in high-risk areas where vaccine hesitancy poses a major problem. Unless drastic measures are taken by the healthcare sector, polio will continue to be a burden on the country's economy and countless more children will fall victim to the disease.

Poliomyelitis in Pakistan: Challenges to polio eradication and future prospects.

Poliomyelitis is a viral disease that causes acute paralysis, muscle weakness and autonomic dysfunction. It primarily affects children under the age of five. It is mainly transmitted via the feco-oral route, through contaminated water. As of the year 2022, Pakistan remains one of the two countries where polio is still endemic, the other being Afghanistan. Numerous myths and misconceptions regarding the polio vaccine, lack of awareness and proper governance, terrorism and difficult access to remote areas due to poor infrastructure are just some of the reasons why polio remains endemic in Pakistan to this day. Therefore, the government should take measures to ensure the safety and wellbeing of health care workers, as well as spread awareness regarding the importance of polio vaccines, while addressing the myths and misconception regarding said vaccines.

The Global Interest in Vaccines and Its Prediction and Perspectives in the Era of COVID-19. Real-Time Surveillance Using Google Trends.

BACKGROUND: The COVID-19 pandemic has globally overwhelmed all sectors of life. The fast development of vaccines against COVID-19 has had a significant impact on the course of the pandemic. METHODS: Global data from Google Trends was analyzed for vaccines against flu, BCG, HPV, pneumococcal disease, polio, and COVID-19. The time frame includes the last five-year period starting from 17 April 2016. Multiple training of time series models with back testing, including Holt-Winters forecasting, Exponential Smoothing State Space, Linear model with trend and seasonal components (tlsm), and ARIMA was conducted. Forecasting according to the best fitting model was performed. RESULTS: Correlation analysis did not reveal a decrease in interest in vaccines during the analyzed period. The prediction models provided a short-term forecast of the dynamics of interest for flu, HPV, pneumococcal and polio vaccines with 5-10% growth in interest for the first quarter of 2022 when compared to the same quarter of 2021. CONCLUSIONS: Despite the huge interest in the COVID-19 vaccine, there has not been a detectable decline in the overall interest in the five analyzed vaccines.

Health care professionals' preference for a fully liquid, ready-to-use hexavalent vaccine in Spain.

Vaccination is an effective health intervention for the prevention of infectious diseases. This study aims to evaluate the response provided by nurses toward the use of ready-to-use (RTU) formulations of hexavalent vaccines and measures to prevent errors during the vaccination process. This observational, descriptive, cross-sectional study took place from March to May 2018. It included 201 interviews with nurses from health centers in Madrid (70), Murcia (59), and Andalusia (72), who had administered RTU vaccines in the last 12 months. Approximately 91.6% of nurses provided a positive feedback for the use of RTU vaccines. The most significant concerns experienced by nurses were during the preparation and administration of vaccines; 84.1% versus 18.9% of nurses felt that the risk of making mistakes was lower while using RTU vaccines compared with non-reconstituted (lyophilized) vaccines, and 74.1% versus 22.4% of nurses felt ease at preparing RTU vaccines compared with lyophilized vaccines. A total of 66.7% of nurses believed that there were risks associated with the preparation of lyophilized vaccines (administration risk [42.8%] and risk of needle injury [42.3%]). Risk percentages reduced to 4% and 9.5%, respectively, with the use of the RTU vaccines. Therefore, nurses adopted an average of seven steps to reduce the risk of errors. The average time saved during the administration of the vaccines was 1.1 min. In summary, nurses highlighted the need for administering vaccines using RTU formulations for ensuring the safety of the recipients, preventing errors, and saving time during the vaccination process.

The spectrum of primary immunodeficiencies at a tertiary care hospital in Pakistan.

