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Background: The objective of this study was to test the hypothesis that subsequent doses of the coronavirus disease 2019 (COVID-19) vaccine are associated with lower incidence of COVID-19-like symptoms at 6 weeks after infection., Methods: This study was a case-control analysis of health care personnel in an ongoing multicenter COVID-19 vaccine effectiveness study. We enrolled participants at the time of COVID-19-like symptoms between December 19, 2021, and April 27, 2022, which corresponded to the early Omicron-predominant period after original monovalent severe acute respiratory syndrome coronavirus 2 additional vaccination doses became available. Our outcome was self-reported symptoms completed 6 weeks after the onset of symptoms., Results: We enrolled 2478 participants, of whom 1422 (57%) had COVID-19. The prevalence of symptoms at 6 weeks was 26% (n = 373) in those with COVID-19 and 18% (n = 195) in those without COVID-19. Fatigue (11%) and difficulty sleeping (7%) were most strongly associated with COVID-19. A total of 1643 (66%) participants received a subsequent vaccine dose (after the primary series). Participants with COVID-19 who had received a subsequent vaccination had lower odds of symptoms at 6 weeks (adjusted odds ratio [aOR], 0.55; 95% CI, 0.43-0.70), but this relationship was not observed in those without COVID-19 (aOR, 0.87; 95% CI, 0.59-1.29)., Conclusions: Health care personnel who received subsequent doses of original monovalent COVID-19 vaccine had a lower prevalence of symptoms at 6 weeks than those that did not., Competing Interests: Potential conflicts of interest. The authors report no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose: To investigate the prevalence, patterns, and predictors of SARS-CoV-2 RNA and culturable virus in tears of a case-ascertained household cohort., Design: Prospective, longitudinal case-ascertained household cohort identified through convenience sampling., Methods: This analysis was restricted to individuals who were non-hospitalized, symptomatic, and tested positive for SARS-CoV-2 by nasal RT-PCR. Tears and anterior nasal biospecimens were serially collected throughout the acute period. Tears specimens were collected by the study staff using Schirmer test strips, and nasal specimens were self-collected. For both, SARS-CoV-2 RNA was quantified using qRT-PCR, and culturable virus was detected using presence of cytopathic effect (CPE) in tissue culture; positive CPE was confirmed by a qRT-PCR step. A series of cross-sectional unadjusted analyses were performed investigating the relationship between different sociodemographic determinants and biological factors associated with tears RNA positivity., Results: Among the 83 SARS-CoV-2 infected participants, 10 (12%) had at least one RNA-positive tears specimen. Amongst these 10, 5 (50%) had concurrent presence of culturable virus, at a median of 7 days postsymptom onset (IQR: 4-7 days) (absolute range: 4-8 days)., Conclusions: In this longitudinal cohort, we found evidence of culturable virus in the tears of a small proportion of nonhospitalized SARS-CoV-2 infected individuals. Current public health infection precautions do not account for transmission via tears, so these findings may improve our understanding of potential sources of SARS-CoV-2 transmission and contribute to developing future guidelines., (Published by Elsevier Inc.)

To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test. Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset. Defining PASC as the presence of any COVID-associated symptom at their 4-month visit, we compared viral markers (quantity and duration of nasal viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. Compared to those who fully recovered, those reporting PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen, burden of RNA and infectious viral shedding, and lower Spike-specific IgG levels within 9 days post-illness onset. No significant differences were identified among a panel of host immune markers. Our results suggest early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC, highlighting the importance of understanding early biological markers in the natural history of PASC., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Although dolutegravir (DTG) is deemed stable, safe, cost-effective, and clinically beneficial, it also carries the risk of side effects, including observed weight gain among patients on DTG-based antiretroviral therapy (ART) regimens. We compared weight changes among adults (≥18 years) initiating tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, and efavirenz (TEE) regimens and those switching from TEE to TLD (TEE-to-TLD switchers) in three large primary care facilities in South Africa METHODS: We conducted a retrospective longitudinal record review using patient medical records, extracting relevant demographic and clinical data from October 2018 to June 2021 from randomly selected adults who initiated TLD or TEE (initiators) and adult TEE-to-TLD switchers. We assessed weight, body mass index (BMI), and percentage weight changes for both groups and fitted linear regression and generalized linear models to determine factors associated with weight and BMI change and percentage weight change ≥10%, respectively, among treatment initiators. We fitted linear mixed-effect models among TEE-to-TLD switchers to consider repeated measures., Results: Of 860 initiators, 450 (52.3%) initiated on TEE and 410 (47.7%) on TLD, with median follow-up of 1.4 years and 1.0 year, respectively. At initiation, 43.3% on TEE and 40.8% on TLD were overweight or obese. TLD initiators had an adjusted higher mean weight gain of 1.6 kg (p < 0.001) and mean BMI gain of 0.51 kg/m 2 (p < 0.001) than TEE initiators. Independent risk factors for higher mean weight and BMI included age ≥50 years, male, on ART for >12 months, initial BMI of <18.5 kg/m 2 , and CD4 counts <200 cells/μL. Of 298 TEE-to-TLD switchers, 36.6% were overweight or obese at TEE initiation. Comparing before and after TLD switch, TEE-to-TLD switchers had an adjusted mean weight of 1.2 kg less while on TLD (p = 0.026). Being overweight and CD4 counts >350 cells/μL were independent risk factors for lower weight gain after TLD switch., Conclusions: We report more weight gain among TLD than among TEE initiators, although to a lesser extent than previously reported. TEE-to-TLD switchers experienced less weight gain after TLD switch; return to health before receiving TLD may be a contributory factor. The current findings are reassuring for those switching to a DTG-based regimen., (© 2024 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Bivalent mRNA vaccines were recommended since September 2022. However, coverage with a recent vaccine dose has been limited, and there are few robust estimates of bivalent VE against symptomatic SARS-CoV-2 infection (COVID-19). We estimated VE of a bivalent mRNA vaccine dose against COVID-19 among eligible U.S. healthcare personnel who had previously received monovalent mRNA vaccine doses., Methods: We conducted a case-control study in 22 U.S. states, and enrolled healthcare personnel with COVID-19 (case-participants) or without COVID-19 (control-participants) during September 2022-May 2023. Participants were considered eligible for a bivalent mRNA dose if they had received 2-4 monovalent (ancestral-strain) mRNA vaccine doses, and were ≥67 days after the most recent vaccine dose. We estimated VE of a bivalent mRNA dose using conditional logistic regression, accounting for matching by region and four-week calendar period. We adjusted estimates for age group, sex, race and ethnicity, educational level, underlying health conditions, community COVID-19 exposure, prior SARS-CoV-2 infection, and days since the last monovalent mRNA dose., Results: Among 3,647 healthcare personnel, 1,528 were included as case-participants and 2,119 as control-participants. Participants received their last monovalent mRNA dose a median of 404 days previously; 1,234 (33.8%) also received a bivalent mRNA dose a median of 93 days previously. Overall, VE of a bivalent dose was 34.1% (95% CI, 22.6%-43.9%) against COVID-19 and was similar by product, days since last monovalent dose, number of prior doses, age group, and presence of underlying health conditions. However, VE declined from 54.8% (95% CI, 40.7%-65.6%) after 7-59 days to 21.6% (95% CI 5.6%-34.9%) after ≥60 days., Conclusions: Bivalent mRNA COVID-19 vaccines initially conferred approximately 55% protection against COVID-19 among U.S. healthcare personnel. However, protection waned after two months. These findings indicate moderate initial protection against symptomatic SARS-CoV-2 infection by remaining up-to-date with COVID-19 vaccines., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Monica Brackney owned stock in Moderna from November 2022–April 2023 stock as part of portfolio managed by Parametric Investments Portfolio LLC. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Published by Elsevier Ltd.)

Louisiana experienced high morbidity and mortality from COVID-19. To assess possible explanatory factors, we conducted a cohort study (ClinSeqSer) of patients hospitalized with COVID-19 in New Orleans during August 2020-September 2021. Following enrollment, we reviewed medical charts, and performed SARS-CoV-2 RT-PCR testing on nasal and saliva specimens. We used multivariable logistic regression to assess associations between patient characteristics and severe illness, defined as ≥ 6 L/min oxygen or intubation. Among 456 patients, median age was 56 years, 277 (60.5%) were Black non-Hispanic, 436 (95.2%) had underlying health conditions, and 358 were unvaccinated (92.0% of 389 verified). Overall, 187 patients (40.1%) had severe illness; 60 (13.1%) died during admission. In multivariable models, severe illness was associated with age ≥ 65 years (OR 2.08, 95% CI 1.22-3.56), hospitalization > 5 days after illness onset (OR 1.49, 95% CI 1.01-2.21), and SARS CoV-2 cycle threshold (Ct) result of < 32 in saliva (OR 4.79, 95% CI 1.22-18.77). Among patients who were predominantly Black non-Hispanic, unvaccinated and with underlying health conditions, approximately 1 in 3 patients had severe COVID-19. Older age and delayed time to admission might have contributed to high case-severity. An association between case-severity and low Ct value in saliva warrants further investigation., (© 2024. The Author(s).)

Importance: Bivalent mRNA COVID-19 vaccines were recommended in the US for children and adolescents aged 12 years or older on September 1, 2022, and for children aged 5 to 11 years on October 12, 2022; however, data demonstrating the effectiveness of bivalent COVID-19 vaccines are limited., Objective: To assess the effectiveness of bivalent COVID-19 vaccines against SARS-CoV-2 infection and symptomatic COVID-19 among children and adolescents., Design, Setting, and Participants: Data for the period September 4, 2022, to January 31, 2023, were combined from 3 prospective US cohort studies (6 sites total) and used to estimate COVID-19 vaccine effectiveness among children and adolescents aged 5 to 17 years. A total of 2959 participants completed periodic surveys (demographics, household characteristics, chronic medical conditions, and COVID-19 symptoms) and submitted weekly self-collected nasal swabs (irrespective of symptoms); participants submitted additional nasal swabs at the onset of any symptoms., Exposure: Vaccination status was captured from the periodic surveys and supplemented with data from state immunization information systems and electronic medical records., Main Outcome and Measures: Respiratory swabs were tested for the presence of the SARS-CoV-2 virus using reverse transcriptase-polymerase chain reaction. SARS-CoV-2 infection was defined as a positive test regardless of symptoms. Symptomatic COVID-19 was defined as a positive test and 2 or more COVID-19 symptoms within 7 days of specimen collection. Cox proportional hazards models were used to estimate hazard ratios for SARS-CoV-2 infection and symptomatic COVID-19 among participants who received a bivalent COVID-19 vaccine dose vs participants who received no vaccine or monovalent vaccine doses only. Models were adjusted for age, sex, race, ethnicity, underlying health conditions, prior SARS-CoV-2 infection status, geographic site, proportion of circulating variants by site, and local virus prevalence., Results: Of the 2959 participants (47.8% were female; median age, 10.6 years [IQR, 8.0-13.2 years]; 64.6% were non-Hispanic White) included in this analysis, 25.4% received a bivalent COVID-19 vaccine dose. During the study period, 426 participants (14.4%) had laboratory-confirmed SARS-CoV-2 infection. Among these 426 participants, 184 (43.2%) had symptomatic COVID-19, 383 (89.9%) were not vaccinated or had received only monovalent COVID-19 vaccine doses (1.38 SARS-CoV-2 infections per 1000 person-days), and 43 (10.1%) had received a bivalent COVID-19 vaccine dose (0.84 SARS-CoV-2 infections per 1000 person-days). Bivalent vaccine effectiveness against SARS-CoV-2 infection was 54.0% (95% CI, 36.6%-69.1%) and vaccine effectiveness against symptomatic COVID-19 was 49.4% (95% CI, 22.2%-70.7%). The median observation time after vaccination was 276 days (IQR, 142-350 days) for participants who received only monovalent COVID-19 vaccine doses vs 50 days (IQR, 27-74 days) for those who received a bivalent COVID-19 vaccine dose., Conclusion and Relevance: The bivalent COVID-19 vaccines protected children and adolescents against SARS-CoV-2 infection and symptomatic COVID-19. These data demonstrate the benefit of COVID-19 vaccine in children and adolescents. All eligible children and adolescents should remain up to date with recommended COVID-19 vaccinations.

