Virus In Individuals Research Articles

Merkel cell polyomavirus protein ALTO modulates TBK1 activity to support persistent infection.

While Merkel cell polyomavirus (MCPyV or MCV) is an abundant virus frequently shed from healthy skin, it is one of the most lethal tumor viruses in immunocompromised individuals, highlighting the crucial role of host immunity in controlling MCPyV oncogenic potential. Despite its prevalence, very little is known about how MCPyV interfaces with the host immune response to maintain asymptomatic persistent infection and how inadequate control of MCPyV infection triggers MCC tumorigenesis. In this study, we discovered that the MCPyV protein, known as the Alternative Large Tumor Open Reading Frame (ALTO), also referred to as middle T, effectively primes and activates the STING signaling pathway. It recruits Src kinase into the complex of STING downstream kinase TBK1 to trigger its autophosphorylation, which ultimately activates the subsequent antiviral immune response. Combining single-cell analysis with both loss- and gain-of-function studies of MCPyV infection, we demonstrated that the activity of ALTO leads to a decrease in MCPyV replication. Thus, we have identified ALTO as a crucial viral factor that modulates the STING-TBK1 pathway, creating a negative feedback loop that limits viral infection and maintains a delicate balance with the host immune system. Our study reveals a novel mechanism by which a tumorigenic virus-encoded protein can link Src function in cell proliferation to the activation of innate immune signaling, thereby controlling viral spread, and sustaining persistent infection. Our previous findings suggest that STING also functions as a tumor suppressor in MCPyV-driven oncogenesis. This research provides a foundation for investigating how disruptions in the finely tuned virus-host balance, maintained by STING, could alter the fate of MCPyV infection, potentially encouraging malignancy.

Systems medicine framework for repurposable drug combinations for COVID-19 comorbidities

Currently, vaccines have shown efficacy against new SARS-CoV-2 variants. This study aimed to develop a systems medicine framework that can predict and validate drug combinations that can be repurposed for treating COVID-19 and its comorbidities, specifically type 2 diabetes and hypertension. This study found that gut microbes could potentially influence the action of drugs, innate immune response, intestinal dysfunction, and susceptibility to the virus in individuals with these comorbidities. It was also discovered that the spike protein of the virus interacts with 57 human genes, many of which are linked to food-borne bacteria. An analysis of disease enrichment showed that arthritis and hypertension were frequently observed as comorbidities in patients infected with SARS-CoV-2. Several drugs, including Fluvoxamine, Donepezil, and Ifenprodil, have been identified as potentially repurposable drugs for treating COVID-19 in individuals with hypertension. Moreover, nitazoxanide and tocilizumab (antivirals), bacitracin (antibacterial), and gliclazide (antidiabetics) were also identified as potential repurposable drugs. Tocilizumab and gliclazide are effective drug combinations for treating COVID-19 in individuals with type 2 diabetes. A combination of tocilizumab and lidocaine has also been suggested for treating COVID-19 in individuals infected with food-borne bacteria.

Low Detection of High-risk Human Papilloma Virus in Individuals with Ameloblastoma in a Tertiary Hospital in Lagos, Nigeria.

Ameloblastoma is a benign but aggressive epithelial odontogenic neoplasm of unknown etiology. The role of human papilloma virus (HPV) in the etiology of oral squamous cell carcinoma has prompted the investigation of HPV as an etiologic factor in ameloblastoma. This study aimed to determine the frequency of high-risk (HR) HPV in conventional ameloblastoma and the clinical parameters associated with infection. The study was approved by the ethical review boards of the institution. DNA was extracted from fresh tissue collected 750 μL of DNA/RNA Shield (Zymo Research, United States) using Invitrogen PureLink Viral RNA/DNA Mini Kit (Invitrogen, USA). The extracted DNA was assayed for the detection of 14 HR HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) using Anyplex™ II HPV HR Detection kit (Cat. No. HP7E00X) (Seegene Inc., Republic of Korea) on CFX-96TM Real-Time Polymerase Chain Reaction (PCR) System (Bio-Rad). Data on gender, age of patient, site of lesion, clinicohistological types of ameloblastoma and history of smoking, alcohol consumption, and practice of oral sex were collected. Data analysis was performed using analysis program SPSS version 25 and statistical significance was set at P < 0.05. Two cases of conventional ameloblastoma were positive with HPV and none of the ameloblastic carcinoma cases were positive. The HPV 16 serotype was observed in both cases. While 5 of the cases had a history of alcohol consumption, none of these cases were positive for HPV serotype. HPV 16 positivity was detected in two cases of conventional ameloblastomas and none in ameloblastic carcinoma using real-time PCR. There was no effect of exposure to smoking, alcohol consumption, and practice of oral sex and HPV in the etiology of ameloblastoma. Data available are suggestive of a limited role of HPV in the etiology of ameloblastoma.

