INTRODUCTION: An error grid compares measured versus reference glucose concentrations to assign clinical risk values to observed errors. Widely used error grids for blood glucose monitors (BGMs) have limited value because they do not also reflect clinical accuracy of continuous glucose monitors (CGMs). METHODS: Diabetes Technology Society (DTS) convened 89 international experts in glucose monitoring to (1) smooth the borders of the Surveillance Error Grid (SEG) zones and create a user-friendly tool-the DTS Error Grid; (2) define five risk zones of clinical point accuracy (A-E) to be identical for BGMs and CGMs; (3) determine a relationship between DTS Error Grid percent in Zone A and mean absolute relative difference (MARD) from analyzing 22 BGM and nine CGM accuracy studies; and (4) create trend risk categories (1-5) for CGM trend accuracy. RESULTS: The DTS Error Grid for point accuracy contains five risk zones (A-E) with straight-line borders that can be applied to both BGM and CGM accuracy data. In a data set combining point accuracy data from 18 BGMs, 2.6% of total data pairs equally moved from Zones A to B and vice versa (SEG compared with DTS Error Grid). For every 1% increase in percent data in Zone A, the MARD decreased by approximately 0.33%. We also created a DTS Trend Accuracy Matrix with five trend risk categories (1-5) for CGM-reported trend indicators compared with reference trends calculated from reference glucose. CONCLUSION: The DTS Error Grid combines contemporary clinician input regarding clinical point accuracy for BGMs and CGMs. The DTS Trend Accuracy Matrix assesses accuracy of CGM trend indicators.

BACKGROUND: Verbal autopsy (VA), though imperfect, serves as a vital tool to determine cause-of-death, particularly for out-of-facility deaths, but challenges persist in integrating VA into Civil Registration and Vital Statistics systems. OBJECTIVE: To describe the challenges and successes of collecting a national sample of verbal autopsy interviews in South Africa to obtain the cause of death profile in 2017/18. METHODS: We recruited next of kin from 27 randomly selected sub-districts (10.5%) across South Africa between September 2017 and April 2018. Trained fieldworkers conducted face-to-face interviews using the WHO2016 VA instrument, with physicians certifying underlying causes of death. Feasibility was evaluated based on response rates, participation, and data quality. RESULTS: Of the total 36,976 deaths registered, only 26% were identified during recruitment, with a 55% overall response rate for VA interviews. Physician-reviewed VA data were deemed of good quality for assigning underlying causes of death in 83% of cases. By comparing cause-specific mortality fractions, physician-reviewed VA identified 22.3% HIV/AIDS and InterVA-5 identified 18.5%, aligning with burden of disease estimates, while Statistics South Africa reported 4.9% HIV/AIDS. CONCLUSIONS: The study demonstrated the feasibility of using VA on a national scale, but immense challenges in identifying and recruiting next of kin highlight the importance of formalising VAs within the country's death notification system. | • Main findings: Next of kin of 9 730 decedents were approached at the time of registration of death and 55% consented to be approached later and agreed to do a VA interview by a trained field-worker; 83% of physician-reviewed VA data were considered high-quality for determining underlying causes and 22.3% of all the deaths were due to HIV/AIDS, much higher than the proportion reported in the national statistical office.• Added knowledge: Implementing the VA on a national scale was achievable but significant challenges in recruiting next of kin, emphasising a need to formalise VAs within the country’s death notification system.• Global health impact for policy and action: Accurate cause-of-death data are crucial for policymakers to make informed decisions about the country’s health system and could be supported by using VAs, particularly for the deaths that occur outside health facilities. | eng

Beginning in late 2023, Oropouche virus was identified as the cause of large outbreaks in Amazon regions with known endemic transmission and in new areas in South America and the Caribbean. The virus is spread to humans by infected biting midges and some mosquito species. Although infection typically causes a self-limited febrile illness, reports of two deaths in patients with Oropouche virus infection and vertical transmission associated with adverse pregnancy outcomes have raised concerns about the threat of this virus to human health. In addition to approximately 8,000 locally acquired cases in the Americas, travel-associated Oropouche virus disease cases have recently been identified in European travelers returning from Cuba and Brazil. As of August 16, 2024, a total of 21 Oropouche virus disease cases were identified among U.S. travelers returning from Cuba. Most patients initially experienced fever, myalgia, and headache, often with other symptoms including arthralgia, diarrhea, nausea or vomiting, and rash. At least three patients had recurrent symptoms after the initial illness, a common characteristic of Oropouche virus disease. Clinicians and public health jurisdictions should be aware of the occurrence of Oropouche virus disease in U.S. travelers and request testing for suspected cases. Travelers should prevent insect bites when traveling, and pregnant persons should consider deferring travel to areas experiencing outbreaks of Oropouche virus disease.

