Long-term evolution of human seasonal influenza virus A(H3N2) is associated with an increase in polymerase complex activity.

Since the influenza pandemic in 1968, influenza A(H3N2) viruses have become endemic. In this state, H3N2 viruses continuously evolve to overcome immune pressure as a result of prior infection or vaccination, as is evident from the accumulation of mutations in the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). However, phylogenetic studies have also demonstrated ongoing evolution in the influenza A(H3N2) virus RNA polymerase complex genes. The RNA polymerase complex of seasonal influenza A(H3N2) viruses produces mRNA for viral protein synthesis and replicates the negative sense viral RNA genome (vRNA) through a positive sense complementary RNA intermediate (cRNA). Presently, the consequences and selection pressures driving the evolution of the polymerase complex remain largely unknown. Here, we characterize the RNA polymerase complex of seasonal influenza A(H3N2) viruses representative of nearly 50 years of influenza A(H3N2) virus evolution. The H3N2 polymerase complex is a reassortment of human and avian influenza virus genes. We show that since 1968, influenza A(H3N2) viruses have increased the transcriptional activity of the polymerase complex while retaining a close balance between mRNA, vRNA, and cRNA levels. Interestingly, the increased polymerase complex activity did not result in increased replicative ability on differentiated human airway epithelial (HAE) cells. We hypothesize that the evolutionary increase in polymerase complex activity of influenza A(H3N2) viruses may compensate for the reduced HA receptor binding and avidity that is the result of the antigenic evolution of influenza A(H3N2) viruses.

Use of In-Training Examination Scores as a Fellowship Candidate Evaluation Metric: Time for a Change.

ABSTRACT: In the field of obstetrics and gynecology (OB/GYN), the Council on Resident Education in Obstetrics and Gynecology (CREOG) administers an annual in-training examination to all OB/GYN residents as a formative educational tool for assessing medical knowledge and promoting self-improvement. Although the CREOG examination is not designed or intended for knowledge certification, many OB/GYN subspecialty fellowship programs request and use CREOG examination scores as a metric to evaluate fellowship candidates. Among the 57 gynecology-based urogynecology fellowship programs, 30 programs (53%) request CREOG examination scores to be submitted by candidates, as of March 2023. Although the use of CREOG examination scores as an evaluation metric may constitute a minor component within the fellowship match process, this practice fundamentally contradicts the intended purpose of the examination as an educational self-assessment. In addition, it introduces the potential for bias in fellowship recruitment, lacks psychometric validity in predicting specialty board examination failure, and shifts the CREOG examination from its original intention as low-stakes self-assessment into a high-stakes examination akin to a certification examination. For these reasons, we call upon the urogynecology community to prioritize the educational mission of the CREOG examination and reconsider the practice of requesting or using CREOG examination scores in the fellowship match progress.

Seasonal influenza vaccine performance and the potential benefits of mRNA vaccines.

Influenza remains a public health threat, partly due to suboptimal effectiveness of vaccines. One factor impacting vaccine effectiveness is strain mismatch, occurring when vaccines no longer match circulating strains due to antigenic drift or the incorporation of inadvertent (eg, egg-adaptive) mutations during vaccine manufacturing. In this review, we summarize the evidence for antigenic drift of circulating viruses and/or egg-adaptive mutations occurring in vaccine strains during the 2011-2020 influenza seasons. Evidence suggests that antigenic drift led to vaccine mismatch during four seasons and that egg-adaptive mutations caused vaccine mismatch during six seasons. These findings highlight the need for alternative vaccine development platforms. Recently, vaccines based on mRNA technology have demonstrated efficacy against SARS-CoV-2 and respiratory syncytial virus and are under clinical evaluation for seasonal influenza. We discuss the potential for mRNA vaccines to address strain mismatch, as well as new multi-component strategies using the mRNA platform to improve vaccine effectiveness.

Scientific highlights of the 9th ESWI Influenza Conference.

