Pre-exposure prophylaxis (PrEP) with a weekly oral regimen of antiretroviral drugs could be a suitable preventative option for individuals who struggle with daily PrEP or prefer not to use long-acting injectables. We assessed in macaques the efficacy of weekly oral tenofovir alafenamide (TAF) at doses of 13.7 or 27.4 mg/kg. Macaques received weekly oral TAF for six weeks and were exposed twice-weekly to SHIV vaginally or rectally on day 3 and 6 after each dose. Median TFV-DP levels in PBMCs following the 13.7 mg/kg dose were 3110 and 1137 fmols/10(6) cells on day 3 and 6, respectively. With the 27.4 mg/kg dose, TFV-DP levels were increased (~2-fold) on day 3 and 6 (6095 and 3290 fmols/10(6) cells, respectively). Both TAF doses (13.7 and 27.4 mg/kg) conferred high efficacy (94.1% and 93.9%, respectively) against vaginal SHIV infection. Efficacy of the 27.4 mg/kg dose against rectal SHIV infection was 80.7%. We estimate that macaque doses of 13.7 and 27.4 mg/kg are equivalent to approximately 230 and 450 mg of TAF in humans, respectively. Our findings demonstrate the effectiveness of a weekly oral PrEP regimen and suggest that a clinically achievable oral TAF dose could be a promising option for non-daily PrEP.

Vaginal inserts that can be used on demand before or after sex may be a desirable HIV prevention option for women. We recently showed that inserts containing tenofovir alafenamide fumarate (TAF/20mg) and elvitegravir (EVG/16mg) were highly protective against repeated SHIV vaginal exposures when administered to macaques 4h before or after virus exposure (93% and 100%, respectively). Here, we show in the same macaque model that insert application 8h or 24h after exposure maintains high efficacy (94.4% and 77.2%, respectively). These data extend the protective window by TAF/EVG inserts and inform their clinical development for on-demand prophylaxis in women.

A universal screening research study was conducted in six hospitals to identify the clinical sensitivity of polymerase chain reaction (PCR) testing on newborn dried blood spots (DBSs) versus saliva specimens for the diagnosis of congenital cytomegalovirus (cCMV). CMV DNA positive results from DBSs or saliva were confirmed with urine testing. Findings of several false-positive (FP) saliva PCR results prompted an examination of a possible association with donor milk. Documentation of the frequency of positive saliva results, including both true-positive (TP) and FP status from clinical confirmation, occurred. The frequency of donor milk use was compared for TP and FP cases. Of 22,079 participants tested between 2016 and 2022, 96 had positive saliva results, 15 were determined to be FP, 79 TP, and 2 were excluded for incomplete clinical evaluation. Newborn donor milk use was identified for 18 (19.14%) of all the positive saliva screens. Among the 15 FPs, 11 (73.33%) consumed donor milk compared to 7 of the 79 TPs (8.8%) (OR 28.29, 95% CI 7.10-112.73, p < 0.001). While milk bank Holder pasteurization inactivates CMV infectivity, CMV DNA may still be detectable. Due to this possible association, screening programs that undertake testing saliva for CMV DNA may benefit from documenting donor milk use as a potential increased risk for FP results.

Climate change, historical practices of fire suppression, and an increase in the growth of the wildland-urban interface are driving forces behind the increased occurrence of large, catastrophic fires in the U.S. (1, 2). While fire itself can lead to extensive damage and detrimental ecological effects, the smoke emitted has substantial adverse impacts on public health. Wildfire smoke consists of a complex mixture, including fine particles (PM2.5; particles with aerodynamic diameter generally ≤ 2.5 μm), which has been shown to impact large geographic domains and contribute to thousands of estimated deaths and illnesses annually (2, 3). As a result, public health agencies at the local, state, and national levels have developed strategies to reduce exposure to smoke and to address wide-ranging health concerns associated with such exposures. These strategies help prepare and educate individuals and communities before, during, and after smoke episodes; and are instituted by well-documented programs (e.g., smoke-ready programs, the Interagency Wildland Fire Air Quality Response Program (IWFAQRP) (https://www.wildlandfiresmoke.net/) with the overarching goal of raising awareness on a suite of public health approaches and preventative measures (4).

PURPOSE: Providing inclusive and comprehensive gender-affirming care is critical to reducing health disparities (gaps in care) experienced by sexual and gender minorities (SGM). Currently, little is known about how medical students and residents are being trained to address the health needs of SGM persons or of the most effective methods. METHODS: We conducted a systematic review of the research literature from 2000 to 2020 on the effectiveness of teaching medical students and residents on knowledge, attitudes, and skills in addressing the health of SGM persons and the strength of the research sample, design, and methods used. RESULTS: We identified a total of 36 articles that assessed the impact of medical student and resident education on knowledge, comfort, attitudes, confidence, and skills in working with SGM patients. All studies utilized quasi-experimental designs, and found efficacious results. No study examined the impact of training on patient outcomes. CONCLUSION: Future studies will need to be powered and designed to assess the impact of training on patient outcomes.

