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Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Abstract Background Cisgender (cis) Black women in the USA are more likely to become HIV positive during their lifetime than other women. We developed and implemented a behavioral intervention, Increasing PrEP (iPrEP), the first pilot randomized controlled trial (RCT) aimed at motivating cis Black women to be willing to use PrEP for HIV prevention and attend an initial PrEP clinic visit following an emergency department visit. Methods Eligible participants were Black cisgender women ages 18–55 years who acknowledged recent condomless sex and substance use. Participants were randomized to iPrEP or usual care (UC). iPrEP is a survey-based intervention designed to raise awareness and knowledge about PrEP. Participants completed an assessment of knowledge of and willingness to use PrEP before and after the intervention, then received a warm-hand off with referral to a local PrEP clinic. Enrolled participants were followed for 6 months. Results Forty enrolled participants were ages 18–54 years. Education levels varied evenly between some high school education and graduate education. Most participants were single (n = 25) or married (n = 7). Twenty-two participants were employed full-time. Pre-test results indicated that 21 of 40 participants had heard of PrEP. All participants identified PrEP as a daily HIV prevention medication. For those randomized to iPrEP, the odds of knowing about PrEP at post-test, when controlling for baseline, were higher relative to UC (OR = 5.22, 95%CrI = 0.50, 94.1]. iPrEP did not have any effect on willingness relative to UC. The estimate for iPrEP on willingness is marginally higher (4.16 vs. 4.04; i.e., 0.12 points higher); however, the posterior probability of 67.9% does not suggest a strong degree of evidence in favor of an effect. During the post-test, those receiving iPrEP were less ready to take PrEP than those receiving UC. Conclusions Findings suggest that iPrEP increased knowledge about the PrEP medication but had a negative impact on readiness to take PrEP relative to UC. It is imperative that future research among cisgender Black women carefully considers the content provided in interventions designed to increase PrEP use, balancing the benefits of PrEP with the side effects and daily pill burden. Trial registration: clinicaltrial.gov Identifier: NCT03930654, 29/04/2019. …

Abstract Background When people with human immunodeficiency virus (HIV) infection (PWH) develop malaria, they are at risk of poor anti-malarial treatment efficacy resulting from impairment in the immune response and/or drug-drug interactions that alter anti-malarial metabolism. The therapeutic efficacy of artemether-lumefantrine was evaluated in a cohort of PWH on antiretroviral therapy (ART) and included measurement of day 7 lumefantrine levels in a subset to evaluate for associations between lumefantrine exposure and treatment response. Methods Adults living with HIV (≥ 18 years), on ART for ≥ 6 months with undetectable HIV RNA viral load and CD4 count ≥ 250/mm3 were randomized to daily trimethoprim-sulfamethoxazole (TS), weekly chloroquine (CQ) or no prophylaxis. After diagnosis of uncomplicated Plasmodium falciparum malaria, a therapeutic efficacy monitoring was conducted with PCR-correction according to WHO guidelines. The plasma lumefantrine levels on day 7 in 100 episodes of uncomplicated malaria was measured. A frailty proportional hazards model with random effects models to account for clustering examined the relationship between participant characteristics and malaria treatment failure within 28 days. Pearson’s Chi—squared test was used to compare lumefantrine concentrations among patients with treatment failure and adequate clinical and parasitological response (ACPR). Results 411 malaria episodes were observed among 186 participants over 5 years. The unadjusted ACPR rate was 81% (95% CI 77–86). However, after PCR correction to exclude new infections, ACPR rate was 94% (95% CI 92–97). Increasing age and living in Ndirande were associated with decreased hazard of treatment failure. In this population of adults with HIV on ART, 54% (51/94) had levels below a previously defined optimal day 7 lumefantrine level of 200 ng/ml. This occurred more commonly among participants who were receiving an efavirenz-based ART compared to other ART regimens (OR 5.09 [95% CI 1.52–7.9]). Participants who experienced treatment failure had lower day 7 median lumefantrine levels (91 ng/ml [95% CI 48–231]) than participants who experienced ACPR (190 ng/ml [95% CI 101–378], p-value < 0.008). Conclusion Recurrent malaria infections are frequent in this population of PWH on ART. The PCR-adjusted efficacy of AL meets the WHO criteria for acceptable treatment efficacy. Nevertheless, lumefantrine levels tend to be low in this population, particularly in those on efavirenz-based regimens, with lower concentrations associated with more frequent malaria infections following treatment. These results highlight the importance of understanding drug-drug interactions when diseases commonly co-occur. …