Coinfection with infectious precocity virus and Decapod iridescent virus 1 in farmed giant freshwater prawn (Macrobrachium rosenbergii)

In the past few years, outbreaks of infections with infectious precocious virus (IPV) and Decapod iridescent virus 1 (DIV1) have significantly hindered the development of the aquaculture industry of giant freshwater prawn (Macrobrachium rosenbergii) and caused severe economic losses in China. To understand the epidemiological information of farmed M. rosenbergii, we collected 79 samples from 23 farming ponds in Jiangsu Province from 2022 to 2023 and detected 8 common pathogens. The results showed that IPV and DIV1 could be detected in collected samples. Infections with IPV or DIV1 and the resulting diseases were confirmed by clinical signs, histopathologic examination, and qPCR. At the same time, we found coinfection with IPV and DIV1 in the same individuals by clinical diagnosis, histopathologic examination, and molecular testing. However, iron prawn syndrome (IPS) or IPS equivale and clinical infection with DIV1 (iDIV1) cases showed mutual exclusion in individuals and ponds. The results revealed significant differences in loads of the two viruses in the same individuals and ponds, with an overall negative correlation. This is the first report of coinfection with IPV and DIV1 in farmed M. rosenbergii.

In-vitro assessment of cutaneous immune responses to aedes mosquito salivary gland extract and dengue virus in Cambodian individuals.

Dengue virus (DENV) poses a global health threat, affecting millions individuals annually with no specific therapy and limited vaccines. Mosquitoes, mainly Aedes aegypti and Aedes albopictus worldwide, transmit DENV through their saliva during blood meals. In this study, we aimed to understand how Aedes mosquito saliva modulate skin immune responses during DENV infection in individuals living in mosquito-endemic regions. To accomplish this, we dissociated skin cells from Cambodian volunteers and incubated them with salivary gland extract (SGE) from three different mosquito strains: Ae. aegypti USDA strain, Ae. aegypti and Ae. albopictus wild type (WT) in the presence/absence of DENV. We observed notable alterations in skin immune cell phenotypes subsequent to exposure to Aedes salivary gland extract (SGE). Specifically, exposure lead to an increase in the frequency of macrophages expressing chemokine receptor CCR2, and neutrophils expressing CD69. Additionally, we noted a substantial increase in the percentage of macrophages that became infected with DENV in the presence of Aedes SGE. Differences in cellular responses were observed when Aedes SGE of three distinct mosquito strains were compared. Our findings deepen the understanding of mosquito saliva's role in DENV infection and skin immune responses in individuals regularly exposed to mosquito bites. This study provides insights into skin immune cell dynamics that could guide strategies to mitigate DENV transmission and other arbovirus diseases.

An Investigation of the Relationship between Henoch-Schönlein Purpura and Viral Infection in Korea Using the Health Insurance Database.

(1) Background: This study investigated the epidemiology and viral connections of Henoch-Schönlein purpura (HSP) using information from the Korea Disease Control and Prevention Agency and the Health Insurance Review and Assessment database. (2) Method: Between 2016 and 2019, a total of 25,443 patients with HSP were identified, with 51.3% of patients under the age of 20 years and the highest incidence in March. (3) Results: The autoregressive integrated moving average model and Granger causality test were used to analyze the association between the virus positivity detection rate and HSP incidence. (4) Conclusions: The incidence of HSP was associated with rotavirus, bocavirus, parainfluenza virus, and respiratory syncytial virus in individuals under 20 years of age, whereas adenovirus, respiratory syncytial virus, and norovirus were associated with individuals above that age.

