Categories
Nevin Manimala Statistics

Performance of Ultrasensitive Polymerase Chain Reaction Testing for JC Polyomavirus in Cerebrospinal Fluid Compared with Pathological Diagnosis of Progressive Multifocal Leukoencephalopathy

Viruses. 2024 Dec 19;16(12):1950. doi: 10.3390/v16121950.

ABSTRACT

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by the JC polyomavirus (JCPyV). Based on the clinical criteria, PML is diagnosed via polymerase chain reaction (PCR) detection of JCPyV DNA in cerebrospinal fluid (CSF) in combination with neurological and imaging findings. Although the utility of CSF JCPyV testing using ultrasensitive PCR assays has been suggested, its potential requires further evaluation. This study retrospectively analyzed the detection performance of ultrasensitive PCR for CSF JCPyV in patients who underwent brain tissue examination based on the pathological diagnostic criteria for PML. Of the 110 patients with pathologically confirmed definite PML or not PML, standard and ultrasensitive CSF testing was performed for 36 and 74 patients, respectively. The sensitivity of ultrasensitive CSF JCPyV testing of the initial specimens was 85%. With the addition of the follow-up testing, this figure increased to 95%. The specificity and false-positive rate of ultrasensitive CSF JCPyV testing, including follow-up, were 100% and 0%, respectively. No statistically significant correlation was observed between CSF and brain JCPyV levels. The results of this study demonstrate the high sensitivity and accuracy of ultrasensitive CSF JCPyV testing and provide essential information for the clinical diagnosis of PML.

PMID:39772255 | DOI:10.3390/v16121950

Categories
Nevin Manimala Statistics

A Randomized, Blinded, Vehicle-Controlled Dose-Ranging Study to Evaluate and Characterize Remdesivir Efficacy Against Ebola Virus in Rhesus Macaques

Viruses. 2024 Dec 18;16(12):1934. doi: 10.3390/v16121934.

ABSTRACT

Ebola virus (EBOV) causes severe disease in humans, with mortality as high as 90%. The small-molecule antiviral drug remdesivir (RDV) has demonstrated a survival benefit in EBOV-exposed rhesus macaques. Here, we characterize the efficacy of multiple intravenous RDV dosing regimens on survival of rhesus macaques 42 days after intramuscular EBOV exposure. Thirty rhesus macaques underwent surgical implantation of telemetry devices for the fine-scale monitoring of body temperature and activity, as well as central venous catheters, to enable treatment administration and blood collection. Treatment, consisting of a loading dose of RDV followed by once-daily maintenance doses for 11 days, was initiated 4 days after virus exposure when all animals were exhibiting disease signs consistent with incipient EBOV disease as well as quantifiable levels of EBOV RNA in plasma. In the RDV treatment groups receiving loading/maintenance doses of 5/2.5 mg/kg, 10/5 mg/kg, and 20/10 mg/kg, a total of 6 of 8 (75%), 7 of 8 (87.5%), and 5 of 7 (71.4%) animals survived, respectively. In the vehicle control group, one of seven animals (14.3%) survived. The improved survival rate compared to the control group was statistically significant only for the 10/5 mg/kg RDV treatment group. This treatment regimen also resulted in a significantly lower systemic viral load compared to the vehicle control after a single RDV treatment. All three RDV regimens produced a significantly lower systemic viral load after two treatments. For most animals, RDV treatment, regardless of dose, resulted in the amelioration of many of the clinical-pathological changes associated with EBOV disease in this model.

PMID:39772240 | DOI:10.3390/v16121934

Categories
Nevin Manimala Statistics

Has COVID-19 Affected the Course of Chickenpox in Children?

Viruses. 2024 Dec 13;16(12):1912. doi: 10.3390/v16121912.

ABSTRACT

OBJECTIVES OF THE STUDY: The aim of this study was to assess the impact of the COVID-19 pandemic on the epidemiology and clinical course of chickenpox in children based on 6 years of self-reported observations.

MATERIAL AND METHODS: The medical records of 350 patients under 18 years of age hospitalised in the Department of Paediatrics, Infectious Diseases, and Hepatology between 1 January 2018 to 31 December 2023 were analysed retrospectively.

RESULTS: During the analysed period, 350 children were hospitalised due to chickenpox, the fewest in the pandemic period, the greatest number in 2023. Complications of chickenpox were diagnosed in 297 children (84.86%). The most commonly diagnosed complications were bacterial dermatitis (168, 48%) and lower respiratory tract infections (13.42%). After the pandemic period, a generalised inflammatory reaction was observed significantly more often (p ≤ 0.01069). Among children hospitalised in 2023, 5.90% of patients with bacterial dermatitis required surgical intervention due to skin abscess or fasciitis. In 2023, 41.46% of cultures from swabs taken from skin lesions grew Streptococcus pyogenes. After the pandemic, children with chickenpox and gastrointestinal symptoms were hospitalised significantly less frequently (p ≤ 0.00001).

