Deaths in Children and Adolescents Associated With COVID-19 and MIS-C in the United States.

OBJECTIVES: To describe the demographics, clinical characteristics, and hospital course among persons <21 years of age with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated death. METHODS: We conducted a retrospective case series of suspected SARS-CoV-2-associated deaths in the United States in persons <21 years of age during February 12 to July 31, 2020. All states and territories were invited to participate. We abstracted demographic and clinical data, including laboratory and treatment details, from medical records. RESULTS: We included 112 SARS-CoV-2-associated deaths from 25 participating jurisdictions. The median age was 17 years (IQR 8.5-19 years). Most decedents were male (71, 63%), 31 (28%) were Black (non-Hispanic) persons, and 52 (46%) were Hispanic persons. Ninety-six decedents (86%) had at least 1 underlying condition; obesity (42%), asthma (29%), and developmental disorders (22%) were most commonly documented. Among 69 hospitalized decedents, common complications included mechanical ventilation (75%) and acute respiratory failure (82%). The sixteen (14%) decedents who met multisystem inflammatory syndrome in children (MIS-C) criteria were similar in age, sex, and race and/or ethnicity to decedents without MIS-C; 11 of 16 (69%) had at least 1 underlying condition. CONCLUSIONS: SARS-CoV-2-associated deaths among persons <21 years of age occurred predominantly among Black (non-Hispanic) and Hispanic persons, male patients, and older adolescents. The most commonly reported underlying conditions were obesity, asthma, and developmental disorders. Decedents with coronavirus disease 2019 were more likely than those with MIS-C to have underlying medical conditions.

Monitoring of diverse enteric pathogens across environmental and host reservoirs with TaqMan array cards and standard qPCR: a methodological comparison study.

BACKGROUND: Multiple bacteria, viruses, protists, and helminths cause enteric infections that greatly impact human health and wellbeing. These enteropathogens are transmited via several pathways through human, animal, and environmental reservoirs. Individual qPCR assays have been extensively used to detect enteropathogens within these types of samples, whereas the TaqMan array card (TAC), which allows simultaneous detection of multiple enteropathogens, has only previously been validated in human clinical samples. METHODS: In this methodological comparison study, we compared the performance of a custom 48-singleplex TAC relative to standard qPCR. We established the sensitivity and specificity of each method for the detection of eight enteric targets, by using spiked samples with varying levels of PCR inhibition. We then tested the prevalence and abundance of pathogens in wastewater from Melbourne (Australia), and human, animal, and environmental samples from informal settlements in Suva, Fiji using both TAC and qPCR. FINDINGS: Both methods exhibited similarly h specificity (TAC 100%, qPCR 94%), sensitivity (TAC 92%, qPCR 100%), and quantitation accuracy (TAC 91%, qPCR 99%) in non-inhibited sample matrices with spiked gene fragments. PCR inhibitors substantially affected detection via TAC, though this issue was alleviated by ten-fold sample dilution. Among samples from informal settlements, the two techniques performed similarly for detection (89% agreement) and quantitation (R2 0·82) for the eight enteropathogen targets. The TAC additionally included 38 other enteric targets, enabling detection of diverse faecal pathogens and extensive environmental contamination that would be prohibitively labour intensive to assay by standard qPCR. INTERPRETATION: The two techniques produced similar results across diverse sample types, with qPCR prioritising greater sensitivity and quantitation accuracy, and TAC trading small reductions in these for a cost-effective larger enteropathogen panel enabling a greater number of enteric pathogens to be analysed concurrently, which is beneficial given the abundance and variety of enteric pathogens in environments such as urban informal settlements. The ability to monitor multiple enteric pathogens across diverse reservoirs could allow better resolution of pathogen exposure pathways, and the design and monitoring of interventions to reduce pathogen load. FUNDING: Wellcome Trust Our Planet, Our Health programme.

Trends in Geographic and Temporal Distribution of US Children With Multisystem Inflammatory Syndrome During the COVID-19 Pandemic.