We present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious viruses in multiple cell culture models for all six families of viruses causing most respiratory diseases in humans. In animals, this chemotype has been demonstrated efficacious for porcine epidemic diarrhoea virus (a coronavirus) and respiratory syncytial virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral life cycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. An advanced analog, PAV-104, is shown to be selective for the virally modified target, thereby avoiding host toxicity. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.

Background: International distribution of contaminated foods can be a source of Salmonella infections in people and can contribute to the spread of antimicrobial-resistant bacteria across countries. We report an investigation led by the United States Centers for Disease Control and Prevention, the Food and Drug Administration (FDA), and state governmental officials into a multistate outbreak of salmonellosis linked to pig ear pet treats. Methods: Pig ear treats and companion dogs were tested for Salmonella by state officials and the FDA. Products were traced back to the country of origin when possible. Cases were defined as outbreak illnesses in people associated with one of seven Salmonella serotypes genetically related to samples from pig ear pet treats, with isolation dates from June 2015 to September 2019. Whole genome sequencing (WGS) of isolates was used to predict antimicrobial resistance. Findings: The outbreak included 154 human cases in 34 states. Of these, 107 of 122 (88%) patients reported dog contact, and 65 of 97 (67%) reported contact with pig ear pet treats. Salmonella was isolated from 137 pig ear treats, including some imported from Argentina, Brazil, and Colombia, and from four dogs. WGS predicted 77% (105/137) of human and 43% (58/135) of pig ear treat isolates were resistant to ≥3 antimicrobial classes. Interpretation: This was the first documented United States multistate outbreak of Salmonella infections linked to pig ear pet treats. This multidrug-resistant outbreak highlights the interconnectedness of human health and companion animal ownership and the need for zoonotic pathogen surveillance to prevent human illness resulting from internationally transported pet food products. Funding: Animal Feed Regulatory Program Standards award. Animal and product testing conducted by FDA Vet-LIRN was funded by Vet-LIRN infrastructure grants ( PAR-22-063). © 2024

AIMS: Contact with backyard poultry (i.e., privately-owned, non-commercial poultry) was first associated with a multistate outbreak of salmonellosis in 1955. In recent years, backyard poultry-associated salmonellosis outbreaks have caused more illnesses in the United States than salmonellosis outbreaks linked to any other type of animal. Here, we describe the epidemiology of outbreaks from 2015-2022 to inform prevention efforts. METHODS AND RESULTS: During 2015-2022, there were 88 multistate backyard poultry-associated salmonellosis outbreaks and 7866 outbreak-associated illnesses caused by 21 different Salmonella serotypes. Salmonella Enteritidis accounted for the most outbreaks (n = 21) and illnesses (n = 2400) of any serotype. Twenty-four percent (1840/7727) of patients with available information were <5 years of age. In total, 30% (1710/5644) of patients were hospitalized, and nine deaths were attributed to Salmonella infection. Throughout this period, patients reported behaviours that have a higher risk of Salmonella transmission, including kissing or snuggling poultry or allowing poultry inside their home. CONCLUSIONS: Despite ongoing efforts to reduce the burden of salmonellosis associated with backyard poultry, outbreak-associated illnesses have nearly tripled and hospitalizations more than quadrupled compared with those in 1990-2014. Because this public health problem is largely preventable, government officials, human and veterinary healthcare providers, hatcheries, and retailers might improve the prevention of illnesses by widely disseminating health and safety recommendations to the public and by continuing to develop and implement prevention measures to reduce zoonotic transmission of Salmonella by backyard poultry.

Candida auris is an emerging fungal pathogen that typically affects patients in healthcare settings. Data on C. auris cases in correctional facilities are limited but are needed to guide public health recommendations. We describe cases and challenges of providing care for 13 patients who were transferred to correctional facilities during January 2020-December 2022 after having a positive C. auris specimen. All patients had positive specimens identified while receiving inpatient care at healthcare facilities in geographic areas with high C. auris prevalence. Correctional facilities reported challenges managing patients and implementing prevention measures; those challenges varied by whether patients were housed in prison medical units or general population units. Although rarely reported, C. auris cases in persons who are incarcerated may occur, particularly in persons with known risk factors. Measures to manage cases and prevent C. auris spread in correctional facilities should address setting-specific challenges in healthcare and nonhealthcare correctional environments.

