Chlorine gas (Cl(2)) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl(2) exposures frequently occur in domestic and occupational environments, and in transportation accidents. Modeling the human etiology of Cl(2)-induced acute lung injury (ALI), forensic biomarkers, and targeted countermeasures development have been hampered by inadequate large animal models. The objective of this study was to develop a translational model of Cl(2)-induced ALI in swine to understand toxico-pathophysiology and is suitable for screening potential medical countermeasures, and identify biomarkers useful for forensic analysis. Specific pathogen-free Yorkshire swine (30-40 kg) of either sex were exposed to Cl(2) (≤ 240 ppm for 1 h) or filtered air under anesthesia and controlled mechanical ventilation. Exposure to Cl(2) resulted in severe hypoxia and hypoxemia, increased airway resistance and peak inspiratory pressure, and decreased dynamic lung compliance. Cl(2) exposure resulted in increased total leucocyte and neutrophil counts in bronchoalveolar lavage fluid (BALF), vascular leakage, and pulmonary edema compared to the air-exposed group. The model recapitulated all three key histopathological features of human ALI, such as neutrophilic alveolitis, deposition of hyaline membranes, and formation of microthrombi. Free and lipid-bound 2‑chlorofatty acids and chlorotyrosine-modified proteins (3-chloro-L-tyrosine and 3,5-dichloro-L-tyrosine) were detected in plasma and lung tissue after Cl(2)‑exposure. In this study, we developed a translational swine model that recapitulates key features of human Cl(2) inhalation injury and is suitable for testing medical countermeasures, and validated chlorinated fatty acids and protein adducts as biomarkers of Cl(2) inhalation.

Despite the availability of effective vaccines against pneumococcal disease, pneumococcus is a common bacterial cause of pneumonia, causing approximately 100,000 hospitalizations among U.S. adults per year. In addition, approximately 30,000 invasive pneumococcal disease (IPD) cases and 3,000 IPD deaths occur among U.S. adults each year. Previous health care provider surveys identified gaps in provider knowledge about and understanding of the adult pneumococcal vaccine recommendations, and pneumococcal vaccine coverage remains suboptimal. To assess the feasibility and acceptability domains of the Advisory Committee on Immunization Practices (ACIP) Evidence to Recommendations (EtR) framework, a health care provider knowledge and attitudes survey was conducted during September 28-October 10, 2022, by the Healthcare and Public Perceptions of Immunizations Survey Collaborative before the October 2022 ACIP meeting. Among 751 provider respondents, two thirds agreed or strongly agreed with the policy option under consideration to expand the recommendations for the new 20-valent pneumococcal conjugate vaccine (PCV20) to adults who had only received the previously recommended 13-valent pneumococcal conjugate vaccine (PCV13). Gaps in providers' knowledge and perceived challenges to implementing recommendations were identified and were included in ACIP's EtR framework discussions in late October 2022 when ACIP updated the recommendations for PCV20 use in adults. Currently, use of PCV20 is recommended for certain adults who have previously received PCV13, in addition to those who have never received a pneumococcal conjugate vaccine. The survey findings indicate a need to increase provider awareness and implementation of pneumococcal vaccination recommendations and to provide tools to assist with patient-specific vaccination guidance. Resources available to address the challenges to implementing pneumococcal vaccination recommendations include the PneumoRecs VaxAdvisor mobile app and other CDC-developed tools, including summary documents and overviews of vaccination schedules and CDC's strategic framework to increase confidence in vaccines and reduce vaccine-preventable diseases, Vaccinate with Confidence.

Rationale: Chlorine gas (Cl<inf>2</inf>) has been repeatedly used as a chemical weapon, first in World War I and most recently in Syria. Life-threatening Cl<inf>2</inf> exposures frequently occur in domestic and occupational environments, and in transportation accidents. There is a knowledge gap in large animal models of Cl<inf>2</inf>-induced acute lung injury (ALI) required to accurately model human etiology and for the development of targeted countermeasures Objective: To develop a translational model of Cl<inf>2</inf>-induced ALI in swine to study toxicopathophysiology and identify biomarkers useful for forensic analysis. Method(s): Specific pathogen-free Yorkshire swine (30-40 kg) of either sex were exposed to Cl<inf>2</inf> gas (<= 240 ppm for 1 h) or filtered air under anesthesia and controlled mechanical ventilation. Result(s): Exposure to Cl<inf>2</inf> resulted in severe hypoxia and hypoxemia, increased airway resistance and peak inspiratory pressure, and decreased dynamic lung compliance. Chlorine exposure resulted in increased total BALF and neutrophil counts, vascular leakage, and edema compared to the control group. The model recapitulated all three key histopathological features of human ALI, such as neutrophilic alveolitis, deposition of hyaline membranes, and formation of microthrombi. Free and lipid-bound 2-chlorofatty acids and chlorotyrosine-modified proteins (3-chloro-L-tyrosine and 3,5-dichloro-L-tyrosine) were detected in plasma and lung after Cl<inf>2</inf>-exposure. Conclusion(s): The translational model developed in this study replicates key features of humans exposed to Cl<inf>2</inf> and is suitable to test medical countermeasures. Specific biomarkers of Cl<inf>2</inf> exposure have been identified in plasma and lung tissue samples. 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.

I congratulate the authors on an interesting, instructive, and timely paper. Certainly, including the testing for SARS‐CoV‐2 example in a paper on a topic—group testing—of wide interest during the current COVID‐19 pandemic emphasizes the relevance of the topic in public health and diagnostic medicine generally. But the thoughtful inclusion of the remaining examples—HIV, HPV, and cancer biomarker detection—illustrates that the issues considered are important even in less urgent times. In this note of discussion I will comment on two particular aspects in the paper that I found particularly informative, and then I will comment on two other, related areas that I believe the conclusions inform.