This cluster-randomised clinical trial shows that prospective audit and feedback is safe and effective in optimising and reducing antibiotic use in adults admitted to hospital with COVID-19. Despite many competing priorities during the COVID-19 pandemic, antimicrobial stewardship should remain a priority to mitigate the overuse of antibiotics in this population.

Ceftazidime-avibactam (CAZ-AVI)-based treatments have been associated with emergence of resistance in KPC-producing Klebsiella pneumoniae (KPC-Kp) isolates following antimicrobial exposure. Herein, we evaluated the CAZ-AVI-resistance development in KPC-Kp isolated from patients treated with CAZ-AVI-based therapy.

Science Advances, Volume 9, Issue 4, January 2023.

Science Advances, Volume 9, Issue 4, January 2023.

The overexploitation of traditional antibiotic targets – including cell envelope biogenesis, DNA replication, protein translation, and transcription – has diminished returns in drug discovery efforts [1]. Therefore, it is critical to identify, characterise, and validate novel drug targets. To this end, some recent efforts have explored essential processes during infection and have adopted in vitro screening conditions mimicking the infection environment to expand the target base for new antimicrobials [2–5].

AbstractFrom two SARS-CoV-2 household transmission studies (enrolling April 2020 – January 2022) with rapid enrollment and specimen collection for 14 days, 61% (43/70) of primary cases had culturable-virus detected ≥6 days post-onset. Risk of secondary infection among household contacts tended to be greater when primary cases had culturable-virus detected after onset. Regardless of duration of culturable-virus, most secondary infections [70% (28/40)] had serial intervals <6 days, suggesting early transmission. These data examine viral culture as a proxy for infectiousness, reaffirm the need for rapid control measures after infection and highlight the potential for prolonged infectiousness (≥6 days) in many individuals.

AbstractBackgroundPatients with sickle-cell disease (SCD) are at high risk for invasive pneumococcal diseases. The immunological efficacy of 13-valent conjugate pneumococcal vaccine (PCV13) followed by a 23-valent polysaccharide vaccine (PPSV23) is poorly documented in adults with SCD.MethodsThis was a randomized open-labelled phase 2 study of the immunogenicity of PCV13 at week (W)0, followed by PPSV23 at W4, compared to PPSV23 alone at W4 in adult patients with SCD. The proportion of responders (four-fold increase of serotype-specific IgG antibodies) to at least 10-shared serotypes was assessed at W8. Secondary endpoints were: i) geometrical mean titers (GMTs), ii) responders to 0-1, 2-5, 6-9, and 10-12 serotypes, iii) pneumococcal opsonophagocytic (OPA) activity, and iv) response durability at W24 and W96.ResultsIn total, 128 patients were randomized in the PCV13/PPSV23 (n=63) or PPSV23-alone groups (n=65). At W8, 24.56% and 8.20% of patients from the PCV13/PPSV23 and PPSV23 groups, respectively, reached the primary endpoint (p=0.016). These numbers were 36.2% and 8.7% for OPA responders (p=0.002). A combined PCV13/PPSV23 strategy improved the breadth of responses to 0-1, 2-5, 6-9, and 10-12 serotypes with 15.8%, 35%, 24.6%, and 24.6% versus 52.5%, 31%, 8%, and 8% in the PPSV23 group. At W96, GMTs were significantly higher in the PCV13/PPSV23 than in the PPSV23 alone group for five serotypes (4, 14, 19A, 19F, 23F).ConclusionsA PCV13/PPSV23 regimen improved the breadth and magnitude of antibody responses against a large range of pneumococcal serotypes in adults with SCD. The sustainability of the immune response requires recall strategies.Clinical Trial Registration: NCT02274415…