Over the past 70 years, significant advances have been made in determining the causes of death in populations not served by official medical certification of cause at the time of death using a technique known as Verbal Autopsy (VA). VA involves an interview of the family or caregivers of the deceased after a suitable bereavement interval about the circumstances, signs and symptoms of the deceased in the period leading to death. The VA interview data are then interpreted by physicians or, more recently, computer algorithms, to assign a probable cause of death. VA was originally developed and applied in field research settings. This paper traces the evolution of VA methods with special emphasis on the World Health Organization's (WHO)'s efforts to standardize VA instruments and methods for expanded use in routine health information and vital statistics systems in low- and middle-income countries (LMICs). These advances in VA methods are culminating this year with the release of the 2022 WHO Standard Verbal Autopsy (VA) Toolkit. This paper highlights the many contributions the late Professor Peter Byass made to the current VA standards and methods, most notably, the development of InterVA, the most commonly used automated computer algorithm for interpreting data collected in the WHO standard instruments, and the capacity building in low- and middle-income countries (LMICs) that he promoted. This paper also provides an overview of the methods used to improve the current WHO VA standards, a catalogue of the changes and improvements in the instruments, and a mapping of current applications of the WHO VA standard approach in LMICs. It also provides access to tools and guidance needed for VA implementation in Civil Registration and Vital Statistics Systems at scale.

BACKGROUND: Re-engaging people with HIV (PWH) who are newly out-of-care remains challenging. Data-to-care (D2C) is a potential strategy to re-engage such individuals. METHODS: A prospective randomized controlled trial compared a D2C strategy using a disease intervention specialist (DIS) vs standard-of-care (SOC) where 23 HIV clinics in 3 counties in Connecticut could re-engage clients using existing methods. Using a data reconciliation process to confirm being newly out-of-care, 655 participants were randomized to DIS (N=333) or SOC (N=322). HIV care continuum outcomes included re-engagement at 90 days, retention in care and viral suppression (VS) by 12 months. Multivariable regression models were used to assess factors predictive of attaining HIV care continuum outcomes. RESULTS: Participants randomized to DIS were more likely to be re-engaged at 90 days (aOR=1.42, p=0.045). Independent predictors of re-engagement at 90 days were: age>40 years (aOR=1.84, p=0.012) and peri-natal HIV risk category (aOR=3.19, p=0.030). Predictors of retention at 12 months included: re-engagement at 90 days (aOR=10.31, p<0.001), drug injection HIV risk category (aOR=1.83, p=0.032), detectable HIV-1 RNA before randomization (aOR=0.40, p=0.003) and county (Hartford aOR=1.74, p=0.049; New Haven aOR=1.80, p=0.030). Predictors of VS included: re-engagement at 90 days (aOR=2.85, p<0.001), retention in HIV care (aOR=7.07, p<0.001), and detectable HIV-1 RNA pre-randomization (aOR=0.23, p<0.001). CONCLUSIONS: A D2C strategy significantly improved re-engagement at 90 days. Early re-engagement improved downstream benefits along the HIV care continuum like retention in care and VS at 12 months. Moreover, other factors predictive of care continuum outcomes can be used to improve D2C strategies.

Tularemia is a disease caused by Francisella tularensis, a highly infectious bacteria that can be transmitted to humans by direct contact with infected animals. Because of the potential for zoonotic transmission of F. tularensis, veterinary occupational risk is a concern. Here, we report on a human case of tularemia in a veterinarian after an accidental needlestick injury during abscess drainage in a sick dog. The veterinarian developed ulceroglandular tularemia requiring hospitalization but fully recovered after abscess drainage and a course of effective antibiotics. To systematically assess veterinary occupational transmission risk of F. tularensis, we conducted a survey of veterinary clinical staff after occupational exposure to animals with confirmed tularemia. We defined a high-risk exposure as direct contact to the infected animal's body fluids or potential aerosol inhalation without use of standard personal protective equipment (PPE). Survey data included information on 20 veterinary occupational exposures to animals with F. tularensis in 4 states. Veterinarians were the clinical staff most often exposed (40%), followed by veterinarian technicians and assistants (30% and 20%, respectively). Exposures to infected cats were most common (80%). Standard PPE was not used during 80% of exposures; a total of 7 exposures were categorized as high risk. Transmission of F. tularensis in the veterinary clinical setting is possible but overall risk is likely low. Veterinary clinical staff should use standard PPE and employ environmental precautions when handling sick animals to minimize risk of tularemia and other zoonotic infections; postexposure prophylaxis should be considered after high-risk exposures to animals with suspected or confirmed F. tularensis infection to prevent tularemia.