Anti-SARS-CoV-2 Antibody Response Among Spectators of Amir Cup 2020 With a History of Recovery From COVID-19 in Qatar: A Historic Cohort Study.

Aim The aim of the study is to describe the antibody response after COVID-19 infection and assess its effectiveness against reinfection. Background COVID-19has recently emerged as a contagious infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus2 (SARS-CoV-2). This infection is followed by a humoral immune antibody response, which may remain in the blood for a number of weeks. Studies have shown that antibodies protect against reinfection for at least seven months. The current study is aimed at investigating the persistence of circulating SARS-CoV-2 antibodies after COVID-19 infection and its behavior over 18 months of follow-up period, in additionto assessing the risk of reinfection of COVID-19 in unvaccinated individuals. Methodology A longitudinal historical cohort study of 3378 COVID-19 recovered individuals in connection with the Amir Cup football tournament held in Qatar, in December 2020 was analyzed. The health records of study participants were followed for a maximum of 18 months after serology testing or until the first dose of COVID-19 vaccination to detect any evidence of recurrent infection. Results The study found a statistically significant association between recurrence risk and the duration of risk exposure since the first COVID-19 episode. Compared to those with the lowest risk of exposure to reinfection (shortest duration after first infection) those beyond 299 days of at-risk exposure since the first episode, have a 51-fold higher risk of developing recurrent COVID-19. Conclusion Immunity developed after primary infection with SARS-CoV-2 may protect against reinfection from subsequent exposure to the virus in seropositive individuals up to nine months post-infection.

Controlled human infection study underpins efficacy of the tetravalent live-attenuated dengue vaccine TV005.

Dengue fever, caused by four distinct serotypes of the dengue virus (DENV1-4), poses a public health concern for much of the world. The NIH's Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases (NIAID) has developed a series of single-dose, live-attenuated tetravalent DENV vaccines, including TV005. However, phase III trials require a lengthy three-to-five year follow-up. In contrast, controlled human infection models (CHIMs) offer a faster means to assess vaccine efficacy for any of the four serotypes. In this issue of the JCI, Pierce, Durbin, and colleagues conducted a CHIM study with attenuated DENV2 and DENV3 challenge viruses in individuals six months after vaccination with TV005. The TV005 vaccine was well tolerated and effectively protected all vaccinated individuals from viremia and rash during challenges with DENV2 or DENV3. Notably, vaccine recipients also showed serotype-specific efficacy. While long-term studies are still needed, these findings represent an important step in providing protection against dengue virus.

Epstein-Barr virus: Ubiquitous virus with multifarious implication in oral diseases material and methods results

Epstein Barr virus (EBV) is the first virus identified to possess the capacity to induce various benign and malignant conditions. These conditions encompass asymptomatic persistent infection, self-limited disease in individuals with a competent immune system, and the propensity to initiate different tumors formation (oncogenesis) even head and neck cancer. Notably, EBV may interact with other viruses including human papillomavirus (HPV) especially in immunosuppressed patients, leading to a synergistic effect. The objective of this study is to conduct a comprehensive literature review on the Epstein-Barr virus (EBV), focusing on its life cycle within the human host, the pathogenic mechanisms associated with the virus, the specific types of head and neck cancers in which EBV is implicated, and the interactions between EBV and other viruses in immunosuppressed individuals. Epstein-Barr virus (EBV) remains in most cases, asymptomatic or leads to the development of infectious mononucleosis. Moreover, it plays a significant role in the development of cancer, particularly in individuals under immunosuppression. The viral infection typically persists within the host organism in either a dormant or lytic state. The research also addresses the topic of chronic activated Epstein-Barr virus (EBV) syndrome, exploring its interactions with other pathogenic viruses. In addition to presenting oral manifestations in the form of infectious mononucleosis, the Epstein-Barr virus (EBV) is linked to the occurrence of nasopharyngeal carcinoma, Hodgkin and Non-Hodgkin lymphomas in the head and neck region. Furthermore, EBV is associated with the development of hairy leukoplakia in individuals with weakened immune systems due to HIV. Overall, EBV may play a role in the etiology and pathogenesis of oral squamous epithelium carcinoma either independently or in conjunction with human papillomavirus (HPV). The manifold role of EBV necessitates the accurate diagnosis of new cases and the vigilant monitoring of the patients in order to avoid or at least delay the long term repercussions on the patients' health and quality of life.

