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Biomeditsinskaia Khimiia Jun 2024Electrochemical profiling of formaldehyde-inactivated poliovirus particles demonstrated a relationship between the D-antigen concentration and the intensity of the...
Electrochemical profiling of formaldehyde-inactivated poliovirus particles demonstrated a relationship between the D-antigen concentration and the intensity of the maximum amplitude currents of the poliovirus samples. The resultant signal was therefore identified as electrochemical oxidation of the surface proteins of the poliovirus. Using registration of electrooxidation of amino acid residues of the capsid proteins, a comparative electrochemical analysis of poliovirus particles inactivated by electrons accelerated with doses of 5 kGy, 10 kGy, 15 kGy, 25 kGy, 30 kGy at room temperature was carried out. An increase in the radiation dose was accompanied by an increase in electrooxidation signals. A significant increase in the signals of electrooxidation of poliovirus capsid proteins was detected upon irradiation at doses of 15-30 kGy. The data obtained suggest that the change in the profile and increase in the electrooxidation signals of poliovirus capsid proteins are associated with an increase in the degree of structural reorganization of surface proteins and insufficient preservation of the D-antigen under these conditions of poliovirus inactivation.
Topics: Poliovirus; Capsid Proteins; Virus Inactivation; Oxidation-Reduction; Formaldehyde; Humans; Virion
PubMed: 38940205
DOI: 10.18097/PBMC20247003161 -
MMWR. Morbidity and Mortality Weekly... Jun 2024Since the launch of the Global Polio Eradication Initiative in 1988, substantial progress has been made in the interruption of wild poliovirus (WPV) transmission...
Since the launch of the Global Polio Eradication Initiative in 1988, substantial progress has been made in the interruption of wild poliovirus (WPV) transmission worldwide: global eradication of WPV types 2 and 3 were certified in 2015 and 2019, respectively, and endemic transmission of WPV type 1 continues only in Afghanistan and Pakistan. After the synchronized global withdrawal of all serotype 2 oral poliovirus vaccines (OPVs) in 2016, widespread outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2) have occurred, which are linked to areas with low population immunity to poliovirus. Officials in Somalia have detected ongoing cVDPV2 transmission since 2017. Polio vaccination coverage and surveillance data for Somalia were reviewed to assess this persistent transmission. During January 2017-March 2024, officials in Somalia detected 39 cVDPV2 cases in 14 of 20 regions, and transmission has spread to neighboring Ethiopia and Kenya. Since January 2021, 28 supplementary immunization activities (SIAs) targeting cVDPV2 were conducted in Somalia. Some parts of the country are security-compromised and inaccessible for vaccination campaigns. Among 1,921 children with nonpolio acute flaccid paralysis, 231 (12%) had not received OPV doses through routine immunization or SIAs, 95% of whom were from the South-Central region, and 60% of whom lived in inaccessible districts. Enhancing humanitarian negotiation measures in Somalia to enable vaccination of children in security-compromised areas and strengthening campaign quality in accessible areas will help interrupt cVDPV2 transmission.
Topics: Humans; Poliomyelitis; Somalia; Poliovirus; Poliovirus Vaccine, Oral; Disease Outbreaks; Child, Preschool; Infant; Population Surveillance; Immunization Programs; Vaccination Coverage; Child
PubMed: 38935565
DOI: 10.15585/mmwr.mm7325a2 -
Global Health Action Dec 2024The Global Polio Eradication Initiative (GPEI) helped develop the standard acute flaccid paralysis surveillance (AFP) system worldwide, including, knowledge, expertise,...
The evolution, facilitators, barriers, and additional activities of acute flaccid paralysis surveillance platform in polio eradication programme Bangladesh: a mixed-method study.
BACKGROUND
The Global Polio Eradication Initiative (GPEI) helped develop the standard acute flaccid paralysis surveillance (AFP) system worldwide, including, knowledge, expertise, technical assistance, and trained personnel. AFP surveillance can complement any disease surveillance system.
OBJECTIVE
This study outlines AFP surveillance evolution in Bangladesh, its success and challenging factors, and its potential to facilitate other health goals.