Wastewater-based epidemiology (WBE) emerged during the coronavirus disease 2019 (COVID-19) pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden. The lack of high-resolution fecal shedding data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) limits our ability to link WBE measurements to disease burden. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as for the commonly used fecal indicators pepper mild mottle virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2-infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding. Of the individuals that provided at least three stool samples spanning more than 14 days, 77% had one or more samples that tested positive for SARS-CoV-2 RNA. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall. CrAssphage DNA was detected in at least one sample from 80% (38/48) of individuals and was detected in 48% (179/371) of all samples. The geometric mean concentrations of PMMoV and crAssphage in stool across all individuals were 8.7 × 10 4 and 1.4 × 10 4 gene copies/milligram-dry weight, respectively, and crAssphage shedding was more consistent for individuals than PMMoV shedding. These results provide us with a missing link needed to connect laboratory WBE results with mechanistic models, and this will aid in more accurate estimates of COVID-19 burden in sewersheds. Additionally, the PMMoV and crAssphage data are critical for evaluating their utility as fecal strength normalizing measures and for source-tracking applications. IMPORTANCE This research represents a critical step in the advancement of wastewater monitoring for public health. To date, mechanistic materials balance modeling of wastewater-based epidemiology has relied on SARS-CoV-2 fecal shedding estimates from small-scale clinical reports or meta-analyses of research using a wide range of analytical methodologies. Additionally, previous SARS-CoV-2 fecal shedding data have not contained sufficient methodological information for building accurate materials balance models. Like SARS-CoV-2, fecal shedding of PMMoV and crAssphage has been understudied to date. The data presented here provide externally valid and longitudinal fecal shedding data for SARS-CoV-2, PMMoV, and crAssphage which can be directly applied to WBE models and ultimately increase the utility of WBE., Competing Interests: The authors declare no conflict of interest.

Background: The influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA level and presence of infectious virus on symptom occurrence is poorly understood, particularly among nonhospitalized individuals., Methods: The study included 85 nonhospitalized, symptomatic adults, who were enrolled from September 2020 to November 2021. Data from a longitudinal cohort studied over 28 days was used to analyze the association of individual symptoms with SARS-CoV-2 viral RNA load, or the presence or level of infectious (culturable) virus. Presence of infectious virus and viral RNA load were assessed daily, depending on specimen availability, and amount of infectious virus was assessed on the day of maximum RNA load. Participants were surveyed for the start and end dates of 31 symptoms at enrollment and at days 9, 14, 21, and 28; daily symptom presence was determined analytically. We describe symptoms and investigate their possible association with viral determinants through a series of single or pooled (multiple days across acute period) cross-sectional analyses., Results: There was an association between viral RNA load and the same-day presence of many individual symptoms. Additionally, individuals with infectious virus were more than three times as likely to have a concurrent fever than individuals without infectious virus, and more than two times as likely to have concurrent myalgia, chills, headache, or sore throat., Conclusions: We found evidence to support the association of viral RNA load and infectious virus on some, but not all symptoms. Fever was most strongly associated with the presence of infectious virus; this may support the potential for symptom-based isolation guidance for COVID-19., Competing Interests: Potential conflicts of interest. M. J. P. reports consulting for Gilead Sciences and AstraZeneca, outside the submitted work. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Introduction: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years., Methods: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays., Analysis: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders., Ethics and Dissemination: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media., Competing Interests: Competing interests: HYC reports consulting with Ellume, Pfizer, The Bill and Melinda Gates Foundation, Glaxo Smith Kline, and Merck. HYC received research funding from Gates Ventures, Sanofi Pasteur, and support and reagents from Ellume and Cepheid outside of the submitted work. JAE reports research support from Gates Ventures, AstraZeneca, GlaxoSmithKline, Merck, and Pfizer, and consulting with Sanofi Pasteur, AstraZeneca, Teva Pharmaceuticals, and Meissa Vaccines, outside of the submitted work. ALN reports research funding from Pfizer and Vir Biotechnology, outside of the submitted work. JLK reports research funding from Vir Biotechnology, outside of the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Data assessing protection conferred from COVID-19 mRNA vaccination and/or prior SARS-CoV-2 infection during Delta and Omicron predominance periods in the United States are limited., Methods: This cohort study included persons ≥18 years who had ≥1 health care encounter across 4 health systems and had been tested for SARS-CoV-2 before 26 August 2021. COVID-19 mRNA vaccination and prior SARS-CoV-2 infection defined the exposure. Cox regression estimated hazard ratios (HRs) for the Delta and Omicron periods; protection was calculated as (1-HR)×100%., Results: Compared to unvaccinated and previously uninfected persons, during Delta predominance, protection against COVID-19-associated hospitalizations was high for those 2- or 3-dose vaccinated and previously infected, 3-dose vaccinated alone, and prior infection alone (range, 91%-97%, with overlapping 95% confidence intervals [CIs]); during Omicron predominance, estimates were lower (range, 77%-90%). Protection against COVID-19-associated emergency department/urgent care (ED/UC) encounters during Delta predominance was high for those exposure groups (range, 86%-93%); during Omicron predominance, protection remained high for those 3-dose vaccinated with or without a prior infection (76%; 95% CI = 67%-83% and 71%; 95% CI = 67%-73%, respectively)., Conclusions: COVID-19 mRNA vaccination and/or prior SARS-CoV-2 infection provided protection against COVID-19-associated hospitalizations and ED/UC encounters regardless of variant. Staying up-to-date with COVID-19 vaccination still provides protection against severe COVID-19 disease, regardless of prior infection., Competing Interests: Potential conflicts of interest. S. A. I., M. G., K. M., and B. E. D. report institutional support from Westat. A. L. N. reports institutional support from Pfizer for a study of meningococcal B vaccine safety during pregnancy and from Vir Biotechnology for an influenza study, unrelated to the current work. K. M. reports institutional support from CDC for 2 influenza studies, unrelated to the current work. M. G. reports institutional support from CDC for 2 influenza studies and 2 COVID-19 studies, all unrelated to the current work. B. E. D. reports support from US National Institutes of Health, CDC, Agency for Healthcare Research and Quality, and Department of Veterans Affairs related to use and evaluation of health information exchange technologies; royalties from Elsevier and Springer Nature for books; and consulting fees from Merck and Co. for advisory panel on HPV vaccination. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Changes in testing behaviors and reporting requirements have hampered the ability to estimate the U.S. SARS-CoV-2 incidence (1). Hybrid immunity (immunity derived from both previous infection and vaccination) has been reported to provide better protection than that from infection or vaccination alone (2). To estimate the incidence of infection and the prevalence of infection- or vaccination-induced antibodies (or both), data from a nationwide, longitudinal cohort of blood donors were analyzed. During the second quarter of 2021 (April-June), an estimated 68.4% of persons aged ≥16 years had infection- or vaccination-induced SARS-CoV-2 antibodies, including 47.5% from vaccination alone, 12.0% from infection alone, and 8.9% from both. By the third quarter of 2022 (July-September), 96.4% had SARS-CoV-2 antibodies from previous infection or vaccination, including 22.6% from infection alone and 26.1% from vaccination alone; 47.7% had hybrid immunity. Prevalence of hybrid immunity was lowest among persons aged ≥65 years (36.9%), the group with the highest risk for severe disease if infected, and was highest among those aged 16-29 years (59.6%). Low prevalence of infection-induced and hybrid immunity among older adults reflects the success of public health infection prevention efforts while also highlighting the importance of older adults staying up to date with recommended COVID-19 vaccination, including at least 1 bivalent dose.* , † ., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Although most adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) fully recover, a proportion have ongoing symptoms, or post-COVID conditions (PCC), after infection. The objective of this analysis was to estimate the number of United States (US) adults with activity-limiting PCC on 1 November 2021., Methods: We modeled the prevalence of PCC using reported infections occurring from 1 February 2020 to 30 September 2021, and population-based, household survey data on new activity-limiting symptoms ≥1 month following SARS-CoV-2 infection. From these data sources, we estimated the number and proportion of US adults with activity-limiting PCC on 1 November 2021 as 95% uncertainty intervals, stratified by sex and age. Sensitivity analyses adjusted for underascertainment of infections and uncertainty about symptom duration., Results: On 1 November 2021, at least 3.0-5.0 million US adults, or 1.2%-1.9% of the US adult population, were estimated to have activity-limiting PCC of ≥1 month's duration. Population prevalence was higher in females (1.4%-2.2%) than males. The estimated prevalence after adjusting for underascertainment of infections was 1.7%-3.8%., Conclusions: Millions of US adults were estimated to have activity-limiting PCC. These estimates can support future efforts to address the impact of PCC on the US population., Competing Interests: Potential conflicts of interest. This project was funded by the CDC, and CDC co-authors took part in the project design, conduct, analysis, and manuscript preparation. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

COVID-19 can lead to severe outcomes in children (1). Vaccination decreases risk for COVID-19 illness, severe disease, and death (2). On December 13, 2020, CDC recommended COVID-19 vaccination for persons aged ≥16 years, with expansion on May 12, 2021, to children and adolescents (children) aged 12-15 years, and on November 2, 2021, to children aged 5-11 years (3). As of March 8, 2023, COVID-19 vaccination coverage among school-aged children remained low nationwide, with 61.7% of children aged 12-17 years and approximately one third (32.7%) of those aged 5-11 years having completed the primary series (3). Intention to receive COVID-19 vaccine and vaccination coverage vary by demographic characteristics, including race and ethnicity and socioeconomic status (4-6). Seattle Public Schools (SPS) implemented a program to increase COVID-19 vaccination coverage during the 2021-22 school year, focusing on children aged 5-11 years during November 2021-June 2022, with an added focus on populations with low vaccine coverage during January 2022-June 2022. † The program included strategic messaging, school-located vaccination clinics, and school-led community engagement. Vaccination data from the Washington State Immunization Information System (WAIIS) were analyzed to examine disparities in COVID-19 vaccination by demographic and school characteristics and trends over time. In December 2021, 56.5% of all SPS students, 33.7% of children aged 5-11 years, and 81.3% of children aged 12-18 years had completed a COVID-19 primary vaccination series. By June 2022, overall series completion had increased to 80.3% and was 74.0% and 86.6% among children aged 5-11 years and 12-18 years, respectively. School-led vaccination programs can leverage community partnerships and relationships with families to improve COVID-19 vaccine access and coverage., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Janet A. Englund reports institutional support from Pfizer, GlaxoSmithKline, AstraZeneca, and Merck; consulting fees from Pfizer, Moderna, Abbvie, Merck, and AstraZeneca; and travel support to attend the 2022 European Society for Paediatric Infectious Diseases meeting from AstraZeneca. No other potential conflicts of interest were disclosed.