The Eradication of Carcinogenic Viruses in Established Solid Cancers.

Carcinogenic viruses (oncoviruses) can initiate cancer, but their impact on established cancer varies. Some of these viruses prolong survival while others shorten it. This study classifies oncoviruses into two categories: viruses which induce a strong CD8+T cell reaction in non-cancerous tissues, and viruses which induce a weak CD8+ T cell reaction in non-cancerous tissues. The classification proves useful in predicting the effect of oncoviruses on the prognosis of solid cancers. Therefore, while eliminating carcinogenic viruses in healthy individuals (for example by immunization) may be important for cancer prevention, this study suggests that only viruses which induce a weak CD8+ T cell reaction should be eradicated in established solid tumors. The model correctly predicts the effect of oncoviruses on survival for six out of seven known oncoviruses, indicating that immune modulation by oncoviruses has a prominent effect on prognosis. It seems that CD8+ T cell response to oncoviruses observed in infected benign tissues is retained in infected tumors. Clinical significance: the effect of oncoviruses on solid cancer prognosis can be predicted with confidence based on immunological responses when clinical data are unavailable.

The impact of multiple population-wide testing and social distancing on the transmission of an infectious disease

Under the background that asymptomatic virus carriers are contagious and the virus in the infected individuals has mild pathogenicity and enhanced transmissivity for an infectious disease, the phenomenon appears that the majority of infected people do not show any symptoms, but can infect others. Multiple population-wide testing can screen out asymptomatic virus carriers in time. Thus, we develop an infectious disease transmission dynamics model that includes three stages: non-testing period, testing period and testing interval, with multiple population-wide testing and social distancing to study the effects of the first testing time, total testing number, and testing interval time on the transmission of infectious diseases in this paper. The existence, uniqueness, boundedness and positivity of the solution, as well as the formulas of the basic reproduction number and the control reproduction number of the established model are established The numerical results show that the earlier the population-wide testing measure is implemented, the fewer the final size and necessary testing frequency. In the initial stage of the larger-scale spread of infectious disease, the existing virus carriers are not the most. But if population-wide testing measure is implemented during this period, the strongest testing force is required to contain the spread of the epidemic. Besides, population-wide testing combined with restrictive social distancing will significantly reduce the final size, necessary testing frequency, and duration of the epidemic. The testing interval time should be no longer than the incubation period of the virus to prevent and control the epidemic accurately. Therefore, the paper provides a theoretic basis for developing and implementing scientific testing strategies.

Detection of SARS-CoV-2 RNA in wastewater from an enclosed college campus serves as an early warning surveillance system.

SARS-CoV-2, the causative agent of Covid-19, is shed from infected persons in respiratory droplets, feces, and urine. Using quantitative PCR (qPCR), our group hypothesized that we could detect SARS-CoV-2 in wastewater samples collected on a university campus prior to the detection of the virus in individuals on campus. Wastewater samples were collected 3 times a week from 5 locations on the main campus of the University of North Carolina Wilmington (UNCW) from July 24, 2020 to December 21, 2020. Post-collection, total RNA was extracted and SARS-CoV-2 RNA in the samples was detected by qPCR. SARS-CoV-2 signal was detected on campus beginning on August 19 as classes began and the signal increased in both intensity and breadth as the Fall semester progressed. A comparison of two RNA extraction methods from wastewater showed that SARS-CoV-2 was detected more frequently on filter samples versus the direct extracts. Aligning our wastewater data with the reported SARS-CoV-2 cases on the campus Covid-19 dashboard showed the virus signal was routinely detected in the wastewater prior to clusters of individual cases being reported. These data support the testing of wastewater for the presence of SARS-CoV-2 and may be used as part of a surveillance program for detecting the virus in a community prior to an outbreak occurring and could ultimately be incorporated with other SARS-CoV-2 metrics to better inform public health enabling a quick response to contain or mitigating spread of the virus.

Tick-Borne Encephalitis Virus and Borrelia burgdorferi Seroprevalence in Balkan Tick-Infested Individuals: A Two-Centre Study.