In 2023, three autochthonous DENV-3 cases were detected in Roraima and one imported case in Parana, fifteen years after the last DENV-3 outbreak in Brazil. Phylogenetic analyses confirmed all belonging to a new Asian lineage recently introduced in the Americas, raising concerns about future large dengue outbreaks in this region. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.

Background: During the 2022 multinational outbreak of monkeypox virus (MPXV) clade IIb, the antiviral drug tecovirimat (TPOXX) was deployed in the US on a large scale for the first time ever. The MPXV F13L gene homolog encodes the target of tecovirimat, and single amino acid changes in the F13 protein are known to cause resistance to tecovirimat in orthopoxviruses (OPXV). Method(s): Whole genome metagenomic sequencing and amplicon-based sequencing targeting the F13L gene was used to identify nine mutations previously reported to cause resistance in other OPXV along with ten novel mutations that have been identified from the 2022 mpox outbreak. A cytopathic effect assay, previously established at CDC as part of WHO smallpox research, was adapted to MPXV for tecovirimat phenotype testing of virus isolated from mpox patients. Result(s): As of March 2023, in total, 70 isolates from 40 patients were tested, and 50 of these isolates from 26 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of TPOXX treatment; while isolates with F13 mutations identified by routine surveillance of patients not treated with TPOXX have remained sensitive. Conclusion(s): These data indicate that tecovirimat resistance is developing in immunocompromised patients treated with TPOXX and that for isolates that we have analyzed, the frequency of resistant viruses remain relatively low (< 1%) compared to the total number of patients treated with TPOXX. These findings inform our understanding of when tecovirimat resistance is likely to occur and highlight the need for additional OPXV therapeutics. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Introduction: Population-level data on durable HIV viral load suppression (VLS) following implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viremia among persons living with HIV in 40 Ugandan communities during UTT scale-up. Method(s): In 2015-2020, we measured VLS (defined as <200 RNA copies/mL) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/mL) or high-level (>1,000 copies/mL) viremia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e., visit-pairs; ~18 month visit intervals) and classified as durable VLS (<200 copies/mL at both visits), new/renewed VLS (<200 copies/mL at follow-up only), viral rebound (<200 copies/mL at initial visit only), or persistent viremia (<200 copies/mL at neither visit). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viremia were also assessed using multivariable Poisson regression with generalized estimating equations. Result(s): Overall, 3,080 participants contributed 4,604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with viremia at the initial visit (n=1,083), 46.9% maintained viremia through follow-up, 91.3% of which was high-level viremia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viremia self-reported antiretroviral therapy (ART) use for >12 months. Prevalence of persistent high-level viremia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (versus 40-49-year-olds; adjusted risk ratio [adjRR]=2.96; 95% confidence interval [95%CI]:2.21-3.96), men (versus women; adjRR=2.40, 95%CI:1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (versus persons with marital/permanent partners only; adjRR=1.38, 95%CI:1.10-1.74), and persons exhibiting hazardous alcohol use (adjRR=1.09, 95%CI:1.03-1.16). The prevalence of persistent high-level viremia was highest among men <30 years (32.0%). Conclusion(s): Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting viremia, nearly half maintain high-level viremia for >12 months and report higher-risk behaviors associated with onward HIV transmission. Enhanced linkage to HIV care and optimized treatment retention could accelerate momentum towards HIV epidemic control. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Drug resistance in Plasmodium falciparum is a major threat to malaria control efforts. We analyzed data from two decades (2000-2020) of continuous molecular surveillance of P. falciparum parasite strains in Senegal to determine how historical changes in drug administration policy may have affected parasite evolution. We profiled several known drug resistance markers and their surrounding haplotypes using a combination of single nucleotide polymorphism (SNP) molecular surveillance and whole-genome sequence (WGS) based population genomics. We observed rapid changes in drug resistance markers associated with the withdrawal of chloroquine and introduction of sulfadoxine-pyrimethamine in 2003. We also observed a rapid increase in Pfcrt K76T and decline in Pfdhps A437G starting in 2014, which we hypothesize may reflect changes in resistance or fitness caused by seasonal malaria chemoprevention (SMC). Parasite populations evolve rapidly in response to drug use, and SMC preventive efficacy should be closely monitored. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