Importance: Multiple inflammatory syndrome in children (MIS-C) occurs in association with the COVID-19 pandemic. Objective: To describe the clinical characteristics and geographic and temporal distribution of the largest cohort of patients with MIS-C in the United States to date. Design, Setting, and Participants: Cross-sectional analysis was conducted on clinical and laboratory data collected from patients with MIS-C. The analysis included patients with illness onset from March 2020 to January 2021 and met MIS-C case definition. Main Outcomes and Measures: Geographic and temporal distribution of MIS-C was compared with that of COVID-19 nationally, by region, and level of urbanicity by county. Clinical and laboratory findings and changes over time were described by age group and by presence or absence of preceding COVID-19. Results: A total of 1733 patients with MIS-C were identified; 994 (57.6%) were male and 1117 (71.3%) were Hispanic or non-Hispanic Black. Gastrointestinal symptoms, rash, and conjunctival hyperemia were reported by 53% (n = 931) to 67% (n = 1153) of patients. A total of 937 patients (54%) had hypotension or shock, and 1009 (58.2%) were admitted for intensive care. Cardiac dysfunction was reported in 484 patients (31.0%), pericardial effusion in 365 (23.4%), myocarditis in 300 (17.3%), and coronary artery dilatation or aneurysms in 258 (16.5%). Patients aged 0 to 4 years had the lowest proportion of severe manifestations, although 171 patients (38.4%) had hypotension or shock and 197 (44.3%) were admitted for intensive care. Patients aged 18 to 20 years had the highest proportions with myocarditis (17 [30.9%]), pneumonia (20 [36.4%]), acute respiratory distress syndrome (10 [18.2%]), and polymerase chain reaction positivity (39 [70.9%]). These older adolescents also had the highest proportion reporting preceding COVID-19-like illness (63%). Nationally, the first 2 MIS-C peaks followed the COVID-19 peaks by 2 to 5 weeks. The cumulative MIS-C incidence per 100 000 persons younger than 21 years was 2.1 and varied from 0.2 to 6.3 by state. Twenty-four patients (1.4%) died. Conclusions and Relevance: In this cross-sectional study of a large cohort of patients with MIS-C, 2 peaks that followed COVID-19 peaks by 2 to 5 weeks were identified. The geographic and temporal association of MIS-C with the COVID-19 pandemic suggested that MIS-C resulted from delayed immunologic responses to SARS-CoV-2 infection. The clinical manifestations varied by age and by presence or absence of preceding COVID-19.

Study design, rationale and methods of the Revitalising Informal Settlements and their Environments (RISE) study: a cluster randomised controlled trial to evaluate environmental and human health impacts of a water-sensitive intervention in informal settlements in Indonesia and Fiji.

INTRODUCTION: Increasing urban populations have led to the growth of informal settlements, with contaminated environments linked to poor human health through a range of interlinked pathways. Here, we describe the design and methods for the Revitalising Informal Settlements and their Environments (RISE) study, a transdisciplinary randomised trial evaluating impacts of an intervention to upgrade urban informal settlements in two Asia-Pacific countries. METHODS AND ANALYSIS: RISE is a cluster randomised controlled trial among 12 settlements in Makassar, Indonesia, and 12 in Suva, Fiji. Six settlements in each country have been randomised to receive the intervention at the outset; the remainder will serve as controls and be offered intervention delivery after trial completion. The intervention involves a water-sensitive approach, delivering site-specific, modular, decentralised infrastructure primarily aimed at improving health by decreasing exposure to environmental faecal contamination. Consenting households within each informal settlement site have been enrolled, with longitudinal assessment to involve health and well-being surveys, and human and environmental sampling. Primary outcomes will be evaluated in children under 5 years of age and include prevalence and diversity of gastrointestinal pathogens, abundance and diversity of antimicrobial resistance (AMR) genes in gastrointestinal microorganisms and markers of gastrointestinal inflammation. Diverse secondary outcomes include changes in microbial contamination; abundance and diversity of pathogens and AMR genes in environmental samples; impacts on ecological biodiversity and microclimates; mosquito vector abundance; anthropometric assessments, nutrition markers and systemic inflammation in children; caregiver-reported and self-reported health symptoms and healthcare utilisation; and measures of individual and community psychological, emotional and economic well-being. The study aims to provide proof-of-concept evidence to inform policies on upgrading of informal settlements to improve environments and human health and well-being. ETHICS: Study protocols have been approved by ethics boards at Monash University, Fiji National University and Hasanuddin University. TRIAL REGISTRATION NUMBER: ACTRN12618000633280; Pre-results.

