Anthony Fauci, who retired as head of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, at the end of 2022, wrote that “The emergence of new infections and the reemergence of old ones are largely the result of human interactions with and encroachment on nature. As human societies expand in a progressively interconnected world and the human–animal interface is perturbed, opportunities are created, often aided by climate changes, for unstable infectious agents to emerge, jump species, and in some cases adapt to spread among humans.” | | Factors that can lead to emergence of pathogens also include contaminated food and water, modern agricultural practices, human migration, use and misuse of antimicrobial agents, and lack of public health resources in some areas. In 2013, Morens and Fauci wrote, “The inevitable, but unpredictable, appearance of new infectious diseases has been recognized for millennia, well before the discovery of causative infectious agents. Today, however, despite extraordinary advances in development of countermeasures (diagnostics, therapeutics, and vaccines), the ease of world travel and increased global interdependence have added layers of complexity to containing these infectious diseases that affect not only the health but the economic stability of societies.”

During the COVID-19 vaccination rollout from March 2021- December 2022, the Centers for Disease Control and Prevention funded 110 primary and 1051 subrecipient partners at the national, state, local, and community-based level to improve COVID-19 vaccination access, confidence, demand, delivery, and equity in the United States. The partners implemented evidence-based strategies among racial and ethnic minority populations, rural populations, older adults, people with disabilities, people with chronic illness, people experiencing homelessness, and other groups disproportionately impacted by COVID-19. CDC also expanded existing partnerships with healthcare professional societies and other core public health partners, as well as developed innovative partnerships with organizations new to vaccination, including museums and libraries. Partners brought COVID-19 vaccine education into farm fields, local fairs, churches, community centers, barber and beauty shops, and, when possible, partnered with local healthcare providers to administer COVID-19 vaccines. Inclusive, hyper-localized outreach through partnerships with community-based organizations, faith-based organizations, vaccination providers, and local health departments was critical to increasing COVID-19 vaccine access and building a broad network of trusted messengers that promoted vaccine confidence. Data from monthly and quarterly REDCap reports and monthly partner calls showed that through these partnerships, more than 295,000 community-level spokespersons were trained as trusted messengers and more than 2.1 million COVID-19 vaccinations were administered at new or existing vaccination sites. More than 535,035 healthcare personnel were reached through outreach strategies. Quality improvement interventions were implemented in healthcare systems, long-term care settings, and community health centers resulting in changes to the clinical workflow to incorporate COVID-19 vaccine assessments, recommendations, and administration or referrals into routine office visits. Funded partners' activities improved COVID-19 vaccine access and addressed community concerns among racial and ethnic minority groups, as well as among people with barriers to vaccination due to chronic illness or disability, older age, lower income, or other factors.

BACKGROUND: Contrary to the World Health Organization's internationally recommended medical certificate of cause of death, the South African (SA) death notification form (DNF) does not allow for the reporting of the manner of death to permit accurate coding of external causes of injury deaths. OBJECTIVES: To describe the injury cause-of-death profile from forensic pathology records collected for the National Cause-of-Death Validation (NCoDV) Project and compare it with profiles from other sources of injury mortality data. In particular, the recording of firearm use in homicides is compared between sources. METHODS: The NCoDV Project was a cross-sectional study of deaths that occurred during a fixed period in 2017 and 2018, from a nationally representative sample of 27 health subdistricts in SA. Trained fieldworkers scanned forensic records for all deaths investigated at the forensic mortuaries serving the sampled subdistricts during the study period. Forensic practitioners reviewed the records and completed a medical certificate of cause of death for each decedent. Causes of death were coded to the International Statistical Classification of Diseases, 10th revision (ICD-10), using Iris automated coding software. Cause-specific mortality fractions for injury deaths were compared with Injury Mortality Survey 2017 (IMS 2017) and Statistics South Africa 2017 (Stats SA 2017) datasets. The cause profile for all firearm-related deaths was compared between the three datasets. RESULTS: A total of 5 315 records were available for analysis. Males accounted for 77.6% of cases, and most decedents were aged between 25 and 44 years. Homicide was the leading cause of death (34.7%), followed by transport injuries (32.6%) and suicide (14.7%). This injury cause profile was similar to IMS 2017 but differed markedly from the official statistics, which showed markedly lower proportions of these three causes (15.0%, 11.6% and 0.7%, respectively), and a much higher proportion of other unintentional causes. Investigation of firearm-related deaths revealed that most were homicides in NCoDV 2017/18 (88.5%) and IMS 2017 (93.1%), while in the Stats SA 2017 data, 98.7% of firearm deaths were classified as accidental. Approximately 7% of firearm-related deaths were suicides in NCoDV 2017/18 and IMS 2017, with only 0.3% in Stats SA 2017. CONCLUSION: The official cause-of-death data for injuries in SA in 2017 differed substantially from findings from the NCoDV 2017/18 study and IMS 2017. Accurate data sources would ensure that public health interventions are designed to reduce the high injury burden. Inclusion of the manner of death on the DNF, as is recommended internationally, is critically important to enable more accurate, reliable and valid reporting of the injury profile.