Antimicrobial Agents and Chemotherapy, Ahead of Print.

by The PLOS ONE Staff …

by Hiroto Takeuchi, Chie Nakajima, Satoru Konnai, Naoya Maekawa, Tomohiro Okagawa, Masaru Usui, Yutaka Tamura, Yasuhiko Suzuki, Shiro Murata, Kazuhiko OhashiCoagulase-positive Staphylococci express protein A, which binds to host antibodies, to evade the immune system. Taking advantage of its specific binding to antibodies, protein A from Staphylococcus aureus, which is called SpA, is commonly used as an affinity chromatography ligand for human therapeutic antibodies. However, among four canine IgG subclasses (A, B, C, and D), only IgG-B binds to SpA strongly and establishing an efficient and robust purification scheme for canine therapeutic antibodies whose IgG subclass is A, C, or D remains difficult and depends on finding a suitable substitute to SpA. S. pseudintermedius, a major coagulase-positive Staphylococci found in dogs, expresses spsQ gene which is orthologous to S. aureus spa. We hypothesized that to serve S. pseudintermedius to better adapt to the dog immune system, SpsQ would bind to canine IgGs stronger than SpA, making it a better affinity chromatography ligand for canine therapeutic antibodies. To characterize SpsQ, we first determined the spsQ nucleotide sequence from S. pseudintermedius isolates. Based on the identified sequence, we prepared recombinant proteins containing the immunoglobulin-binding domains of SpA (r-SpA) and SpsQ (r-SpsQ) and determined their binding capacity for each canine IgG subclass. The binding capacity of r-SpsQ for IgG-B was almost as high as that of r-SpA. Interestingly, while both r-SpsQ and r-SpA showed no binding to IgG-C, the binding capacity of r-SpsQ for IgG-A and IgG-D was significantly higher than that of r-SpA. Finally, we performed affinity chromatography using r-SpsQ- or r-SpA-immobilized resin and revealed that the recovery rates of IgG-A and IgG-D using r-SpsQ were significantly higher than those using r-SpA. Our findings indicate that SpsQ has a strong potential to be used as an affinity chromatography ligand for canine therapeutic antibodies of subclass A, B, and D.

by Roni Kraut, Fabiola Diaz Carvallo, Richard Golonka, Sandra M. Campbell, Anoush Rehmani, Oksana Babenko, Mao-Cheng Lee, Pedro Vieira-BaptistaBackground Cytolytic vaginosis (CV) is a little-known, controversial condition that is typically not considered for women presenting with vulvovaginitis symptoms. Objective: The objective of this scoping review was to identify and compile the global evidence on CV. Methods A medical librarian searched Prospero, Wiley Cochrane Library, Ovid Embase, Ovid Medline, EBSCO CINAHL, ProQuest Dissertations and Theses Global, and Scopus, from inception to April 4, 2019 and updated to October 17, 2021. Studies were eligible if they discussed CV. Two independent reviewers conducted study selection and data extraction. Results Sixty-four studies were identified, with 67% of studies (n = 43) published since 2007. Studies were from around the world, including the United States (28%, n = 18), Brazil (11%, n = 7), Portugal (11%, n = 7), and China (11%, n = 7). Fifty percent of studies (n = 32) were reviews; the remainder were observational; and of these, 78% (n = 25) were cross-sectional. The most frequent topics included: diagnosis (19%, n = 12), prevalence (17%, n = 11), and overview of CV (50%, n = 32). Evidence for prevalence in symptomatic women (median prevalence of 5%, interquartile range 3%-8%) was based only on 16% of studies (n = 10) with minimal evidence on prevalence in asymptomatic women and across different geographic regions. Microbiological findings, including abundant lactobacilli and fragmented epithelial cells, were found useful to distinguish between CV and vulvovaginal candidiasis, and Lactobacillus crispatus was noted to dominate the vaginal flora in women with CV. Most studies used subjective criteria to diagnose CV as the condition lacks gold-standard microscopic criteria. The suggested primary treatment (baking soda irrigations) was largely based on expert opinion, and there was minimal evidence on associations between CV and other conditions. Conclusion Knowledge gaps currently exist in all realms of CV research. Additional research is needed to confirm the validity of CV and ensure that women are diagnosed and treated effectively.…