Enteric bacterial infections are common among people who travel internationally. During 2017– | 23 2020, CDC investigated 41 multistate outbreaks of nontyphoidal Salmonella and Shiga toxin24 producing Escherichia coli (STEC) linked to international travel. Resistance to one or more | 25 antimicrobial agents was detected in at least 10% of isolates in 16 of 30 (53%) nontyphoidal | 26 Salmonella outbreaks and 8 of 11 (73%) STEC outbreaks evaluated by the National | 27 Antimicrobial Resistance Monitoring System. At least 10% of the isolates in 14 nontyphoidal | 28 Salmonella outbreaks conferred resistance to one or more of the clinically significant | 29 antimicrobials used in human medicine. This report describes the epidemiology and | 30 antimicrobial resistance patterns of these travel-associated multistate outbreaks. Investigating | 31 illnesses among returned travelers and collaboration with international partners could result in | 32 implementation of public health interventions to improve hygiene practices and food safety | 33 standards, and to prevent illness and spread of multidrug resistant organisms domestically and | 34 internationally

Animal contact is an established risk factor for nontyphoidal Salmonella infections and outbreaks. During 2015-2018, the U.S. Centers for Disease Control and Prevention (CDC) and other U.S. public health laboratories began implementing whole-genome sequencing (WGS) of Salmonella isolates. WGS was used to supplement the traditional methods of pulsed-field gel electrophoresis for isolate subtyping, outbreak detection, and antimicrobial susceptibility testing (AST) for the detection of resistance. We characterized the epidemiology and antimicrobial resistance (AMR) of multistate salmonellosis outbreaks linked to animal contact during this time period. An isolate was considered resistant if AST yielded a resistant (or intermediate, for ciprofloxacin) interpretation to any antimicrobial tested by the CDC or if WGS showed a resistance determinant in its genome for one of these agents. We identified 31 outbreaks linked to contact with poultry (n = 23), reptiles (n = 6), dairy calves (n = 1), and guinea pigs (n = 1). Of the 26 outbreaks with resistance data available, we identified antimicrobial resistance in at least one isolate from 20 outbreaks (77%). Of 1,309 isolates with resistance information, 247 (19%) were resistant to ≥1 antimicrobial, and 134 (10%) were multidrug-resistant to antimicrobials from ≥3 antimicrobial classes. The use of resistance data predicted from WGS increased the number of isolates with resistance information available fivefold compared with AST, and 28 of 43 total resistance patterns were identified exclusively by WGS; concordance was high (>99%) for resistance determined by AST and WGS. The use of predicted resistance from WGS enhanced the characterization of the resistance profiles of outbreaks linked to animal contact by providing resistance information for more isolates.

Salmonella infection causes epidemic death in wild songbirds, with potential to spread to humans. In February 2021, public health officials in Oregon and Washington, USA, isolated a strain of Salmonella enterica serovar Typhimurium from humans and a wild songbird. Investigation by public health partners ultimately identified 30 illnesses in 12 states linked to an epidemic of Salmonella Typhimurium in songbirds. We report a multistate outbreak of human salmonellosis associated with songbirds, resulting from direct handling of sick and dead birds or indirect contact with contaminated birdfeeders. Companion animals might have contributed to the spread of Salmonella between songbirds and patients; the outbreak strain was detected in 1 ill dog, and a cat became ill after contact with a wild bird. This outbreak highlights a One Health issue where actions like regular cleaning of birdfeeders might reduce the health risk to wildlife, companion animals, and humans.

The sale and distribution of small turtles (shell length <4 inches) as pets has been banned in the United States since 1975 because of the risk of Salmonella transmission, especially to children. Despite this 48-year-old ban, salmonellosis outbreaks continue to be linked to contact with small turtles. During investigations of turtle-associated outbreaks, information regarding the turtle farm of origin is difficult to obtain because turtles are commonly sold by transient vendors. During 2020-2021, public health officials investigated a multistate illness outbreak caused by Salmonella enterica serotype Typhimurium linked to pet small turtles. Cases were defined as a laboratory-confirmed Salmonella Typhimurium infection highly related (within 0-6 allele differences) to the outbreak strain based on whole-genome sequencing analysis by core-genome multilocus sequence typing with illness onset occurring during 27 August 2020-14 May 2021. Forty-three patients were identified from 12 states; of these, 35% (15/43) were children <5 years old. Among patients with available information, 37% (14/38) were hospitalized, and one death was reported. Seventy-four percent (25/34) of patients reported turtle exposure in the week before illness onset, and 84% (16/19) specified exposure to small turtles. The outbreak strain was isolated from samples collected from a Pennsylvania patient's small turtle tank. Two patients reported purchasing their small turtles from pet stores. Salmonella Braenderup was isolated from samples collected from small turtles and their habitat at one of these stores; however, at that time, this strain was not associated with any human illnesses. This investigation was notable because of the documented sale of small turtles from several pet stores combined with the identification of a single small turtle supplier to these pet stores. The high proportion of children involved in this outbreak highlights the continued need to educate the pet industry as well as parents and caregivers about the risk of turtle-associated salmonellosis especially in children. Understanding and addressing the persisting challenges related to the illegal sale and distribution of small turtles could reduce the burden of turtle-associated salmonellosis.