Lyme borreliosis (LB) and tick-borne encephalitis (TBE) are important tick-borne diseases in Europe. This study aimed to investigate the seroreactivity against Borrelia burgdorferi and TBE virus (TBEV) in tick-infested individuals in North Macedonia and Serbia. Serum samples were collected from tick-infested individuals and from healthy individuals in the same regions. Samples were tested for anti-Borrelia IgG reactivity and TBEV-neutralizing antibodies. Results showed higher seroreactivity against Borrelia antigens in patients and healthy donors from Novi Sad compared to those from the Skopje region. However, there was no statistically significant difference between tick-infested patients and healthy donors within each region. No TBEV-neutralizing antibodies were detected in participants from Novi Sad or in the control groups, except for one person from North Macedonia who had a moderate TBEV-neutralizing reaction. The study highlights the need for improved surveillance and diagnostic capabilities for LB and TBE in these regions. It also suggests the potential existence of TBEV foci in North Macedonia. The findings provide a complementary understanding of the LB and TBE epidemiology in the studied regions; however, further research is needed to investigate the presence and distribution of Borrelia spp. and TBEV in ticks to assess the significance of detected seroreactivity.

Evaluation and comparison of risk-based and universal prenatal HCV screening programs in Alberta, Canada

Canadian clinical practice guidelines currently recommend risk-based screening for hepatitis C virus (HCV) in pregnant individuals. However, no provinces or territories have ever compared the effectiveness of risk-based versus universal screening for diagnosing prenatal HCV. We aimed to evaluate and compare HCV screening programs after implementing a universal population-level pilot program among prenatal patients in Alberta, Canada. The Alberta Prenatal Screening Program for Select Communicable Diseases was amended to include universal HCV antibody screening. Cohorts of pregnant individuals screened for HCV through risk-based or universal programs were generated over one-year periods. HCV screening rates and prevalence was analyzed and compared between cohorts to evaluate effectiveness of screening methods. Social and demographic risk factors for HCV positive individuals were compared between screening cohorts to identify which populations may be overlooked with risk-based guidelines. HCV antibody screening rates were 11.9% and 99.9% among pregnant individuals in the risk-based and universal cohorts respectively. HCV prevalence among the cohorts was 0.07% and 0.11% (difference=0.04%, p=0.032), with an average of 21 additional HCV positive pregnant individuals identified annually with universal screening. HCV positive prenatal patients diagnosed through universal screening were more likely to engage in high-risk sexual behaviours/sex work compared to those diagnosed through risk-based screening (47.6% versus 12.5%, respectively p=0.035), suggesting risk-based screening is missing these high-risk women. Universal HCV screening diagnoses significantly higher numbers of pregnant individuals infected with HCV compared to risk-based screening. Universal HCV screening or amending risk-based guidelines to incorporate more proxy variables for risk factors should be considered to improve prenatal HCV screening guidelines in Canada and help achieve HCV elimination in the next decade. Hepatitis C virus (HCV) is a bloodborne pathogen that can cause severe liver disease and be vertically transmitted from a mother to her baby during pregnancy. Pregnant individuals in Alberta are currently only tested for HCV if they disclose to their physician engagement in activities that put them at risk for acquiring the infection (risk-based screening). Using a population-wide universal prenatal HCV screening program, our work shows testing based on patient disclosed risk alone significantly underdiagnoses HCV in pregnant individuals and suggests individuals engaging in sex work or risky sexual behaviours are being overlooked with the current risk-based program. Our outcomes represent the first province-wide study to evaluate and compare prenatal HCV risk-based and universal screening programs in Canada and can be used as evidence-based data for updating prenatal HCV screening policies across the country and in similar jurisdictions.

COVID-19 Antigen Results Correlate with the Quantity of Replication-Competent SARS-CoV-2 in a Cross-Sectional Study of Ambulatory Adults during the Delta Wave.