OBJECTIVE: To provide guidance to rheumatology providers on the use of COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious diseases specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID-19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 9-point numerical scoring system, using a modified Delphi process and the RAND/University of California Los Angeles Appropriateness Method, with refinement and iteration over 2 sessions. Consensus was determined based on the distribution of ratings. RESULTS: Despite a paucity of direct evidence, statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID-19 vaccines, including supplemental/booster dosing, in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination. CONCLUSION: These guidance statements are intended to provide direction to rheumatology health care providers on how to best use COVID-19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.

Laboratory confirmation of infection is an essential component of measles surveillance. Detection of measles specific IgM in serum by enzyme linked immunosorbent assay (ELISA) is the most used method for confirming measles infection. ELISA formats vary as does the sensitivity and specificity of each assay. Specimens collected within 3 days of rash onset can yield a false negative result, which can delay confirmation of measles cases. Interfering substances can yield a false positive result, leading to unnecessary public health interventions. The IgM capture assay developed at the Centers for Disease Control (CDC) was compared against 5 commercially available ELISA kits for the ability to detect measles virus-specific IgM in a panel of 90 well-characterized specimens. Serum samples were tested in triplicate using each commercial kit as recommended by the manufacturer. Using the CDC measles IgM capture assay as the reference test; sensitivity and specificity for the commercial kits ranged from 50 to 83% and 86.9 to 98%, respectively. Discrepant results were observed for samples tested with all five commercial kits and ranged from 13.8 to 28.8% of the specimens tested. False positive results occurred in 2.0 to 13.1% of sera while negative results were observed in 16.7 to 50% of sera that were positive by the CDC measles IgM capture assay. Evaluation and interpretation of measles IgM serologic results can be complex, particularly in measles elimination settings. The performance characteristics of a measles IgM assay should be carefully considered when selecting an assay to achieve high quality measles surveillance. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

BACKGROUND: Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. METHODS: We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1-59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. FINDINGS: Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6-97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3-65·6) of causes, whereas bacteria accounted for 27·3% (23·3-31·6) and Mycobacterium tuberculosis for 5·9% (3·9-8·3). Viruses were less common (54·5%, 95% CrI 47·4-61·5 vs 68·0%, 62·7-72·7) and bacteria more common (33·7%, 27·2-40·8 vs 22·8%, 18·3-27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4-34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis, and H influenzae each accounted for 5% or more of the aetiological distribution. We observed differences in aetiological fraction by age for Bordetella pertussis, parainfluenza types 1 and 3, parechovirus-enterovirus, P jirovecii, RSV, rhinovirus, Staphylococcus aureus, and S pneumoniae, and differences by severity for RSV, S aureus, S pneumoniae, and parainfluenza type 3. The leading ten pathogens of each site accounted for 79% or more of the site's aetiological fraction. INTERPRETATION: In our study, a small set of pathogens accounted for most cases of pneumonia requiring hospital admission. Preventing and treating a subset of pathogens could substantially affect childhood pneumonia outcomes. FUNDING: Bill & Melinda Gates Foundation.