The US President's Emergency Plan for AIDS Relief (PEPFAR) is the largest HIV program globally, serving roughly 58% of the estimated 28.7 million people with HIV (PWH) on antiretroviral therapy (ART) in 2021 [1,2]. Tuberculosis (TB) remains the leading cause of death among PWH; an estimated 46% of TB cases are undiagnosed at the time of death, emphasizing the challenge of TB detection among this population [3]. The WHO four-symptom screen at every clinical encounter is the primary TB case finding strategy implemented in PEPFAR. Recent program data show 87% of PWH were screened for TB symptoms and, among those, only 2.7% screened positive and were referred for further TB evaluation [2]. Although the expected rate of TB symptom positivity among PWH is debated, PEPFAR's yield is not yet optimal compared with reports from the literature ranging from 30% to 67% [4]. Poor case detection leads to PWH with undiagnosed, untreated, and unreported TB, which contributes to subsequent TB-attributable mortality among PWH. The extent of gaps in case detection and mortality have been difficult to quantify. | | We estimated the number of missed TB/HIV diagnoses and TB-attributable deaths in the populations PEPFAR serves using data from PEPFAR, WHO, and the Joint United Nations Programme on HIV/AIDS (UNAIDS) [1,5]. Data was analyzed for 2018–2021, reflecting data from before the COVID-19 pandemic through the most recently available year. WHO and UNAIDS reporting periods were aligned with PEPFAR data wherever possible. Country-level data was analyzed by year for the 32 countries where PEPFAR operated and reported TB data. All datasets were downloaded in April 2023 and analyzed in Tableau, version 2022.1.

We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease. 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.

Novel community-based approaches are needed to achieve and sustain HIV epidemic control in Zambia. Under the Stop Mother and Child HIV Transmission (SMACHT) project, the Community HIV Epidemic Control (CHEC) differentiated service delivery model used community health workers to support HIV testing, ART linkage, viral suppression, and prevention of mother-to-child transmission (MTCT). A multi-methods assessment included programmatic data analysis from April 2015 to September 2020, and qualitative interviews from February to March 2020. CHEC provided HIV testing services to 1,379,387 clients; 46,138 were newly identified as HIV-positive (3.3% yield), with 41,366 (90%) linked to ART. By 2020, 91% (60,694/66,841) of clients on ART were virally suppressed. Qualitatively, healthcare workers and clients benefitted from CHEC, with provision of confidential services, health facility decongestion, and increased HIV care uptake and retention. Community-based models can increase uptake of HIV testing and linkage to care, and help achieve epidemic control and elimination of MTCT.

In the original article, there was a mistake in Figure 1 and Figure 2 as published. The graphics used are different than those originally submitted.

Enteric pathogens, such as non-typhoidal Salmonella, Campylobacter and Escherichia coli, can reside in the intestinal tract of many animals, including livestock, companion animals, small mammals and reptiles. Often, these animals can appear healthy; nonetheless, humans can become infected after direct or indirect contact, resulting in a substantial illness burden. An estimated 14% of the 3.2 million illnesses that occur in the United States of America (USA) each year from such enteric pathogens are attributable to animal contact. Surveillance for enteric pathogens in the USA includes the compilation and interpretation of both laboratory and epidemiologic data. However, the authors feel that a collaborative, multisectoral and transdisciplinary - or One Health - approach is needed for data collection and analysis, at every level. In addition, they suggest that the future of enteric illness surveillance lies in the development of improved technologies for pathogen detection and characterisation, such as genomic sequencing and metagenomics. In particular, using whole-genome sequencing to compare genetic sequences of enteric pathogens from humans, food, animals and the environment, can help to predict antimicrobial resistance among these pathogens, determine their genetic relatedness and identify outbreaks linked to a common source. In this paper, the authors describe three recent, multi-state human enteric illness outbreaks linked to animal contact in the USA and discuss how integrated disease surveillance was essential to outbreak detection and response. Additional datasharing between public health and animal health laboratories and epidemiologists at the local, national, regional and international level may help to improve surveillance for emerging animal and human health threats and lead to new opportunities for prevention.