BACKGROUND: Primary Immunodeficiency Disorders (PIDs) are well-known disorders in the West. but the recognition and diagnosis of these disorders is challenging in developing countries. We present the spectrum of PIDs seen at a tertiary care center in Pakistan, identified using clinical case definitions and molecular methods. METHODS: A retrospective chart review of children suspected to have PID was conducted at the Aga Khan University Hospital (AKUH) Karachi, Pakistan from 2010 to 2016. Data on demographics, clinical features, family history of consanguinity, sibling death, details of laboratory workup done for PID and molecular tests targeted panel next generation sequencing (NGS) or whole exome sequencing (WES) performed at the Geha laboratory at Boston Children's Hospital, USA was collected. The study was exempted from the Ethical Review Committee of AKUH. RESULTS: A total of 43 children visited the hospital with suspected PID during the study period. Genetic testing was performed in 31/43 (72.1%) children. A confirmed diagnosis of PID was established in 20/43 (46.5%) children. A pathogenic gene variant was identified in 17(85%) of the 20 confirmed cases (Table 1). Twelve (60%) of the confirmed cases of PID were male. The most common presenting symptom was recurrent diarrhea 11/20 (55%). The mean (±S.D) age of the cases at the time of diagnosis was 4.2 (±4.1) years. Chronic granulomatous disease (CGD) was the most common 6/20 (30%) disorder, followed by severe combined immunodeficiency (SCID) 3/20 (15%), leukocyte adhesion deficiency (LAD) 3/20 (15%), agammaglobulinemia/hypogammaglobulinemia 3/20 (15%), and Hermansky-Pudlak Syndrome (HPS) 2/20 (10%). Wiskott-Aldrich Syndrome, Immunodeficiency Centromeric Instability and Facial Anomalies Syndrome (ICF 2), Trichohepatoenteric syndrome (TRES), and C3 deficiency were each diagnosed once {1/20 (4.3%) each} (Table 1). Of these 20 confirmed cases, almost all 19/20 (95%) had a family history of consanguinity. Sibling death was reported in 5/20 (25%) of these cases. Five out of the 20 (25%) children died over the 7-year period for various reasons. CONCLUSION: PIDs are not uncommon in Pakistan; their diagnosis may be missed or delayed due to the overlapping of clinical features of PID with other diseases and a lack of diagnostic facilities. There is a need to build capacity for early recognition and diagnosis of PIDs to decrease morbidity and mortality.

Anti-NMDA Receptor Encephalitis, Vaccination and Virus.

Anti-N-methyl-d-aspartate (Anti-NMDA) receptor encephalitis is an acute autoimmune disorder. The symptoms range from psychiatric symptoms, movement disorders, cognitive impairment, and autonomic dysfunction. Previous studies revealed that vaccination might induce this disease. A few cases were reported to be related to H1N1 vaccine, tetanus/diphtheria/pertussis and polio vaccine, and Japanese encephalitis vaccine. Although vaccination is a useful strategy to prevent infectious diseases, in a low risk, it may trigger serious neurological symptoms. In addition to anti-NMDA receptor encephalitis, other neurological diseases were reported to be associated with a number of vaccines. In this paper, the anti-NMDA receptor encephalitis cases related to a number of vaccines and other neurological symptoms that might be induced by these vaccines were reviewed. In addition, anti-NMDA receptor encephalitis cases that were induced by virus infection were also reviewed.

Relato de um caso de reação à vacina oral contra a poliomielite tratado com homeopatia / Report of a case of reaction to oral polio vaccine treated with homeopathy

Este estudo relata um caso de paresia flácida assimétrica após administração da vacina oral contra poliomielite, com acometimento do membro inferior esquerdo. A primeira dose de medicamento homeopático foi prescrita no 20º dia após o início dos sintomas. Evoluiu com desaparecimento da paresia e normalização do padrão de marcha nos 40 dias subsequentes. Pode-se considerar a homeopatia como escolha terapêutica em casos de paresias agudas. (AU)

We report a case of asymmetric flaccid paresis which developed following intake of oral polio vaccine affecting the left lower limb. Homeopathic treatment was started 20 days after the onset of symptoms. Paresis disappeared and the gait pattern became normal along the following 40 days. Homeopathy might be considered for treatment of acute paresis. (AU)

Incompatibility of lyophilized inactivated polio vaccine with liquid pentavalent whole-cell-pertussis-containing vaccine.