India has one of the highest estimated burdens of enteric fever globally. Prior to implementation of Typbar-TCV typhoid conjugate vaccine (TCV) in a public sector pediatric immunization campaign in Navi Mumbai, India, we conducted a retrospective review of blood culture-confirmed cases of typhoid and paratyphoid fevers to estimate the local burden of disease. This review included all blood cultures processed at a central microbiology laboratory, serving multiple hospitals, in Navi Mumbai (January 2014-May 2018) that tested positive for either Salmonella Typhi or Salmonella Paratyphi A. Of 40,670 blood cultures analyzed, 1,309 (3.2%) were positive for S. Typhi (1,201 [92%]) or S. Paratyphi A (108 [8%]). Culture positivity was highest in the last months of the dry season (April-June). Our findings indicate a substantial burden of enteric fever in Navi Mumbai and support the importance of TCV immunization campaigns and improved water, sanitation, and hygiene. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Redefining viral load suppression (VLS) using lower cutpoints could impact progress towards the UNAIDS 95-95-95 targets. We assessed impacts of lowering the VLS cutpoint on achieving the 95-95-95 VLS target in the Rakai Community Cohort Study. Population VLS fell from 86% to 84% and 76%, respectively, after lowering VLS cutpoints from <1,000 to <200 and <50 copies/mL. The fraction of viremic persons increased by 17% after lowering the VLS cutpoint from <1,000 to <200 copies/mL. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Background Healthcare workers (HCWs) have experienced high rates of COVID-19 morbidity and mortality. We estimated COVID-19 two-dose primary series and monovalent booster vaccine effectiveness (VE) against symptomatic SARS-CoV-2 Omicron (BA.1 and BA.2) infection among HCWs in three Albanian hospitals during January-May 2022. Methods Study participants completed weekly symptom questionnaires, underwent PCR testing when symptomatic, and provided quarterly blood samples for serology. We estimated VE using Cox regression models (1-hazard ratio), with vaccination status as the time-varying exposure and unvaccinated HCWs as the reference group, adjusting for potential confounders: age, sex, prior SARS-CoV-2 infection (detected by PCR, rapid-antigen test or serology), and household size. Results At the start of the analysis period, 76% of 1,462 HCWs had received a primary series, 10% had received a booster dose, and 9% were unvaccinated; 1,307 (89%) HCWs had evidence of prior infection. Overall, 86% of primary series and 98% of booster doses received were BNT162b2. The median time interval from the second dose and the booster dose to the start of the analysis period was 289 days (IQR:210-292) and 30 days (IQR:22-46), respectively. VE against symptomatic PCR-confirmed infection was 34% (95%CI: -36;68) for the primary series and 88% (95%CI: 38;98) for the booster. Conclusions Among Albanian HCWs, most of whom had been previously infected, COVID-19 booster dose offered improved VE during a period of Omicron BA.1 and BA.2 circulation. Our findings support promoting booster dose uptake among Albanian HCWs, which, as of January 2023, was only 20%. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Background: Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment-follow-up. Method(s): We analyzed data on 1,991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using five approaches for handling post-treatment deaths, we estimated the six-month post-treatment TB recurrence risk overall, and by HIV status. We used inverse-probability-weighting to account for patients with missing follow-up and investigated the impact of potential bias from excluding these patients without applying inverse-probability weights. Result(s): The estimated TB recurrence risk was 6.6 per 1000 (95% confidence interval (CI):3.2,11.2) when deaths were handled as non-recurrences, and 6.7 per 1000 (95% CI:2.8,12.2) when deaths were censored and inverse-probability weights were applied to account for the excluded deaths. The estimated risk of composite recurrence outcomes were 24.2 (95% CI:14.1,37.0), 10.5 (95% CI:5.6,16.6), and 7.8 (95% CI:3.9,13.2) per 1000 for recurrence or 1) any death, 2) death with unknown or TB-related cause, 3) TB-related death, respectively. Corresponding relative risks for HIV status varied in direction and magnitude. Exclusion of patients with missing follow-up without inverse-probability-weighting had a small but apparent impact on estimates. Conclusion(s): The estimated six-month TB recurrence risk was low, and the association with HIV status was inconclusive due to few recurrence events. Estimation of post-treatment recurrence will be enhanced by explicit assumptions about deaths and appropriate adjustment for missing follow-up data. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Introduction: Although South Africa adopted the World Health Organization's Test and Treat strategy for HIV epidemic control in 2016, antiretroviral therapy (ART) treatment initiation and retention remain below target. In 2017, an estimated 56.3% of men living with HIV were on ART. We aimed to investigate factors associated with non-use of ART among men in South Africa. Method(s): Utilizing data from the fifth South African National HIV Prevalence, Incidence, Behavior and Communication (SABSSM V) cross-sectional survey conducted in 2017, a subset of data from HIV-positive men was stratified based on presence/absence of antiretroviral drugs (ARVs) detected in dried blood spot samples. Data were weighted to be representative of the national population and analyzed using multivariable logistic regression to assess predictors of non-use of ART; p<0.05 was considered significant. Result(s): A total of 6,920 men aged >=15 years old were enrolled in the study, of whom 953 (13.8%) tested HIV-positive. Among those HIV-positive, 810 (85%) had a known ARV test result: 470 (58%) had ARVs detected, and 340 (42%) did not have ARVs detected. Non-use of ART in men was associated with high-risk alcohol use (adjusted odds ratio (AOR)=3.68, 95% confidence interval (CI): 1.03-13.23), being a widower compared to being unmarried (AOR=6.99, 95%CI: 1.46-33.42), and having drug-resistant HIV (AOR=28.12, 95%CI: 13.89-56.94). Per year increase in age (AOR=0.67, 95%CI: 0.47-0.96), residence in rural tribal localities compared to urban localities (AOR=0.38, 95%CI: 0.18-0.78), or having a comorbidity such as tuberculosis or diabetes (AOR=0.06, 95%CI: 0.03-0.14) were positively associated with ART use. Conclusion(s): Non-use of ART was strongly associated with HIV drug resistance. Young men who are living with HIV, those with high-risk alcohol use, and widowers, should be a priority for HIV programming and linkage to care. Identifying interventions that are effective at linking these men to ART will help reduce the burden of HIV in South Africa. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Objective The COVID-19 pandemic was associated with widespread social disruptions, as governments implemented lockdowns to quell disease spread. To advance knowledge of consequences for households in lower-income countries, we examine food insecurity during the pandemic period. Design Cross-sectional study using logistic regression to examine factors associated with food insecurity. Data were collected between August and September of 2021 through a Health and Demographic Surveillance System (HDSS) using a survey instrument focused on knowledge regarding the spread of COVID-19; food availability; COVID-19 related shocks/coping; under-five child healthcare services; and healthcare services for pregnant women. Setting The study is set in two communities in Eastern Ethiopia, one rural and one urban. Participants A random sample of 880 households residing in Kersa and Harar. Results Roughly 16% of households reported not having enough food to eat during the pandemic, an increase of 6% since before the pandemic. After adjusting for other variables, households were more likely to report food insecurity if they were living in an urban area, were a larger household, had a family member lose employment, reported an increase in food prices, or were food insecure before the pandemic. Households were less likely to report food insecurity if they were wealthier or had higher household income. Discussion After taking other characteristics into consideration, households in urban areas were at higher risk for food insecurity. These findings point to the need for expanding food assistance programs to more urban areas to help mitigate the impact of lockdowns on more vulnerable households. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Background: COVID-19 caused enormous disruption to life in the 21st century. To quell disease spread, governments implemented lockdowns that likely created hardships for households. To improve knowledge of consequences, we examine how the pandemic period was associated with household hardships and assess factors associated with these hardships. Method(s): We conducted a cross-sectional study using quasi-Poisson regression to examine factors associated with household hardships. Data were collected between August and September of 2021 from a random sample of 880 households living within a Health and Demographic Surveillance System (HDSS) located in the Harari Region and the District of Kersa, both in Eastern Ethiopia. Result(s): Having a head of household with no education, residing in a rural area, larger household size, lower income and/or wealth, and community responses to COVID-19, including lockdowns and travel restrictions, were independently associated with experiencing household hardships. Conclusion(s): Our results identify characteristics of groups at-risk for household hardships during the pandemic; these findings may inform efforts to mitigate the consequences of COVID-19 and future disease outbreaks. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Enterovirus D68 (EV-D68) has caused recurring respiratory disease outbreaks in the United States since 2014. The dominant circulating EV-D68 strain has evolved from clade B1 to the more recent B2 and B3 clades. As recurrent outbreaks and continued virus evolution are expected for EV-D68, a robust real-time PCR assay that detects known strains as well as potential emerging strains is critical for national surveillance and clinical diagnostics. We describe a type-specific EV-D68 real-time RT-PCR (rRT-PCR) assay termed CDC2022, which targets sequences encoding conserved amino acid regions of all extant EV-D68 strains. We targeted three motifs conserved among all strains in the last 60 years. The assay achieved 100% (270/270) sensitivity and 100% (344/344) specificity when tested with a collection of 613 respiratory specimens, compared to the gold-standard EV semi-nested VP1 PCR and sequencing assay (snPCR/Seq). CDC2022 gave negative results with 289/289 non-target viruses, including 104 EV A-D isolates, 165 rhinovirus (RV) isolates or clinical specimens, and 14 other common respiratory viruses. The assay can detect as few as 0.28 CCID<inf>50</inf> per reaction. An in silico "phylo-primer-mismatch" analysis was performed to visualize primer/probe mismatches and to compare CDC2022 with other EV-D68 rRT-PCR assays, including the previous CDC assay (CDC2015) developed in 2014 for clade B1 strains. It showed that CDC2022 has the fewest primer/probe mismatches among all assays analyzed and is suitable for all clades. We additionally tested 11 EV-D68-positive clinical specimens from 2022 that were confirmed by snPCR/Seq, and all were detected. CDC2022 assay could provide a critical tool for molecular surveillance of EV-D68. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Background: Those responding to humanitarian crises have an ethical imperative to respond most where the need is greatest. Metrics are used to estimate the severity of a given crisis. The INFORM Severity Index, one such metric, has become widely used to guide policy makers in humanitarian response decision making. The index, however, has not undergone critical statistical review. If imprecise or incorrect, the quality of decision making for humanitarian response will be affected. This analysis asks, how precise and how well does this index reflect the severity of conditions for people affected by disaster or war? Results: The INFORM Severity Index is calculated from 35 publicly available indicators, which conceptually reflect the severity of each crisis. We used 172 unique global crises from the INFORM Severity Index database that occurred January 1 to November 30, 2019 or were ongoing by this date. We applied exploratory factor analysis (EFA) to determine common factors within the dataset. We then applied a second-order confirmatory factor analysis (CFA) to predict crisis severity as a latent construct. Model fit was assessed via chi-square goodness-of-fit statistic, Comparative Fit Index (CFI), Tucker-Lewis Index (TLI), and Root Mean Square Error of Approximation (RMSEA). The EFA models suggested a 3- or 4- factor solution, with 46% and 53% variance explained in each model, respectively. The final CFA was parsimonious, containing three factors comprised of 11 indicators, with reasonable model fit (Chi-squared=107, with 40 degrees of freedom, CFI=0.94, TLI=0.92, RMSEA=0.10). In the second-order CFA, the magnitude of standardized factor-loading on the 'societal governance' latent construct had the strongest association with the latent construct of 'crisis severity' (0.73), followed by the 'humanitarian access/safety' construct (0.56). Conclusion(s): A metric of crisis-severity is a critical step towards improving humanitarian response, but only when it reflects real life conditions. Our work is a first step in refining an existing framework to better quantify crisis severity. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting the infection to the broad inflammatory syndrome remains unknown. Here we leveraged a large set of MIS-C patient samples (n=199) to identify a distinct set of host proteins that are differentially targeted by patient autoantibodies relative to matched controls. We identified an autoreactive epitope within SNX8, a protein expressed primarily in immune cells which regulates an antiviral pathway associated with MIS-C pathogenesis. In parallel, we also probed the SARS-CoV-2 proteome-wide MIS-C patient antibody response and found it to be differentially reactive to a distinct domain of the SARS-CoV-2 nucleocapsid (N) protein relative to controls. This viral N region and the mapped SNX8 epitope bear remarkable biochemical similarity. Furthermore, we find that many children with anti-SNX8 autoantibodies also have T-cells cross-reactive to both SNX8 and this distinct domain of the SARS-CoV-2 N protein. Together, these findings suggest that MIS-C patients develop a distinct immune response against the SARS-CoV-2 N protein that is associated with cross reactivity to the self-protein SNX8, demonstrating a link from the infection to the inflammatory syndrome. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.