The European Scientific Working Group on Influenza (ESWI) held the 9th ESWI Influenza Conference in Valencia from 17-20 September 2023. Here we provide a summary of twelve key presentations, covering major topics on influenza virus, respiratory syncytial virus (RSV) and SARS coronavirus 2 (SARS-CoV-2) including: infection processes beyond acute respiratory disease, long COVID, vaccines against influenza and RSV, the implications of the potential extinction of influenza B virus Yamagata lineage, and the threats posed by zoonotic highly pathogenic avian influenza viruses.

Impact and cost-effectiveness of SARS-CoV-2 self-testing strategies in schools: a multicountry modelling analysis.

OBJECTIVES: To determine the most epidemiologically effective and cost-effective school-based SARS-CoV-2 antigen-detection rapid diagnostic test (Ag-RDT) self-testing strategies among teachers and students. DESIGN: Mathematical modelling and economic evaluation. SETTING AND PARTICIPANTS: Simulated school and community populations were parameterised to Brazil, Georgia and Zambia, with SARS-CoV-2 self-testing strategies targeted to teachers and students in primary and secondary schools under varying epidemic conditions. INTERVENTIONS: SARS-CoV-2 Ag-RDT self-testing strategies for only teachers or teachers and students-only symptomatically or symptomatically and asymptomatically at 5%, 10%, 40% or 100% of schools at varying frequencies. OUTCOME MEASURES: Outcomes were assessed in terms of total infections and symptomatic days among teachers and students, as well as total infections and deaths within the community under the intervention compared with baseline. The incremental cost-effectiveness ratios (ICERs) were calculated for infections prevented among teachers and students. RESULTS: With respect to both the reduction in infections and total cost, symptomatic testing of all teachers and students appears to be the most cost-effective strategy. Symptomatic testing can prevent up to 69·3%, 64·5% and 75·5% of school infections in Brazil, Georgia and Zambia, respectively, depending on the epidemic conditions, with additional reductions in community infections. ICERs for symptomatic testing range from US$2 to US$19 per additional school infection averted as compared with symptomatic testing of teachers alone. CONCLUSIONS: Symptomatic testing of teachers and students has the potential to cost-effectively reduce a substantial number of school and community infections.

Host and viral determinants of airborne transmission of SARS-CoV-2 in the Syrian hamster.

It remains poorly understood how SARS-CoV-2 infection influences the physiological host factors important for aerosol transmission. We assessed breathing pattern, exhaled droplets, and infectious virus after infection with Alpha and Delta variants of concern (VOC) in the Syrian hamster. Both VOCs displayed a confined window of detectable airborne virus (24-48 hr), shorter than compared to oropharyngeal swabs. The loss of airborne shedding was linked to airway constriction resulting in a decrease of fine aerosols (1-10 µm) produced, which are suspected to be the major driver of airborne transmission. Male sex was associated with increased viral replication and virus shedding in the air. Next, we compared the transmission efficiency of both variants and found no significant differences. Transmission efficiency varied mostly among donors, 0-100% (including a superspreading event), and aerosol transmission over multiple chain links was representative of natural heterogeneity of exposure dose and downstream viral kinetics. Co-infection with VOCs only occurred when both viruses were shed by the same donor during an increased exposure timeframe (24-48 hr). This highlights that assessment of host and virus factors resulting in a differential exhaled particle profile is critical for understanding airborne transmission.

Determinants of epidemic size and the impacts of lulls in seasonal influenza virus circulation.

During the COVID-19 pandemic, levels of seasonal influenza virus circulation were unprecedentedly low, leading to concerns that a lack of exposure to influenza viruses, combined with waning antibody titres, could result in larger and/or more severe post-pandemic seasonal influenza epidemics. However, in most countries the first post-pandemic influenza season was not unusually large and/or severe. Here, based on an analysis of historical influenza virus epidemic patterns from 2002 to 2019, we show that historic lulls in influenza virus circulation had relatively minor impacts on subsequent epidemic size and that epidemic size was more substantially impacted by season-specific effects unrelated to the magnitude of circulation in prior seasons. From measurements of antibody levels from serum samples collected each year from 2017 to 2021, we show that the rate of waning of antibody titres against influenza virus during the pandemic was smaller than assumed in predictive models. Taken together, these results partially explain why the re-emergence of seasonal influenza virus epidemics was less dramatic than anticipated and suggest that influenza virus epidemic dynamics are not currently amenable to multi-season prediction.