CONCLUSIONS: In the post-pandemic period, there were more hospitalisations of patients with chickenpox complicated by bacterial skin infection progressing to a generalised inflammatory reaction or septicaemia, related to the increase in invasive group A streptococcal infections observed in Europe. On the other hand, thanks to the widespread adaption of hygiene practices and infection prevention measures, the number of patients with gastrointestinal symptoms significantly decreased.

PMID:39772219 | DOI:10.3390/v16121912

Categories
Nevin Manimala Statistics

Cardiac Biomarkers in a Brazilian Indigenous Population Exposed to Arboviruses: A Cross-Sectional Study

Viruses. 2024 Dec 10;16(12):1902. doi: 10.3390/v16121902.

ABSTRACT

Arthropod-borne viral diseases are acute febrile illnesses, sometimes with chronic effects, that can be debilitating and even fatal worldwide, affecting particularly vulnerable populations. Indigenous communities face not only the burden of these acute febrile illnesses, but also the cardiovascular complications that are worsened by urbanization. A cross-sectional study was conducted in an Indigenous population in the Northeast Region of Brazil to explore the association between arboviral infections (dengue, chikungunya, and Zika) and cardiac biomarkers, including cardiotrophin 1, growth differentiation factor 15, lactate dehydrogenase B, fatty-acid-binding protein 3, myoglobin, N-terminal pro-B-type natriuretic peptide, cardiac troponin I, big endothelin 1, and creatine kinase-MB, along with clinical and anthropometric factors. The study included 174 individuals from the Fulni-ô community, with a median age of 47 years (interquartile range 39.0 to 56.0). High rates of previous exposure to dengue, chikungunya, and Zika were observed (92.5%, 78.2%, and 95.4% anti-IgG, respectively), while acute exposure (anti-IgM) remained low. The biomarkers were linked to age (especially in the elderly), obesity, chronic kidney disease, and previous or recent exposure to chikungunya. This study pioneers the use of Luminex xMAP technology to reveal the association between cardiac inflammatory biomarkers and exposure to classical arboviruses in an Indigenous population undergoing urbanization.

PMID:39772209 | DOI:10.3390/v16121902

Categories
Nevin Manimala Statistics

Real-World Comparison of Maribavir to Foscarnet for the Treatment of Cytomegalovirus in Solid Organ and Hematopoietic Stem Cell Transplant Recipients

Viruses. 2024 Dec 7;16(12):1889. doi: 10.3390/v16121889.

ABSTRACT

Cytomegalovirus (CMV) infection in solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients may increase the risk of rejection or allograft dysfunction, other infection(s), and morbidity and mortality. Treatment can be challenging due to medication-associated toxicities. Maribavir (MBV) is a promising option for the treatment of resistant or refractory (R/R) CMV infection in lieu of foscarnet (FOS), which has long been the recommended therapy for (val)ganciclovir-resistant infection. This was a single-center retrospective study of clinical outcomes of patients who received MBV compared to a control group who received FOS for an episode of CMV infection. Each cohort consisted of 27 episodes of CMV infection. Twenty patients in the MBV cohort and from the FOS cohort cleared the infection, with five and three patients developing MBV or FOS resistance, respectively. There were no statistically significant differences in failure of therapy as evidenced by persistent DNAemia (p = 0.56) or development of antiviral resistance (p = 0.24). In conclusion, MBV was as effective as FOS for the treatment of R/R CMV infection and was better tolerated without increased risk of antiviral resistance.

PMID:39772196 | DOI:10.3390/v16121889

Categories
Nevin Manimala Statistics

Wolbachia-Based Approaches to Controlling Mosquito-Borne Viral Threats: Innovations, AI Integration, and Future Directions in the Context of Climate Change

Viruses. 2024 Nov 30;16(12):1868. doi: 10.3390/v16121868.

