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Lassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa and causes 5000 fatalities every year. The true prevalence and incidence rates of LF are unknown as infections are often asymptomatic, clinical presentations are varied, and surveillance systems are not robust. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries. The core protocol described here harmonises key study components, such as eligibility criteria, case definitions, outcome measures, and laboratory tests, which will maximise the comparability of data for between-country analyses. We are conducting a prospective cohort study in Benin, Guinea, Liberia, Nigeria (three sites), and Sierra Leone from 2020 to 2023, with 24 months of follow-up. Each site will assess the incidence of LASV infection, LF disease, or both. When both incidences are assessed the LASV cohort (nmin = 1000 per site) will be drawn from the LF cohort (nmin = 5000 per site). During recruitment participants will complete questionnaires on household composition, socioeconomic status, demographic characteristics, and LF history, and blood samples will be collected to determine IgG LASV serostatus. LF disease cohort participants will be contacted biweekly to identify acute febrile cases, from whom blood samples will be drawn to test for active LASV infection using RT-PCR. Symptom and treatment data will be abstracted from medical records of LF cases. LF survivors will be followed up after four months to assess sequelae, specifically sensorineural hearing loss. LASV infection cohort participants will be asked for a blood sample every six months to assess LASV serostatus (IgG and IgM). Data on LASV infection and LF disease incidence in West Africa from this research programme will determine the feasibility of future Phase IIb or III clinical trials for LF vaccine candidates.

Sexual transmission of Ebola virus (EBOV) is well established and has been implicated in multiple resurgences during the West African Ebola epidemic. Given the persistence of viral RNA in semen, guidelines from the World Health Organization (WHO) recommend abstinence or condom use for at least 1 year or until two semen PCR tests are negative. To better understand the impact of semen testing on sexual behavior, male EVD survivors were surveyed regarding their sexual behavior before and after semen testing. Of the 171 men who enrolled, 148 reported being sexually active following discharge from an ETU with 59% reporting episodes of condomless sex. At least one semen sample for testing was provided by 149 men and 13 of these men had EBOV RNA detected in their semen. When comparing sexual behaviors before and after semen testing, a positive semen test result had limited impact on behavior. Of those with seminal EBOV RNA detected, 61% reported no change in behavior pre- and post-semen testing with 46% engaging in condomless sex before and after testing and only 1 adopted safer sex behaviors following receipt of a positive result. Similarly, among men with undetectable EBOV in their semen, 66% reported no change in sexual behaviors with semen testing, with 55% forgoing condoms during sex. In only 11% was a negative semen result followed by abandoning condoms. There were no known sexual transmission events of Ebola virus in this cohort despite viral presence in semen during periods of condomless sex. This highlights the need to better understand the infectious potential of viral RNA persistence and determine what constitutes effective counseling for survivors and their partners.

Lassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa and causes 5000 fatalities every year. The true prevalence and incidence rates of LF are unknown as infections are often asymptomatic, clinical presentations are varied, and surveillance systems are not robust. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries. The core protocol described here harmonises key study components, such as eligibility criteria, case definitions, outcome measures, and laboratory tests, which will maximise the comparability of data for between-country analyses. We are conducting a prospective cohort study in Benin, Guinea, Liberia, Nigeria (three sites), and Sierra Leone from 2020 to 2023, with 24 months of follow-up. Each site will assess the incidence of LASV infection, LF disease, or both. When both incidences are assessed the LASV cohort (n.sub.min = 1000 per site) will be drawn from the LF cohort (n.sub.min = 5000 per site). During recruitment participants will complete questionnaires on household composition, socioeconomic status, demographic characteristics, and LF history, and blood samples will be collected to determine IgG LASV serostatus. LF disease cohort participants will be contacted biweekly to identify acute febrile cases, from whom blood samples will be drawn to test for active LASV infection using RT-PCR. Symptom and treatment data will be abstracted from medical records of LF cases. LF survivors will be followed up after four months to assess sequelae, specifically sensorineural hearing loss. LASV infection cohort participants will be asked for a blood sample every six months to assess LASV serostatus (IgG and IgM). Data on LASV infection and LF disease incidence in West Africa from this research programme will determine the feasibility of future Phase IIb or III clinical trials for LF vaccine candidates.

[This corrects the article DOI: 10.1371/journal.pone.0283643.].

Background Lassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa and causes 5000 fatalities every year. The true prevalence and incidence rates of LF are unknown as infections are often asymptomatic, clinical presentations are varied, and surveillance systems are not robust. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries. The core protocol described here harmonises key study components, such as eligibility criteria, case definitions, outcome measures, and laboratory tests, which will maximise the comparability of data for between-country analyses. Method We are conducting a prospective cohort study in Benin, Guinea, Liberia, Nigeria (three sites), and Sierra Leone from 2020 to 2023, with 24 months of follow-up. Each site will assess the incidence of LASV infection, LF disease, or both. When both incidences are assessed the LASV cohort (nmin = 1000 per site) will be drawn from the LF cohort (nmin = 5000 per site). During recruitment participants will complete questionnaires on household composition, socioeconomic status, demographic characteristics, and LF history, and blood samples will be collected to determine IgG LASV serostatus. LF disease cohort participants will be contacted biweekly to identify acute febrile cases, from whom blood samples will be drawn to test for active LASV infection using RT-PCR. Symptom and treatment data will be abstracted from medical records of LF cases. LF survivors will be followed up after four months to assess sequelae, specifically sensorineural hearing loss. LASV infection cohort participants will be asked for a blood sample every six months to assess LASV serostatus (IgG and IgM). Discussion Data on LASV infection and LF disease incidence in West Africa from this research programme will determine the feasibility of future Phase IIb or III clinical trials for LF vaccine candidates.