We appreciate the comment by Dr. Mortezavi and colleagues describing COVID‐19 vaccine response and the frequency of disease worsening in patients receiving tofacitinib. The ACR COVID‐19 Vaccine Clinical Guidance Task Force was aware of the 2 studies cited and appreciate their summary of the results. We would point out that in the rheumatoid arthritis study by Winthrop et al (1), patients receiving tofacitinib in Study A had a lower likelihood of a satisfactory response to pneumococcal vaccination (45.1%) compared to placebo‐treated patients (68.4%), a difference of 23.3% (95% confidence interval [95% CI] −36.6, −9.6%). The differences were numerically even larger for patients receiving concomitant tofacitinib and methotrexate (31.6% of patients with a satisfactory response, difference of −30.2% [95% CI] −47.3, −11.4%) compared to methotrexate monotherapy. Our challenge was in considering the appropriateness of extrapolating results from vaccine studies of influenza, pneumococcal, and tetanus toxoid vaccines to make inferences regarding the anticipated response to vaccination against SARS–CoV‐2, a novel antigen to which most individuals have not previously been exposed. | | The Task Force recognized that infection rates, and perhaps response to vaccinations against those infections, might be heterogeneous according to pathogen. For example, JAK inhibitors approximately double the incidence of herpes zoster compared to biologics such as tumor necrosis factor inhibitors, yet they do not meaningfully increase rates of other infections (e.g., pneumonia) (1, 2, 3). We noted that in the Oral Strategy study, adalimumab‐treated patients receiving vaccination with the live herpes zoster vaccine had lower incidence rates of herpes zoster (0.0 per 100 patient‐years) compared to non‐vaccinated patients (incidence rate 2.1 per 100 patient‐years) (4). In contrast, and recognizing that numbers were small, tofacitinib‐treated patients had similar rates of herpes zoster regardless of vaccination (incidence rate 3.0 per 100 patient‐years in vaccinated versus 2.2 per 100 patient‐years in unvaccinated patients). | | We also appreciate the data provided by Dr. Mortezavi and colleagues regarding the rate of disease worsening in patients whose treatment with tofacitinib was briefly interrupted. At ~ 2 weeks, the mean worsening in the 4‐variable DAS28 of 0.7 units was of smaller magnitude than typically considered the minimum clinically important difference (MCID) for the DAS28 (i.e., >1.2 units) (5). The MCID for defining disease worsening using the CDAI in patients who had moderate disease activity at the start of treatment is undefined, although a 1‐unit change in each of the 4 CDAI components (tender joint count, swollen joint count, patient global, and physician global) is often considered to be the measurement error for each of these (6). Taken together, the mean amount of disease worsening associated with brief interruptions in therapy seems small and likely not of clinical importance for most patients, especially in light of the guidance recommending that JAK inhibitors be withheld for 1 week at the time of each vaccine administration, rather than for 2 consecutive weeks. | | Ultimately, we await prospective data regarding the influence of JAK inhibitors and other immunomodulatory therapies used at the time of COVID‐19 vaccination on immunogenicity and correlates of serologic protection. Since the ACR COVID‐19 Vaccine Guidance is a living document, our plan is to rapidly update it and incorporate new evidence as it accumulates.

OBJECTIVE: To provide guidance to rheumatology providers on the use of coronavirus disease 2019 (COVID-19) vaccines for patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious disease specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID-19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 9-point numerical scoring system, using a modified Delphi process and the RAND/University of California Los Angeles Appropriateness Method, with refinement and iteration over 2 sessions. Consensus was determined based on the distribution of ratings. RESULTS: Despite a paucity of direct evidence, 74 draft guidance statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID-19 vaccines in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination. CONCLUSION: These guidance statements, made in the context of limited clinical data, are intended to provide direction to rheumatology health care providers on how to best use COVID-19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.

Laboratory confirmation of infection is an essential component of measles surveillance. Detection of measles-specific IgM in serum by enzyme-linked immunosorbent assay (ELISA) is the most common method used to confirm measles infection. ELISA formats vary, as does the sensitivity and specificity of each assay. Specimens collected within 3 days of rash onset can yield a false-negative result, which can delay confirmation of measles cases. Interfering substances can yield a false-positive result, leading to unnecessary public health interventions. The IgM capture assay developed at the Centers for Disease Control (CDC) was compared against five commercially available ELISA kits for the ability to detect measles virus-specific IgM in a panel of 90 well-characterized specimens. Serum samples were tested in triplicate using each commercial kit as recommended by the manufacturer. Using the CDC measles IgM capture assay as the reference test; the sensitivity and specificity for each commercial kit ranged from 50 to 83% and 86.9 to 98%, respectively. Discrepant results were observed for samples tested with all five commercial kits and ranged from 13.8 to 28.8% of the specimens tested. False-positive results occurred in 2.0 to 13.1% of sera, while negative results were observed in 16.7 to 50% of sera that were positive by the CDC measles IgM capture assay. Evaluation and interpretation of measles IgM serologic results can be complex, particularly in measles elimination settings. The performance characteristics of a measles IgM assay should be carefully considered when selecting an assay to achieve high-quality measles surveillance.