Appropriate interpretation of various diagnostic tests for COVID-19 is critical, yet the association among rapid antigen tests, reverse transcription (RT)-PCR, and viral culture has not been fully defined. To determine whether rapid antigen testing correlates with the presence and quantity of replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in ambulatory adults, 626 adult participants were enrolled in a cross-sectional diagnostic study. Each participant had two anterior nasal swabs obtained for rapid antigen and RT-PCR testing and SARS-CoV-2 viral culture. The primary outcomes were the presence and quantification of SARS-CoV-2 growth in VeroE6-ACE2-TMPRSS2 cells in asymptomatic and symptomatic ambulatory adults. In this cross-sectional study of 626 adult outpatients, the sensitivity of a single positive antigen test to identify replication-competent SARS-CoV-2 was 63.6% in asymptomatic and 91.0% in symptomatic participants. Viral culture titers were the highest at the onset of symptoms and rapidly declined by 7 days after symptom onset. The positive agreement of the rapid antigen test with RT-PCR at a cycle threshold CT less than 30 was 66.7% in asymptomatic and 90.7% in symptomatic participants. Among symptomatic participants a with a CT less than 30, a single antigen test had a positive agreement of 90.7% (95% confidence interval [CI], 84.8% to 94.8%). There was 100% negative agreement as all 425 RT-PCR-negative participants had a negative antigen test. A positive antigen test in symptomatic adults with COVID-19 has a strong correlation with replication-competent SARS-CoV-2. Rapid antigen test results may be a suitable proxy for infectiousness. IMPORTANCE Do rapid antigen test results correlate with replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (i.e., infectious) virus? In this cross-sectional diagnostic study of 626 adults, the sensitivity of the antigen test to identify replication-competent SARS-CoV-2 was 63.6% in asymptomatic and 91.0% in symptomatic participants. Viral culture titers were the highest at the onset of symptoms and rapidly declined by 7 days after symptom onset. The positive agreement of the rapid antigen test with reverse transcription (RT)-PCR at a CT of less than 30 was 66.7% in asymptomatic participants and 90.7% in symptomatic participants. A positive antigen test may be an appropriate surrogate for identifying replication-competent virus in symptomatic individuals with COVID-19.

POST HERPETIC NEURALGIA

Postherpetic neuralgia (PHN) is a chronic neuropathic pain condition that lasts 3 months or more after an outbreak of shingles. Herpes zoster, especially acute herpes zoster, is associated with the reactivation of the inactivated varicella zoster virus in individuals who have had chickenpox. PHN is associated with persistent and often refractory neuropathic pain. Patients may experience several types of pain, including deep pain, intolerable pain, burning, paroxysmal pain, stabbing pain, hyperalgesia, and allodynia. Pharmacological treatment of PHN may include a variety of drugs, including alpha-2 delta ligands (gabapentin and pregabalin), other anticonvulsants (carbamazepine), tricyclic antidepressants (amitriptyline, nortriptyline, doxepin), topical analgesics (5% lidocaine patch, capsaicin) tramadol, or other opioids. The sizeable side effect profile of commonly used oral drugs often limits their practical use, and a combination of topical and systemic agents may be required for optimal results. Doctors and other care providers must adapt treatment based on individual patient responses.

Shedding of rubella virus in postsymptomatic individuals; viral RNA load is a potential indicator to estimate candidate patients excreting infectious rubella virus.

Since the first isolation of rubella virus (RuV) in 1962, comprehensive data regarding the quantitative evaluation of RuV shedding remain unavailable. In this study, we evaluated the shedding of viral RNA and infectious virus in patients with acute RuV infection. We analyzed 767 specimens, including serum/plasma, peripheral blood mononuclear cells (PBMCs), throat swabs, and urine, obtained from 251 patients with rubella. The viral RNA load and the presence of infectious RuV were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and virus isolation. Virus excretion peaked 0-2 days after rash onset and decreased over time. The median viral RNA load dropped to an undetectable level on day 3 after rash onset in serum/plasma, day 2 in PBMCs, days 10-13 in throat swabs, and days 6-7 in urine. Infectious virus could be isolated for up to day 2 after rash onset in serum/plasma, day 1 in PBMCs, days 8-9 in throat swabs, and days 4-5 in urine. The minimum viral RNA load that allowed virus isolation was 961 copies/mL in serum/plasma, 784 copies/mL in PBMCs, 650 copies/mL in throat swabs, and 304 copies/mL in urine. A higher viral RNA load indicated a higher likelihood of the presence of infectious virus. These findings would contribute to improve algorithms for rubella surveillance and diagnosis. In addition, this study indicates that the results of RT-qPCR enable efficient rubella control by estimating candidate patients excreting infectious virus, which could help prevent viral transmission at an early stage and eliminate rubella ultimately.