INTRODUCTION: Data-to-care programmes utilize surveillance data to identify persons who are out of HIV care, re-engage them in care and improve HIV care outcomes. We assess the costs and cost-effectiveness of re-engagement in an HIV care intervention in the United States. METHODS: The Cooperative Re-engagement Control Trial (CoRECT) employed a data-to-care collaborative model between health departments and HIV care providers, August 2016-July 2018. The health departments in Connecticut (CT), Massachusetts (MA) and Philadelphia (PHL) collaborated with HIV clinics to identify newly out-of-care patients and randomize them to receive usual linkage and engagement in care services (standard-of-care control arm) or health department-initiated active re-engagement services (intervention arm). We used a microcosting approach to identify the activities and resources involved in the CoRECT intervention, separate from the standard-of-care, and quantified the costs. The cost data were collected at the start-up and recurrent phases of the trial to incorporate potential variation in the intervention costs. The costs were estimated from the healthcare provider perspective. RESULTS: The CoRECT trial in CT, MA and PHL randomly assigned on average 327, 316 and 305 participants per year either to the intervention arm (n = 166, 159 and 155) or the standard-of-care arm (n = 161, 157 and 150), respectively. Of those randomized, the number of participants re-engaged in care within 90 days in the intervention and standard-of-care arms was 85 and 70 in CT, 84 and 70 in MA, and 98 and 67 in PHL. The additional number of participants re-engaged in care in the intervention arm compared with those in the standard-of-care arm was 15 (CT), 14 (MA) and 31 (PHL). We estimated the annual total cost of the CoRECT intervention at $490,040 in CT, $473,297 in MA and $439,237 in PHL. The average cost per participant enrolled was $2952, $2977 and $2834 and the average cost per participant re-engaged in care was $5765, $5634 and $4482. We estimated an incremental cost per participant re-engaged in care at $32,669 (CT), $33,807 (MA) and $14,169 (PHL). CONCLUSIONS: The costs of the CoRECT intervention that identified newly out-of-care patients and re-engaged them in HIV care are comparable with other similar interventions, suggesting a potential for its cost-effectiveness in the US context.

AIMS/HYPOTHESIS: Mortality has declined in people with type 1 diabetes in recent decades. We examined how the pattern of decline differs by country, age and sex, and how mortality trends in type 1 diabetes relate to trends in general population mortality. METHODS: We assembled aggregate data on all-cause mortality during the period 2000-2016 in people with type 1 diabetes aged 0-79 years from Australia, Denmark, Latvia, Scotland, Spain (Catalonia) and the USA (Kaiser Permanente Northwest). Data were obtained from administrative sources, health insurance records and registries. All-cause mortality rates in people with type 1 diabetes, and standardised mortality ratios (SMRs) comparing type 1 diabetes with the non-diabetic population, were modelled using Poisson regression, with age and calendar time as quantitative variables, describing the effects using restricted cubic splines with six knots for age and calendar time. Mortality rates were standardised to the age distribution of the aggregate population with type 1 diabetes. RESULTS: All six data sources showed a decline in age- and sex-standardised all-cause mortality rates in people with type 1 diabetes from 2000 to 2016 (or a subset thereof), with annual changes in mortality rates ranging from -2.1% (95% CI -2.8%, -1.3%) to -5.8% (95% CI -6.5%, -5.1%). All-cause mortality was higher for male individuals and for older individuals, but the rate of decline in mortality was generally unaffected by sex or age. SMR was higher in female individuals than male individuals, and appeared to peak at ages 40-70 years. SMR declined over time in Denmark, Scotland and Spain, while remaining stable in the other three data sources. CONCLUSIONS/INTERPRETATION: All-cause mortality in people with type 1 diabetes has declined in recent years in most included populations, but improvements in mortality relative to the non-diabetic population are less consistent.

BACKGROUND: South Africa uses a courier network for transporting specimens to public laboratories. After the daily collection of specimens from the facility by the courier, patients not yet attended to are unlikely to receive same-day blood draws, potentially inhibiting access to viral load (VL) testing for HIV patients. OBJECTIVE: We aimed to design an optimised courier network and assess whether this improves VL testing access. METHODS: We optimised the specimen transport network in South Africa for 4046 facilities (November 2019). For facilities with current specimen transport times (n = 356), we assessed the relationship between specimen transport time and VL testing access (number of annual VL tests per antiretroviral treatment patient) using regression analysis. We compared our optimised transport times with courier collection times to determine the change in access to same-day blood draws. RESULTS: The number of annual VL tests per antiretroviral treatment patient (1.14, standard deviation: 0.02) was higher at facilities that had courier collection after 13:36 (the average latest collection time) than those that had their last collection before 13:36 (1.06, standard deviation: 0.03), even when adjusted for facility size. Through network optimisation, the average time for specimen transport was delayed to 14:35, resulting in a 6% - 13% increase in patient access to blood draws. CONCLUSION: Viral load testing access depends on the time of courier collection at healthcare facilities. Simple solutions are frequently overlooked in the quest to improve healthcare. We demonstrate how simply changing specimen transportation timing could markedly improve access to VL testing.