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests have had limited recommended clinical application during the coronavirus disease 2019 (COVID-19) pandemic. To inform clinical practice, an understanding is needed of current perspectives of United States-based infectious disease (ID) physicians on the use, interpretation, and need for SARS-CoV-2 antibody tests., Methods: In March 2022, members of the Emerging Infections Network (EIN), a national network of practicing ID physicians, were surveyed on types of SARS-CoV-2 antibody assays ordered, interpretation of test results, and clinical scenarios for which antibody tests were considered., Results: Of 1867 active EIN members, 747 (40%) responded. Among the 583 who managed or consulted on COVID-19 patients, a majority (434/583 [75%]) had ordered SARS-CoV-2 antibody tests and were comfortable interpreting positive (452/578 [78%]) and negative (405/562 [72%]) results. Antibody tests were used for diagnosing post-COVID-19 conditions (61%), identifying prior SARS-CoV-2 infection (60%), and differentiating prior infection and response to COVID-19 vaccination (37%). Less than a third of respondents had used antibody tests to assess need for additional vaccines or risk stratification. Lack of sufficient evidence for use and nonstandardized assays were among the most common barriers for ordering tests. Respondents indicated that statements from professional societies and government agencies would influence their decision to order SARS-CoV-2 antibody tests for clinical decision making., Conclusions: Practicing ID physicians are using SARS-CoV-2 antibody tests, and there is an unmet need for clarifying the appropriate use of these tests in clinical practice. Professional societies and US government agencies can support clinicians in the community through the creation of appropriate guidance., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background: Prisoners generally have a higher prevalence of HIV infection compared to the general population from which they come. Whether this higher prevalence reflects a higher HIV prevalence in those entering prisons or intramural transmission of HIV within prisons or both is unclear. Any of these possibilities would increase the prevalence found in resident prisoners above that in the general population. Moreover, comparisons of HIV prevalence in entrants and residents and in men and women in African prisons are not well documented. The purpose of this study was to estimate and compare the prevalence and risk factors for HIV infection amongst both male as well as female and entrant and resident prisoners in a large Ethiopian Federal Prison., Methods: We studied consenting prisoners cross-sectionally from August 2014 through November 2016. Prison entrants were screened continuously for HIV infection and its associated risk factors and residents were screened in two waves one year apart. HIV was diagnosed at the prison hospital laboratory based on the Ethiopian national HIV rapid antibody testing protocol. An external, internationally-accredited reference laboratory confirmed results. Agreement of results between the laboratories were assessed., Results: A total of 10,778 participants were screened for HIV. Most participants were young (median age of 26 years, IQR: 21-33), male (84%), single (61%), literate (89%), and urban residents (91%) without prior incarceration (96%). Prevalence of HIV was 3.4% overall. Rates of HIV (p = 0.80) were similar in residents and entrants in wave 1 and in entrants in both waves, but were 1.9-fold higher (5.4% vs 2.8%) in residents than entrants in wave 2 (both p<0.001). At entrance to the prison women were more likely to be HIV+ than men (5.5% in women vs 2.5% in men, p< 0.001). In contrast resident women were less likely to be HIV+, but this difference was not statistically significant (3.2% in women vs 4.3% in men, p = 0.125). Other risk factors associated with HIV infection were increasing age (p<0.001), female gender (p<0.001), marital status (never vs other categories, p = 0.016), smaller number of rooms in their houses pre-imprisonment (p = 0.031), TB diagnosis ever (p<0.001), number of lifetime sex partners (especially having 2-10, p<0.001), and genital ulcer (p = 0.037)., Conclusions: Prevalence of HIV in the residents at this large, central Ethiopian prison was higher than that estimated for the general population and lower than in many other studies from other smaller Ethiopian prisons. A higher prevalence in residents than in entrants were found only in our second wave of screening after one year of continuous screening and treatment, possibly representing increased willingness of residents at increased risk of HIV to participate in the second wave. Thus, this findings did not clearly support intramural transmission of HIV or the effectiveness of screening to reduce prevalence. Finally, the higher HIV prevalence in women than men requires that they be similarly screened and treated for HIV infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Objectives: Although COVID-19 vaccines offer protection against infection and severe disease, there is limited information on the effect of vaccination on prolonged symptoms following COVID-19. Our objective was to determine differences in prevalence of prolonged symptoms 6 weeks after onset of COVID-19 among healthcare personnel (HCP) by vaccination status, and to assess differences in timing of return to work., Design: Cohort analysis of HCP with COVID-19 enrolled in a multicentre vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset., Setting: Health systems in 12 US states., Participants: HCP participating in a vaccine effectiveness study were eligible for inclusion if they had laboratory-confirmed symptomatic SARS-CoV-2 with mRNA vaccination (symptom onset ≥14 days after two doses) or no prior vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey to assess symptoms reported 6 weeks after illness onset., Exposures: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine., Main Outcome Measures: Prevalence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work., Results: Among 419 HCP with COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants compared with unvaccinated participants (60.6% vs 79.1%; adjusted risk ratio 0.70, 95% CI 0.58 to 0.84). Following their illness, vaccinated HCP returned to work a median 2.0 days (95% CI 1.0 to 3.0) sooner than unvaccinated HCP (adjusted HR 1.37, 95% CI 1.04 to 1.79)., Conclusions: Receipt of two doses of a COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased prevalence of COVID-like symptoms at 6 weeks and earlier return to work., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

As COVID-19 cases increased during the first weeks of the pandemic in South Africa, the National Institute of Communicable Diseases requested assistance with epidemiologic and surveillance expertise from the US Centers for Disease Control and Prevention South Africa. By leveraging its existing relationship with the National Institute of Communicable Diseases for >2 months, the US Centers for Disease Control and Prevention South Africa supported data capture and file organization, data quality reviews, data analytics, laboratory strengthening, and the development and review of COVID-19 guidance This case study provides an account of the resources and the technical, logistical, and organizational capacity leveraged to support a rapid response to the COVID-19 pandemic in South Africa.