METHODS
This mixed-method study includes a grey literature review, survey, and key informant interviews (KIIs). We collected grey literature from online websites and paper documentation from GPEI stakeholders. Online and in-person surveys were conducted in six divisions of Bangladesh, including Dhaka, Rajshahi, Rangpur, Chittagong, Sylhet, and Khulna, to map tacit knowledge ideas, approaches, and experiences. We also conducted KIIs, and Data were then combined on focused emerging themes, including the history, challenges, and successes of AFP surveillance programme.
RESULTS
According to the grey literature review, survey, and KII, AFP surveillance successfully contributed to decreasing polio in Bangladesh. The major facilitating factors were multi-sectoral collaboration, Surveillance Immunization Medical Officer (SIMO) network activities, social environment, community-based surveillance, and promising political commitment. On the other hand, high population growth, hard-to-reach areas, people residing in risky zones, and polio transition planning were significant challenges. Bangladesh is also utilizing these polio surveillance assets for other vaccine-preventable diseases.
CONCLUSION
As the world is so close to eradicating polio, the knowledge, and other assets of the AFP surveillance, could be used for other health programmes. In addition, its strengths can be leveraged for combating new and emerging diseases.
Topics: Humans; Poliomyelitis; Bangladesh; Disease Eradication; Population Surveillance; Surveys and Questionnaires; Paralysis
PubMed: 38932666
DOI: 10.1080/16549716.2024.2370096 -
Viruses Jun 2024Recently, a multiplex PCR-based titration (MPBT) assay was developed for simultaneous determination of infectious titers of all three Sabin strains of the oral...
Recently, a multiplex PCR-based titration (MPBT) assay was developed for simultaneous determination of infectious titers of all three Sabin strains of the oral poliovirus vaccine (OPV) to replace the conventional CCID assay, which is both time-consuming and laborious. The MPBT assay was shown to be reproducible, robust and sensitive. The conventional and MPBT assays showed similar results and sensitivity. The MPBT assay can be completed in two to three days, instead of ten days for the conventional assay. To prevent attenuated vaccine strains of poliovirus from reversion to virulence, a novel, genetically stable OPV (nOPV) was developed by modifying the genomes of conventional Sabin strains used in OPV. In this work, we evaluated the MPBT assay as a rapid screening tool to support trivalent nOPV (tnOPV) formulation development by simultaneous titration of the three nOPV strains to confirm stability as needed, for the selection of the lead tnOPV formulation candidate. We first assessed the ability of the MPBT assay to discriminate a 0.5 log titer difference by titrating the two tnOPV samples (undiluted and threefold-diluted) on the same plate. Once the assay was shown to be discriminating, we then tested different formulations of tnOPV drug products (DPs) that were subjected to different exposure times at 37 °C (untreated group and treated groups: 2 and 7 days at 37 °C), and to three freeze and thaw (FT) cycles. Final confirmation of the down selected formulation candidates was achieved by performing the conventional CCID assay, comparing the stability of untreated and treated groups and FT stability testing on the top three candidates. The results showed that the MPBT assay generates similar titers as the conventional assay. By testing two trivalent samples in the same plate, the assay can differentiate a 0.5 log difference between the titers of the tested nOPV samples. Also, the assay was able to detect the gradual degradation of nOPV viruses with different formulation compositions and under different time/temperature conditions and freeze/thaw cycles. We found that there were three tnOPV formulations which met the stability criteria of less than 0.5 log loss after 2 days' exposure to 37 ℃ and after three FT cycles, maintaining the potency of all three serotypes in these formulations. The ability of the MPBT assay to titrate two tnOPV lots (six viruses) in the same plate makes it cheaper and gives it a higher throughput for rapid screening. The assay detected the gradual degradation of the tnOPV and was successful in the selection of optimal formulations for the tnOPV. The results demonstrated that the MPBT method can be used as a stability indicating assay to assess the thermal stability of the nOPV. It can be used for rapid virus titer determination during the vaccine manufacturing process, and in clinical trials. The MPBT assay can be automated and applied for other viruses, including those with no cytopathic effect.