A hexavalent vaccine containing diphtheria toxoid, tetanus toxoid, whole cell pertussis, Haemophilius influenza type B, hepatitis B and inactivated polio vaccine (IPV) may: (i) increase the efficiency of vaccination campaigns, (ii) reduce the number of injections thereby reducing needlestick injuries, and (iii) ensure better protection against pertussis as compared to vaccines containing acellular pertussis antigens. An approach to obtain a hexavalent vaccine might be reconstituting lyophilized polio vaccine (IPV-LYO) with liquid pentavalent vaccine just before intramuscular delivery. The potential limitations of this approach were investigated including thermostability of IPV as measured by D-antigen ELISA and rat potency, the compatibility of fluid and lyophilized IPV in combination with thimerosal and thimerosal containing hexavalent vaccine. The rat potency of polio type 3 in IPV-LYO was 2 to 3-fold lower than standardized on the D-antigen content, suggesting an alteration of the polio type 3 D-antigen particle by lyophilization. Type 1 and 2 had unaffected antigenicity/immunogenicity ratios. Alteration of type 3 D-antigen could be detected by showing reduced thermostability at 45°C compared to type 3 in non-lyophilized liquid controls. Reconstituting IPV-LYO in the presence of thimerosal (TM) resulted in a fast temperature dependent loss of polio type 1-3 D-antigen. The presence of 0.005% TM reduced the D-antigen content by ∼20% (polio type 2/3) and ∼60% (polio type 1) in 6h at 25°C, which are WHO open vial policy conditions. At 37°C, D-antigen was diminished even faster, suggesting that very fast, i.e., immediately after preparation, intramuscular delivery of the conceived hexavalent vaccine would not be a feasible option. Use of the TM-scavenger, l-cysteine, to bind TM (or mercury containing TM degradation products), resulted in a hexavalent vaccine mixture in which polio D-antigen was more stable.

Intradermal vaccination using the novel microneedle device MicronJet600: Past, present, and future.

Intradermal immunization has become a forefront of vaccine improvement, both scientifically and commercially. Newer technologies are being developed to address the need to reduce the dose required for vaccination and to improve the reliability and ease of injection, which have been major hurdles in expanding the number of approved vaccines using this route of administration. In this review, 7 y of clinical experience with a novel intradermal delivery device, the MicronJet600, which is a registered hollow microneedle that simplifies the delivery of liquid vaccines, are summarized. This device has demonstrated both significant dose-sparing and superior immunogenicity in various vaccine categories, as well as in diverse subject populations and age groups. These studies have shown that intradermal delivery using this device is safe, effective, and preferred by the subjects. Comparison with other intradermal devices and potential new applications for intradermal delivery that could be pursued in the future are also discussed.

The muscle findings in a pediatric patient with live attenuated oral polio vaccine-related flaccid monoplegia.

A pediatric patient, who was given live-attenuated oral polio vaccine twice without distinct gait disturbance during infancy, begun to present limp at 3 years. His gait disturbance became remarkable with aging. At 7 years, he was unable to dorsiflex the left ankle, and presented flaccid monoplegia of the left lower extremity, and the left Achilles tendon reflex was diminished. Magnetic resonance imaging revealed multiple crack-lines in the left anterior tibial muscle, but was unable to detect any distinct lesion at responsible level of L4, L5 and S1 anterior horn cells' degeneration. Electromyography showed continuous fibrillation potentials, but muscle biopsy presented nearly normal in this muscle. The serum levels of polio antibody type 1 and type 2 titers were elevated 64× respectively, while the type 3 antibody titer was not elevated 4×. This patient was diagnosed as live attenuated oral polio vaccine-related flaccid monoplegia, with mild clinical course.

Community circulation patterns of oral polio vaccine serotypes 1, 2, and 3 after Mexican national immunization weeks.

BACKGROUND: With wild poliovirus nearing eradication, preventing circulating vaccine-derived poliovirus (cVDPV) by understanding oral polio vaccine (OPV) community circulation is increasingly important. Mexico, where OPV is given only during biannual national immunization weeks (NIWs) but where children receive inactivated polio vaccine (IPV) as part of their primary regimen, provides a natural setting to study OPV community circulation. METHODS: In total, 216 children and household contacts in Veracruz, Mexico, were enrolled, and monthly stool samples and questionnaires collected for 1 year; 2501 stool samples underwent RNA extraction, reverse transcription, and real-time polymerase chain reaction (PCR) to detect OPV serotypes 1, 2, and 3. RESULTS: OPV was detected up to 7 months after an NIW, but not at 8 months. In total, 35% of samples collected from children vaccinated the prior month, but only 4% of other samples, contained OPV. Although each serotype was detected in similar proportions among OPV strains shed as a result of direct vaccination, 87% of OPV acquired through community spread was serotype 2 (P < .0001). CONCLUSIONS: Serotype 2 circulates longer and is transmitted more readily than serotypes 1 or 3 after NIWs in a Mexican community primarily vaccinated with IPV. This may be part of the reason why most isolated cVDPV has been serotype 2.