COVID-19 Outbreaks in US Immigrant Detention Centers: The Urgent Need to Adopt CDC Guidelines for Prevention and Evaluation.

There have been several significant outbreaks of COVID-19 in federal immigrant detention centers, which lack clear and consistent guidelines across Department of Homeland Security (DHS) agencies to limit the spread of COVID-19. The Centers for Disease Control and Prevention (CDC) has issued detailed guidelines for the control, prevention, and evaluation of COVID-19 in detention facilities. Although the DHS's Immigration and Customs Enforcement agency has stated that it complies with CDC recommendations, its policies significantly differ from these CDC guidelines, placing detainees at risk for contracting COVID-19. This submission urges the adoption of CDC guidelines across DHS-associated facilities. Such a policy change has the potential to protect and save the lives of the most vulnerable populations under the auspices of the federal government.

Inadequate Minority Representation within SARS-CoV-2 Vaccine Trials.

Minority communities have borne the brunt of COVID-19 disease in the United States. Nonwhites have contracted most of the SARS-CoV-2 infections; COVID-19 mortality rates for Black Americans are more than twice those for whites. Given this, studying the most effective ways to prevent and treat SARS-CoV-2 in these populations should be a research priority, particularly with respect to vaccine trials. Federal guidelines from the National Institutes of Health and Food and Drug Administration emphasize the need for inclusion of minority groups in these trials, but none of the publicly available SARS-CoV-2 vaccine trial protocols requires representative sampling of minorities. This piece emphasizes the importance of adequate inclusion of minority communities in SARS-CoV-2 vaccine trials, and the implications of this inclusion for SARS-CoV-2 vaccine distribution.

SARS-CoV-2-Associated Deaths Among Persons Aged <21 Years - United States, February 12-July 31, 2020.

Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED).† These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 infections, deaths, and other severe outcomes among persons aged <21 years remains particularly important as schools reopen in the United States. Ongoing evaluation of effectiveness of prevention and control strategies will also be important to inform public health guidance for schools and parents and other caregivers.

COVID-19, Quarantines, Sheltering-in-Place, and Human Rights: The Developing Crisis.

As COVID-19 has spread across the globe, quarantines and sheltering-in-place orders have become important public health tools but, as currently implemented, have eroded human rights, particularly for the marginalized, including essential workers, detainees, women, and children. Quarantines and sheltering-in-place orders must include explicit guarantees of human rights protections. We outline protections for the quarantined that communities and governments should strive to guarantee.

Hospital-based zoonotic disease surveillance in Bangladesh: design, field data and difficulties.

Early detection of zoonotic diseases allows for the implementation of early response measures, reducing loss of human life and economic disruption. We implemented a surveillance system in hospitals in Bangladesh to screen acutely ill hospitalized patients with severe respiratory infection and meningoencephalitis for zoonotic exposures. Patients were screened for the risk of zoonotic exposures with five questions covering vocational exposures, sick domestic animal and wild animal contact, and date palm sap consumption in the three weeks preceding illness onset. Patients giving at least one positive response were considered a potential zoonotic exposure. From September 2013 to March 2017, a total of 11 429 hospitalized patients across 14 participating hospitals were screened for exposures. Overall, 2% of patients reported a potential zoonotic exposure in the three-week period prior to becoming ill. Sixteen per cent of hospitalized patients with reported exposures died. After routine surveillance diagnostic testing, 88% of patients admitted to the hospital after a potential zoonotic exposure did not have a laboratory diagnosed aetiology for their illness. Hospital-based surveillance systems such as the Bangladeshi example presented here could play an important future role in the early detection of zoonotic spillover diseases. This article is part of the theme issue 'Dynamic and integrative approaches to understanding pathogen spillover'.

High prevalence of taeniasis and Taenia solium cysticercosis in children in western Sichuan, China.