Topics: Poliovirus Vaccine, Oral; Poliovirus; Humans; Multiplex Polymerase Chain Reaction; Poliomyelitis; Vaccines, Attenuated; Reproducibility of Results; Sensitivity and Specificity
PubMed: 38932253
DOI: 10.3390/v16060961 -
Tropical Medicine and Infectious Disease May 2024Despite the implementation of various control strategies aimed at eliminating canine-mediated rabies, the disease is still endemic in up to 150 countries across the...
Despite the implementation of various control strategies aimed at eliminating canine-mediated rabies, the disease is still endemic in up to 150 countries across the world. Rabies remains endemic to South Africa, with various reservoir species (both wildlife species and domestic dogs) capable of maintaining rabies infection, and the epidemiology of the disease is yet to be adequately defined. As such, this study used surveillance data collected between 1998 and 2019 from the two diagnostic laboratories in the country for a statistical space-time analysis to determine regions where significant disease clusters could occur. In addition, the robustness of surveillance activities across the country was evaluated through the mathematical evaluation and visualization of testing rates based on the average number of samples tested per species group. In our study, various significant disease clusters were detected for domestic animals, wildlife and livestock. The significant disease clusters for domestic animals and livestock were primarily restricted to eastern South Africa, while the significant disease clusters in wildlife species were detected across northern and western South Africa. Furthermore, the testing rates identified districts from various provinces where surveillance activities could be considered inadequate, consequently influencing the geographical range of the observed clusters. These results could be used to direct intervention campaigns towards high-risk areas, while also allocating the required resources to improve surveillance in the surrounding areas where surveillance was deemed inadequate.
PubMed: 38922034
DOI: 10.3390/tropicalmed9060122 -
Virology Journal Jun 2024HIV-1 produces Tat, a crucial protein for transcription, viral replication, and CNS neurotoxicity. Tat interacts with TAR, enhancing HIV reverse transcription. Subtype C...
BACKGROUND
HIV-1 produces Tat, a crucial protein for transcription, viral replication, and CNS neurotoxicity. Tat interacts with TAR, enhancing HIV reverse transcription. Subtype C Tat variants (C31S, R57S, Q63E) are associated with reduced transactivation and neurovirulence compared to subtype B. However, their precise impact on Tat-TAR binding is unclear. This study investigates how these substitutions affect Tat-TAR interaction.
METHODS
We utilized molecular modelling techniques, including MODELLER, to produce precise three-dimensional structures of HIV-1 Tat protein variants. We utilized Tat subtype B as the reference or wild type, and generated Tat variants to mirror those amino acid variants found in Tat subtype C. Subtype C-specific amino acid substitutions were selected based on their role in the neuropathogenesis of HIV-1. Subsequently, we conducted molecular docking of each Tat protein variant to TAR using HDOCK, followed by molecular dynamic simulations.
RESULTS
Molecular docking results indicated that Tat subtype B (TatWt) showed the highest affinity for the TAR element (-262.07), followed by TatC31S (-261.61), TatQ63E (-256.43), TatC31S/R57S/Q63E (-238.92), and TatR57S (-222.24). However, binding free energy analysis showed higher affinities for single variants TatQ63E (-349.2 ± 10.4 kcal/mol) and TatR57S (-290.0 ± 9.6 kcal/mol) compared to TatWt (-247.9 ± 27.7 kcal/mol), while TatC31S and TatC31S/R57SQ/63E showed lower values. Interactions over the protein trajectory were also higher for TatQ63E and TatR57S compared to TatWt, TatC31S, and TatC31S/R57SQ/63E, suggesting that modifying amino acids within the Arginine/Glutamine-rich region notably affects TAR interaction. Single amino acid mutations TatR57S and TatQ63E had a significant impact, while TatC31S had minimal effect. Introducing single amino acid variants from TatWt to a more representative Tat subtype C (TatC31S/R57SQ/63E) resulted in lower predicted binding affinity, consistent with previous findings.