The observed epidemiology of SARS-CoV-2 in sub-Saharan Africa has varied greatly from that in Europe and the United States, with much lower reported incidence. Population-based studies are needed to estimate true cumulative incidence of SARS-CoV-2 to inform public health interventions. This study estimated SARS-CoV-2 seroprevalence in four selected states in Nigeria in October 2020. We implemented a two-stage cluster sample household survey in four Nigerian states (Enugu, Gombe, Lagos, and Nasarawa) to estimate age-stratified prevalence of SARS-CoV-2 antibodies. All individuals in sampled households were eligible for interview, blood draw, and nasal/oropharyngeal swab collection. We additionally tested participants for current/recent malaria infection. Seroprevalence estimates were calculated accounting for the complex survey design. Across all four states, 10,629 (96.5%) of 11,015 interviewed individuals provided blood samples. The seroprevalence of SARS-CoV- 2 antibodies was 25.2% (95% CI 21.8-28.6) in Enugu State, 9.3% (95% CI 7.0-11.5) in Gombe State, 23.3% (95% CI 20.5-26.4) in Lagos State, and 18.0% (95% CI 14.4-21.6) in Nasarawa State. Prevalence of current/recent malaria infection ranged from 2.8% in Lagos to 45.8% in Gombe and was not significantly related to SARS-CoV-2 seroprevalence. The prevalence of active SARS-CoV-2 infection in the four states during the survey period was 0.2% (95% CI 0.1-0.4). Approximately eight months after the first reported COVID-19 case in Nigeria, seroprevalence indicated infection levels 194 times higher than the 24,198 officially reported COVID-19 cases across the four states; however, most of the population remained susceptible to COVID-19 in October 2020.

OBJECTIVE: To provide guidance to rheumatology providers on the use of COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious disease specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID-19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 9-point numerical scoring system, using a modified Delphi process and the RAND/University of California Los Angeles Appropriateness Method, with refinement and iteration over 2 sessions. Consensus was determined based on the distribution of ratings. RESULTS: Despite a paucity of direct evidence, statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID-19 vaccines, including supplemental/booster dosing, in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination. CONCLUSION: These guidance statements are intended to provide direction to rheumatology health care providers on how to best use COVID-19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.

BACKGROUND: Beyond alcohol retail establishments, most business and property types receive limited attention in studies of violent crime. We sought to provide a comprehensive examination of which properties experience the most violent crime in a city and how that violence is distributed throughout a city. METHODS: For a large urban city, we merged violent incident data from police reports with municipal tax assessor data from 2012-2017 and tabulated patterns of violent crime for 15 commercial and public property types. To describe outlier establishments, we calculated the proportion of individual parcels within each property-type that experienced more than 5 times the average number of crimes for that property-type and also mapped the 25 parcels with the highest number of violent incidents to explore what proportion of violent crime in these block groups were contributed by the outlier establishments. RESULTS: While the hotel/lodging property-type experienced the highest number of violent crimes per parcel (2.72), each property-type had outlier establishments experiencing more than 5 times the average number of violent crimes per business. Twelve of 15 property-types (80%) had establishments with more than 10 times the mean number of violent incidents. The 25 parcels with the most violent crime comprised a wide variety of establishments, ranging from a shopping center, grocery store, gas station, motel, public park, vacant lot, public street, office building, transit station, hospital, pharmacy, school, community center, and movie theatre, and were distributed across the city. Eight of the 25 parcels with the highest amount of violent crime, accounted for 50% or more of the violent crime within a 400-meter buffer. CONCLUSIONS: All property-types had outlier establishments experiencing elevated counts of violent crimes. Furthermore, the 25 most violent properties in the city demonstrated remarkable diversity in property-type. Further studies assessing the risk of violent crime among additional property-types may aid in violence prevention.

OBJECTIVE: To provide guidance to rheumatology providers on the use of coronavirus disease 2019 (COVID-19) vaccines for patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious disease specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID-19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 9-point numerical scoring system, using a modified Delphi process and the RAND/University of California Los Angeles Appropriateness Method, with refinement and iteration over 2 sessions. Consensus was determined based on the distribution of ratings. RESULTS: Despite a paucity of direct evidence, 74 draft guidance statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID-19 vaccines in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination. CONCLUSION: These guidance statements, made in the context of limited clinical data, are intended to provide direction to rheumatology health care providers on how to best use COVID-19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.

Infectious disease is recognized as the greatest threat to the endangered chimpanzees made famous by the groundbreaking work of Dr. Jane Goodall at Gombe National Park (GNP), Tanzania. The permeable boundary of this small protected area allows for regular wildlife-human and wildlife-domestic animal overlap, which may facilitate cross-species transmission of pathogens and antimicrobial resistance. Few studies have examined the prevalence of antimicrobial resistance in wild ape populations. We used molecular techniques to investigate the presence of genes conferring resistance to sulfonamides (often used to treat diarrheal illness in human settings in this region) and tetracycline (used in the past-though much less so now) in fecal specimens from humans, domestic animals, chimpanzees, and baboons in and around GNP. We also tested stream water used by these groups. Sulfonamide resistance was common in humans (74%), non-human primates (43%), and domestic animals (17%). Tetracycline resistance was less common in all groups: humans (14%), non-human primates (3%), and domestic animals (6%). Sul resistance genes were detected from 4/22 (18%) of streams sampled. Differences in sul gene frequencies did not vary by location in humans nor in chimpanzees.

