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Chronic Respiratory Disease 2024This state-of-the-art review provides an overview of the history of home mechanical ventilation (HMV), including early descriptions of mechanical ventilation from... (Review)
Review
This state-of-the-art review provides an overview of the history of home mechanical ventilation (HMV), including early descriptions of mechanical ventilation from ancient and Renaissance perspectives and the mass development of ventilators designed for long-term use during the poliomyelitis epidemic. Seminal data from key clinical trials supports the application of HMV in certain patients with chronic obstructive pulmonary disease, neuromuscular disease and obesity-related respiratory failure. Innovative engineering coupled with refined physiological understanding now permits widespread delivery of home mechanical ventilation to a global population, using portable devices with advanced ventilatory modes and telemonitoring capabilities. Exponential growth in digital technology continues, and ongoing research is needed to understand how to harness clinical and physiological data to benefit patients and healthcare services in a clinically- and cost-effective manner.
Topics: Humans; Respiration, Artificial; Obesity; Pulmonary Disease, Chronic Obstructive
PubMed: 38512223
DOI: 10.1177/14799731241240776 -
Human Vaccines & Immunotherapeutics Dec 2024This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase 3 randomized, open-label study evaluating the immunogenicity and safety of concomitant and staggered administration of a live, pentavalent rotavirus vaccine and an inactivated poliomyelitis vaccine in healthy infants in China.
This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from - 4.3% to - 1.6%, for all poliovirus types, < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.
Topics: Humans; Infant; Antibodies, Neutralizing; Antibodies, Viral; China; Immunogenicity, Vaccine; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Rotavirus Vaccines; Vaccines, Attenuated
PubMed: 38509699
DOI: 10.1080/21645515.2024.2324538 -
Vaccine Apr 2024Sabin Inactivated Poliovirus Vaccine (sIPV) has become one of the preferred vaccination options for the last step in the Poliovirus eradication program. Sequencing of...
Sabin Inactivated Poliovirus Vaccine (sIPV) has become one of the preferred vaccination options for the last step in the Poliovirus eradication program. Sequencing of poliovirus samples is needed during the manufacturing of poliovirus vaccines to assure the safety and immunogenicity of these vaccines. Next-generation sequencing analysis is the current costly and time-consuming gold standard for monitoring the manufacturing processes. We developed a low-cost and quick, highly sensitive, and allele-specific locked nucleic acid-probe-based reverse transcription quantitative PCR alternative that can accurately detect mutations in poliovirus vaccine samples during process development, scaling up, and release. Using the frequently in vitro occurring and viral replication-impacting VP1-EK mutation as a showcase, we show that this technology can accurately detect EK mutations in poliovirus 2 samples to similar levels as NGS. The qPCR technology was developed employing a synthetic dsDNA fragment-based standard curve containing mixes of EK-WT (wildtype) and Mut (mutant) synthetic dsDNA fragments ranging from 1 × 10 copies/µL to 1 × 10 copies/µL to achieve a linear correlation with R > 0.999, and PCR efficiencies of 95-105 %. Individual standard concentration levels achieved accuracies of ≥92 % (average 96 %) and precisions of ≤17 % (average 3.3 %) RSD. Specificity of locked nucleic acid (LNA)-probes was confirmed in the presence and absence of co-mutations in the probe-binding region. Application of the developed assay to Sabin Poliovirus type 2 production run samples, illustrated a linear relationship with an R of 0.994, and an average accuracy of 97.2 % of the variant (allele)-specific AS LNA qPCR result, compared to NGS. The assay showed good sensitivity for poliovirus samples, containing EK mutation levels between 0 % and 95 % (quantification range). In conclusion, the developed AS LNA qPCR presents a valuable low-cost, and fast tool, suitable for the process development and quality control of polio vaccines.
Topics: Humans; Poliomyelitis; Poliovirus Vaccine, Oral; Poliovirus; Poliovirus Vaccine, Inactivated; Mutation; Quality Control; Oligonucleotides
PubMed: 38503660
DOI: 10.1016/j.vaccine.2024.01.103 -
Journal of Rehabilitation Medicine Mar 2024To evaluate the 2-year course of walking adaptability in persons with late effects of polio.
OBJECTIVE
To evaluate the 2-year course of walking adaptability in persons with late effects of polio.
DESIGN
Prospective cohort study.