CONCLUSIONS
These identified amino acid positions likely contribute significantly to Tat-TAR interaction and the differential pathogenesis and neuropathogenesis observed between subtype B and subtype C. Additional experimental investigations should prioritize exploring the influence of these amino acid signatures on TAR binding to gain a comprehensive understanding of their impact on viral transactivation, potentially identifying them as therapeutic targets.
Topics: tat Gene Products, Human Immunodeficiency Virus; HIV-1; Molecular Dynamics Simulation; Protein Binding; Humans; Amino Acid Substitution; Molecular Docking Simulation; HIV Long Terminal Repeat; Amino Acids; Models, Molecular
PubMed: 38918875
DOI: 10.1186/s12985-024-02419-6 -
Journal of Rehabilitation Medicine Jun 2024To explore and characterize somatosensory dysfunction in patients with post-polio syndrome and chronic pain, by conducting examinations with Quantitative Sensory Testing.
OBJECTIVE
To explore and characterize somatosensory dysfunction in patients with post-polio syndrome and chronic pain, by conducting examinations with Quantitative Sensory Testing.
DESIGN
A cross-sectional, descriptive, pilot study conducted during 1 month.
SUBJECTS/PATIENTS
Six patients with previously established post-polio syndrome and related chronic pain.
METHODS
All subjects underwent a neurological examination including neuromuscular function, bedside sensory testing, a thorough pain anamnesis, and pain drawing. Screening for neuropathic pain was done with 2 questionnaires. A comprehensive Quantitative Sensory Testing battery was conducted with z-score transformation of obtained data, enabling comparison with published reference values and the creation of sensory profiles, as well as comparison between the study site (more polio affected extremity) and internal control site (less affected extremity) for each patient.
RESULTS
Derived sensory profiles showed signs of increased prevalence of sensory aberrations compared with reference values, especially Mechanical Pain Thresholds, with significant deviation from reference data in 5 out of 6 patients. No obvious differences in sensory functions were seen between study sites and internal control sites.
CONCLUSION
Post-polio syndrome may be correlated with a mechanical hyperalgesia/allodynia and might be correlated to a somatosensory dysfunction. With lack of evident side-to-side differences, the possibility of a generalized dysfunction in the somatosensory system might be considered.
Topics: Humans; Postpoliomyelitis Syndrome; Pilot Projects; Cross-Sectional Studies; Female; Male; Middle Aged; Aged; Pain Measurement; Pain Threshold; Chronic Pain; Somatosensory Disorders; Adult; Neurologic Examination; Hyperalgesia; Neuralgia
PubMed: 38915293
DOI: 10.2340/jrm.v56.26192 -
Journal of Orthopaedic Case Reports Jun 2024The results of primary total knee replacement (TKR) using hinge implants performed in the Indian population with post-polio residual paresis (PPRP) are unknown. The...
INTRODUCTION
The results of primary total knee replacement (TKR) using hinge implants performed in the Indian population with post-polio residual paresis (PPRP) are unknown. The purpose of this study was to report the outcome of primary rotating hinge TKR in Indian patients with PPRP at a minimum follow-up of 12 months.
MATERIALS AND METHODS
We retrospectively reviewed the clinical and radiological records of six patients treated with primary rotating hinge TKR. Pre-and post-operative (at final follow-up) knee range of motion (ROM), knee sagittal deformity, knee society score (KSS), and Oxford knee score (OKS) were compared to determine improvement in function.
RESULTS
Six rotating hinge TKRs (five female and one male patient) were analyzed for this study. At a mean follow-up of 27 ± 22 months (range, 12-71 months), the mean pre-operative KSS of 50.6 ± 2.5 significantly improved (P < 0.0001) to 72.5 ± 1.6, and the mean pre-operative OKS of 23.6 ± 1.6 significantly improved (P < 0.0001) to 35.3 ± 1.7. The mean pre-operative knee ROM of 94° ± 10° changed to 92° ± 4° (P = 0.64) and the mean pre-operative sagittal deformity of 7° ± 23.5° changed to -3° ± 2.5° (P = 0.32) at final follow-up. None of the knees had any intra- or post-operative complications or showed radiologic evidence of post-operative loosening, subsidence, or periprosthetic radiolucent lines at the final follow-up.
