A Moving Target: Impacts of Lowering Viral Load Suppression Cutpoints on Progress Towards HIV Epidemic Control Goals (preprint)
Rosen JG , Reynolds SJ , Galiwango RM , Kigozi G , Quinn TC , Ratmann O , Ndyanabo A , Nelson LJ , Nakigozi G , Nalugemwa M , Rucinski KB , Kennedy CE , Chang LW , Kagaayi J , Serwadda D , Grabowski MK . medRxiv 2023 20 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. |
Social Contact Patterns and Implications for Infectious Disease Transmission: A Systematic Review and Meta-Analysis of Contact Surveys (preprint)
Mousa A , Winskill P , Watson OJ , Ratmann O , Monod M , Ajelli M , Diallo A , Dodd PJ , Grijalva CG , Kiti MC , Krishnan A , Kumar R , Kumar S , Kwok KO , Lanata CF , Le Polain de Waroux O , Leung K , Mahikul W , Melegaro A , Morrow CD , Mossong J , Neal EF , Nokes DJ , Pan-Ngum W , Potter GE , Russell FM , Saha S , Sugimoto JD , Wei WI , Wood RR , Wu JT , Zhang J , Walker PG , Whittaker C . medRxiv 2021 BACKGROUND: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. METHODS: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. RESULTS: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. CONCLUSIONS: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. FUNDING: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1). |
Surface-aerosol stability and pathogenicity of diverse MERS-CoV strains from 2012 - 2018 (preprint)
van Doremalen N , Letko M , Fischer RJ , Bushmaker T , Yinda CK , Schulz J , Seifert SN , Kim NJ , Hemida MG , Kayali G , Park WB , Perera RA , Tamin A , Thornburg NJ , Tong S , Queen K , van Kerkhove MD , Choi YK , Oh MD , Assiri AM , Peiris M , Gerber SI , Munster VJ . bioRxiv 2021 Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a coronavirus that infects both humans and dromedary camels and is responsible for an ongoing outbreak of severe respiratory illness in humans in the Middle East. While some mutations found in camel-derived MERS-CoV strains have been characterized, the majority of natural variation found across MERS-CoV isolates remains unstudied. Here we report on the environmental stability, replication kinetics and pathogenicity of several diverse isolates of MERS-CoV as well as SARS-CoV-2 to serve as a basis of comparison with other stability studies. While most of the MERS-CoV isolates exhibited similar stability and pathogenicity in our experiments, the camel derived isolate, C/KSA/13, exhibited reduced surface stability while another camel isolate, C/BF/15, had reduced pathogenicity in a small animal model. These results suggest that while betacoronaviruses may have similar environmental stability profiles, individual variation can influence this phenotype, underscoring the importance of continual, global viral surveillance. |
Projected resurgence of COVID-19 in the United States in July-December 2021 resulting from the increased transmissibility of the Delta variant and faltering vaccination (preprint)
Truelove S , Smith CP , Qin M , Mullany LC , Borchering RK , Lessler J , Shea K , Howerton E , Contamin L , Levander J , Salerno J , Hochheiser H , Kinsey M , Tallaksen K , Wilson S , Shin L , Rainwater-Lovett K , Lemaitre JC , Dent J , Kaminsky J , Lee EC , Perez-Saez J , Hill A , Karlen D , Chinazzi M , Davis JT , Mu K , Xiong X , Piontti APY , Vespignani A , Srivastava A , Porebski P , Venkatramanan S , Adiga A , Lewis B , Klahn B , Outten J , Schlitt J , Corbett P , Telionis PA , Wang L , Peddireddy AS , Hurt B , Chen J , Vullikanti A , Marathe M , Hoops S , Bhattacharya P , Machi D , Chen S , Paul R , Janies D , Thill JC , Galanti M , Yamana T , Pei S , Shaman J , Reich NG , Healy JM , Slayton RB , Biggerstaff M , Johansson MA , Runge MC , Viboud C . medRxiv 2021 WHAT IS ALREADY KNOWN ABOUT THIS TOPIC? The highly transmissible SARS-CoV-2 Delta variant has begun to cause increases in cases, hospitalizations, and deaths in parts of the United States. With slowed vaccination uptake, this novel variant is expected to increase the risk of pandemic resurgence in the US in July-December 2021. WHAT IS ADDED BY THIS REPORT? Data from nine mechanistic models project substantial resurgences of COVID-19 across the US resulting from the more transmissible Delta variant. These resurgences, which have now been observed in most states, were projected to occur across most of the US, coinciding with school and business reopening. Reaching higher vaccine coverage in July-December 2021 reduces the size and duration of the projected resurgence substantially. The expected impact of the outbreak is largely concentrated in a subset of states with lower vaccination coverage. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE? Renewed efforts to increase vaccination uptake are critical to limiting transmission and disease, particularly in states with lower current vaccination coverage. Reaching higher vaccination goals in the coming months can potentially avert 1.5 million cases and 21,000 deaths and improve the ability to safely resume social contacts, and educational and business activities. Continued or renewed non-pharmaceutical interventions, including masking, can also help limit transmission, particularly as schools and businesses reopen. |
Strengthening health system's capacity for pre-exposure Prophylaxis for adolescent girls and young women and adolescent boys and young men in South Africa (SHeS'Cap - PrEP): Protocol for a mixed methods study in KwaZulu-Natal, South Africa (preprint)
Nicol E , Ramraj T , Hlongwa M , Basera W , Jama N , Lombard C , McClinton-Appollis T , Govindasamy D , Pass D , Funani N , Aheron S , Paredes-Vincent A , Drummond J , Cheyip M , Dladla S , Bedford J , Mathews C . medRxiv 2022 22 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. |
Of masks and methylene blue - The use of methylene blue photochemical treatment to decontaminate surgical masks contaminated with a tenacious small non-enveloped norovirus (preprint)
Wielick C , Fries A , Dams L , Razafimahefa RM , Heyne B , Harcourt BH , Lendvay TS , Willaert JF , de Jaeger S , Haubruge E , Thiry E , Ludwig-Begall LF . medRxiv 2021 04 Background In the context of the SARS-CoV-2 pandemic, reuse of personal protective equipment, specifically that of medical face coverings, has been recommended. The reuse of these typically single-use only items necessitates procedures to inactivate contaminating human respiratory and gastrointestinal pathogens. We previously demonstrated decontamination of surgical masks and respirators contaminated with infectious SARS-CoV-2 and various animal coronaviruses via low concentration- and short exposure methylene blue photochemical treatment (10 microM methylene blue, 30 minutes of 12,500-lux red light or 50,000 lux white light exposure). Methods Here, we describe the adaptation of this protocol to the decontamination of a more resistant, non-enveloped gastrointestinal virus and demonstrate efficient photodynamic inactivation of murine norovirus, a human norovirus surrogate. Results Methylene blue photochemical treatment (100 microM methylene blue, 30 minutes of 12,500-lux red light exposure) of murine norovirus-contaminated masks reduced infectious viral titres by over four orders of magnitude on surgical mask surfaces. Discussion and Conclusions Inactivation of a norovirus, the most difficult to inactivate of the respiratory and gastrointestinal human viruses, can predict the inactivation of any less resistant viral mask contaminant. The protocol developed here thus solidifies the position of methylene blue photochemical decontamination as an important tool in the package of practical pandemic preparedness. 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. |
Can Severity of a Humanitarian Crisis be Quantified? Assessment of the INFORM Severity Index (preprint)
Lopez VK , Nika A , Blanton C , Talley L , Garfield R . medRxiv 2020 11 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. |
Impact of close interpersonal contact on COVID-19 incidence: evidence from one year of mobile device data (preprint)