In the past two decades, testing services for diseases such as HIV, TB and malaria have expanded dramatically. Investments in testing capacity and supportive health systems have often been disease specific, resulting in siloed testing programs with suboptimal capacity, reduced efficiency, and limited ability to introduce additional tests or respond to new outbreaks. Emergency demand for SARS-CoV2 testing overcame these silos and demonstrated the feasibility of integrated testing. Moving forward, an integrated public laboratory infrastructure that services multiple diseases, including SARS-CoV-2, influenza, HIV, TB, hepatitis, malaria, sexually transmitted diseases, and other infections will help improve universal healthcare delivery and pandemic preparedness. However, integrated testing faces many barriers including poorly aligned health systems, funding and policies. Strategies to overcome these include greater implementation of policies that support multi-disease testing and treatment systems, diagnostic network optimization, bundled test procurement, and more rapid spread of innovation and best practices across disease programs.

We investigated the first 152 laboratory-confirmed SARS-CoV-2 cases (125 primary and 27 secondary) and their 248 close contacts in Kisumu County, Kenya. Conducted June 10–October 8, 2020, this study included interviews and sample collection at enrolment and 14–21 days later. Median age was 35 years (IQR 28–44); 69.0% reported COVID-19 related symptoms, most commonly cough (60.0%), headache (55.2%), fever (53.3%) and loss of taste or smell (43.8%). One in five were hospitalized, 34.4% >25 years of age had at least one comorbidity, and all deaths had comorbidities. Adults ≥25 years with a comorbidity were 3.15 (95% CI 1.37–7.26) times more likely to have been hospitalized or died than participants without a comorbidity. Infectious comorbidities included HIV, tuberculosis, and malaria, but no current cases of influenza, respiratory syncytial virus, dengue fever, leptospirosis or chikungunya were identified. Thirteen (10.4%) of the 125 primary infections transmitted COVID-19 to 27 close contacts, 158 (63.7%) of whom resided or worked within the same household. Thirty-one percent (4 of 13) of those who transmitted COVID-19 to secondary cases were health care workers; no known secondary transmissions occurred between health care workers. This rapid assessment early in the course of the COVID-19 pandemic identified some context-specific characteristics which conflicted with the national line-listing of cases, and which have been substantiated in the year since. These included over two-thirds of cases reporting the development of symptoms during the two weeks after diagnosis, compared to the 7% of cases reported nationally; over half of cases reporting headaches, and nearly half of all cases reporting loss of taste and smell, none of which were reported at the time by the World Health Organization to be common symptoms. This study highlights the importance of rapid in-depth assessments of outbreaks in understanding the local epidemiology and response measures required.

INTRODUCTION: Since August 2009, the Democratic Republic of Congo (DRC) has implemented sentinel site surveillance for rotavirus gastroenteritis. Limited hospital studies have been carried out, in DRC, describing the epidemiology of rotavirus diarrhea before rotavirus vaccine introduction in October 2019. This analysis describes the epidemiology of rotavirus gastroenteritis and characteristics of circulating viral strains from 2009 to 2019. MATERIALS AND METHODS: We analyzed demographic and clinic data collected from children < 5 years old enrolled at three rotavirus sentinel surveillance sites in DRC during 2009-2019, prior to rotavirus vaccine introduction in 2019. Data have been described and presented as mean ± standard deviation for quantitative variables with normal distribution, or as median with an interquartile range [Q1-Q3] for quantitative variables with non-normal distribution, or as absolute value with percentage for qualitative variables. RESULTS: Between August 2009 and December 2019, 4,928 children < 5 years old were admitted to sentinel surveillance sites for gastroenteritis in the DRC; the rotavirus positivity rate was 60 %. There was a slight male gender predominance (56 %), and the majority of children (79 %) were 0-11 months of age. Every year, the incidence was highest between May and September corresponding to the dry and cool season. Genotyping was performed for 50 % of confirmed rotavirus cases. The most common G genotypes were G1 (39 %) and G2 (24 %) and most common P genotypes were P[6] (49 %) and P[8] (37 %). The most common G-P genotype combinations were G1P[8] (22 %), G2P[6] (16 %) and G1P[6] (14 %). Genotype distribution varied by site, age group, and year. CONCLUSION: From 2009 to 2019, rotavirus-associated gastroenteritis represented a significant burden among DRC children under 5 who were admitted to sentinel sites. G1P[8] was the most commonly identified genotype. Continued monitoring after the introduction of rotavirus vaccine will be essential to monitor any changes in epidemiology.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (73%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (07%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (914%), moxifloxacin (916%) and ethambutol (933%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation. 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.