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2,500 COVID-19 cases associated with this variant have been detected in the United States (US) since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight that the primary ports of entry for B.1.1.7 in the US were in New York, California, and Florida. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid- to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.

The U.S. Centers for Disease Control and Prevention (CDC), state, tribal, and local health departments assess available and promising interventions and individual and population health outcomes when crafting public health recommendations. This supplement provides a snapshot of some of the science, experience, and expertise supporting the COVID-19 response.

BACKGROUND: Severity of viral respiratory illnesses can be increased with bacterial coinfection and can vary by sex, but influence of coinfection and sex on human endemic coronavirus (CoV) species, which generally cause mild to moderate respiratory illness, is unknown. We evaluated CoV and pneumococcal co-detection by sex in childhood pneumonia. METHODS: In the 2011-2014 Pneumonia Etiology Research for Child Health study, nasopharyngeal and oropharyngeal (NP/OP) swabs and other samples were collected from 3981 children <5 years hospitalized with severe or very severe pneumonia in 7 countries. Severity by NP/OP detection status of CoV (NL63, 229E, OC43 or HKU1) and high-density (≥6.9 log10 copies/mL) pneumococcus (HDSpn) by real-time polymerase chain reaction was assessed by sex using logistic regression adjusted for age and site. RESULTS: There were 43 (1.1%) CoV+/HDSpn+, 247 CoV+/HDSpn-, 449 CoV-/HDSpn+ and 3149 CoV-/HDSpn- cases with no significant difference in co-detection frequency by sex (range 51.2%-64.0% male, P = 0.06). More CoV+/HDSpn+ pneumonia was very severe compared with other groups for both males (13/22, 59.1% versus range 29.1%-34.7%, P = 0.04) and females (10/21, 47.6% versus 32.5%-43.5%, P = 0.009), but only male CoV+/HDSpn+ required supplemental oxygen more frequently (45.0% versus 20.6%-28.6%, P < 0.001) and had higher mortality (35.0% versus 5.3%-7.1%, P = 0.004) than other groups. For females with CoV+/HDSpn+, supplemental oxygen was 25.0% versus 24.8%-33.3% (P = 0.58) and mortality was 10.0% versus 9.2%-12.9% (P = 0.69). CONCLUSIONS: Co-detection of endemic CoV and HDSpn was rare in children hospitalized with pneumonia, but associated with higher severity and mortality in males. Findings may warrant investigation of differences in severity by sex with co-detection of HDSpn and SARS-CoV-2.

BACKGROUND: Antimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance. METHODS: Here we present a public health-focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch ( https://pathogen.watch/ngonorrhoeae ). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization. RESULTS: AMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin-resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasising the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern. CONCLUSIONS: The N. gonorrhoeae scheme in Pathogenwatch provides customised bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower-resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.

OBJECTIVE: To provide guidance to rheumatology providers on the use of COVID-19 vaccines for patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: A task force was assembled that included 9 rheumatologists/immunologists, 2 infectious disease specialists, and 2 public health physicians. After agreeing on scoping questions, an evidence report was created that summarized the published literature and publicly available data regarding COVID-19 vaccine efficacy and safety, as well as literature for other vaccines in RMD patients. Task force members rated their agreement with draft consensus statements on a 1 to 9 point numerical rating scale using a modified Delphi process and the RAND/UCLA appropriateness method, with refinement and iteration over two sessions. Consensus was determined based on the distribution of ratings. RESULTS: Despite a paucity of direct evidence, seventy-four draft guidance statements were developed by the task force and agreed upon with consensus to provide guidance for use of the COVID-19 vaccines in RMD patients and to offer recommendations regarding the use and timing of immunomodulatory therapies around the time of vaccination. CONCLUSION: These guidance statements, made in the context of limited clinical data, are intended to provide direction to rheumatology healthcare providers on how to best use COVID-19 vaccines and to facilitate implementation of vaccination strategies for RMD patients.