Objectives: Our research questions are often chosen based on the existence of suitable data for analysis or prior research in the area. For new interdisciplinary research areas, such as occupational health equity, suitable data might not yet exist. In this manuscript, we describe how we approached a research project in the absence of suitable data, using the example of identifying inequities in adequate bathrooms in U.S. workplaces. Method(s): We created a conceptual model that explained the causation of occupational health inequities, and from this model identified a series of questions that could be answered using separate datasets. Breaking up the analysis into multiple steps allowed us to use multiple data sources and analysis methods, which helped compensate for limitations in each dataset. Result(s): Using the conceptual model as a guide, we were able to identify jobs that likely have inadequate bathrooms as well as subpopulations potentially at higher risk for inadequate bathrooms. We also identified specific data gaps by reflecting on the challenges we faced in our multi-step analysis. Conclusion(s): We share our conceptual model and our example analysis to motivate epidemiologists to avoid letting availability of data limit the research questions they pursue. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Homeless shelter residents and staff may be at higher risk of SARS-CoV-2 infection. However, SARS-CoV-2 infection estimates in this population have been reliant on cross-sectional or outbreak investigation data. We conducted routine surveillance and outbreak testing in 23 homeless shelters in King County, Washington to estimate the occurrence of laboratory-confirmed SARS-CoV-2 infection and risk factors during 1/1/2020 -5/31/2021. Symptom surveys and nasal swabs were collected for SARS-CoV-2 testing by RT-PCR for residents aged >=3 months and staff. We collected 12,915 specimens from 2,930 unique participants. We identified 4.74 (95% CI 4.00 - 5.58) SARS-CoV-2 infections per 100 individuals (residents: 4.96, 95% CI 4.12 - 5.91; staff: 3.86, 95% CI 2.43 - 5.79). Most infections were asymptomatic at time of detection (74%) and detected during routine surveillance (73%). Outbreak testing yielded higher test positivity compared to routine surveillance (2.7% vs. 0.9%). Among those infected, residents were less likely to report symptoms than staff. Participants who were vaccinated against seasonal influenza and were current smokers had lower odds of having an infection detected. Active surveillance that includes SARS-CoV-2 testing of all persons is essential in ascertaining the true burden of SARS-CoV-2 infections among residents and staff of congregate settings. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Over 230,000 COVID-19 cases and over 2,200 deaths have been reported in Mozambique though May 2023. Understanding community members' knowledge of SARS-CoV-2 transmission and prevention is essential for directing public health interventions to reduce disease spread and improve vaccination coverage. Here, we describe knowledge of COVID-19 transmission, prevention, and symptoms among community residents in Mozambique. We conducted a cross-sectional survey among 33,087 households in a Health and Demographic Surveillance System in Manhica, Mozambique. Participants were recruited at the tail end of the Delta variant wave in September 2021 to the peak of Omicron cases in January 2022. Principal components analysis was used to create scores representing knowledge of COVID-19 symptoms, transmission, and prevention. Multiple imputation and quasi-Poisson regression were used to examine associations between demographic characteristics and sources of COVID-19 information, and knowledge of COVID-19 symptoms, transmission, and prevention. We examined whether sources of COVID-19 information mediated the relationship between educational attainment and knowledge of symptoms, transmission, and prevention. Across this rural community, 98.2%, 97.0%, and 85.1% of respondents reported knowing how COVID-19 could be prevented, that SARS-CoV-2 can cause disease, and how SARS-CoV-2 is transmitted, respectively. Most cited symptoms were cough (51.2%), headaches (44.9%), and fever (44.5%); transmission mechanisms were droplets (50.5%) or aerosol (<5 microm diameter) (46.9%) from an infected person; and prevention measures were handwashing (91.9%) and mask-wearing (91.8%). Characteristics associated with greater knowledge of symptoms, transmission, and prevention included having at least primary education, older age, employment, higher wealth, and Christian religion. Respondents who had had COVID-19 symptoms were also more likely to have knowledge of symptoms, transmission, and prevention. Gathering information from TV, WhatsApp, radio, and hospital mediated the relationship between educational attainment and knowledge scores. These findings support the need for outreach and for community-engaged messaging to promote prevention measures, particularly among people with low education. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Background: The natural history of SARS-CoV-2 infection and transmission dynamics may have changed as SARS-CoV-2 has evolved and population immunity has shifted. Method(s): Household contacts, enrolled from two multi-site case-ascertained household transmission studies (April 2020-April 2021 and September 2021-September 2022), were followed for 10-14 days after enrollment with daily collection of nasal swabs and/or saliva for SARS-CoV-2 testing and symptom diaries. SARS-CoV-2 virus lineage was determined by whole genome sequencing, with multiple imputation where sequences could not be recovered. Adjusted infection risks were estimated using modified Poisson regression. Finding(s): 858 primary cases with 1473 household contacts were examined. Among unvaccinated household contacts, the infection risk adjusted for presence of prior infection and age was 58% (95% confidence interval [CI]: 49-68%) in households currently exposed to pre-Delta lineages and 90% (95% CI: 74-100%) among those exposed to Omicron BA.5 (detected May - September 2022). The fraction of infected household contacts reporting any symptom was similarly high between pre-Delta (86%, 95% CI: 81-91%) and Omicron lineages (77%, 70-85%). Among Omicron BA.5-infected contacts, 48% (41-56%) reported fever, 63% (56-71%) cough, 22% (17-28%) shortness of breath, and 20% (15-27%) loss of/change in taste/smell. Interpretation(s): The risk of infection among household contacts exposed to SARS-CoV-2 is high and increasing with more recent SARS-CoV-2 lineages. This high infection risk highlights the importance of vaccination to prevent severe disease. Funding(s): Funded by the Centers for Disease Control and Prevention and the Food and Drug Administration. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Transmission heterogeneity plays a critical role in the dynamics of an epidemic. During an outbreak of an emerging infectious disease, efforts to characterize transmission heterogeneity are generally limited to quantifications during a small outbreak or a limited number of generations of a larger outbreak. Understanding how transmission heterogeneity itself varies over the course of a large enduring outbreak not only improves understanding of observed disease dynamics but also informs public health strategy and response. In this study, we employ a method, adaptable to other emerging infectious disease outbreaks, to quantify spatiotemporal variation in transmission heterogeneity for the 2022 mpox outbreak in the United States. Based on past research on mpox and following reports of potential superspreading events early in this outbreak, we expected to find high transmission heterogeneity as quantified by the dispersion parameter of the offspring distribution, k. Our methods use maximum likelihood estimation to fit a negative binomial distribution to transmission chain offspring distributions informed by a large mpox contact tracing dataset. We find that, while estimates of transmission heterogeneity varied across the outbreak with spatiotemporal pockets of higher heterogeneity, overall transmission heterogeneity was low. When testing our methods on simulated data from an outbreak with high transmission heterogeneity, k estimate accuracy depended on the contact tracing data completeness. Because the actual contact tracing data had high incompleteness, our values of k estimated from the empirical data may be artificially high. However, it is also possible that our estimates accurately reflect low transmission heterogeneity for the United States mpox outbreak. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.