To prevent transmission of SARS-CoV-2, the virus that causes COVID-19, colleges and universities have implemented multiple strategies including testing, isolation, quarantine, contact tracing, masking, and vaccination. In April 2021, the Chicago Department of Public Health (CDPH) was notified of a large cluster of students with COVID-19 at an urban university after spring break. A total of 158 cases of COVID-19 were diagnosed among undergraduate students during March 15-May 3, 2021; the majority (114; 72.2%) lived in on-campus dormitories. CDPH evaluated the role of travel and social connections, as well as the potential impact of SARS-CoV-2 variants, on transmission. Among 140 infected students who were interviewed, 89 (63.6%) reported recent travel outside Chicago during spring break, and 57 (40.7%) reported indoor social exposures. At the time of the outbreak, undergraduate-aged persons were largely ineligible for vaccination in Chicago; only three of the students with COVID-19 (1.9%) were fully vaccinated. Whole genome sequencing (WGS) of 104 specimens revealed multiple distinct SARS-CoV-2 lineages, suggesting several nearly simultaneous introductions. Most specimens (66; 63.5%) were B.1.1.222, a lineage not widely detected in Chicago before or after this outbreak. These results demonstrate the potential for COVID-19 outbreaks on university campuses after widespread student travel during breaks, at the beginning of new school terms, and when students participate in indoor social gatherings. To prevent SARS-CoV-2 transmission, colleges and universities should encourage COVID-19 vaccination; discourage unvaccinated students from travel, including during university breaks; implement serial COVID-19 screening among unvaccinated persons after university breaks; encourage masking; and implement universal serial testing for students based on community transmission levels.

In January 2020, Santa Clara County, California, USA, began identifying laboratory-confirmed coronavirus disease among residents. County staff conducted case and contact investigations focused on households and collected detailed case demographic, occupation, exposure, and outcome information. We describe the first 200 test-positive cases during January 31-March 20, 2020, to inform future case and contact investigations. Probable infection sources included community transmission (104 cases), known close contact with a confirmed case-patient (66 cases), and travel (30 cases). Disease patterns across race and ethnicity, occupational, and household factors suggested multiple infection risk factors. Disproportionately high percentages of case-patients from racial and ethnic subgroups worked outside the home (Hispanic [86%] and Filipino [100%]); household transmission was more common among persons from Vietnam (53%). Even with the few initial cases, detailed case and contact investigations of household contacts capturing occupational and disaggregated race and ethnicity data helped identify at-risk groups and focused solutions for disease control.

BACKGROUND: Insecticide resistance is threatening the effectiveness of efforts to control malaria vectors in Benin. This study explores the levels and mechanisms of insecticide resistance in An. gambiae s.l. to pyrethroids. METHODS: Larvae were collected from August 2017 to July 2018 in five communes in southern Benin (Adjohoun, Allada, Bohicon, Cotonou, and Porto-Novo) representing diverse ecological regions, and were reared in Benin's insectary. Two- to five-day-old female mosquitoes from each district were exposed to multiple doses of deltamethrin and permethrin (1×, 2×, 5×, and 10×) using the WHO insecticide resistance intensity bioassay. The effect of pre-exposure to the synergist, piperonyl butoxide (PBO), was also tested at different pyrethroid doses. Molecular allele frequencies of kdr (1014F) and ace-1R (119S) insecticide resistance mutations and levels of detoxification enzymes were determined for mosquitoes sampled from each study area. RESULTS: An. gambiae s.l. were resistant to pyrethroid-only exposure up to 10× the diagnostic doses in all the study sites for both deltamethrin and permethrin. Mortality was significantly higher in An. gambiae s.l. pre-exposed to PBO followed by exposure to deltamethrin or permethrin compared to mosquitoes exposed to deltamethrin or permethrin only (p < 0.001). The difference in mortality between deltamethrin only and PBO plus deltamethrin was the smallest in Cotonou (16-64%) and the greatest in Bohicon (12-93%). The mortality difference between permethrin only and PBO plus permethrin was the smallest in Cotonou (44-75%) and the greatest in Bohicon (22-72%). In all the study sites, the kdr resistance allele (1014F) frequency was high (75-100%), while the ace-1 resistance allele (G119S) frequency was low (0-3%). Analysis of the metabolic enzymatic activity of An. gambiae s.l. showed overexpression of nonspecific esterases and glutathione S-transferases (GST) in all study sites. In contrast to the PBO results, oxidase expression was low and was similar to the susceptible An. gambiae s.s. Kisumu strain in all sites. CONCLUSION: There is high-intensity resistance to pyrethroids in southern Benin. However, pre-exposure to PBO significantly increased susceptibility to the pyrethroids in the different An. gambiae s.l. populations sampled. The use of PBO insecticide-treated bed nets may help maintain the gains in An. gambiae (s.l.) control in southern Benin.

COVID-19 has disproportionately affected persons who identify as non-Hispanic American Indian or Alaska Native (AI/AN) (1). The Blackfeet Tribal Reservation, the northern Montana home of the sovereign Blackfeet Nation, with an estimated population of 10,629 (2), detected the first COVID-19 case in the community on June 16, 2020. Following CDC guidance,* and with free testing widely available, the Indian Health Service and Blackfeet Tribal Health Department began investigating all confirmed cases and their contacts on June 25. The relationship between three community mitigation resolutions passed and enforced by the Blackfeet Tribal Business Council and changes in the daily COVID-19 incidence and in the distributions of new cases was assessed. After the September 28 issuance of a strictly enforced stay-at-home order and adoption of a mask use resolution, COVID-19 incidence in the Blackfeet Tribal Reservation decreased by a factor of 33 from its peak of 6.40 cases per 1,000 residents per day on October 5 to 0.19 on November 7. Other mitigation measures the Blackfeet Tribal Reservation used included closing the east gate of Glacier National Park for the summer tourism season, instituting remote learning for public school students throughout the fall semester, and providing a Thanksgiving meal to every household to reduce trips to grocery stores. CDC has recommended use of routine public health interventions for infectious diseases, including case investigation with prompt isolation, contact tracing, and immediate quarantine after exposure to prevent and control transmission of SARS-CoV-2, the virus that causes COVID-19 (3). Stay-at-home orders, physical distancing, and mask wearing indoors, outdoors when physical distancing is not possible, or when in close contact with infected or exposed persons are also recommended as nonpharmaceutical community mitigation measures (3,4). Implementation and strict enforcement of stay-at-home orders and a mask use mandate likely helped reduce the spread of COVID-19 in the Blackfeet Tribal Reservation.