Consumption of unpasteurised milk in the United States has presented a public health challenge for decades because of the increased risk of pathogen transmission causing illness outbreaks. We analysed Foodborne Disease Outbreak Surveillance System data to characterise unpasteurised milk outbreaks. Using Poisson and negative binomial regression, we compared the number of outbreaks and outbreak-associated illnesses between jurisdictions grouped by legal status of unpasteurised milk sale based on a May 2019 survey of state laws. During 2013-2018, 75 outbreaks with 675 illnesses occurred that were linked to unpasteurised milk; of these, 325 illnesses (48%) were among people aged 0-19 years. Of 74 single-state outbreaks, 58 (78%) occurred in states where the sale of unpasteurised milk was expressly allowed. Compared with jurisdictions where retail sales were prohibited (n = 24), those where sales were expressly allowed (n = 27) were estimated to have 3.2 (95% CI 1.4-7.6) times greater number of outbreaks; of these, jurisdictions where sale was allowed in retail stores (n = 14) had 3.6 (95% CI 1.3-9.6) times greater number of outbreaks compared with those where sale was allowed on-farm only (n = 13). This study supports findings of previously published reports indicating that state laws resulting in increased availability of unpasteurised milk are associated with more outbreak-associated illnesses and outbreaks.

BACKGROUND: Use of a standardized verbal autopsy (VA) questionnaire, such as the World Health Organization (WHO) instrument, can improve the consistency and reliability of the data it collects. Systematically revising a questionnaire, however, requires evidence about the performance of its questions. The purpose of this investigation was to use a mixed methods approach to evaluate the performance of questions related to 14 previously reported issues in the 2016 version of the WHO questionnaire, where there were concerns of potential confusion, redundancy, or inability of the respondent to answer the question. The results from this mixed methods analysis are discussed across common themes that may have contributed to the underperformance of questions and have been compiled to inform decisions around the revision of the current VA instrument. METHODS: Quantitative analysis of 19,150 VAs for neonates, children, and adults from five project teams implementing VAs predominately in Sub-Saharan Africa included frequency distributions and cross-tabulations to evaluate response patterns among related questions. The association of respondent characteristics and response patterns was evaluated using prevalence ratios. Qualitative analysis included results from cognitive interviewing, an approach that provides a detailed understanding of the meanings and processes that respondents use to answer interview questions. Cognitive interviews were conducted among 149 participants in Morocco and Zambia. Findings from the qualitative and quantitative analyses were triangulated to identify common themes. RESULTS: Four broad themes contributing to the underperformance or redundancy within the instrument were identified: question sequence, overlap within the question series, questions outside the frame of reference of the respondent, and questions needing clarification. The series of questions associated with one of the 14 identified issues (the series of questions on injuries) related to question sequence; seven (tobacco use, sores, breast swelling, abdominal problem, vomiting, vaccination, and baby size) demonstrated similar response patterns among questions within each series capturing overlapping information. Respondent characteristics, including relationship to the deceased and whether or not the respondent lived with the deceased, were associated with differing frequencies of non-substantive responses in three question series (female health related issues, tobacco use, and baby size). An inconsistent understanding of related constructs was observed between questions related to sores/ulcers, birth weight/baby size, and diagnosis of dementia/presence of mental confusion. An incorrect association of the intended construct with that which was interpreted by the respondent was observed in the medical diagnosis question series. CONCLUSIONS: In this mixed methods analysis, we identified series of questions which could be shortened through elimination of redundancy, series of questions requiring clarification due to unclear constructs, and the impact of respondent characteristics on the quality of responses. These changes can lead to a better understanding of the question constructs by the respondents, increase the acceptance of the tool, and improve the overall accuracy of the VA instrument.

The risk for monkeypox transmission to health care personnel (HCP) caring for symptomatic patients is thought to be low but has not been thoroughly assessed in the context of the current global outbreak (1). Monkeypox typically spreads through close physical (often skin-to-skin) contact with lesions or scabs, body fluids, or respiratory secretions of a person with an active monkeypox infection. CDC currently recommends that HCP wear a gown, gloves, eye protection, and an N95 (or higher-level) respirator while caring for patients with suspected or confirmed monkeypox to protect themselves from infection(†) (1,2). The Colorado Department of Public Health and Environment (CDPHE) evaluated HCP exposures and personal protective equipment (PPE) use in health care settings during care of patients who subsequently received a diagnosis of Orthopoxvirus infection (presumptive monkeypox determined by a polymerase chain reaction [PCR] DNA assay) or monkeypox (real-time PCR assay and genetic sequencing performed by CDC). During May 1-July 31, 2022, a total of 313 HCP interacted with patients with subsequently diagnosed monkeypox infections while wearing various combinations of PPE; 23% wore all recommended PPE during their exposures. Twenty-eight percent of exposed HCP were considered to have had high- or intermediate-risk exposures and were therefore eligible to receive postexposure prophylaxis (PEP) with the JYNNEOS vaccine(§); among those, 48% (12% of all exposed HCP) received the vaccine. PPE use varied by facility type: HCP in sexually transmitted infection (STI) clinics and community health centers reported the highest adherence to recommended PPE use, and primary and urgent care settings reported the lowest adherence. No HCP developed a monkeypox infection during the 21 days after exposure. These results suggest that the risk for transmission of monkeypox in health care settings is low. Infection prevention training is important in all health care settings, and these findings can guide future updates to PPE recommendations and risk classification in health care settings.