"If You Need a Psychiatrist, It's BAD": Stigma Associated with Seeking Mental Health Care Among Obstetric Providers in Ghana.

Purpose: Globally, the COVID-19 pandemic has brought attention to the impact of negative patient outcomes on healthcare providers. In Ghana, obstetric providers regularly face maternal and neonatal mortality, yet limited research has focused on provision of mental health support for these providers. This study sought to understand how obstetric providers viewed seeking mental health support after poor clinical outcomes, with a focus on the role of mental health stigma. Patients and Methods: Participants were 52 obstetric providers (20 obstetrician/gynecologists and 32 midwives) at two tertiary care hospitals in Ghana. Five focus groups, led by a trained facilitator and lasting approximately two hours, were conducted to explore provider experiences and perceptions of support following poor maternal and neonatal outcomes. Discussions were audiotaped and transcribed verbatim, then analyzed qualitatively using grounded theory methodology. Results: Most participants (84.3%, N=43) were finished with training, and 46.2% (N=24) had been in practice more than 10 years. Emerging themes included pervasive stigma associated with seeking mental health care after experiencing poor clinical outcomes, which was derived from two overlapping dimensions. First, societal-level stigma resulted from a cultural norm to keep emotions hidden, and the perception that psychiatry is equated with severe mental illness. Second, provider-level stigma resulted from the belief that healthcare workers should not have mental health problems, a perception that mental health care is acceptable for patients but not for providers, and a fear about lack of confidentiality. Despite many providers acknowledging negative mental health impacts following poor clinical outcomes, these additive layers of stigma limited their willingness to engage in formal mental health care. Conclusion: This study demonstrates that stigma creates significant barriers to acceptance of mental health support among obstetric providers. Interventions to support providers will need to respect provider concerns without reinforcing the stigma associated with seeking mental health care.

Estimating the potential impact and diagnostic requirements for SARS-CoV-2 test-and-treat programs.

Oral antivirals have the potential to reduce the public health burden of COVID-19. However, now that we have exited the emergency-phase of the COVID-19 pandemic, declining SARS-CoV-2 clinical testing rates (average testing rates = [Formula: see text]10 tests/100,000 people/day in low-and-middle income countries; <100 tests/100,000 people/day in high-income countries; September 2023) make the development of effective test-and-treat programs challenging. We used an agent-based model to investigate how testing rates and strategies affect the use and effectiveness of oral antiviral test-to-treat programs in four country archetypes of different income levels and demographies. We find that in the post-emergency-phase of the pandemic, in countries where low testing rates are driven by limited testing capacity, significant population-level impact of test-and-treat programs can only be achieved by both increasing testing rates and prioritizing individuals with greater risk of severe disease. However, for all countries, significant reductions in severe cases with antivirals are only possible if testing rates were substantially increased with high willingness of people to seek testing. Comparing the potential population-level reductions in severe disease outcomes of test-to-treat programs and vaccination shows that test-and-treat strategies are likely substantially more resource intensive requiring very high levels of testing (≫100 tests/100,000 people/day) and antiviral use suggesting that vaccination should be a higher priority.

Co-evolution of immunity and seasonal influenza viruses.