BACKGROUND: Multidisciplinary and multisectoral approaches such as One Health and related concepts (e.g., Planetary Health, EcoHealth) offer opportunities for synergistic expertise to address complex health threats. The connections between humans, animals, and the environment necessitate collaboration among sectors to comprehensively understand and reduce risks and consequences on health and wellbeing. One Health approaches are increasingly emphasized for national and international plans and strategies related to zoonotic diseases, food safety, antimicrobial resistance, and climate change, but to date, the possible applications in clinical practice and benefits impacting human health are largely missing. METHODS: In 2018 the "Application of the One Health Approach to Global Health Centers" conference held at the Albert Einstein College of Medicine convened experts involved in One Health policy and practice. The conference examined issues relevant to One Health approaches, sharing examples of challenges and successes to guide application to medical school curricula and clinical practice for human health. This paper presents a synthesis of conference proceedings, framed around objectives identified from presentations and audience feedback. FINDINGS AND RECOMMENDATIONS: The following objectives provide opportunities for One Health involvement and benefits for medical schools and global health centers by: 1) Improving One Health resource sharing in global health and medical education; 2) Creating pathways for information flow in clinical medicine and global health practice; 3) Developing innovative partnerships for improved health sector outcomes; and 4) Informing and empowering health through public outreach. These objectives can leverage existing resources to deliver value to additional settings and stakeholders through resource efficiency, more holistic and effective service delivery, and greater ability to manage determinants of poor health status. We encourage medical and global health educators, practitioners, and students to explore entry points where One Health can add value to their work from local to global scale.

The majority of Plasmodium falciparum malaria diagnoses in Africa are made using rapid diagnostic tests (RDTs) that detect histidine-rich protein 2. Increasing reports of false-negative RDT results due to parasites with deletions of the pfhrp2 and/or pfhrp3 genes (pfhrp2/3) raise concern about existing malaria diagnostic strategies. We previously identified pfhrp2-negative parasites among asymptomatic children in the Democratic Republic of the Congo (DRC), but their impact on diagnosis of symptomatic malaria is unknown. We performed a cross-sectional study of false-negative RDTs in symptomatic subjects in 2017. Parasites were characterized by microscopy; RDT; pfhrp2/3 genotyping and species-specific PCR assays; a bead-based immunoassay for Plasmodium antigens; and/or whole-genome sequencing. Among 3627 symptomatic subjects, 427 (11.8%) had RDT-/microscopy + results. Parasites from eight (0.2%) samples were initially classified as putative pfhrp2/3 deletions by PCR, but antigen testing and whole-genome sequencing confirmed the presence of intact genes. 56.8% of subjects had PCR-confirmed malaria. Non-falciparum co-infection with P. falciparum was common (13.2%). Agreement between PCR and HRP2-based RDTs was satisfactory (Cohen's kappa = 0.66) and superior to microscopy (0.33). Symptomatic malaria due to pfhrp2/3-deleted P. falciparum was not observed. Ongoing HRP2-based RDT use is appropriate for the detection of falciparum malaria in the DRC.

Many kindergarten through grade 12 (K-12) schools offering in-person learning have adopted strategies to limit the spread of SARS-CoV-2, the virus that causes COVID-19 (1). These measures include mandating use of face masks, physical distancing in classrooms, increasing ventilation with outdoor air, identification of close contacts,* and following CDC isolation and quarantine guidance(†) (2). A 2-week pilot investigation was conducted to investigate occurrences of SARS-CoV-2 secondary transmission in K-12 schools in the city of Springfield, Missouri, and in St. Louis County, Missouri, during December 7-18, 2020. Schools in both locations implemented COVID-19 mitigation strategies; however, Springfield implemented a modified quarantine policy permitting student close contacts aged ≤18 years who had school-associated contact with a person with COVID-19 and met masking requirements during their exposure to continue in-person learning.(§) Participating students, teachers, and staff members with COVID-19 (37) from 22 schools and their school-based close contacts (contacts) (156) were interviewed, and contacts were offered SARS-CoV-2 testing. Among 102 school-based contacts who received testing, two (2%) had positive test results indicating probable school-based SARS-CoV-2 secondary transmission. Both contacts were in Springfield and did not meet criteria to participate in the modified quarantine. In Springfield, 42 student contacts were permitted to continue in-person learning under the modified quarantine; among the 30 who were interviewed, 21 were tested, and none received a positive test result. Despite high community transmission, SARS-CoV-2 transmission in schools implementing COVID-19 mitigation strategies was lower than that in the community. Until additional data are available, K-12 schools should continue implementing CDC-recommended mitigation measures (2) and follow CDC isolation and quarantine guidance to minimize secondary transmission in schools offering in-person learning.