IMPORTANCE: Risks for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among health care personnel (HCP) are unclear. OBJECTIVE: To evaluate the risk factors associated with SARS-CoV-2 seropositivity among HCP with the a priori hypothesis that community exposure but not health care exposure was associated with seropositivity. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted among volunteer HCP at 4 large health care systems in 3 US states. Sites shared deidentified data sets, including previously collected serology results, questionnaire results on community and workplace exposures at the time of serology, and 3-digit residential zip code prefix of HCP. Site-specific responses were mapped to a common metadata set. Residential weekly coronavirus disease 2019 (COVID-19) cumulative incidence was calculated from state-based COVID-19 case and census data. EXPOSURES: Model variables included demographic (age, race, sex, ethnicity), community (known COVID-19 contact, COVID-19 cumulative incidence by 3-digit zip code prefix), and health care (workplace, job role, COVID-19 patient contact) factors. MAIN OUTCOME AND MEASURES: The main outcome was SARS-CoV-2 seropositivity. Risk factors for seropositivity were estimated using a mixed-effects logistic regression model with a random intercept to account for clustering by site. RESULTS: Among 2 749 HCP, most were younger than 50 years (17 233 [69.6%]), were women (19 361 [78.2%]), were White individuals (15 157 [61.2%]), and reported workplace contact with patients with COVID-19 (12 413 [50.2%]). Many HCP worked in the inpatient setting (8893 [35.9%]) and were nurses (7830 [31.6%]). Cumulative incidence of COVID-19 per 10 000 in the community up to 1 week prior to serology testing ranged from 8.2 to 275.6; 20 072 HCP (81.1%) reported no COVID-19 contact in the community. Seropositivity was 4.4% (95% CI, 4.1%-4.6%; 1080 HCP) overall. In multivariable analysis, community COVID-19 contact and community COVID-19 cumulative incidence were associated with seropositivity (community contact: adjusted odds ratio [aOR], 3.5; 95% CI, 2.9-4.1; community cumulative incidence: aOR, 1.8; 95% CI, 1.3-2.6). No assessed workplace factors were associated with seropositivity, including nurse job role (aOR, 1.1; 95% CI, 0.9-1.3), working in the emergency department (aOR, 1.0; 95% CI, 0.8-1.3), or workplace contact with patients with COVID-19 (aOR, 1.1; 95% CI, 0.9-1.3). CONCLUSIONS AND RELEVANCE: In this cross-sectional study of US HCP in 3 states, community exposures were associated with seropositivity to SARS-CoV-2, but workplace factors, including workplace role, environment, or contact with patients with known COVID-19, were not. These findings provide reassurance that current infection prevention practices in diverse health care settings are effective in preventing transmission of SARS-CoV-2 from patients to HCP.

BACKGROUND: Simulation exercises can functionally validate World Health Organization (WHO) International Health Regulations (IHR 2005) core capacities. In 2018, the Vietnam Ministry of Health (MOH) conducted a full-scale exercise (FSX) in response to cases of severe viral pneumonia with subsequent laboratory confirmation for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) to evaluate the country's early warning and response capabilities for high-risk events. METHODS: An exercise planning team designed a complex fictitious scenario beginning with one case of severe viral pneumonia presenting at the hospital level and developed all the materials required for the exercise. Actors, controllers and evaluators were trained. In August 2018, a 3-day exercise was conducted in Quang Ninh province and Hanoi city, with participation of public health partners at the community, district, province, regional and national levels. Immediate debriefings and an after-action review were conducted after all exercise activities. Participants assessed overall exercise design, conduction and usefulness. RESULTS: FSX findings demonstrated that the event-based surveillance component of the MOH surveillance system worked optimally at different administrative levels. Detection and reporting of signals at the community and health facility levels were appropriate. Triage, verification and risk assessment were successfully implemented to identify a high-risk event and trigger timely response. The FSX identified infection control, coordination with internal and external response partners and process documentation as response challenges. Participants positively evaluated the exercise training and design. CONCLUSIONS: This exercise documents the value of exercising surveillance capabilities as part of a real-time operational scenario before facing a true emergency. The timing of this exercise and choice of disease scenario was particularly fortuitous given the subsequent appearance of COVID-19. As a result of this exercise and subsequent improvements made by the MOH, the country may have been better able to deal with the emergence of SARS-CoV-2 and contain it.

Protecting health care workers from COVID-19 remains a priority during the ongoing pandemic. Accurate assessment of the risk for infection among health care workers is important in determining the effectiveness of infection control plans. In late March 2020, a total of 591 U.S. Army personnel from three units were deployed from areas in which COVID-19 incidence was low to the Javits New York Medical Station (JMS), a 452-bed Federal Emergency Management Agency Federal Medical Station in New York City (NYC), to provide care to COVID-19 patients. Army personnel followed a rigorous infection control plan and remained largely isolated from the surrounding community while in NYC. During April 3–25, a total of 1,095 COVID-19 patients were admitted from NYC area hospitals to the JMS ward or intensive care unit (ICU). A cross-sectional study of the prevalence of SARS-CoV-2 infection among 336 active duty soldiers enrolled in a prevalence study identified an infection rate of 1.7% overall and 0.9% in the 223 (66.4%) enrolled soldiers who provided direct care to COVID-19 patients. A well-designed and well-implemented infection control plan can mitigate the risk for SARS-CoV-2, the virus that causes COVID-19, infection in health care settings, including nontraditional settings.