Seasonal influenza viruses cause recurring global epidemics by continually evolving to escape host immunity. The viral constraints and host immune responses that limit and drive the evolution of these viruses are increasingly well understood. However, it remains unclear how most of these advances improve the capacity to reduce the impact of seasonal influenza viruses on human health. In this Review, we synthesize recent progress made in understanding the interplay between the evolution of immunity induced by previous infections or vaccination and the evolution of seasonal influenza viruses driven by the heterogeneous accumulation of antibody-mediated immunity in humans. We discuss the functional constraints that limit the evolution of the viruses, the within-host evolutionary processes that drive the emergence of new virus variants, as well as current and prospective options for influenza virus control, including the viral and immunological barriers that must be overcome to improve the effectiveness of vaccines and antiviral drugs.

A modelling framework for translating discrete choice experiment results into cost-effectiveness estimates: an application to designing tailored and scalable HIV and contraceptive services for adolescents in Gauteng, South Africa.

INTRODUCTION: South African youth and adolescents face a high burden of (Sexually Transmitted Infections) STIs, HIV and unintended pregnancies, but uptake of services remains low. To address this, tailored and scalable interventions are urgently needed. We developed a framework to fill the gap and translate the impact of facility-level attributes into a cost-effectiveness analysis for increasing HIV/contraceptive service uptake in adolescents using a discrete choice experiment (DCE). METHODS: We used a DCE (n = 805) conducted in Gauteng, South Africa, which found that staff attitude, confidentiality, Wi-Fi, subsidized food, afternoon hours and youth-only services were preferred attributes of health services. Based on this, we simulated the uptake of services adapted for these preferences. We divided preferences into modifiable attributes that could readily be adapted (e.g. Wi-Fi), and challenging to modify (more nuanced attributes that are more challenging to cost and evaluate): staff attitude and estimated the incremental change in the uptake of services using adapted services. Costs for modifiable preferences were estimated using data from two clinics in South Africa (2019 US$). We determined the incremental cost-effectiveness ratio (ICER) for additional adolescents using services of 15 intervention combinations, and report the results of interventions on the cost-effectiveness frontier. RESULTS: Greatest projected impact on uptake was from friendly and confidential services, both of which were considered challenging to modify (18.5% 95% CI: 13.0%-24.0%; 8.4% 95% CI: 3.0%-14.0%, respectively). Modifiable factors on their own resulted in only small increases in expected uptake. (Food: 2.3% 95% CI: 4.0%-9.00%; Wi-Fi: 3.0% 95% CI: -4.0% to 10.0%; Youth-only services: 0.3% 95% CI: -6.0% to 7.0%; Afternoon services: 0.8% 95% CI: -6.0% to 7.0%). The order of interventions on the cost-effectiveness frontier are Wi-Fi and youth-only services (ICER US$7.01-US$9.78 per additional adolescent utilizing HIV and contraceptive services), Wi-Fi, youth-only services and food (ICER US$9.32-US$10.45), followed by Wi-Fi, youth-only services and extended afternoon hours (ICER US$14.46-US$43.63). CONCLUSIONS: Combining DCE results and costing analyses within a modelling framework provides an innovative way to inform decisions on effective resource utilization. Modifiable preferences, such as Wi-Fi provision, youth-only services and subsidized food, have the potential to cost-effectively increase the proportion of adolescents accessing HIV and contraceptive services.

Mutual information networks reveal evolutionary relationships within the influenza A virus polymerase.

The influenza A virus (IAV) RNA polymerase is an essential driver of IAV evolution. Mutations that the polymerase introduces into viral genome segments during replication are the ultimate source of genetic variation, including within the three subunits of the IAV polymerase (polymerase basic protein 2, polymerase basic protein 1, and polymerase acidic protein). Evolutionary analysis of the IAV polymerase is complicated, because changes in mutation rate, replication speed, and drug resistance involve epistatic interactions among its subunits. In order to study the evolution of the human seasonal H3N2 polymerase since the 1968 pandemic, we identified pairwise evolutionary relationships among ∼7000 H3N2 polymerase sequences using mutual information (MI), which measures the information gained about the identity of one residue when a second residue is known. To account for uneven sampling of viral sequences over time, we developed a weighted MI (wMI) metric and demonstrate that wMI outperforms raw MI through simulations using a well-sampled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dataset. We then constructed wMI networks of the H3N2 polymerase to extend the inherently pairwise wMI statistic to encompass relationships among larger groups of residues. We included hemagglutinin (HA) in the wMI network to distinguish between functional wMI relationships within the polymerase and those potentially due to hitch-hiking on antigenic changes in HA. The wMI networks reveal coevolutionary relationships among residues with roles in replication and encapsidation. Inclusion of HA highlighted polymerase-only subgraphs containing residues with roles in the enzymatic functions of the polymerase and host adaptability. This work provides insight into the factors that drive and constrain the rapid evolution of influenza viruses.