Despite being linked to a number of recent poultry-associated outbreaks in the United States, few reference genomes are available for Salmonella enterica serotype Hadar. Here, we address this need by reporting 18 Salmonella Hadar genomes from samples collected from patients in the United States between 2014 and 2020.

Non-typhoidal Salmonella cause an estimated 1.4 million human illnesses, 26,000 hospitalizations and 400 deaths annually in the United States. Approximately 11% of these infections are attributed to animal contact. Reptiles and amphibians are known sources of salmonellosis; young children (aged <5 years) are disproportionately affected by reptile- and amphibian-associated salmonellosis (RAAS) outbreaks. We describe multistate RAAS outbreaks to characterize illnesses and inform prevention efforts. RAAS outbreaks were defined as ≥2 culture-confirmed human Salmonella infections with similar pulsed-field gel electrophoresis patterns and epidemiologic, laboratory or traceback evidence linking them to a common reptile/amphibian exposure. Data sources included the Animal Contact Outbreak Surveillance System; CDC Outbreak Response and Prevention Branch's outbreak management database; PulseNet, the national molecular subtyping network for foodborne disease surveillance in the United States; and the National Antimicrobial Resistance Monitoring System. Twenty-six RAAS outbreaks were reported during 2009–2018, resulting in 1465 illnesses and 306 hospitalizations. The outbreaks were associated with turtles (19), lizards (5), snakes (1) and frogs (1). Sixteen (61.5%) outbreaks were linked to small turtles (<4 inches), resulting in 914 illnesses. Forty-nine percent of outbreak-associated patients were aged <5 years. Of 362 patients/caregivers interviewed, 111 (30.7%) were aware that reptiles/amphibians can carry Salmonella. Among 267 patient isolates with antimicrobial susceptibility information, 20 (7.5%) were non-susceptible to ≥1 antibiotic used to treat human salmonellosis. RAAS outbreaks result in considerable morbidity, particularly among young children. Illnesses linked to small turtles are preventable through education, targeted outreach to caregivers and paediatricians, and when appropriate, enforcement. Historically, individual states and jurisdictions have enforced existing or promulgated new authorities to address outbreaks. Preventing future RAAS outbreaks requires addressing challenges related to the illegal sale/distribution of small turtles; and for legal reptile sales, providing information on RAAS risk to consumers at point of sale to support informed pet ownership decisions. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Zoonoses and Public Health published by Wiley-VCH GmbH.

The influence of childhood contexts on adult blood pressure is an important yet understudied topic. Using a developmental perspective, this study examines the association between neighborhood socioeconomic disadvantage in early childhood (0-5 yrs), middle childhood (6-12 yrs) and adolescence (13-18 yrs) on subsequent blood pressure in young adulthood. Data were from 263 college students (52% Black; M(age) = 19.21 years) and neighborhood socioeconomic disadvantage was measured using a tract-level Area Deprivation Index. Neighborhood disadvantage in early childhood was significantly associated with diastolic blood pressure and explained 22% of the race difference between Black and White adults. The findings are consistent with the notion that early childhood may be a sensitive period for the effects of neighborhood disadvantage on blood pressure.

Zoonotic diseases represent a heavy global burden, causing important economic losses, impacting animal health and production, and costing millions of human lives. The vaccination of animals and humans to prevent inter-species zoonotic disease transmission is an important intervention. However, efforts to develop and implement vaccine interventions to reduce zoonotic disease impacts are often limited to the veterinary and agricultural sectors and do not reflect the shared burden of disease. Multisectoral collaboration, including co-development opportunities for human and animal vaccines, expanding vaccine use to include animal reservoirs such as wildlife, and strategically using vaccines to interrupt complex transmission cycles is needed. Addressing zoonoses requires a multi-faceted One Health approach, wherein vaccinating people and animals plays a critical role.