We aimed to describe coronavirus disease 2019 (COVID-19) deaths among first responders early in the COVID-19 pandemic. We used media reports to gather timely information about COVID-19-related deaths among first responders during March 30-April 30, 2020, and evaluated the sensitivity of media scanning compared with traditional surveillance. We abstracted information about demographic characteristics, occupation, underlying conditions, and exposure source. Twelve of 19 US public health jurisdictions with data on reported deaths provided verification, and 7 jurisdictions reported whether additional deaths had occurred; we calculated the sensitivity of media scanning among these 7 jurisdictions. We identified 97 COVID-19-related first-responder deaths during the study period through media and jurisdiction reports. Participating jurisdictions reported 5 deaths not reported by the media. Sixty-six decedents worked in law enforcement, and 31 decedents worked in fire/emergency medical services. Media reports rarely noted underlying conditions. The media scan sensitivity was 88% (95% CI, 73%-96%) in the subset of 7 jurisdictions. Media reports demonstrated high sensitivity in documenting COVID-19-related deaths among first responders; however, information on risk factors was scarce. Routine collection of data on industry and occupation could improve understanding of COVID-19 morbidity and mortality among all workers.

On January 10, 2020, the first genomic sequence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from a patient in Wuhan, China, was posted online. As of February 3, 2021, 468 000 sequences of SARS-CoV-2 from COVID-19 cases globally have been uploaded into publicly available data-bases, including more than 93 000 from individuals in the US. SARS-CoV-2, like other RNA viruses, constantly changes through mutation, with new variants occurring over time. Generally, when new variants become more common, they do so because of some selective advantage to the virus. Among the numerous SARS-CoV-2 variants that have been detected, only a very small proportion are of public health concern because they are more transmissible, cause more severe illness, or can elude the immune response that develops following infection and possibly from vaccination. In the recent months, 3 specific viral lineages reflecting variants of concern have emerged and merit close monitoring: B.1.1.7, B.1.351, and P.1.

BACKGROUND: Intermittent preventive treatment of malaria in infants (IPTi) with sulfadoxine-pyrimethamine (SP) is a proven strategy to protect infants against malaria. Sierra Leone is the first country to implement IPTi nationwide. IPTi implementation was evaluated in Kambia, one of two initial pilot districts, to assess quality and coverage of IPTi services. METHODS: This mixed-methods evaluation had two phases, conducted 3 (phase 1) and 15-17 months (phase 2) after IPTi implementation. Methods included: assessments of 18 health facilities (HF), including register data abstraction (phases 1 and 2); a knowledge, attitudes and practices survey with 20 health workers (HWs) in phase 1; second-generation sequencing of SP resistance markers (pre-IPTi and phase 2); and a cluster-sample household survey among caregivers of children aged 3-15 months (phase 2). IPTi and vaccination coverage from the household survey were calculated from child health cards and maternal recall and weighted for the complex sampling design. Interrupted time series analysis using a Poisson regression model was used to assess changes in malaria cases at HF before and after IPTi implementation. RESULTS: Most HWs (19/20) interviewed had been trained on IPTi; 16/19 reported feeling well prepared to administer it. Nearly all HFs (17/18 in phase 1; 18/18 in phase 2) had SP for IPTi in stock. The proportion of parasite alleles with dhps K540E mutations increased but remained below the 50% WHO-recommended threshold for IPTi (4.1% pre-IPTi [95%CI 2-7%]; 11% post-IPTi [95%CI 8-15%], p < 0.01). From the household survey, 299/459 (67.4%) children ≥ 10 weeks old received the first dose of IPTi (versus 80.4% for second pentavalent vaccine, given simultaneously); 274/444 (62.5%) children ≥ 14 weeks old received the second IPTi dose (versus 65.4% for third pentavalent vaccine); and 83/217 (36.4%) children ≥ 9 months old received the third IPTi dose (versus 52.2% for first measles vaccine dose). HF register data indicated no change in confirmed malaria cases among infants after IPTi implementation. CONCLUSIONS: Kambia district was able to scale up IPTi swiftly and provide necessary health systems support. The gaps between IPTi and childhood vaccine coverage need to be further investigated and addressed to optimize the success of the national IPTi programme.