ABSTRACT

Wolbachia-based mosquito control strategies have gained significant attention as a sustainable approach to reduce the transmission of vector-borne diseases such as dengue, Zika, and chikungunya. These endosymbiotic bacteria can limit the ability of mosquitoes to transmit pathogens, offering a promising alternative to traditional chemical-based interventions. With the growing impact of climate change on mosquito population dynamics and disease transmission, Wolbachia interventions represent an adaptable and resilient strategy for mitigating the public health burden of vector-borne diseases. Changes in temperature, humidity, and rainfall patterns can alter mosquito breeding habitats and extend the geographical range of disease vectors, increasing the urgency for effective control measures. This review highlights innovations in Wolbachia-based mosquito control and explores future directions in the context of climate change. It emphasizes the integration of Wolbachia with other biological approaches and the need for multidisciplinary efforts to address climate-amplified disease risks. As ecosystems shift, Wolbachia interventions could be crucial in reducing mosquito-borne diseases, especially in vulnerable regions. AI integration in Wolbachia research presents opportunities to enhance mosquito control strategies by modeling ecological data, predicting mosquito dynamics, and optimizing intervention outcomes. Key areas include refining release strategies, real-time monitoring, and scaling interventions. Future opportunities lie in advancing AI-driven approaches for integrating Wolbachia with other vector control measures, promoting adaptive, data-driven responses to climate-amplified disease transmission.

PMID:39772178 | DOI:10.3390/v16121868

Categories
Nevin Manimala Statistics

The Epidemiology, Clinical, and Economic Burdens of Respiratory Syncytial Virus Infections Amongst Hospitalized Children Under 5 Years of Age in Jordan: A National Multi-Center Cross-Sectional Study

Viruses. 2024 Nov 30;16(12):1867. doi: 10.3390/v16121867.

ABSTRACT

Respiratory syncytial virus (RSV) has been recognized as a highly important cause of morbidity and mortality among children and adults. A cross-sectional study at representative sites in Jordan was undertaken to provide an assessment of the epidemiology and health and economic burdens of RSV and influenza infections in Jordan amongst hospitalized children under 5 years old for the period between 15 November 2022 and 14 April 2023. This study involved 1000 patients with a mean age of 17.10 (SD: 16.57) months. Of these, half (n = 506, 50.6%) had positive results for RSV. Furthermore, 33% and 17.4% of the participants had positive results for RSV-B and RSV-A, respectively. The findings underscore the severity of RSV infections, where a significant proportion of the children experienced severe respiratory distress, which led to bronchiolitis and pneumonia. This study meticulously documented the clinical outcomes, including the need for intensive care, mechanical ventilation, and prolonged hospital stays. There was no statistically significant difference in the financial burdens between the RSV-positive and RSV-negative patients. This study revealed the urgent need for preventive measures to control the substantial burden of RSV among children under 5 years old in Jordan.

PMID:39772177 | DOI:10.3390/v16121867

Categories
Nevin Manimala Statistics

Emerging SARS-CoV-2 Variants in Uganda in the Era of COVID-19 Vaccination

Viruses. 2024 Nov 29;16(12):1860. doi: 10.3390/v16121860.

ABSTRACT

The emergence of SARS-CoV-2 variants has heightened concerns about vaccine efficacy, posing challenges in controlling the spread of COVID-19. As part of the COVID-19 Vaccine Effectiveness and Variants (COVVAR) study in Uganda, this study aimed to genotype and characterize SARS-CoV-2 variants in patients with COVID-19-like symptoms who tested positive on a real-time PCR. Amplicon deep sequencing was performed on 163 oropharyngeal/nasopharyngeal swabs collected from symptomatic patients. Genome assembly, lineage classification and phylogenetic analysis was performed using the Edge Bioinformatics pipeline version 2.4.0, Pangolin version 4.3.1 and iqtree version 2.3.6 software respectively. Of the 163 deep sequences analyzed between April 2023 and March 2024, the most common were XBB.1 lineages and sublineages (113, 69.3%), followed by JN.1* (12, 7.4%), XBB.2* (11, 6.7%) and FL* (11, 6.7%), EG* (7, 4.3%), others (BQ.1.1, FY.4.1, FY.4.1.2, GY.2.1, HK.27.1) (5, 3.1%) and CM* (4, 2.5%). XBB.1* dominated from April to July 2023; thereafter, other variants, including JN.1* were increasingly detected. There was no statistically significant association between vaccine status and lineage assignment (Fisher’s exact test, p-value = 0.994). Our findings showed that the Omicron variant, specifically the XBB.1* lineage, was the dominant circulating virus. However, the emergence of the JN.1 variant that exhibits a significant spike protein mutation profile could impact COVID-19 transmission in Uganda.

PMID:39772170 | DOI:10.3390/v16121860

Categories
Nevin Manimala Statistics

Predictive Efficacy of Dual Therapies Combining Integrase Strand Transfer Inhibitors with Second-Generation Non-Nucleoside Reverse Transcriptase Inhibitors Following HIV-1 Treatment Failure in Cameroon: Implications for the Use of a Long-Acting Therapeutic Strategy in Low- and Middle-Income Countries

Viruses. 2024 Nov 29;16(12):1853. doi: 10.3390/v16121853.