Complications After Orchiectomy and Vaginoplasty for Gender Affirmation: An Analysis of Concurrent Versus Separate Procedures Using a National Database.

IMPORTANCE: Gender-affirming orchiectomy may be performed in isolation, as a bridge to vaginoplasty, or concurrently with vaginoplasty for transgender and nonbinary persons, although there is a paucity of data on immediate postoperative outcomes on the various procedural approaches. OBJECTIVE: The aim of the study is to compare 30-day surgical outcomes after gender-affirming orchiectomy and vaginoplasty as separate and isolated procedures. STUDY DESIGN: This was a retrospective cohort study of patients in the American College of Surgeons National Surgical Quality Improvement Program database to compare surgical outcomes of orchiectomy alone and vaginoplasty alone to concurrent orchiectomy with vaginoplasty using bivariate and adjusted multivariable regression statistics. RESULTS: Concurrent orchiectomy and vaginoplasty were associated with greater 30-day surgical complications compared with orchiectomy alone (15.4% vs 2.9%, P < 0.01) and similar odds of 30-day surgical complications compared with vaginoplasty alone (15.4% vs 11.1%, P = 0.15). On multivariable logistic regression analysis, compared with orchiectomy alone, concurrent orchiectomy and vaginoplasty were associated with higher increased odds of 30-day surgical complications (adjusted odds ratio, 6.48; 95% confidence interval, 2.83-14.86) as well as vaginoplasty alone (adjusted odds ratio 4.30; 95% confidence interval, 1.85-10.00). CONCLUSIONS: This study highlights the perioperative outcomes for isolated versus concurrent gender-affirming orchiectomy and vaginoplasty, demonstrating lower morbidity for orchiectomy alone and similar morbidity for vaginoplasty alone when compared with concurrent procedures. These data will aid health care providers in preoperative counseling and surgical planning for gender-affirming genital surgery, particularly for patients considering concurrent versus staged orchiectomy and vaginoplasty.

Mutual information networks reveal evolutionary relationships within the influenza A virus polymerase.

The influenza A (IAV) RNA polymerase is an essential driver of IAV evolution. Mutations that the polymerase introduces into viral genome segments during replication are the ultimate source of genetic variation, including within the three subunits of the IAV polymerase (PB2, PB1, and PA). Evolutionary analysis of the IAV polymerase is complicated, because changes in mutation rate, replication speed, and drug resistance involve epistatic interactions among its subunits. In order to study the evolution of the human seasonal H3N2 polymerase since the 1968 pandemic, we identified pairwise evolutionary relationships among ∻7000 H3N2 polymerase sequences using mutual information (MI), which measures the information gained about the identity of one residue when a second residue is known. To account for uneven sampling of viral sequences over time, we developed a weighted MI metric (wMI) and demonstrate that wMI outperforms raw MI through simulations using a well-sampled SARS-CoV-2 dataset. We then constructed wMI networks of the H3N2 polymerase to extend the inherently pairwise wMI statistic to encompass relationships among larger groups of residues. We included HA in the wMI network to distinguish between functional wMI relationships within the polymerase and those potentially due to hitchhiking on antigenic changes in HA. The wMI networks reveal coevolutionary relationships among residues with roles in replication and encapsidation. Inclusion of HA highlighted polymerase-only subgraphs containing residues with roles in the enzymatic functions of the polymerase and host adaptability. This work provides insight into the factors that drive and constrain the rapid evolution of influenza viruses.