Background: Households have emerged as important venues for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Little is known, however, regarding the magnitude and determinants of household transmission in increasingly vaccinated populations., Methods: From September 2020 to January 2022, symptomatic nonhospitalized individuals with SARS-CoV-2 infection by RNA detection were identified within 5 days of symptom onset; all individuals resided with at least 1 other SARS-CoV-2-uninfected household member. These infected persons (cases) and their household members (contacts) were subsequently followed with questionnaire-based measurement and serial nasal specimen collection. The primary outcome was SARS-CoV-2 infection among contacts., Results: We evaluated 42 cases and their 74 household contacts. Among the contacts, 32 (43%) became infected, of whom 5 (16%) were asymptomatic; 81% of transmissions occurred by 5 days after the case's symptom onset. From 21 unvaccinated cases, 14-day cumulative incidence of SARS-CoV-2 infection among contacts was 18/40 (45% [95% confidence interval {CI}, 29%-62%]), most of whom were unvaccinated. From 21 vaccinated cases, 14-day cumulative incidence of SARS-CoV-2 infection was 14/34 (41% [95% CI, 25%-59%]) among all contacts and 12/29 (41% [95% CI, 24%-61%]) among vaccinated contacts. At least 1 comorbid condition among cases and 10 or more days of RNA detection in cases were associated with increased risk of infection among contacts., Conclusions: Among households including individuals with symptomatic SARS-CoV-2 infection, both vaccinated-to-vaccinated and unvaccinated-to-unvaccinated transmission of SARS-CoV-2 to household contacts was common. Because vaccination alone did not notably reduce risk of infection, household contacts will need to employ additional interventions to avoid infection., Competing Interests: Potential conflicts of interest. M. B. H. reports funding support from the CDC. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P = 0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset., Competing Interests: The authors have declared that no competing interests exist.

Before emergence in late 2021 of the highly transmissible B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19 (1,2), several studies demonstrated that SARS-CoV-2 was unlikely to be cultured from specimens with high cycle threshold (Ct) values § from real-time reverse transcription-polymerase chain reaction (RT-PCR) tests (suggesting low viral RNA levels) (3). Although CDC and others do not recommend attempting to correlate Ct values with the amount of infectious virus in the original specimen (4,5), low Ct values are sometimes used as surrogate markers for infectiousness in clinical, public health, or research settings without access to virus culture (5). However, the consistency in reliability of this practice across SARS-CoV-2 variants remains uncertain because Omicron-specific data on infectious virus shedding, including its relationship with RNA levels, are limited. In the current analysis, nasal specimens collected from an ongoing longitudinal cohort ¶ (6,7) of nonhospitalized participants with positive SARS-CoV-2 test results living in the San Francisco Bay Area** were used to generate Ct values and assess for the presence of culturable SARS-CoV-2 virus; findings were compared between specimens from participants infected with pre-Omicron variants and those infected with the Omicron BA.1 sublineage. Among specimens with culturable virus detected, Ct values were higher (suggesting lower RNA levels) during Omicron BA.1 infections than during pre-Omicron infections, suggesting variant-specific differences in viral dynamics. Supporting CDC guidance, these data show that Ct values likely do not provide a consistent proxy for infectiousness across SARS-CoV-2 variants., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Miguel Garcia-Knight reports a postdoctoral fellowship grant from the Global Virus Network given to the University of California at San Francisco. No other potential conflicts of interest were disclosed.

By November 30, 2021, approximately 130,781 COVID-19-associated deaths, one in six of all U.S. deaths from COVID-19, had occurred in California and New York.* COVID-19 vaccination protects against infection with SARS-CoV-2 (the virus that causes COVID-19), associated severe illness, and death (1,2); among those who survive, previous SARS-CoV-2 infection also confers protection against severe outcomes in the event of reinfection (3,4). The relative magnitude and duration of infection- and vaccine-derived protection, alone and together, can guide public health planning and epidemic forecasting. To examine the impact of primary COVID-19 vaccination and previous SARS-CoV-2 infection on COVID-19 incidence and hospitalization rates, statewide testing, surveillance, and COVID-19 immunization data from California and New York (which account for 18% of the U.S. population) were analyzed. Four cohorts of adults aged ≥18 years were considered: persons who were 1) unvaccinated with no previous laboratory-confirmed COVID-19 diagnosis, 2) vaccinated (14 days after completion of a primary COVID-19 vaccination series) with no previous COVID-19 diagnosis, 3) unvaccinated with a previous COVID-19 diagnosis, and 4) vaccinated with a previous COVID-19 diagnosis. Age-adjusted hazard rates of incident laboratory-confirmed COVID-19 cases in both states were compared among cohorts, and in California, hospitalizations during May 30-November 20, 2021, were also compared. During the study period, COVID-19 incidence in both states was highest among unvaccinated persons without a previous COVID-19 diagnosis compared with that among the other three groups. During the week beginning May 30, 2021, compared with COVID-19 case rates among unvaccinated persons without a previous COVID-19 diagnosis, COVID-19 case rates were 19.9-fold (California) and 18.4-fold (New York) lower among vaccinated persons without a previous diagnosis; 7.2-fold (California) and 9.9-fold lower (New York) among unvaccinated persons with a previous COVID-19 diagnosis; and 9.6-fold (California) and 8.5-fold lower (New York) among vaccinated persons with a previous COVID-19 diagnosis. During the same period, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates in California followed a similar pattern. These relationships changed after the SARS-CoV-2 Delta variant became predominant (i.e., accounted for >50% of sequenced isolates) in late June and July. By the week beginning October 3, compared with COVID-19 cases rates among unvaccinated persons without a previous COVID-19 diagnosis, case rates among vaccinated persons without a previous COVID-19 diagnosis were 6.2-fold (California) and 4.5-fold (New York) lower; rates were substantially lower among both groups with previous COVID-19 diagnoses, including 29.0-fold (California) and 14.7-fold lower (New York) among unvaccinated persons with a previous diagnosis, and 32.5-fold (California) and 19.8-fold lower (New York) among vaccinated persons with a previous diagnosis of COVID-19. During the same period, compared with hospitalization rates among unvaccinated persons without a previous COVID-19 diagnosis, hospitalization rates in California followed a similar pattern. These results demonstrate that vaccination protects against COVID-19 and related hospitalization, and that surviving a previous infection protects against a reinfection and related hospitalization. Importantly, infection-derived protection was higher after the Delta variant became predominant, a time when vaccine-induced immunity for many persons declined because of immune evasion and immunologic waning (2,5,6). Similar cohort data accounting for booster doses needs to be assessed, as new variants, including Omicron, circulate. Although the epidemiology of COVID-19 might change with the emergence of new variants, vaccination remains the safest strategy to prevent SARS-CoV-2 infections and associated complications; all eligible persons should be up to date with COVID-19 vaccination. Additional recommendations for vaccine doses might be warranted in the future as the virus and immunity levels change., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

