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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 -
Metabolomics : Official Journal of the... Mar 2024Because cerebrospinal fluid (CSF) samples are difficult to obtain for paediatric HIV, few studies have attempted to profile neurometabolic dysregulation.
INTRODUCTION
Because cerebrospinal fluid (CSF) samples are difficult to obtain for paediatric HIV, few studies have attempted to profile neurometabolic dysregulation.
AIM AND OBJECTIVE
The aim of this exploratory study was to profile the neurometabolic state of CSF from a South African paediatric cohort using GCxGC-TOF/MS. The study included 54 paediatric cases (< 12 years), 42 HIV-negative controls and 12 HIV-positive individuals.
RESULTS
The results revealed distinct metabolic alterations in the HIV-infected cohort. In the PLS-DA model, 18 metabolites significantly discriminated between HIV-infected and control groups. In addition, fold-change analysis, Mann-Whitney U tests, and effect size measurements verified these findings. Notably, lactose, myo-inositol, and glycerol, although not significant by p-value alone, demonstrated practical significance based on the effect size.
CONCLUSIONS
This study provided valuable insights on the impact of HIV on metabolic pathways, including damage to the gut and blood-brain barrier, disruption of bioenergetics processes, gliosis, and a potential marker for antiretroviral therapy. Nevertheless, the study recognized certain constraints, notably a limited sample size and the absence of a validation cohort. Despite these limitations, the rarity of the study's focus on paediatric HIV research underscores the significance and unique contributions of its findings.
Topics: Humans; Child; South Africa; Metabolomics; HIV Infections; Metabolome
PubMed: 38427142
DOI: 10.1007/s11306-024-02098-y -
PloS One 2024Acute Flaccid Paralysis (AFP) surveillance is the gold standard in the polio eradication initiative. The environmental component of polio surveillance can detect...
BACKGROUND
Acute Flaccid Paralysis (AFP) surveillance is the gold standard in the polio eradication initiative. The environmental component of polio surveillance can detect circulating Polioviruses from sewage without relying on clinical presentation. The effectiveness of the Environmental Surveillance (ES) is crucial to global polio eradication. We assessed the usefulness and attributes of the ES system in the Northern region and determined if the system is meeting its objectives.
METHODS
We conducted a descriptive cross-sectional evaluation in the Northern region from 2019 to 2020 using the updated US Centers for Disease Control and Prevention guideline. We interviewed stakeholders, reviewed records, and observed surveillance activities from 29th March to 7th May, 2021. Quantitative data were analyzed manually as frequencies and proportions whiles thematic analysis was used for the qualitative data.
RESULTS
One of 48 (2.1%) samples collected tested positive for circulating vaccine-derived Poliovirus (cVDPV). The cVDPV detection triggered enhanced AFP surveillance that resulted in the identification of a case of AFP. Three rounds of polio vaccination campaigns were organized. All surveillance officers interviewed were willing to continue providing their services for the ES. Reporting form has few variables and is easy to complete. The completeness of forms was 97.9% (47/48). Samples collected were dispatched on the same day to the testing laboratory. The system's data was managed manually.
CONCLUSION
The system was useful in detecting polio outbreaks. Data quality was good, the system was simple, flexible, acceptable, representative, and fairly stable. Sensitivity was high but predictive value positive was low. Timeliness in reporting was good but feedback from the national level could not be assessed. There is a need to improve on the feedback system and ensure that, the surveillance data is managed electronically.
Topics: Humans; alpha-Fetoproteins; Cross-Sectional Studies; Environmental Monitoring; Ghana; Poliomyelitis; Poliovirus
PubMed: 38422061
DOI: 10.1371/journal.pone.0294305 -
Antiviral Research Apr 2024Enteroviruses are a significant global health concern, causing a spectrum of diseases from the common cold to more severe conditions like hand-foot-and-mouth disease,...
The combination of pleconaril, rupintrivir, and remdesivir efficiently inhibits enterovirus infections in vitro, delaying the development of drug-resistant virus variants.
Enteroviruses are a significant global health concern, causing a spectrum of diseases from the common cold to more severe conditions like hand-foot-and-mouth disease, meningitis, myocarditis, pancreatitis, and poliomyelitis. Current treatment options for these infections are limited, underscoring the urgent need for effective therapeutic strategies. To find better treatment option we analyzed toxicity and efficacy of 12 known broad-spectrum anti-enterovirals both individually and in combinations against different enteroviruses in vitro. We identified several novel, synergistic two-drug and three-drug combinations that demonstrated significant inhibition of enterovirus infections in vitro. Specifically, the triple-drug combination of pleconaril, rupintrivir, and remdesivir exhibited remarkable efficacy against echovirus (EV) 1, EV6, EV11, and coxsackievirus (CV) B5, in human lung epithelial A549 cells. This combination surpassed the effectiveness of single-agent or dual-drug treatments, as evidenced by its ability to protect A549 cells from EV1-induced cytotoxicity across seven passages. Additionally, this triple-drug cocktail showed potent antiviral activity against EV-A71 in human intestinal organoids. Thus, our findings highlight the therapeutic potential of the pleconaril-rupintrivir-remdesivir combination as a broad-spectrum treatment option against a range of enterovirus infections. The study also paves the way towards development of strategic antiviral drug combinations with virus family coverage and high-resistance barriers.
Topics: Animals; Humans; Enterovirus A, Human; Enterovirus; Enterovirus Infections; Enterovirus B, Human; Antiviral Agents; Drug Combinations; Adenosine Monophosphate; Oxadiazoles; Pyrrolidinones; Oxazoles; Valine; Isoxazoles; Phenylalanine; Alanine
PubMed: 38417531
DOI: 10.1016/j.antiviral.2024.105842