Introduction: Historically, lack of data on cost-effectiveness of influenza vaccination has been identified as a barrier to vaccine use in low- and middle-income countries. We conducted a systematic review of economic evaluations describing (1) costs of influenza illness, (2) costs of influenza vaccination programs, and (3) vaccination cost-effectiveness from low- and middle-income countries to assess if gaps persist. Method(s): We performed a systematic search in Medline, Embase, Cochrane Library, CINAHL, and Scopus using a combination of the following key words: "influenza" AND "cost" OR "economic." The search included studies with publication years 2012 through 2021. We abstracted general study characteristics and data specific to each of the three areas of review. Result(s): Of 50 included studies, 24 presented data on cost-effectiveness, 23 on cost-of-illness, and four on program costs. Represented countries were classified as upper-middle income (UMIC; n=11), lower-middle income (LMIC; n=7), and low-income (LIC; n=3). The most evaluated target groups were children (n=26 studies), older adults (n=16), and persons with chronic medical conditions (n=12); fewer studies evaluated pregnant persons (n=8), healthcare workers (n=4), and persons in congregate living settings (n=1). Costs-of-illness were generally higher in UMICs than in LMICs/LICs; however, the highest total costs, as a percent of gross domestic product and national health expenditure, were reported from an LIC. Among studies that evaluated the cost-effectiveness of influenza vaccine introduction, most (83%) interpreted at least one scenario per target group as either cost-effective or cost-saving, based on thresholds designated in the study. Conclusion(s): Continued evaluation of the economic burden of influenza illness and costs and cost-effectiveness of influenza vaccination, particularly in low-income countries and among underrepresented target groups (e.g., healthcare workers and pregnant persons), is needed; use of standardized methodology could facilitate pooling across settings. Robust, global economic data are critical to design and maintain sustainable influenza vaccination programs. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Introduction Pre-exposure prophylaxis (PrEP) is an effective prevention intervention that can be used to control HIV incidence especially among people who are at increased risk for HIV such as adolescent girls and young women (AGYW) and adolescent boys and young men (ABYM). In South Africa, various approaches of delivering PrEP have been adopted at different service delivery points (facility-based only, school-based only, community-based only and hybrid school-facility and community-facility models) to overcome challenges associated with individual, structural, and health systems related barriers that may hinder access to and uptake of PrEP among these populations. However, little is known about how to optimize PrEP implementation and operational strategies to achieve high sustained uptake of good quality services for AGYW and ABYM. This study aims to identify effective and feasible PrEP models of care for improving PrEP uptake, continuation, and adherence among AGYW and ABYM. Methods and analysis A sequential explanatory mixed-methods study will be conducted in 22 service delivery points (SDPs) in uMgungundlovu district, KwaZulu-Natal, South Africa. We will recruit 600 HIV negative, sexually active, high risk, AGYW (aged 15-24 years) and ABYM (aged 15-35 years). Enrolled participants will be followed up at 1-, 4- and 7-months to determine continuation and adherence to PrEP. We will conduct two focus group discussions (with 8 participants in each group) across four groups (i. Initiated PrEP within 1 month, ii. Did not initiate PrEP within 1 month, iii. Continued PrEP at 4/7 months and iv. Did not continue PrEP at 4/7 months) and 48 in-depth interviews from each of the four groups (12 per group). Twelve key informant interviews with stakeholders working in HIV programs will also be conducted. Associations between demographic characteristics stratified by PrEP initiation and by various service-delivery models will be assessed using Chi-square/Fishers exact tests or t-test/Mann Whitney test. A general inductive approach will be used to analyze the qualitative data. Ethics and dissemination The protocol was approved by the South African Medical Research Council Health Research Ethics Committee (EC051-11/2020). This project was reviewed by the U.S. Centers for Disease Control and Prevention (Atlanta, GA), Centers for Global Health Associate Director for Science in accordance with CDC human research protection procedures and was determined to be research, but CDC investigators did not interact with human subjects or have access to identifiable data or specimens for research purposes. Provincial and district level approval has been granted. Findings from the study will be communicated to the study population and results will be presented to stakeholders and at appropriate local and international conferences. Outputs will also include a policy brief, peer-reviewed journal articles and research capacity building through research degrees. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