SARS-CoV-2 diagnostic testing rates determine the sensitivity of genomic surveillance programs.

The first step in SARS-CoV-2 genomic surveillance is testing to identify people who are infected. However, global testing rates are falling as we emerge from the acute health emergency and remain low in many low- and middle-income countries (mean = 27 tests per 100,000 people per day). We simulated COVID-19 epidemics in a prototypical low- and middle-income country to investigate how testing rates, sampling strategies and sequencing proportions jointly impact surveillance outcomes, and showed that low testing rates and spatiotemporal biases delay time to detection of new variants by weeks to months and can lead to unreliable estimates of variant prevalence, even when the proportion of samples sequenced is increased. Accordingly, investments in wider access to diagnostics to support testing rates of approximately 100 tests per 100,000 people per day could enable more timely detection of new variants and reliable estimates of variant prevalence. The performance of global SARS-CoV-2 genomic surveillance programs is fundamentally limited by access to diagnostic testing.

Outcomes After Lysis of Adhesions and Dilator Placement for Treatment of Vulvovaginal Agglutination Due to Lichen Planus.

OBJECTIVE: The aim of the study is to determine intraoperative and postoperative surgical outcomes for the treatment of vulvovaginal agglutination secondary to lichen planus (LP) following a standard protocol using intraoperative dilator placement and postoperative intravaginal steroid use. MATERIALS AND METHODS: This was a retrospective chart review of patients who underwent surgical management of vulvovaginal agglutination due to LP following a protocol that included surgical lysis of vulvovaginal adhesions, intraoperative dilator placement and removal 48 hours later, and high-potency intravaginal corticosteroid and regular dilator use thereafter. Demographic and clinical data were abstracted from the medical record and analyzed using descriptive statistics. RESULTS: Thirty-four patients, with mean age 51.2 ± 11 years and body mass index 32.8 ± 8.5 kg/m 2 , underwent lysis of vulvovaginal adhesions between 1999 and 2021 with 8 different surgeons at a single institution. The mean preoperative, immediate postoperative, and 6-week postoperative vaginal lengths were 2.8 ± 1.8 cm ( n = 18), 8.0 ± 1.9 cm ( n = 21), and 7.9 ± 2.2 cm ( n = 16), respectively. The mean estimated blood loss intraoperatively was 16 ± 15 mL. No patients had a documented surgical site infection or reoperation within 30 days after surgery. Of patients who had it documented ( n = 26), 70% (18/26) reported postoperative sexual activity. Where documented, 100% (18/18) reported preoperative dyspareunia, while 17% (3/18) did postoperatively. Six percent (2/34) had recurrent severe agglutination and 3% (1/34) underwent reoperation. CONCLUSIONS: Lysis of vulvovaginal adhesions, intraoperative dilator placement, and postoperative intravaginal corticosteroids with dilator use is a safe and effective treatment option to restore vaginal length for those with vulvovaginal LP.

Contribution of Reinfection to Annual Rate of Tuberculosis Infection (ARI) and Incidence of Tuberculosis Disease.

BACKGROUND: Modeling studies have concluded that 60-80% of tuberculosis (TB) infections result from reinfection of previously infected persons. The annual rate of infection (ARI), a standard measure of the risk of TB infection in a community, may not accurately reflect the true risk of infection among previously infected persons. We constructed a model of infection and reinfection with Mycobacterium tuberculosis to explore the predictive accuracy of ARI and its effect on disease incidence. METHODS: We created a deterministic simulation of the progression from TB infection to disease and simulated the prevalence of TB infection at the beginning and end of a theoretical year of infection. We considered 10 disease prevalence scenarios ranging from 100/100 000 to 1000/100 000 in simulations where TB exposure probability was homogeneous across the whole simulated population or heterogeneously stratified into high-risk and low-risk groups. ARI values, rates of progression from infection to disease, and the effect of multiple reinfections were obtained from published studies. RESULTS: With homogeneous exposure risk, observed ARI values produced expected numbers of infections. However, when heterogeneous risk was introduced, observed ARI was seen to underestimate true ARI by 25-58%. Of the cases of TB disease that occurred, 36% were among previously infected persons when prevalence was 100/100 000, increasing to 79% of cases when prevalence was 1000/100 000. CONCLUSIONS: Measured ARI underestimates true ARI as a result of heterogeneous population mixing. The true force of infection in a community may be greater than previously appreciated. Hyperendemic communities likely contribute disproportionally to the global TB disease burden.