Crawford FW , Jones SA , Cartter M , Dean SG , Warren JL , Li ZR , Barbieri J , Campbell J , Kenney P , Valleau T , Morozova O . medRxiv 2021 Close contact between people is the primary route for transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). We sought to quantify interpersonal contact at the population-level by using anonymized mobile device geolocation data. We computed the frequency of contact (within six feet) between people in Connecticut during February 2020 - January 2021. Then we aggregated counts of contact events by area of residence to obtain an estimate of the total intensity of interpersonal contact experienced by residents of each town for each day. When incorporated into a susceptible-exposed-infective-removed (SEIR) model of COVID-19 transmission, the contact rate accurately predicted COVID-19 cases in Connecticut towns during the timespan. The pattern of contact rate in Connecticut explains the large initial wave of infections during March-April, the subsequent drop in cases during June-August, local outbreaks during August-September, broad statewide resurgence during September-December, and decline in January 2021. Contact rate data can help guide public health messaging campaigns to encourage social distancing and in the allocation of testing resources to detect or prevent emerging local outbreaks more quickly than traditional case investigation. ONE SENTENCE SUMMARY: Close interpersonal contact measured using mobile device location data explains dynamics of COVID-19 transmission in Connecticut during the first year of the pandemic. |
Incidence of SARS-CoV-2 infection and associated risk factors among staff and residents at homeless shelters in King County, Washington: an active surveillance study
Rogers JH , Cox SN , Link AC , Nwanne G , Han PD , Pfau B , Chow EJ , Wolf CR , Boeckh M , Hughes JP , Halloran ME , Uyeki TM , Shim MM , Duchin J , Englund JA , Mosites E , Rolfes MA , Starita LA , Chu HY . Epidemiol Infect 2023 151 1-48 Homeless shelter residents and staff may be at higher risk of SARS-CoV-2 infection. However, | 34 SARS-CoV-2 infection estimates in this population have been reliant on cross-sectional or | 35 outbreak investigation data. We conducted routine surveillance and outbreak testing in 23 | 36 homeless shelters in King County, Washington to estimate the occurrence of laboratory37 confirmed SARS-CoV-2 infection and risk factors during 1/1/2020 -5/31/2021. Symptom surveys | 38 and nasal swabs were collected for SARS-CoV-2 testing by RT-PCR for residents aged ≥3 | 39 months and staff. We collected 12,915 specimens from 2,930 unique participants. We identified | 40 4.74 (95% CI 4.00 – 5.58) SARS-CoV-2 infections per 100 individuals (residents: 4.96, 95% CI | 41 4.12 – 5.91; staff: 3.86, 95% CI 2.43 – 5.79). Most infections were asymptomatic at time of | 42 detection (74%) and detected during routine surveillance (73%). Outbreak testing yielded higher | 43 test positivity compared to routine surveillance (2.7% vs. 0.9%). Among those infected, | 44 residents were less likely to report symptoms than staff. Participants who were vaccinated | 45 against seasonal influenza and were current smokers had lower odds of having an infection | 46 detected. Active surveillance that includes SARS-CoV-2 testing of all persons is essential in | 47 ascertaining the true burden of SARS-CoV-2 infections among residents and staff of congregate | 48 settings. |
COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support (preprint)
Shea K , Borchering RK , Probert WJM , Howerton E , Bogich TL , Li S , van Panhuis WG , Viboud C , Aguás R , Belov A , Bhargava SH , Cavany S , Chang JC , Chen C , Chen J , Chen S , Chen Y , Childs LM , Chow CC , Crooker I , Valle SYD , España G , Fairchild G , Gerkin RC , Germann TC , Gu Q , Guan X , Guo L , Hart GR , Hladish TJ , Hupert N , Janies D , Kerr CC , Klein DJ , Klein E , Lin G , Manore C , Meyers LA , Mittler J , Mu K , Núñez RC , Oidtman R , Pasco R , Piontti APY , Paul R , Pearson CAB , Perdomo DR , Perkins TA , Pierce K , Pillai AN , Rael RC , Rosenfeld K , Ross CW , Spencer JA , Stoltzfus AB , Toh KB , Vattikuti S , Vespignani A , Wang L , White L , Xu P , Yang Y , Yogurtcu ON , Zhang W , Zhao Y , Zou D , Ferrari M , Pannell D , Tildesley M , Seifarth J , Johnson E , Biggerstaff M , Johansson M , Slayton RB , Levander J , Stazer J , Salerno J , Runge MC . medRxiv 2020 Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes. |
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