The global SARS-CoV-2 immune landscape and population protection against emerging variants is largely unknown. We assessed SARS-CoV-2 antibody changes in the Dominican Republic and implications for immunological protection against variants of concern. Between March 2021 and August 2022, 2,300 patients with undifferentiated febrile illnesses were prospectively enrolled. Sera was tested for total anti-spike antibodies and simultaneously collected nasopharyngeal samples for acute SARSCoV-2 infection with RT-PCR. Geometric mean anti-spike titers increased from 6.6 BAU/ml (95% CI 5.1-8.7) to 1,332 BAU/ml (1055-1,682). Multivariable binomial odds ratios for acute SARS-CoV-2 infection were 0.55 (0.40-0.74), 0.38 (0.27-0.55), and 0.27 (0.18-0.40) for the second, third, and fourth versus the first anti-S quartile, with similar findings by viral strain. Integrated serological and virological screening can leverage existing acute fever surveillance platforms to monitor population-level immunological markers and concurrently characterize implications for emergent variant transmission in near real-time. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Introduction: During March-December 2020, Zambia recorded 20,725 confirmed COVID-19 cases, with the first wave peaking between July and August. Of the 388 COVID-19-related deaths occurring nationwide, most occurred in the community. We report findings from COVID-19 mortality surveillance among community deaths brought to the University Teaching Hospital (UTH) mortuary in Lusaka. Method(s): In Zambia, when a person dies in the community, and is brought into a health facility mortuary, they are recorded as 'brought in dead' (BID). The UTH mortuary accepts persons BID for Lusaka District, the most populated district in Zambia. We analyzed data for persons BID at UTH during 2020. We analyzed two data sources: weekly SARS-CoV-2 test results for persons BID and monthly all-cause mortality numbers among persons BID. For all-cause mortality among persons BID, monthly deaths during 2020 that were above the upper bound of the 95% confidence interval for the historic mean (2017-2019) were considered significant. Spearman's rank test was used to correlate the overall percent positivity in Zambia with all-cause mortality and SARS-CoV-2 testing among persons BID at UTH mortuary. Result(s): During 2020, 7,756 persons were BID at UTH (monthly range 556-810). SARS-CoV-2 testing began in April 2020, and through December 3,131 (51.9%) of 6,022 persons BID were tested. Of these, 212 (6.8%) were SARS-CoV-2 positive with weekly percent test positivity ranging from 0-32%, with the highest positivity occurring during July 2020. There were 1,139 excess persons BID from all causes at UTH mortuary in 2020 compared to the 2017-2019 mean. The monthly number of persons BID from all causes was above the upper bound of the 95% confidence interval during June-September and December. Conclusion(s): Increases in all-cause mortality and SARS-CoV-2 test positivity among persons BID at UTH mortuary corresponded with the first peak of the COVID-19 epidemic in June and August 2020, indicating possible increased mortality related to the COVID-19 epidemic in Zambia. Combining all-cause mortality and SARS-CoV-2 testing for persons BID provides useful information about the severity of the epidemic in Lusaka and should be implemented throughout Zambia. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

Anopheles stephensi is a major vector of malaria in Asia and the Arabian Peninsula, and its recent invasion into Africa poses a significant threat to malaria control and elimination efforts on the continent. The mosquito is well-adapted to urban environments, and its presence in Africa could potentially lead to an increase in malaria transmission in cities. Most of the knowledge about An. stephensi ecology in Africa has been generated from studies conducted during the rainy season, when vectors are most abundant. Here, we provide evidence from the peak of the dry season in the city of Jigjiga, Ethiopia, and report the finding of An. stephensi immature stages infesting predominantly water reservoirs made to support construction operations (in construction sites or associated with brick manufacturing businesses). Political and economic changes in Ethiopia (and particularly the Somali Region) have fueled an unprecedented construction boom since 2018 that, in our opinion, has been instrumental in the establishment, persistence and propagation of An. stephensi via the year-round availability of perennial larval habitats associated with construction. We argue that larval source management during the dry season may provide a unique opportunity for focused control of An. stephensi in Jigjiga and similar areas. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.