This study, a secondary analysis of the HPTN 068 randomized control trial, aimed to quantify the association of father and male presence with HIV incidence and first pregnancy among 2533 school-going adolescent girls and young women (AGYW) in rural South Africa participating in the trial between March 2011 and April 2017. Participants' ages ranged from 13-20 years at study enrollment and 17-25 at the post-intervention visit. HIV and pregnancy incidence rates were calculated for each level of the exposure variables using Poisson regression, adjusted for age using restricted quadratic spline variables, and, in the case of pregnancy, also adjusted for whether the household received a social grant. Our study found that AGYW whose fathers were deceased and adult males were absent from the household were most at risk for incidence of first pregnancy and HIV (pregnancy: aIRR = 1.30, Wald 95% CI 1.05, 1.61, Wald chi-square p = 0.016; HIV: aIRR = 1.27, Wald 95% CI 0.84, 1.91, Wald chi-square p = 0.263) as compared to AGYW whose biological fathers resided with them. For AGYW whose fathers were deceased, having other adult males present as household members seemed to attenuate the incidence (pregnancy: aIRR = 0.92, Wald 95% CI 0.74, 1.15, Wald chi-square p = 0.462; HIV: aIRR = 0.90, Wald 95% CI 0.58, 1.39, Wald chi-square p = 0.623) such that it was similar, and therefore not statistically significantly different, to AGYW whose fathers were present in the household.

Twenty-five years after the influenza pandemic of 1918, the first inactivated influenza vaccine was produced by the US Army for use in US troops.1 Since 1960, the US Surgeon General and US Centers for Disease and Control Advisory Committee on Immunization Practices have recommended influenza vaccination for people living with chronic disease such as atherosclerotic cardiovascular disease (ASCVD) and heart failure.2 A scientific advisory from the American Heart Association and the American College of Cardiology supports influenza as a class I recommendation for secondary cardiovascular prevention (level of evidence, B).3 Despite compelling data regarding this safe and evidence-based preventive health measure, influenza vaccination rates remain suboptimal, even among those living with high-risk conditions and other vulnerable populations including marginalized racial/ethnic groups, persons without insurance, and individuals with lower socioeconomic status.4

BACKGROUND: Small-quantity lipid-based nutrient supplements (SQ-LNS) are efficacious in controlled settings; data are scarce on the effectiveness utilizing health care delivery platforms. OBJECTIVE: We evaluated the impact of an infant young child feeding (IYCF)-SQ-LNS intervention on anemia and growth in children aged 6-18 mo in the Democratic Republic of Congo following a quasi-experimental effectiveness design. METHODS: An intervention health zone (HZ) received enhanced IYCF including improved counseling on IYCF during pregnancy until 12 mo after birth and daily use of SQ-LNS for infants 6-12 mo; the control HZ received the standard IYCF package. We analyzed data from 2995 children, collected in repeated cross-sectional surveys. We used adjusted difference-in-difference analyses to calculate changes in anemia, iron and vitamin A deficiencies, stunting, wasting, and underweight. RESULTS: Of mothers, 70.5% received SQ-LNS at least once in the intervention HZ, with 99.6% of their children consuming SQ-LNS at least once. The mean number of batches of SQ-LNS (28 sachets per batch, 6 batches total) received was 2.3 ± 0.8 (i.e., 64.4 ± 22.4 d of SQ-LNS). The enhanced program was associated with an 11.0% point (95% CI: -18.1, -3.8; P < 0.01) adjusted relative reduction in anemia prevalence and a mean +0.26-g/dL (95% CI: 0.04, 0.48; P = 0.02) increase in hemoglobin but no effect on anthropometry or iron or vitamin A deficiencies. At endline in the intervention HZ, children aged 8-13 mo who received ≥3 monthly SQ-LNS batch distributions had higher anthropometry z scores [length-for-age z score (LAZ): +0.40, P = 0.04; weight-for-age z score (WAZ): +0.37, P = 0.04] and hemoglobin (+0.65 g/dL, P = 0.007) and a lower adjusted prevalence difference of stunting (-16.7%, P = 0.03) compared with those who received none. CONCLUSIONS: The enhanced IYCF-SQ-LNS intervention using the existing health care delivery platform was associated with a reduction in prevalence of anemia and improvement in mean hemoglobin. At endline among the subpopulation receiving ≥3 mo of SQ-LNS, their LAZ, WAZ, and hemoglobin improved. Future research could explore contextual tools to maximize coverage and intake adherence in programs using SQ-LNS.

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused epidemic spread of coronavirus disease 2019 (COVID-19) in the Seattle, Washington, metropolitan area, with morbidity and mortality concentrated among residents of skilled nursing facilities. The prevalence of COVID-19 among older adults in independent/assisted living is not understood. Objectives: To conduct surveillance for SARS-CoV-2 and describe symptoms of COVID-19 among residents and staff of an independent/assisted living community. Design, Setting, and Participants: In March 2020, public health surveillance of staff and residents was conducted on site at an assisted and independent living residence for older adults in Seattle, Washington, after exposure to 2 residents who were hospitalized with COVID-19. Exposures: Surveillance for SARS-CoV-2 infection in a congregate setting implementing social isolation and infection prevention protocols. Main Outcomes and Measures: SARS-CoV-2 real-time polymerase chain reaction was performed on nasopharyngeal swabs from residents and staff; a symptom questionnaire was completed assessing fever, cough, and other symptoms for the preceding 14 days. Residents were retested for SARS-CoV-2 7 days after initial screening. Results: Testing was performed on 80 residents; 62 were women (77%), with mean age of 86 (range, 69-102) years. SARS-CoV-2 was detected in 3 of 80 residents (3.8%); none felt ill, 1 male resident reported resolved cough and 1 loose stool during the preceding 14 days. Virus was also detected in 2 of 62 staff (3.2%); both were symptomatic. One week later, resident SARS-CoV-2 testing was repeated and 1 new infection detected (asymptomatic). All residents remained in isolation and were clinically stable 14 days after the second test. Conclusions and Relevance: Detection of SARS-CoV-2 in asymptomatic residents highlights challenges in protecting older adults living in congregate settings. In this study, symptom screening failed to identify residents with infections and all 4 residents with SARS-CoV-2 remained asymptomatic after 14 days. Although 1 asymptomatic infection was found on retesting, a widespread facility outbreak was avoided. Compared with skilled nursing settings, in assisted/independent living communities, early surveillance to identify asymptomatic persons among residents and staff, in combination with adherence to recommended preventive strategies, may reduce viral spread.