We quantify antibody and memory B-cell responses to severe acute respiratory syndrome coronavirus 2 at 6 and 12 months postinfection among 7 unvaccinated US coronavirus disease 2019 cases. All had detectable S-specific memory B cells and immunoglobulin G at both time points, with geometric mean titers of 117.2 BAU/mL and 84.0 BAU/mL at 6 and 12 months, respectively., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Background: Early antiretroviral therapy (ART) is necessary for HIV epidemic control and depends on early diagnosis and successful linkage to care. Since 2014, annual household-based HIV testing and counseling and linkage services have been provided through the Chókwè Health and Demographic Surveillance System for residents testing HIV positive in this high HIV-burden district., Methods: District-wide Test and Start [T&S, ART for all people living with HIV (PLHIV)] began in August 2016, supported by systematic interventions to improve linkage to care and treatment. Annual rounds (R) of random household surveys were conducted to assess trends in population prevalence of ART use and viral load suppression (<1000 viral RNA copies/mL)., Results: Between R1 (April 2014-April 2015) and R5 (April 2018-Mar 2019), 46,090 (67.2%) of 68,620 residents aged 15-59 years were tested for HIV at home at least once, and 3711 were newly diagnosed with HIV and provided linkage services. Population prevalence of current ART use among PLHIV increased from 65.0% to 87.5% between R1 and R5. ART population prevalence was lowest among men aged 25-34 years (67.8%) and women aged 15-24 (78.0%), and highest among women aged 35-44 years (93.6%) and 45-59 years (93.7%) in R5. Viral load suppression prevalence increased among all PLHIV aged 15-59 years from 52.0% in R1 to 78.3% in R5., Discussion: Between 2014 and 2019, Chókwè Health and Demographic Surveillance System residents surpassed the UNAIDS targets of ≥81% of PLHIV on ART and ≥73% virally suppressed. This achievement supports the combination of efforts from household-based HIV testing and counseling, support for linkage to care and treatment, and continued investments in T&S implementation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Measuring progress towards the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 treatment targets is key to assessing progress towards turning the HIV epidemic tide. In 2017, the UNAIDS model estimated that 75% of people living with HIV (PLHIV) globally knew their HIV positive status, 79% of those who knew their status were on antiretroviral therapy (ART), and 81% of those who knew their HIV status and were on ART had a suppressed viral load. The fifth South African national HIV sero-behavioural survey collected nationally representative data that enabled the empirical estimation of these 90-90-90 targets for the country stratified by a variety of key factors., Methods: To evaluate progress towards achievement of the 90-90-90 targets for South Africa, data obtained from a national, representative, cross-sectional population-based multi-stage stratified cluster random survey conducted in 2017 were analysed. The Fifth South African National HIV Prevalence, Incidence, Behaviour and Communication Survey (SABSSM V), collected behavioural and biomarker data from individuals residing in households from 1000 randomly selected Small Area Layers (SALs), across all nine provinces of the country. Structured questionnaires were used to collect socio-demographic data, knowledge and perceptions about HIV, and related risk behaviours. Blood samples were collected to test for HIV infection, antiretroviral use, and viral suppression (defined as < 1000 copies/ml). Weighted proportions of study participants aged 15 years and older who tested HIV positive were computed for those who reported awareness of their status (1st 90), and among these, those who were currently on ART (2nd 90) and of these, those who were virally suppressed (3rd 90)., Results: Among persons 15 years and older who were HIV positive, 84.8% were aware of their HIV positive status, of whom 70.7% were currently on ART, with 87.4% of these estimated to have suppressed viral load at the time of the survey. These estimates varied by sex, age, and geo-location type. Relatively higher percentages across all three indicators for women compared to men were observed: 88.7% versus 78.2% for those aware of their status, 72.3% versus 67.7% for on ART, and 89.8% versus 82.3% for viral suppression. Knowing one's positive HIV status increased with age: 74.0, 85.8, and 88.1% for age groups 15-24 years old, 25-49 years old and 50-64 years old, although for those 65 years and older, 78.7% knew their HIV positive status. A similar pattern was observed for the 2nd 90, among those who knew their HIV positive status, 51.7% of 15 to 24 year olds, 70.5% of those aged 25-49 years old, 82.9% of those aged 50-64 years old and 82.4% of those aged 65 years or older were currently on ART. Viral suppression for the above mentioned aged groups, among those who were on ART was 85.2, 87.2, 89.5, and 84.6% respectively. The 90-90-90 indicators for urban areas were 87.7, 66.5, and 87.2%, for rural settings was 85.8, 79.8, and 88.4%, while in commercial farming communities it was 56.2, 67.6 and 81.4%., Conclusions: South Africa appears to be on track to achieve the first 90 indicator by 2020. However, it is behind on the second 90 indicator with ART coverage that was ~ 20-percentage points below the target among people who knew their HIV status, this indicates deficiencies around linkage to and retention on ART. Overall viral suppression among those on ART is approaching the target at 87.4%, but this must be interpreted in the context of low reported ART coverage as well as with variation by age and sex. Targeted diagnosis, awareness, and treatment programs for men, young people aged 15-24 years old, people who reside in farming communities, and in specific provinces are needed. More nuanced 90-90-90 estimates within provinces, specifically looking at more granular sub-national level (e.g. districts), are needed to identify gaps in specific regions and to inform provincial interventions.