ABSTRACT

Dual therapies (DT) combining integrase strand transfer inhibitors (INSTIs) with second-generation non-nucleoside reverse transcriptase inhibitors (2nd-Gen-NNRTIs) offer new possibilities for HIV treatment to improve adherence. However, drug resistance associated mutations (RAMs) to prior antiretrovirals may jeopardize the efficacy of DT. We herein describe the predicted efficacy of DT combining INSTIs + 2nd-Gen-NNRTI following treatment failure among Cameroonian patients. We genotyped the HIV-1 pol gene using Sanger sequencing and assessed acquired RAMs to NNRTIs and INSTIs in patients failing treatment from March 2019 to December 2023. Drug susceptibility was interpreted using Stanford HIVdb v9.5, and statistical analyses were performed using SPSS v22. Of 130 successfully genotyped participants (median age (IQR): 38 (27-46) years; 59.2% female), 92.3% had RAMs to NNRTIs and 1.5% to INSTIs. Prevailing RAMs were Y181C (32.3%) among NNRTIs and R263K (0.7%) among INSTIs. Among 2nd-Gen-NNRTIs, etravirine, doravirine and rilpivirine had 43.85%, 41.54% and 38.46% genotypic sensitivity, respectively. Among INSTIs, we found 97.69% efficacy for dolutegravir/bictegravir, 96.15% for cabotegravir and 92.31% for elvitegravir/raltegravir. The overall predictive efficacy of DT was lower among participants who failed 1st-Gen-NNRTI (p < 0.001); with etravirine + dolutegravir/bictegravir combination showing the highest score (43.8%). Conclusively, DT combining INSTIs + 2nd-Gen-NNRTIs might be suboptimal in the context of previous ART failure, especially with NNRTI-based treatment in low- and middle-income countries. The general data clearly indicate that without resistance testing, it is nearly impossible to use long-acting dual therapies in previously failing patients.

PMID:39772163 | DOI:10.3390/v16121853

Categories
Nevin Manimala Statistics

A Possible Protective Effect of IgA Against Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) in Bronchoalveolar Lavage in COVID-19 Patients Admitted to Intensive Care Unit

Viruses. 2024 Nov 28;16(12):1851. doi: 10.3390/v16121851.

ABSTRACT

SARS-CoV-2 infection induces a humoral immune response, producing virus-specific antibodies such as IgM, IgG, and IgA. IgA antibodies are present at mucosal sites, protecting against respiratory and other mucosal infections, including SARS-CoV-2, by neutralizing viruses or impeding attachment to epithelial cells. Since SARS-CoV-2 spreads through the nasopharynx, the specific IgAs of SARS-CoV-2 are produced quickly after infection, effectively contributing to virus neutralization. Dimeric IgA has been reported to be 10 to 15 times more potent than its equivalent IgG, suggesting that this isotype may be particularly interesting in developing new monoclonal antibodies and/or new vaccines efficiently neutralizing the virus at the mucosal sites. It is still unclear whether IgA antibodies in BAL might play a role in the disease course and if their presence may have a prognostic significance. However, a harmful effect on diseases with high IgA titers has been reported. This study evaluated mucosal-specific IgA and IgG profiles in BAL of patients with COVID-19 acute respiratory failure admitted to the ICU. We included 57 patients (41 males and 16 females), admitted to the ICU of the University of Foggia. We used a commercially available ELISA assay to evaluate the presence of SARS-CoV-2 IgG and IgA antibodies in plasma and BAL of the 57 hospitalized patients with severe COVID-19 respiratory failure. However, 40/57 BAL and plasma from infected patients were available for the ELISA test; the remaining specimens were unsuitable. IgG and IgA antibodies against SARS-CoV-2 were detectable in 37 (92.5%) and 40 (100%) plasma specimens, respectively. IgG antibodies were found in a single sample, while IgAs were detected in 19 of 40 BAL samples analyzed. Correlations between these parameters and patient outcomes reveal a signature associated with survival. Interestingly, a statistically significant inverse correlation was found between the mortality rate and the presence of IgA to SARS-CoV-2 in BAL specimens. None of the 19 patients with a positive IgA died, compared to 7 out of 12 patients with a negative IgA-BAL (p: <0.0004). Despite being limited in size, this study suggests a significant protective effect of mucosal immunity in COVID-19 patients, even in advanced disease stages, and a role of IgA in the defense against the virus, as well as the possible use of effective vaccines and therapeutic strategies based on IgA antibodies.

PMID:39772161 | DOI:10.3390/v16121851