We examined the relationship between CSF immune cells and neurocognition and neuronal damage in HIV+ individuals before and after initiating antiretroviral therapy. Multivariate analysis at baseline indicated that greater CD4+ T cell abundance was associated with better cognition (p = .017), while higher CSF HIV RNA was associated with increased neuronal damage (p = .014). Following 24 weeks of antiretroviral therapy, CD8+ T cells, HLA-DR expressing CD4+ and CD8+ T cells, B cells, NK cells, and non-classical monocyte percentage decreased in CSF. Female gender was negatively associated with cognitive performance over time, as was higher percentage of HLA-DR expressing CD8+ T cells at baseline.

In the Seattle, Washington metropolitan area, where the first case of novel coronavirus 2019 disease (COVID-19) in the United States was reported (1), a community-level outbreak is ongoing with evidence of rapid spread and high morbidity and mortality among older adults in long-term care skilled nursing facilities (SNFs) (2,3). However, COVID-19 morbidity among residents of senior independent and assisted living communities, in which residents do not live as closely together as do residents in SNFs and do not require skilled nursing services, has not been described. During March 5-9, 2020, two residents of a senior independent and assisted living community in Seattle (facility 1) were hospitalized with confirmed COVID-19 infection; on March 6, social distancing and other preventive measures were implemented in the community. UW Medicine (the health system linked to the University of Washington), Public Health - Seattle & King County, and CDC conducted an investigation at the facility. On March 10, all residents and staff members at facility 1 were tested for SARS-CoV-2, the virus that causes COVID-19, and asked to complete a questionnaire about their symptoms; all residents were tested again 7 days later. Among 142 residents and staff members tested during the initial phase, three of 80 residents (3.8%) and two of 62 staff members (3.2%) had positive test results. The three residents had no symptoms at the time of testing, although one reported an earlier cough that had resolved. A fourth resident, who had negative test results in the initial phase, had positive test results 7 days later. This resident was asymptomatic on both days. Possible explanations for so few cases of COVID-19 in this residential community compared with those in several Seattle SNFs with high morbidity and mortality include more social distancing among residents and less contact with health care providers. In addition, early implementation of stringent isolation and protective measures after identification of two COVID-19 cases might have been effective in minimizing spread of the virus in this type of setting. When investigating a potential outbreak of COVID-19 in senior independent and assisted living communities, symptom screening is unlikely to be sufficient to identify all persons infected with SARS-CoV-2. Adherence to CDC guidance to prevent COVID-19 transmission in senior independent and assisted living communities (4) could be instrumental in preventing a facility outbreak.

OBJECTIVE: To evaluate the impact of an infant, young child feeding practices-small-quantity lipid nutrient supplements (SQ-LNS) intervention on child development scores in children aged 6-18 months in the Katanga Province, Democratic Republic of Congo (DRC). STUDY DESIGN: We analyzed data of 2595 children from 2 health zones in a quasi-experimental design with preimplementation and postimplementation surveys to evaluate program impact on child development scores. Standard care was received in the comparison health zone and the intervention health zone received standard care plus enhanced infant, young child feeding practices with a monthly supply of 28 SQ-LNS sachets for up to 1 year. Program exposure and communication and motor domains of the Ages and Stages questionnaire were collected to assess changes in child development scores. A quasi-intent-to-treat and adjusted difference-in-difference analyses were used to quantify impact of the enhanced compared with the standard package. RESULTS: In adjusted models contrasting endline with baseline, there was a greater relative increase in proportion of children with normal communication (difference-in-difference, +13.7% [95%CI, 7.9-19.6; P < .001] and gross motor scores, +7.4% [95% CI: 1.3-13.5; P < .001]) in the intervention vs comparison health zones. Further, in separate analyses among children of intervention health zone at endline, each additional SQ-LNS distribution was associated with +0.09 (95% CI, 0.03-0.16) z-score unit increase in gross motor scores (P < .01). CONCLUSIONS: The integrated infant, young child feeding practice-SQ-LNS intervention was positively associated with larger relative improvements in measures of child communication and motor development in the Katanga province of DRC.

Network modelling is a valuable tool for simulating hepatitis C virus (HCV) and HIV transmission among people who inject drugs (PWID) and assessing the potential impact of treatment and harm-reduction interventions. In this paper, we review literature on network simulation models, highlighting key structural considerations and questions that network models are well suited to address. We describe five approaches (Erdos-Renyi, Stochastic Block, Watts-Strogatz, Barabasi-Albert, and Exponential Random Graph Model) used to model partnership formation with emphasis on the strengths of each approach in simulating different features of real-world PWID networks. We also review two important structural considerations when designing or interpreting results from a network simulation study: (1) dynamic vs. static network and (2) injection only vs. both injection and sexual networks. Dynamic network simulations allow partnerships to evolve and disintegrate over time, capturing corresponding shifts in individual and population-level risk behaviour; however, their high level of complexity and reliance on difficult-to-observe data has driven others to develop static network models. Incorporating both sexual and injection partnerships increases model complexity and data demands, but more accurately represents HIV transmission between PWID and their sexual partners who may not also use drugs. Network models add the greatest value when used to investigate how leveraging network structure can maximize the effectiveness of health interventions and optimize investments. For example, network models have shown that features of a given network and epidemic influence whether the greatest community benefit would be achieved by allocating hepatitis C or HIV treatment randomly, versus to those with the most partners. They have also demonstrated the potential for syringe services and "buddy sharing" programs to reduce disease transmission.