Background: Pulmonary Tuberculosis (PTB) is a major health problem in prisons. Multiple studies of TB in regional Ethiopian prisons have assessed prevalence and risk factors but have not examined recently implemented screening programs for TB in prisons. This study compares bacteriologically-confirmed PTB (BC-PTB) prevalence in prison entrants versus residents and identifies risk factors for PTB in Kality prison, a large federal Ethiopian prison located in Addis Ababa, through a study of an enhanced TB screening program., Methods: Participating prisoners (n = 13,803) consisted of 8,228 entrants screened continuously and 5,575 residents screened in two cross-sectional waves for PTB symptoms, demographics, TB risk factors, and medical history. Participants reporting at least one symptom of PTB were asked to produce sputum which was examined by microscopy for acid-fast bacilli, Xpert MTB/RIF assay and MGIT liquid culture. Prevalence of BC-PTB, defined as evidence of Mycobacterium tuberculosis (MTB) in sputum by the above methods, was compared in entrants and residents for the study. Descriptive analysis of prevalence was followed by bivariate and multivariate analyses of risk factors., Results: Prisoners were mainly male (86%), young (median age 26 years) and literate (89%). Prevalence of TB symptoms by screening was 17% (2,334/13,803) with rates in residents >5-fold higher than entrants. Prevalence of BC-PTB detected by screening in participating prisoners was 0.16% (22/13,803). Prevalence in residents increased in the second resident screening compared to the first (R1 = 0.10% and R2 = 0.39%, p = 0.027), but remained higher than in entrants (4.3-fold higher during R1 and 3.1-fold higher during R2). Drug resistance (DR) was found in 38% (5/13) of culture-isolated MTB. Risk factors including being ever diagnosed with TB, history of TB contact and low Body Mass Index (BMI) (<18.5) were significantly associated with BC-PTB (p<0.05)., Conclusions: BC-PTB prevalence was strikingly lower than previously reported from other Ethiopian prisons. PTB appears to be transmitted within this prison based on its higher prevalence in residents than in entrants. Whether a sustained program of PTB screening of entrants and/or residents reduces prevalence of PTB in prisons is not clear from this study, but our findings suggest that resources should be prioritized to resident, rather than entrant, screening due to higher BC-PTB prevalence. Detection of multi- and mono-DR TB in both entrant and resident prisoners warrants regular screening for active TB and adoption of methods to detect drug resistance., Competing Interests: The authors have read the journal's policy and the authors of this manuscript have the following competing interests: [ET, JB, SJ, SS, JY, TS, HW, RH, WA, JAM] were paid full or partial salary support by the CDC. [BF, ZR, MB] are paid employees of the CDC. RH is currently a paid employee of Gilead Biosciences, however he was not an employee at the time of the study. Gilead played no role in funding, performing or interpreting the study. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no parents, products in development or marketed products to declare.

Background: With 71% of Malawians living on < $1.90 a day, high household costs associated with severe malaria are likely a major economic burden for low income families and may constitute an important barrier to care seeking. Nevertheless, few efforts have been made to examine these costs. This paper describes household costs associated with seeking and receiving inpatient care for malaria in health facilities in Malawi., Methods: A cross-sectional survey was conducted in a representative nationwide sample of 36 health facilities providing inpatient treatment for malaria from June-August, 2012. Patients admitted at least 12 h before study team visits who had been prescribed an antimalarial after admission were eligible to provide cost information for their malaria episode, including care seeking at previous health facilities. An ingredients-based approach was used to estimate direct costs. Indirect costs were estimated using a human capital approach. Key drivers of total household costs for illness episodes resulting in malaria admission were assessed by fitting a generalized linear model, accounting for clustering at the health facility level., Results: Out of 100 patients who met the eligibility criteria, 80 (80%) provided cost information for their entire illness episode to date and were included: 39% of patients were under 5 years old and 75% had sought care for the malaria episode at other facilities prior to coming to the current facility. Total household costs averaged $17.48 per patient; direct and indirect household costs averaged $7.59 and $9.90, respectively. Facility management type, household distance from the health facility, patient age, high household wealth, and duration of hospital stay were all significant drivers of overall costs., Conclusions: Although malaria treatment is supposed to be free in public health facilities, households in Malawi still incur high direct and indirect costs for malaria illness episodes that result in hospital admission. Finding ways to minimize the economic burden of inpatient malaria care is crucial to protect households from potentially catastrophic health expenditures.

Background: Severe malaria has a case fatality rate of 10-20 %; however, few studies have addressed the quality of severe malaria case management. This study evaluated the diagnostic and treatment practices of malaria patients admitted to inpatient health facilities (HF) in Malawi., Methods: In July-August 2012, a nationwide, cross-sectional survey of severe malaria management was conducted in 36 HFs selected with equal probability from all eligible public sector HFs in Malawi. Patient records from all admissions during October 2011 and April 2012 (low and high season, respectively) were screened for an admission diagnosis of malaria or prescription of any anti-malarial. Eligible records were stratified by age (< 5 or ≥ 5 years). A maximum of eight records was randomly selected within each age and month stratum. Severe malaria was defined by admission diagnosis or documentation of at least one sign or symptom of severe malaria. Treatment with intravenous (IV) quinine or artesunate was considered correct. Patients without documentation of severe malaria were analysed as uncomplicated malaria patients; treatment with an artemisinin-based combination therapy (ACT) or oral quinine based on malaria test results was considered correct. All analyses accounted for HF level clustering and sampling weights., Results: The analysis included 906 records from 35 HFs. Among these, 42 % (95 % confidence interval [CI] 35-49) had a severe malaria admission diagnosis and 50 % (95 % CI 44-57) had at least one severe malaria sign or symptom documented. Severe malaria patients defined by admission diagnosis (93, 95 % CI 86-99) were more likely to be treated correctly compared to patients defined by a severe sign (82, 95 % CI 75-89) (p < 0.0001). Among uncomplicated malaria patients, 26 % (95 % CI 18-35) were correctly treated and 53 % (95 % CI 42-64) were adequately treated with IV quinine alone or in combination with an ACT or oral quinine., Conclusions: A majority of patients diagnosed with severe malaria received the recommended IV therapy in accordance with national treatment guidelines. However, the inconsistencies between diagnosis of severe malaria and documentation of severe signs and symptoms highlight the need to improve healthcare worker recognition and documentation of severe signs and symptoms.