There are few data on the prevalence of cervical high-risk human papillomavirus (hrHPV), the necessary cause of cervical cancer, and its determinants among Rwandan women living with human immunodeficiency virus (HIV). We therefore aimed to assess the determinants of hrHPV positivity among Rwandan women living with HIV (WLWH). We conducted a cervical cancer screening study of ~5,000 WLWH aged 30-54 years and living in Kigali, Rwanda, but originally from all provinces in the country, from 2016-2018. Women were tested for hrHPV by the Xpert assay (Cepheid, Sunnyvale, CA, USA). A nurse-administered questionnaire collected data on demographics and HPV/cervical cancer risk factors. Women without evidence of cervical precancer and cancer were included in the analysis. Women included in this analysis (N = 4,880) had a mean age of 40 years, > 98% were on antiretroviral therapy, and 61% had a CD4 count of ≥500 cells/µL. High-risk HPV prevalence was 25.5% [95% confidence interval (CI)=24.3%-26.8%] and the prevalence decreased with older ages and higher CD4 counts (ptrend<0.001 for both). High-risk HPV prevalence was higher for those who reported their first sex before 16 years, had their first child before 18 years, had more sexual partners over their lifetime and in the last six months, and those with lower CD4 cell count (ptrend<0.001 for all). A CD4 count of <200 (vs. > 500) per µL was most strongly associated with being hrHPV positive (adjusted odds ratio = 2.7, 95%CI = 2.1-3.6). Our findings highlight the role of CD4 counts, as a measure of HIV control and immunity, in controlling hrHPV infection, which could potentially impact cervical cancer control among this high-risk population. Raising awareness on various associated factors coupled with integrating HPV and cervical cancer awareness in HIV care could help control this double burden of disease.

Background Electronic portal imaging devices (EPIDs) enhance linear accelerator (linac) quality assurance (QA) efficiency but are not universally used beyond patient‐specific IMRT QA. A multi‐institutional Consortium seeks to standardize linac QA utilizing an EPID‐based test suite. Purpose This study evaluates the sensitivity of a test suite to intentional linac and plan errors and the concordance with linac fluctuations over time. Methods Baseline and error‐introduced tests were performed on a Varian TrueBeam and Clinac. Evaluated parameters included enhanced dynamic wedge factors (EDW) (6MV), central axis dose (6MV, 6MV FFF, 16MV), focal spot alignment and beam symmetry (6MV, 16MV), dose rate‐gantry speed and multi‐leaf collimator (MLC) leaf speed (6MV). Errors included varying EDW angles (10°–60°), output changes, beam steering for focal spot and symmetry inaccuracies, and meterset adjustments of control points for dose rate‐gantry speed and MLC leaf speed tests. Measurements were performed with an EPID, analyzed via test suite software, and compared to an ion chamber (IC) or array. Concordance analysis was performed on a single linac over 5 months to assess the test suite's ability to quantify deviations during routine operations. Measurement reproducibility was assessed. Results Results were reported as differences between EPID and an IC or array. For each EDW, wedge factor differences were <0.5% (TrueBeam) and <1.5% (Clinac). Central axis dose variations stayed within ±0.8%. For focal spot, EPID underestimated the radial direction and overestimated the transverse direction. Symmetry measurements showed strong linearity (r > 0.99), though EPID measurements underestimated changes in symmetry relative to baseline. Maximum differences for dose rate‐gantry speed and MLC leaf speed were <0.4%. In the concordance study, output differences averaged 0.3% ± 0.3% (6MV), 0.5% ± 0.3% (6MV FFF), and 0.3% ± 0.2% (16MV). Systematic differences in symmetry were observed between EPID and a 2D‐array with standard deviations <0.2%. Conclusions Comparisons with traditional detectors showed the EPID test suite can detect errors and supports commissioning and clinical integration.

Cdc14 protein phosphatases play an important role in plant infection by several fungal pathogens. This and other properties of Cdc14 enzymes make them an intriguing target for development of new antifungal crop treatments. Active site architecture and substrate specificity of Cdc14 from the model fungus Saccharomyces cerevisiae (ScCdc14) are well-defined and unique among characterized phosphatases. Cdc14 appears absent from some model plants. However, the extent of conservation of Cdc14 sequence, structure, and specificity in fungal plant pathogens is unknown. We addressed this by performing a comprehensive phylogenetic analysis of the Cdc14 family and comparing the conservation of active site structure and specificity among a sampling of plant pathogen Cdc14 homologs. We show that Cdc14 was lost in the common ancestor of angiosperm plants but is ubiquitous in ascomycete and basidiomycete fungi. The unique substrate specificity of ScCdc14 was invariant in homologs from eight diverse species of dikarya, suggesting it is conserved across the lineage. A synthetic substrate mimetic inhibited diverse fungal Cdc14 homologs with similar low µM K i values, but had little effect on related phosphatases. Our results justify future exploration of Cdc14 as a broad spectrum antifungal target for plant protection.