OBJECTIVES: Early diagnosis of tuberculosis (TB) and multidrug-resistant TB (MDR-TB) is a priority for Viet Nam's National TB Control Programme. In many laboratories, quality systems are weak; few have attained accreditation. We implemented a structured training and mentoring program for TB laboratories and measured impact on quality. METHODS: Six TB culture laboratories implemented the Strengthening TB Laboratory Management Towards Accreditation (TB SLMTA) program, consisting of three training workshops and on-site mentoring between workshops to support improvement projects. Periodic audits, using standardized checklists, monitored laboratories' progress toward accreditation readiness. RESULTS: At baseline, all six laboratories achieved a zero-star level. At exit, five laboratories attained three stars and another one star. Overall checklist scores increased by 44.2% on average, from 29.8% to 74.0%; improvements occurred across all quality system essentials. CONCLUSIONS: The program led to improved quality systems. Sites should be monitored to ensure sustainability of improvements and country capacity expanded for national scaleup.

BACKGROUND: This study aims to determine reported prevalence of hypertensive disorders in pregnancy (HDP) and maternal and neonatal outcomes associated with these disorders among women delivering at selected hospitals across Haiti. METHODS: A retrospective review of 8822 singleton deliveries between January 2012 and December 2014 was conducted at four hospitals in separate Departments across Haiti. Researchers examined the proportion of women with reported HDP (hypertension, preeclampsia, eclampsia) and the association between women with HDP and three neonatal outcomes: low birth weight, preterm birth, and stillbirths; and two maternal outcomes: placental abruption and maternal death in Hopital Albert Schweitzer (HAS). Odds ratios for associations between HDP and perinatal outcomes at HAS were assessed using logistic regression, adjusting for potential confounders. RESULTS: Of the 8822 singleton births included in the study, 510 (5.8%) had a reported HDP (including 285 (55.9%) preeclampsia, 119 (23.3%) eclampsia, and 106 (20.8%) hypertension). Prevalence of HDP among each hospital was: HAS (13.5%), Hopital Immaculee Conception des Cayes (HIC) (3.2%), Fort Liberte (4.3%), and Hopital Sacre Coeur de Milot (HSC) (3.0%). Among women at HAS with HDP, the adjusted odds of having a low birth weight baby was four times that of women without HDP (aOR 4.17, 95% CI 3.19-5.45), more than three times that for stillbirths (aOR 3.51, 95% CI 2.43-5.06), and five times as likely to result in maternal death (aOR 5.13, 95% CI 1.53-17.25). Among the three types of HDP, eclampsia was associated with the greatest odds of adverse events with five times the odds of having a low birth weight baby (aOR 5.00, 95% CI 2.84-8.79), six times the odds for stillbirths (aOR 6.34, 95% CI 3.40-11.82), and more than twelve times as likely to result in maternal death (aOR 12.70, 95% CI 2.33-69.31). CONCLUSIONS: A high prevalence of HDP was found among a cohort of Haitian mothers. HDP was associated with higher rates of adverse maternal and neonatal outcomes in HAS, which is comparable to studies of HDP conducted in high-income countries.

INTRODUCTION: Experimental Ebola vaccines were introduced during the 2014-2015 Ebola outbreak in West Africa. Planning for the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) was underway in late 2014. We examined hypothetical acceptability and perceptions of experimental Ebola vaccines among health care workers (HCWs), frontline workers, and the general public to guide ethical communication of risks and benefits of any experimental Ebola vaccine. METHODS: Between December 2014 and January 2015, we conducted in-depth interviews with public health leaders (N=31), focus groups with HCWs and frontline workers (N=20), and focus groups with members of the general public (N=15) in Western Area Urban, Western Area Rural, Port Loko, Bombali, and Tonkolili districts. Themes were identified using qualitative content analysis. RESULTS: Across all participant groups, not knowing the immediate and long-term effects of an experimental Ebola vaccine was the most serious concern. Some respondents feared that experimental vaccines may cause Ebola, lead to death, or result in other adverse events. Among HCWs, not knowing the level of protection provided by experimental Ebola vaccines was another concern. HCWs and frontline workers were motivated to help find a vaccine for Ebola to help end the outbreak. General public participants cited positive experiences with routine childhood immunization in Sierra Leone. DISCUSSION: Our formative assessment prior to STRIVE's implementation in Sierra Leone helped identify concerns, motivations, and information gaps among potential participants of an experimental Ebola vaccine trial, at the time when an unprecedented outbreak was occurring in the country. The findings from this assessment were incorporated early in the process to guide ethical communication of risks and benefits when discussing informed consent for possible participation in the vaccine trial that was launched later in 2015.