Post-licensure rapid immunization safety monitoring program (PRISM) data characterization.

BACKGROUND: The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) program is the immunization safety monitoring component of FDA's Mini-Sentinel project, a program to actively monitor the safety of medical products using electronic health information. FDA sought to assess the surveillance capabilities of this large claims-based distributed database for vaccine safety surveillance by characterizing the underlying data. METHODS: We characterized data available on vaccine exposures in PRISM, estimated how much additional data was gained by matching with select state and local immunization registries, and compared vaccination coverage estimates based on PRISM data with other available data sources. We generated rates of computerized codes representing potential health outcomes relevant to vaccine safety monitoring. Standardized algorithms including ICD-9 codes, number of codes required, exclusion criteria and location of the encounter were used to obtain the background rates. RESULTS: The majority of the vaccines routinely administered to infants, children, adolescents and adults were well captured by claims data. Immunization registry data in up to seven states comprised between 5% and 9% of data for all vaccine categories with the exception of 10% for hepatitis B and 3% and 4% for rotavirus and zoster respectively. Vaccination coverage estimates based on PRISM's computerized data were similar to but lower than coverage estimates from the National Immunization Survey and Healthcare Effectiveness Data and Information Set. For the 25 health outcomes of interest studied, the rates of potential outcomes based on ICD-9 codes were generally higher than rates described in the literature, which are typically clinically confirmed cases. CONCLUSION: PRISM program's data on vaccine exposures and health outcomes appear complete enough to support robust safety monitoring.

Polio / Polio

Polio continúa endémica en: Nigeria, Afganistán Pakistán e India. La iniciativa global de erradicación de polio de la OMS estableció que para 2013 no debe haber ningún niño paralítico en el mundo por el virus salvaje o por el virus derivado de la vacuna. En esta revisión se describen ambas vacunas contra el polio, la oral y la inactivada, su inmunogenicidad, seguridad y las condiciones a cumplir por un paíspara que cambie su esquema de vacunación de polio oral a inactivada. La vacuna polio oral ha permitido la erradicación de la enfermedaden varios continentes incluyendo América; sin embargo conlleva riesgos, tales como polio paralítica asociada a vacuna (VAP-siglas en inglés-) y parálisis producida por polio virus derivado de la vacuna (VDP-siglas en inglés-). La Vacuna Polio Inactivada (VPI) es segura e inmunogénica, puede ser administrada en combinaciones vacunales. Para que un país cambie a VPI debe tener cobertura y esquemaóptimo de esta vacuna, 90% de, cobertura de DTP3, vigilancia adecuada de parálisis flácida, no estar próximo en la actualidad o recientemente a un país con polio endémico. Altas coberturas vacunales son esenciales par asegurar una inmunidad adecuada de lapoblación

Polio remains endemic in Nigeria, Afghanistan, Pakistan, India. Strategic plan of Global Poliomyelitis Eradication Initiative (GPEI) of the WHO is that by 2013 no child will be paralyzed by a wild or vaccine derived poliovirus. This paper describes both oral and inactivated vaccine, safety concerns with the use of OPV, immunogenicity of IPV and the conditions to be full filled in order for a country to deliverIPV as a regular vaccine schedule. Oral polio vaccine has successfully contributed to global polio eradication in several continents including America. However, it carries risks, such as Vaccine Derived Poliovirus (VDP) and Vaccine Associated Paralytic Polio (VAPP). Inactivated Poliovirus Vaccine (IPV) is safe and immunogenic; it may be administered as monovalent or in a combined shot. Countries opting to switch from OPV to IPV should have: optimal IPV coverage and schedule, 90% of DTP 3 coverage, good surveillance of flaccid paralysis cases, and should not be near a country with endemic polio recently or at the present time. Are neither currently or were notrecently polio endemic nor has close contacts with such areas. High immunization coverage is essential to ensure adequate populationimmunity