CONCLUSION
Rotating hinge TKR gave excellent clinical and radiological results at a mean follow-up of 27 months in the present study. Despite TKR being a technically challenging procedure in patients with poliomyelitis-affected limbs, a rotating hinge design, along with meticulous surgical technique, can significantly improve function in such patients.
PubMed: 38910982
DOI: 10.13107/jocr.2024.v14.i06.4542 -
Annals of Indian Academy of Neurology May 2024To investigate the presence and severity of central sensitization (CS) and its associations with clinical measures and quality of life (QoL) in individuals with a...
OBJECTIVES
To investigate the presence and severity of central sensitization (CS) and its associations with clinical measures and quality of life (QoL) in individuals with a history of paralytic poliomyelitis with and without post-polio syndrome (PPS).
METHODS
In this cross-sectional study, we included 98 individuals with a history of poliomyelitis, in whom 82 (83.6%) met the criteria of PPS. We used CS Inventory (CSI) to evaluate the presence and severity of CS. We evaluated the severity of fatigue, pain, polio-related impairments, and QoL using a Numerical Rating Scale in addition to Fatigue Severity Scale, Self-reported Impairments in Persons with late effects of Polio rating scale (SIPP), and Nottingham Health Profile (NHP).
RESULTS
CS was present in 52.4% of patients with PPS, of which 63% are classified as severe to extreme. Those with CS reported more severe symptoms, more polio-related impairments, and worse QoL than those without CS. Severity of CS showed significant positive correlations with severity of fatigue, pain, SIPP, and NHP scales in those with PPS. CSI did not indicate CS in any of those without PPS.
CONCLUSION
CS was present in more than half of the individuals with PPS and correlated with more severe pain, fatigue, and more polio-related impairments, in addition to poorer QoL. These findings suggest that CS may contribute to the clinical picture in a subgroup of individuals with PPS. Thus, identification and appropriate management of CS patients may potentially help alleviate their symptoms and improve their QoL.
PubMed: 38907687
DOI: 10.4103/aian.aian_1040_23 -
JMIR Public Health and Surveillance Jun 2024Geospatial data reporting from surveillance and immunization efforts is a key aspect of the World Health Organization (WHO) Global Polio Eradication Initiative in...
Geospatial data reporting from surveillance and immunization efforts is a key aspect of the World Health Organization (WHO) Global Polio Eradication Initiative in Africa. These activities are coordinated through the WHO Regional Office for Africa Geographic Information Systems Centre. To ensure the accuracy of field-collected data, the WHO Regional Office for Africa Geographic Information Systems Centre has developed mobile phone apps such as electronic surveillance (eSURV) and integrated supportive supervision (ISS) geospatial data collection programs. While eSURV and ISS have played a vital role in efforts to eradicate polio and control other communicable diseases in Africa, disease surveillance efforts have been hampered by incomplete and inaccurate listings of health care sites throughout the continent. To address this shortcoming, data compiled from eSURV and ISS are being used to develop, update, and validate a Health Facility master list for the WHO African region that contains comprehensive listings of the names, locations, and types of health facilities in each member state. The WHO and Ministry of Health field officers are responsible for documenting and transmitting the relevant geospatial location information regarding health facilities and traditional medicine sites using the eSURV and ISS form; this information is then used to update the Health Facility master list and is also made available to national ministries of health to update their respective health facility lists. This consolidation of health facility information into a single registry is expected to improve disease surveillance and facilitate epidemiologic research for the Global Polio Eradication Initiative, as well as aid public health efforts directed at other diseases across the African continent. This review examines active surveillance using eSURV at the district, country, and regional levels, highlighting its role in supporting polio surveillance and immunization efforts, as well as its potential to serve as a fundamental basis for broader public health initiatives and research throughout Africa.
Topics: World Health Organization; Humans; Poliomyelitis; Africa; Health Facilities; Population Surveillance; Geographic Information Systems; Disease Eradication
PubMed: 38904997
DOI: 10.2196/54250