Gender Differences of Endowed Professorship in Obstetrics and Gynecology Departments at Top Academic Institutions.

Background: Gender equity is a critical issue in academic medicine. Whether there is equitable access to the prestige and resources of endowed professorships merits evaluation. We investigated this question in obstetrics and gynecology, a field that focuses on the health of women and in which women are much better represented than other specialties of medicine. Materials and Methods: We compiled a list of the top 25 United States departments of obstetrics and gynecology and contacted department chairs (and used department websites) to obtain lists of faculty and their positions. Scopus, department websites, and National Institutes of Health (NIH) RePORTER were used to collect h-Index, number of publications and citations, graduation year, degrees, gender, and NIH-funding. We conducted a bivariate comparison of endowed professorship attainment by gender using a chi-square test and created a multiple variable regression model. Results: Of the 680 obstetrics and gynecology faculty across 23 departments that had endowed chairs, 64 out of 400 women (16%) and 66 out of 280 men (24%) held endowed chairs (p = 0.01). The multivariable model suggested no independent gender difference in attainment of an endowed chair after adjusting for covariates. Conclusion: To our knowledge, this study is the first to examine gender as a variable in endowed chair allocation in top obstetrics and gynecology academic departments. Our findings suggest a significant gender difference in the allocation of endowed chairs. That difference is driven by gender differences in academic rank, graduation year, publications, and funding. To promote the intraprofessional equity necessary to optimally advance women's health, further research and intervention are necessary.

Strategies for Using Antigen Rapid Diagnostic Tests to Reduce Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in Low- and Middle-Income Countries: A Mathematical Modelling Study Applied to Zambia.

BACKGROUND: Increasing the availability of antigen rapid diagnostic tests (Ag-RDTs) in low- and middle-income countries (LMICs) is key to alleviating global SARS-CoV-2 testing inequity (median testing rate in December 2021-March 2022 when the Omicron variant was spreading in multiple countries: high-income countries = 600 tests/100 000 people/day; LMICs = 14 tests/100 000 people/day). However, target testing levels and effectiveness of asymptomatic community screening to impact SARS-CoV-2 transmission in LMICs are unclear. METHODS: We used Propelling Action for Testing and Treating (PATAT), an LMIC-focused agent-based model to simulate coronavirus disease 2019 (COVID-19) epidemics, varying the amount of Ag-RDTs available for symptomatic testing at healthcare facilities and asymptomatic community testing in different social settings. We assumed that testing was a function of access to healthcare facilities and availability of Ag-RDTs. We explicitly modelled symptomatic testing demand from individuals without SARS-CoV-2 and measured impact based on the number of infections averted due to test-and-isolate. RESULTS: Testing symptomatic individuals yields greater benefits than any asymptomatic community testing strategy until most symptomatic individuals who sought testing have been tested. Meeting symptomatic testing demand likely requires at least 200-400 tests/100 000 people/day, on average, as symptomatic testing demand is highly influenced by individuals without SARS-CoV-2. After symptomatic testing demand is satisfied, excess tests to proactively screen for asymptomatic infections among household members yield the largest additional infections averted. CONCLUSIONS: Testing strategies aimed at reducing transmission should prioritize symptomatic testing and incentivizing test-positive individuals to adhere to isolation to maximize effectiveness.