PATIENTS
A total of 48 persons with late effects of polio (69% female, mean age 63.1 years) with a fall history and/or fear of falling.
METHODS
Walking adaptability (i.e. variable target-stepping and reactive obstacle-avoidance) was assessed on an interactive treadmill at baseline, 1 year and 2 years. Further, leg-muscle strength and balance were assessed at baseline. The course of walking adaptability was analysed with linear mixed models. Based on median values, subgroups were defined for low vs high baseline walking-adaptability and for clinical characteristics. Tme by subgroup interactions were analysed.
RESULTS
Variable target-stepping and reactive obstacle-avoidance did not change (p > 0.285). Reactive obstacle-avoidance improved for persons with a high balance score at baseline (p = 0.037), but not for those with lower scores (p = 0.531). No other time by subgroup interactions were found (p > 0.126).
CONCLUSION
Walking adaptability did not change in persons with late effects of polio over 2 years, and walking adaptability course did not differ between subgroups stratified for walking adaptability determinants, except for balance. Since falls are a major problem among persons with late effects of polio, future studies should investigate whether walking adaptability declines over a longer time and which persons are most at risk.
Topics: Humans; Female; Middle Aged; Male; Accidental Falls; Fear; Prospective Studies; Disease Progression; Poliomyelitis; Walking
PubMed: 38497608
DOI: 10.2340/jrm.v56.14727 -
BMC Infectious Diseases Mar 2024The outbreaks of circulating Vaccine Derived Polio Viruses (cVDPVs) have emerged as a major challenge for the final stage of polio eradication. In Yemen, an explosive...
BACKGROUND
The outbreaks of circulating Vaccine Derived Polio Viruses (cVDPVs) have emerged as a major challenge for the final stage of polio eradication. In Yemen, an explosive outbreak of cVDPV2 was reported from August 2021 to December 2022. This study aims to compare the patterns of cVDPV2 outbreak, response measures taken by health authorities, and impacts in southern and northern governorates.
METHOD
A retrospective descriptive study of confirmed cases of VDPV2 was performed. The data related to cVDPV2 as well as stool specimens and environmental samples that were shipped to WHO-accredited labs were collected by staff of surveillance. Frequencies and percentages were used to characterize and compare the confirmed cases from the southern and northern governorates. The average delayed time as a difference in days between the date of sample collection and lab confirmation was calculated.
RESULTS
The cVDPV2 was isolated from 227 AFP cases reported from 19/23 Yemeni governorates and from 83% (39/47) of environmental samples with an average of 7 months delayed from sample collection. However, the non-polio AFP (NPAFP) and adequate stool specimen rates in the north were 6.7 and 87% compared to 6.4 and 87% in the south, 86% (195) and 14%(32) out of the total 227 confirmed cases were detected from northern and southern governorates, respectively. The first and second cases of genetically linked isolates experienced paralysis onset on 30 August and 1st September 2021. They respectively were from Taiz and Marib governorates ruled by southern authorities that started vaccination campaigns as a response in February 2022. Thus, in contrast to 2021, the detected cases in 2022 from the total cases detected in the south were lower accounting for 22% (7 of 32) of compared to 79% (155 of 195) of the total cases the north.
CONCLUSION
A new emerging cVDPV2 was confirmed in Yemen. The result of this study highlighted the impact of vaccination campaigns in containing the cVDPV2 outbreak. Maintaining a high level of immunization coverage and switching to nOPV2 instead of tOPV and mOPV2 in campaigns are recommended and environmental surveillance should be expanded in such a risky country.
Topics: Humans; Poliovirus; Yemen; Retrospective Studies; alpha-Fetoproteins; Poliomyelitis; Poliovirus Vaccine, Oral; Disease Outbreaks
PubMed: 38491425
DOI: 10.1186/s12879-024-09215-1 -
Virus Research Jun 2024The emergence of SARS-CoV-2 variants has led to several cases among children. However, limited information is available from North African countries. This study...