BACKGROUND: Microbial endocrinology, which is the study of neuroendocrine-based interkingdom signaling, provides a causal mechanistic framework for understanding the bi-directional crosstalk between the host and microbiome, especially as regards the effect of stress on health and disease. The importance of the cecal microbiome in avian health is well-recognized, yet little is understood regarding the mechanisms underpinning the avian host-microbiome relationship. Neuroendocrine plasticity of avian tissues that are focal points of host-microbiome interaction, such as the gut and lung, has likewise received limited attention. Avian in vivo models that enable the study of the neuroendocrine dynamic between host and microbiome are needed. As such, we utilized Japanese quail (Coturnix japonica) that diverge in corticosterone response to stress to examine the relationship between stress-related neurochemical concentrations at sites of host-microbe interaction, such as the gut, and the cecal microbiome. RESULTS: Our results demonstrate that birds which contrast in corticosterone response to stress show profound separation in cecal microbial community structure as well as exhibit differences in tissue neurochemical concentrations and structural morphologies of the gut. Changes in neurochemicals known to be affected by the microbiome were also identified in tissues outside of the gut, suggesting a potential relationship in birds between the cecal microbiome and overall avian physiology. CONCLUSIONS: The present study provides the first evidence that the structure of the avian cecal microbial community is shaped by selection pressure on the bird for neuroendocrine response to stress. Identification of unique region-dependent neurochemical changes in the intestinal tract following stress highlights environmental stressors as potential drivers of microbial endocrinology-based mechanisms of avian host-microbiome dialogue. Together, these results demonstrate that tissue neurochemical concentrations in the avian gut may be related to the cecal microbiome and reveal the Japanese quail as a novel avian model in which to further examine the mechanisms underpinning these relationships. Video abstract.

The novel coronavirus disease 2019, COVID-19, which is caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2) [1] was first reported in December 2019 by Chinese Health Authorities following an outbreak of pneumonia of unknown origin in Wuhan, Hubei Province [2,3]. SARS-CoV-2 is likely of zoonotic origin, similar to SARS and Middle East Respiratory Syndrome (MERS), and transmitted between humans through respiratory droplets and fomites. Since its emergence, it has rapidly spread globally [4].

Elections occurring during the coronavirus disease 2019 (COVID-19) pandemic have been affected by notable changes in the methods of voting, the number and type of polling locations, and in-person voting procedures (1). To mitigate transmission of COVID-19 at polling locations, jurisdictions have adopted changes to protocols and procedures, informed by CDC's interim guidance, developed in collaboration with the Election Assistance Commission (2). The driving principle for this guidance is that voting practices with lower infection risk will be those which reduce the number of voters who congregate indoors in polling locations by offering a variety of methods for voting and longer voting periods. The guidance for in-person voting includes considerations for election officials, poll workers, and voters to maintain healthy environments and operations. To assess knowledge and adoption of mitigation strategies, CDC collaborated with the Delaware Department of Health and Social Services and the Delaware State Election Commission on a survey of poll workers who served during the statewide primary election on September 15, 2020. Among 522 eligible poll workers, 93% correctly answered all three survey questions about COVID-19 transmission. Respondents noted that most voters and poll workers wore masks. However, masks were not always worn correctly (i.e., covering both the nose and mouth). Responses suggest that mitigation measures recommended for both poll workers and voters were widely adopted and feasible, but also highlighted gaps in infection prevention control efforts. Strengthening of measures intended to minimize the risk of poll workers acquiring COVID-19 from ill voters, such as additional training and necessary personal protective equipment (PPE), as well as support for alternative voting options for ill voters, are needed. Adherence to mitigation measures is important not only to protect voters but also to protect poll workers, many of whom are older adults, and thus at higher risk for severe COVID-19-associated illness. Enhanced attention to reducing congregation in polling locations, correct mask use, and providing safe voting options for ill voters are critical considerations to minimize risk to voters and poll workers. Evidence from the Delaware election supports the feasibility and acceptability of implementing current CDC guidance for election officials, poll workers, and voters for mitigating COVID-19 transmission at polling locations (2).

Increases in injection drug use (IDU) as a result of increasing levels of opioid misuse in the United States may increase risk for new, rapidly transmitted HIV infections in communities with otherwise low HIV prevalence.1 Changing characteristics and geographic locations of persons at risk for HIV infection due to injection-related risk behavior present ongoing challenges to partner services for HIV prevention. These jurisdictions have historically had less need for HIV-related partner services and therefore less investment in HIV outbreak preparedness and prevention infrastructure. Jurisdictions with low HIV prevalence have also had to rely on cluster investigation methods that were developed for primary use in urban areas. In early 2019, the US strategic plan to end the HIV epidemic in the United States within 10 years was announced, which prioritizes the rapid detection and response to emerging clusters of HIV infection to further reduce new transmissions as 1 of the 4 main pillars of the initiative.2

In March 2020, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. At the genus rank, 20 new genera were added, two were deleted, one was moved, and three were renamed. At the species rank, 160 species were added, four were deleted, ten were moved and renamed, and 30 species were renamed. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.