Reactogenicidad asociada a la administración intradérmica de la vacuna de polio inactivada con un inyector sin aguja / Reactogenicity associated to the intradermally administered inactivated poliovirus vaccine with a needle-free injector

INTRODUCCIÓN: en la medida en que la meta de la erradicación de la poliomielitis llega a su concreción, la necesidad de contar con una vacuna de polio inactivada asequible y apropiada para el uso en países en vías de desarrollo se ha convertido en una meta para la Organización Mundial de la Salud. OBJETIVO: la evaluación de la reactogenicidad de la vacuna de polio inactivada. MÉTODOS: se realizó un estudio multicéntrico con diseño experimental, correspondiente a Fase I-II de un ensayo clínico controlado, aleatorio y a simple ciegas, en 471 lactantes sanos de ambos sexos nacidos entre los meses de julio y agosto de 2006 en Camagüey, cuyos padres brindaron su consentimiento por escrito y que cumplieron con los criterios de inclusión establecidos. Los niños recibieron a las 6, 10 y 14 semanas del nacimiento, tres dosis de vacuna de polio inactivada del Instituto de Sueros de Dinamarca, autorizada para su uso en esta investigación por las autoridades regulatorias nacionales. Al grupo de estudio A, se le administró por la vía intradérmica la dosis reducida de 0,1 mL de vacuna de polio inactivada en la cara anterolateral del muslo izquierdo utilizando el inyector sin aguja Biojector® 2000. El grupo control B recibió la dosis usual de 0,5 mL por la vía intramuscular profunda, administrada en el mismo sitio descrito antes con una jeringuilla prellenada. Se observaron los eventos adversos durante la primera hora, 24, 48, y 72 h subsiguientes, así como a los 7 y 30 d de administrada la vacuna. La reactogenicidad se evaluó inicialmente por el pediatra del área y luego por el médico de familia mediante la observación de los eventos adversos. RESULTADOS: 79,6 por ciento del total de niños asignados al grupo A y 75 por ciento del grupo B finalizaron el protocolo de investigación. No se detectaron eventos adversos moderados o serios. Predominaron las reacciones adversas locales menores, sobre todo induración, dolor y enrojecimiento en el sitio de la inyección. CONCLUSIÓN: el ensayo demostró la seguridad de la vacuna de polio inactivada para su uso por vía intramuscular y reconoció la seguridad del uso de la vía intradérmica y del inyector sin agujas.

INTRODUCTION: as the goal of poliomyelitis eradication is about to be accomplished, the need for an affordable and appropriate inactivated poliovirus vaccine (IPV) for use in developing countries has become a target for WHO. OBJECTIVE: to evaluate the reactogenicity of the inactivated poliovirus vaccine. METHOD: an experimental-type multicenter study was conducted, as part of a Phase I-II controlled clinical randomized and blinded assay, in 471 healthy infants of both sexes born in July and August 2006 in Camagüey province. The parents of the children who met the inclusion criteria gave their consent in writing. The children received three doses of the inactivated poliovirus vaccine at 6, 10 and 14 weeks after birth. This vaccine came form the Institute of Sera in Denmark and had been approved for use in this assay by the Cuban regularoty authorities, Low 0.1 ml inactivated poliovirus vaccine dose was intradermally administered to the study group A in the anterolateral side of the left thigh using the needle-free injector called Biojector ® 2000. The usual 0.5 mL dose was intramuscularly administered on the same site using a pre-filled syringe. The adverse events were observed during the first hour, 24, 48, and 72 hours after the immunization, as well as 7 and 30 days afterwards. The pediatrician in charge of the health area evaluated the reactogenicity at first and then the family physician was in charge of observing the adverse events in the remaining period. RESULTS: the 79.6 percent of children in group A and 75 percent in group B completed the research protocol. Mild local adverse reactions prevailed, mainly induration, pain and redness at the injection site. CONCLUSION: the clinical trial proved the safety of the inactivated poliovirus vaccine for intramuscular administration, and also showed the safety of the intradermal route of administration and of the needle-free injector.