The emergence of SARS-CoV-2 variants has led to several cases among children. However, limited information is available from North African countries. This study describes the SARS-CoV-2 strains circulating in Tunisian pediatric population during successive waves. A total of 447 complete sequences were obtained from individuals aged from 13 days to 18 years, between March 2020 and September 2022: 369 sequences generated during this study and 78 ones, available in GISAID, previously obtained from Tunisian pediatric patients. These sequences were compared with 354 and 274 ones obtained from Tunisian adults and a global dataset, respectively. The variant circulation dynamics of predominant variants were investigated during the study period using maximum-likelihood phylogenetic analysis. Among the studied population, adolescents were the predominant age group, comprising 55.26% of cases. Twenty-three lineages were identified; seven of which were not previously reported in Tunisia. Phylogenetic analysis showed a close relationship between the sequences from Tunisian adults and children. The connections of sequences from other countries were variable according to variants: close relationships were observed for Alpha, B1.160 and Omicron variants, while independent Tunisian clusters were observed for Delta and B.1.177 lineages. These findings highlight the pivotal role of children in virus transmission and underscore the impact of vaccination on virus spread. Vaccination of children, with booster doses, may be considered for better management of future emergences.
Topics: Humans; Tunisia; COVID-19; Child; SARS-CoV-2; Child, Preschool; Infant; Adolescent; Phylogeny; Male; Infant, Newborn; Female
PubMed: 38490581
DOI: 10.1016/j.virusres.2024.199353 -
Journal of Infection in Developing... Feb 2024Poliovirus (PV) and non-polio enteroviruses (NPEV) belong to the Picornaviridae family. They are found worldwide and are responsible for a wide range of diseases such as...
INTRODUCTION
Poliovirus (PV) and non-polio enteroviruses (NPEV) belong to the Picornaviridae family. They are found worldwide and are responsible for a wide range of diseases such as acute flaccid paralysis (AFP). This study aimed to evaluate the detection rate of PV and NPEV in stool samples from children under fifteen years of age presenting with AFP in Cameroon and their distribution over time.
METHODOLOGY
Stool samples were collected as part of poliovirus surveillance throughout Cameroon from 2015 to 2020. Virus isolation was performed using RD and L20B cells maintained in culture. Molecular methods such as intratypic differentiation were used to identify PVs serotypes and analysis of the VP1 genome was performed.
RESULTS
A total of 12,354 stool samples were analyzed. The EV detection rate by virus isolation was 11.42% (1411/12354). This rate varied from year to year with a mean distribution of 11.41 with a 95% confidence interval [11.37; 11.44]. Of the viruses detected, suspected poliovirus accounted for 31.3% (442/1411) and NPEV 68.67% (969/1411). No wild poliovirus (WPV) was isolated. Sabin types 1 and 3 were continuously isolated. Surprisingly, from February 2020, vaccine-derived PV type 2 (VDPV2) was detected in 19% of cases, indicating its resurgence.
CONCLUSIONS
This study strongly supports the successful elimination of WPV in Cameroon and the resurgence of VDPV2. However, as long as VDPV outbreaks continue to be detected in Africa, it remains essential to monitor how they spread.
Topics: Child; Humans; Poliovirus; Enterovirus; Cameroon; alpha-Fetoproteins; Poliomyelitis; Enterovirus Infections; Myelitis; Neuromuscular Diseases; Central Nervous System Viral Diseases
PubMed: 38484358
DOI: 10.3855/jidc.18279 -
Emerging Microbes & Infections Dec 2024Tick-borne encephalitis virus (TBEV) causes a severe disease, tick-borne encephalitis (TBE), that has a substantial epidemiological importance for Northern Eurasia....
Tick-borne encephalitis virus (TBEV) causes a severe disease, tick-borne encephalitis (TBE), that has a substantial epidemiological importance for Northern Eurasia. Between 10,000 and 15,000 TBE cases are registered annually despite the availability of effective formaldehyde-inactivated full-virion vaccines due to insufficient vaccination coverage, as well as sporadic cases of vaccine breakthrough. The development of improved vaccines would benefit from the atomic resolution structure of the antigen. Here we report the refined single-particle cryo-electron microscopy (cryo-EM) structure of the inactivated mature TBEV vaccine strain Sofjin-Chumakov (Far-Eastern subtype) at a resolution of 3.0 Å. The increase of the resolution with respect to the previously published structures of TBEV strains Hypr and Kuutsalo-14 (European subtype) was reached due to improvement of the virus sample quality achieved by the optimized preparation methods. All the surface epitopes of TBEV were structurally conserved in the inactivated virions. ELISA studies with monoclonal antibodies supported the hypothesis of TBEV protein shell cross-linking upon inactivation with formaldehyde.