Introduction: Many non-pregnant women see obstetrician-gynecologists as their sole source of medical care, yet little is known about vaccination practices of obstetrician-gynecologists for non-pregnant patients. The objectives were to assess, among a national sample of obstetrician-gynecologists, practices related to vaccine delivery in non-pregnant patients and factors associated with stocking and administering more than three different vaccines to non-pregnant patients. Methods: E-mail and mail surveys were administered July–October 2015, with analyses performed during October–November 2015 and April–June 2018. Results: The response rate was 73% (353/482). Human papillomavirus (92%); influenza (82%); and tetanus, diphtheria, acellular pertussis vaccines (50%) were the vaccines most commonly assessed, with the remaining vaccines assessed by <40% of respondents. Vaccines most commonly administered by obstetrician-gynecologists to non-pregnant patients included human papillomavirus (81%); influenza (70%); and tetanus, diphtheria, acellular pertussis (54%). The remaining vaccines were administered by <30% of obstetrician-gynecologists. Factors associated with routinely administering more than three vaccines to non-pregnant patients included working in a hospital-, public health– or university-associated clinic (RR=1.87, 95% CI=1.35, 2.58, referent to private practice); a larger practice (more than five providers; RR=1.54, 95% CI=1.05, 2.27); perceiving fewer financial barriers (RR=0.74, 95% CI=0.57, 0.96); fewer practice-associated barriers (RR=0.71, 95% CI=0.55, 0.92); and greater patient barriers (RR=1.62, 95% CI=1.33, 1.98). Conclusions: Human papillomavirus; influenza; and tetanus, diphtheria, acellular pertussis vaccines are the only vaccines routinely assessed and administered to non-pregnant patients by most obstetrician-gynecologists. Given their role as the sole source of care for many women, obstetrician-gynecologists could make a positive impact on the vaccination status of their non-pregnant patients.

Integrating small-quantity lipid-based nutrient supplements (SQ-LNS) into infant and young child feeding (IYCF) programs can increase consumption of essential nutrients among children in vulnerable populations; however, few studies have assessed the impact of integrated IYCF-SQ-LNS programs on IYCF practices. A two-year, enhanced IYCF intervention targeting pregnant women and infants (0-12 months) was implemented in a health zone in the Democratic Republic of Congo (DRC). The enhanced IYCF intervention included community- and facility-based counselling for mothers on handwashing, SQ-LNS and IYCF practices, plus monthly SQ-LNS distributions for children 6-12 months; a control zone received the national IYCF program (facility-based IYCF counselling with no SQ-LNS distributions). Cross-sectional pre- and post-intervention surveys (n=650 and 638 in intervention and control areas at baseline; n=654 and 653 in each area at endline, respectively) were conducted in mothers of children 6-18 months representative of both zones. Difference-in-difference (DiD) analyses used mixed linear regression models. There were significantly greater increases in the proportion of mothers in the intervention (versus control) zone who reported: initiating breastfeeding within 1hr. of birth [Adj. DiD (95%CI): +56.4% (49.3, 63.4), p<0.001], waiting until 6 months to introduce water [+66.9% (60.6, 73.2), p<0.001] and complementary foods [+56.4% (49.3, 63.4), p<0.001], feeding the minimum meal frequency the previous day [+9.2% (2.7, 15.7), p=0.005]; feeding the child in a separate bowl [+9.7% (2.2, 17.2), p=0.01]; awareness of anemia [+16.9% (10.4, 23.3), p<0.001]; owning soap [+14.9% (8.3, 21.5), p<0.001]; and washing hands after defecating and before cooking and feeding the child the previous day [+10.5% (5.8, 15.2), +12.5% (9.3, 15.6) and +15.0% (11.2, 18.8) respectively, p<0.001 for all)]. The enhanced IYCF intervention in the DRC was associated with an improvement in several important IYCF practices, but was not associated with a change in dietary diversity (minimum dietary diversity and minimum acceptable diet remained below 10% in both zones without significant differences between zones). The provision of fortified complementary foods, such as SQ-LNS, may be an important source of micro- and macro-nutrients for young children in areas with high rates of poverty and limited access to diverse foods. Future research should verify the potential of integrated IYCF-SQ-LNS to improve IYCF practices, and ultimately children's nutritional status.

The association of immunodeficiency-related vaccine-derived rubella virus (iVDRV) with cutaneous and visceral granulomatous disease has been reported in patients with primary immunodeficiency disorders (PIDs). The majority of these PID patients with rubella-positive granulomas had DNA repair disorders. To support this line of inquiry, we provide additional descriptive data on seven previously reported patients with Nijmegen breakage syndrome (NBS) (n = 3) and ataxia telangiectasia (AT) (n = 4) as well as eight previously unreported patients with iVDRV-induced cutaneous granulomas and DNA repair disorders including NBS (n = 1), AT (n = 5), DNA ligase 4 deficiency (n = 1), and Artemis deficiency (n = 1). We also provide descriptive data on several previously unreported PID patients with iVDRV-induced cutaneous granulomas including cartilage hair hypoplasia (n = 1), warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (WHIM) syndrome (n = 1), MHC class II deficiency (n = 1), Coronin-1A deficiency (n = 1), X-linked severe combined immunodeficiency (X-SCID) (n = 1), and combined immunodeficiency without a molecular diagnosis (n = 1). At the time of this report, the median age of the patients with skin granulomas and DNA repair disorders was 9 years (range 3-18). Cutaneous granulomas have been documented in all, while visceral granulomas were observed in six cases (40%). All patients had received rubella virus vaccine. The median duration of time elapsed from vaccination to the development of cutaneous granulomas was 48 months (range 2-152). Hematopoietic cell transplantation was reported to result in scarring resolution of cutaneous granulomas in two patients with NBS, one patient with AT, one patient with Artemis deficiency, one patient with DNA Ligase 4 deficiency, one patient with MHC class II deficiency, and one patient with combined immunodeficiency without a known molecular etiology. Of the previously reported and unreported cases, the majority share the diagnosis of a DNA repair disorder. Analysis of additional patients with this complication may clarify determinants of rubella pathogenesis, identify specific immune defects resulting in chronic infection, and may lead to defect-specific therapies.