by Emily Cooper, Adam Lound, Christina J. Atchison, Matthew Whitaker, Caroline Eccles, Graham S. Cooke, Paul Elliott, Helen WardBackground Long COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID. Methods People were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis. Results We interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID. Conclusion This pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation shows the value of recruiting from a nationally representative sample of participants who are experiencing persistent symptoms.…

by Yuval Shahar, Osnat MokrynEpidemics and pandemics require an early estimate of the cumulative infection prevalence, sometimes referred to as the infection 'Iceberg,' whose tip are the known cases. Accurate early estimates support better disease monitoring, more accurate estimation of infection fatality rate, and an assessment of the risks from asymptomatic individuals. We find the Pivot group, the population sub-group with the highest probability of being detected and confirmed as positively infected. We differentiate infection susceptibility, assumed to be almost uniform across all population sub-groups at this early stage, from the probability of being confirmed positive. The latter is often related to the likelihood of developing symptoms and complications, which differs between sub-groups (e.g., by age, in the case of the COVID-19 pandemic). A key assumption in our method is the almost-random subgroup infection assumption: The risk of initial infection is either almost uniform across all population sub-groups or not higher in the Pivot sub-group. We then present an algorithm that, using the lift value of the pivot sub-group, finds a lower bound for the cumulative infection prevalence in the population, that is, gives a lower bound on the size of the entire infection 'Iceberg.' We demonstrate our method by applying it to the case of the COVID-19 pandemic. We use UK and Spain serological surveys of COVID-19 in its first year to demonstrate that the data are consistent with our key assumption, at least for the chosen pivot sub-group. Overall, we applied our methods to nine countries or large regions whose data, mainly during the early COVID-19 pandemic phase, were available: Spain, the UK at two different time points, New York State, New York City, Italy, Norway, Sweden, Belgium, and Israel. We established an estimate of the lower bound of the cumulative infection prevalence for each of them. We have also computed the corresponding upper bounds on the infection fatality rates in each country or region. Using our methodology, we have demonstrated that estimating a lower bound for an epidemic’s infection prevalence at its early phase is feasible and that the assumptions underlying that estimate are valid. Our methodology is especially helpful when serological data are not yet available to gain an initial assessment on the prevalence scale, and more so for pandemics with an asymptomatic transmission, as is the case with Covid-19.

by Karikalan Nagarajan, Malaisamy Muniyandi, Senthil Sellappan, Srimathi Karunanidhi, Keerthana Senthilkumar, Bharathidasan Palani, Lavanya Jeyabal, Rajendran KrishnanBackground Disclosure of tuberculosis (TB) status by patients is a critical step in their treatment cascade of care. There is a lack of systematic assessment of TB disclosure patterns and its positive outcomes which happens dynamically over the disease period of individual patients with their family and wider social network relations. Methods This prospective observational study was conducted in Chennai Corporation treatment units during 2019–2021. TB patients were recruited and followed-up from treatment initiation to completion. Information on disease disclosures made to different social members at different time points, and outcomes were collected and compared. Bivariate and multi variate analysis were used to identify the patients and contact characteristics predictive of TB disclosure status. Results A total of 466 TB patients were followed-up, who listed a total of 4039 family, extra familial and social network contacts of them. Maximum disclosures were made with family members (93%) and half of the relatives, occupational contacts and friendship contacts (44–58%) were disclosed within 15 days of treatment initiation. Incremental disclosures made during the 150–180 days of treatment were highest among neighbourhood contacts (12%), and was significantly different between treatment initiation and completion period. Middle aged TB patients (31 years and 46–55 years) were found less likely to disclose (AOR 0.56 and 0.46 respectively; p…

Background: Early antiretroviral therapy (ART) during infancy reduces cognitive impairment due to HIV, but the extent of benefit is unclear.Setting: Children were recruited from hospital and health centers providing HIV care and treatment in Nairobi, Kenya.Methods: Cognitive, behavioral and motor outcomes were assessed in children with HIV (CWHIV) and early-ART (…

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.