High-Throughput Neutralization and Serology Assays Reveal Correlated but Highly Variable Humoral Immune Responses in a Large Population of Individuals Infected with SARS-CoV-2 in the US between March and August 2020.

The ability to measure neutralizing antibodies on large scale can be important for understanding features of the natural history and epidemiology of infection, as well as an aid in determining the efficacy of interventions, particularly in outbreaks such as the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Because of the assay's rapid scalability and high efficiency, serology measurements that quantify the presence rather than function of serum antibodies often serve as proxies of immune protection. Here, we report the development of a high-throughput, automated fluorescence-based neutralization assay using SARS-CoV-2 virus to quantify neutralizing antibody activity in patient specimens. We performed large-scale testing of over 19,000 COVID-19 convalescent plasma (CCP) samples from patients who had been infected with SARS-CoV-2 between March and August 2020 across the United States. The neutralization capacity of the samples was moderately correlated with serological measurements of anti-receptor-binding domain (RBD) IgG levels. The neutralizing antibody levels within these convalescent-phase serum samples were highly variable against the original USA-WA1/2020 strain with almost 10% of individuals who had had PCR-confirmed SARS-CoV-2 infection having no detectable antibodies either by serology or neutralization, and ~1/3 having no or low neutralizing activity. Discordance between neutralization and serology measurements was mainly due to the presence of non-IgG RBD isotypes. Meanwhile, natural infection with the earliest SARS-CoV-2 strain USA-WA1/2020 resulted in weaker neutralization of subsequent B.1.1.7 (alpha) and the B.1.351 (beta) variants, with 88% of samples having no activity against the BA.1 (omicron) variant. IMPORTANCE The ability to directly measure neutralizing antibodies on live SARS-CoV-2 virus in individuals can play an important role in understanding the efficacy of therapeutic interventions or vaccines. In contrast to functional neutralization assays, serological assays only quantify the presence of antibodies as a proxy of immune protection. Here, we have developed a high-throughput, automated neutralization assay for SARS-CoV-2 and measured the neutralizing activity of ~19,000 COVID-19 convalescent plasma (CCP) samples collected across the United States between March and August of 2020. These data were used to support the FDA's interpretation of CCP efficacy in patients with SARS-CoV-2 infection and their issuance of emergency use authorization of CCP in 2020.

Treponema pallidum infection rate in patients attending the general hospital of Benguela, Angola

The objectives of this study were to estimate the rate of infection by Treponema pallidum and co-infection with Human Immunodeficiency Virus (HIV) in individuals attending the General Hospital of Benguela (GHB), Angola, to verify the Rapid Plasma Reagin (RPR) test performance for its diagnosis when compared with other RPR tests, and to compare a rapid treponemal test with the Treponema pallidum hemagglutination assay (TPHA). This is a cross-sectional study carried out between August 2016 and January 2017, at the GHB, 546 individuals attending the emergency room, the outpatient service or hospitalized at the GHB were included. All the samples were tested at the GHB with the routine hospital RPR test and a rapid treponemal test. The samples were then transported to the Institute of Hygiene and Tropical Medicine (IHMT) where RPR testing and TPHA testing were performed. The rate of T. pallidum active infection, demonstrated by a reactive RPR and TPHA result, was 2.9%, of which 81.2% corresponded to indeterminate latent syphilis and 18.8% to secondary syphilis. HIV co-infection was detected in 62.5% of individuals diagnosed with syphilis. Past infection, defined as a non-reactive RPR and reactive TPHA test, was diagnosed in 4.1% of individuals. The high rate of syphilis/HIV co-infection emphasizes the urgent requirement for adequate sexually transmitted infections (STIs) screening, prevention and treatment programs. In addition, implementation of quality control measures within RPR testing protocols at GHB are needed, including training for laboratory personnel, adequate equipment and introduction of other rapid testing.

Hepatitis C virus in pregnant individuals with opioid use disorder and association with preterm birth

Hepatitis C virus in pregnant individuals with opioid use disorder and association with preterm birth