Topics: Humans; Antibodies, Viral; Encephalitis Viruses, Tick-Borne; Cryoelectron Microscopy; Encephalitis, Tick-Borne; Vaccines, Inactivated; Formaldehyde
PubMed: 38465849
DOI: 10.1080/22221751.2024.2313849 -
Journal of Virological Methods May 2024Polioviruses (PV), the main causative agent of acute flaccid paralysis (AFP), are positive-sense single-stranded RNA viruses of the family Picornaviridae. As we approach...
Polioviruses (PV), the main causative agent of acute flaccid paralysis (AFP), are positive-sense single-stranded RNA viruses of the family Picornaviridae. As we approach polio eradication, accurate and timely detection of poliovirus in stool from AFP cases becomes vital to success for the eradication efforts. Direct detection of PV from clinical diagnostic samples using nucleic acid (NA) extraction and real-time reverse transcriptase polymerase chain reaction (rRT-PCR) instead of the current standard method of virus isolation in culture, eliminates the long turn-around time to diagnosis and the need for high viral titer amplification in laboratories. An essential component of direct detection of PV from AFP surveillance samples is the efficient extraction of NA. Potential supply chain issues and lack of vendor presence in certain areas of the world necessitates the validation of multiple NA extraction methods. Using retrospective PV-positive surveillance samples (n=104), two extraction kits were compared to the previously validated Zymo Research Quick-RNA™ Viral Kit. The Roche High Pure Viral RNA Kit, a column-based manual extraction method, and the MagMaX™ Pathogen RNA/DNA kit used in the automated Kingfisher Flex system were both non-inferior to the Zymo kit, with similar rates of PV detection in pivotal rRT-PCR assays, such as pan-poliovirus (PanPV), poliovirus serotype 2 (PV2), and wild poliovirus serotype 1 (WPV1). These important assays allow the identification and differentiation of PV genotypes and serotypes and are fundamental to the GPLN program. Validation of two additional kits provides feasible alternatives to the current piloted method of NA extraction for poliovirus rRT-PCR assays.
Topics: Humans; Poliovirus; Retrospective Studies; alpha-Fetoproteins; Poliomyelitis; Enterovirus; RNA, Viral
PubMed: 38458353
DOI: 10.1016/j.jviromet.2024.114914 -
Virology Journal Mar 2024The novel coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Data from the COVID-19...
Aspergillus fumigatus secretes a protease(s) that displays in silico binding affinity towards the SARS-CoV-2 spike protein and mediates SARS-CoV-2 pseudovirion entry into HEK-293T cells.
BACKGROUND
The novel coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Data from the COVID-19 clinical control case studies showed that this disease could also manifest in patients with underlying microbial infections such as aspergillosis. The current study aimed to determine if the Aspergillus (A.) fumigatus culture media (i.e., supernatant) possessed protease activity that was sufficient to activate the SARS-CoV-2 spike protein.
METHODS
The supernatant was first analysed for protease activity. Thereafter, it was assessed to determine if it possessed proteolytic activity to cleave a fluorogenic mimetic peptide of the SARS-CoV-2 spike protein that contained the S1/S2 site and a full-length spike protein contained in a SARS-CoV-2 pseudovirion. To complement this, a computer-based tool, HADDOCK, was used to predict if A. fumigatus alkaline protease 1 could bind to the SARS-CoV-2 spike protein.
RESULTS
We show that the supernatant possessed proteolytic activity, and analyses of the molecular docking parameters revealed that A. fumigatus alkaline protease 1 could bind to the spike protein. To confirm the in silico data, it was imperative to provide experimental evidence for enzymatic activity. Here, it was noted that the A. fumigatus supernatant cleaved the mimetic peptide as well as transduced the HEK-293T cells with SARS-CoV-2 pseudovirions.
CONCLUSION
These results suggest that A. fumigatus secretes a protease(s) that activates the SARS-CoV-2 spike protein. Importantly, should these two infectious agents co-occur, there is the potential for A. fumigatus to activate the SARS-CoV-2 spike protein, thus aggravating COVID-19 development.
Topics: Humans; Peptide Hydrolases; Spike Glycoprotein, Coronavirus; Aspergillus fumigatus; SARS-CoV-2; HEK293 Cells; Molecular Docking Simulation; COVID-19; Peptides
PubMed: 38448991
DOI: 10.1186/s12985-024-02331-z