Data in China on human Taenia infections, including Taenia solium cysticercosis, is largely lacking. We aimed to determine the prevalence of taeniasis with all three human Taenia species as well as T. solium cysticercosis in primary school-aged children in minority areas of western Sichuan, China. During April 2016 to December 2017, we did a cross-sectional study in five western Sichuan Province primary schools in Liangshan (3 schools), Ganzi (1 school) and Aba (1 school) prefectures. Diagnosis of taeniasis was made by stool microscopy for presence of Taenia eggs, as well as recovery of taeniid tapeworms or proglottids by medicinal treatment followed by species identification using multiplex PCR. Diagnosis of T. solium cysticercosis was made serologically using an ELISA with low-molecular-weight antigens purified from T. solium cyst fluid to detect specific IgG antibodies. A total of 1672 children were screened for taeniasis and 1639 were evaluated for cysticercosis antibodies. Overall prevalence of taeniasis was 7.5% but was as high as 15.6% at one school site (e.g., Shuiluo). Of the three known human Taenia species, adult T. solium tapeworms were detected in 42 children from four of the five schools (all three schools in Liangshan and one in Aba), giving a prevalence of T. solium taeniasis of 2.5% (95% confidence interval 0-6.7%). Cysticercosis antibody seropositivity by school varied from 2.3% to 15.6% (overall 7.5%). T. solium taeniasis carriers were more likely to have cysticercosis antibodies than children without T. solium taeniasis (43.6% vs 6.6%). Schools with higher prevalences of T. solium taeniasis were more likely to have children with human cysticercosis IgG antibodies. This study shows a high prevalence of taeniasis and T. solium cysticercosis in primary school-aged children in minority areas of western Sichuan, suggesting an urgent necessity for school-based disease control.

Structural Equation Modeling (SEM) of Cysticercosis in School-Aged Children in Tibetan Rural Farming Areas of Western China: Implications for Intervention Planning.

Neurocysticercosis (NCC) significantly contributes to morbidity in developing countries. We recently published a study of prevalence and risk factors in school-aged children in three mountainous areas in Sichuan province of western China. Using structural equation modeling (SEM) on data from that study to guide intervention planning, here we examine risk factors grouped into three broad interventional categories: sociodemographics, human behavior, and sources of pork and pig husbandry. Because neuroimaging is not easily available, using SEM allows for the use of multiple observed variables (serological tests and symptoms) to represent probable NCC cases. Data collected from 2608 students was included in this analysis. Within this group, seroprevalence of cysticercosis IgG antibodies was 5.4%. SEM results showed that sociodemographic factors (ß = 0.33, p < 0.05), sources of pork and pig husbandry (ß = 0.26, p < 0.001), and behavioral factors (ß = 0.33, p < 0.05) were all directly related to probable NCC in school-aged children. Sociodemographic factors affected probable NCC indirectly via sources of pork and pig husbandry factors (ß = 0.07, p < 0.001) and behavioral variables (ß = 0.07, p < 0.001). Both sociodemographic factors (ß = 0.07, p < 0.05) and sources of pork and pig husbandry factors (ß = 0.10, p < 0.01) affected probable NCC indirectly via behavioral variables. Because behavioral variables not only had a large direct effect but also served as a critical bridge to strengthen the effect of sociodemographics and sources of pork and pig husbandry on probable NCC, our findings suggest that interventions targeting behavioral factors may be the most effective in reducing disease.

Prevalence and risk factors for Taenia solium cysticercosis in school-aged children: A school based study in western Sichuan, People's Republic of China.

BACKGROUND: Taenia solium cysticercosis affects millions of impoverished people worldwide and can cause neurocysticercosis, an infection of the central nervous system which is potentially fatal. Children may represent an especially vulnerable population to neurocysticercosis, due to the risk of cognitive impairment during formative school years. While previous epidemiologic studies have suggested high prevalence in rural China, the prevalence in children as well as risk factors and impact of disease in low-resource areas remain poorly characterized. METHODOLOGY/PRINCIPAL FINDINGS: Utilizing school based sampling, we conducted a cross-sectional study, administering a questionnaire and collecting blood for T. solium cysticercosis antibodies in 2867 fifth and sixth grade students across 27 schools in west Sichuan. We used mixed-effects logistic regression models controlling for school-level clustering to study associations between risk factors and to characterize factors influencing the administration of deworming medication. Overall prevalence of cysticercosis antibodies was 6%, but prevalence was significantly higher in three schools which all had prevalences of 15% or higher. Students from households owning pigs (adjusted odds ratio [OR] 1.81, 95% CI 1.08-3.03), from households reporting feeding their pigs human feces (adjusted OR 1.49, 95% CI 1.03-2.16), and self-reporting worms in their feces (adjusted OR 1.85, 95% CI 1.18-2.91) were more likely to have cysticercosis IgG antibodies. Students attending high prevalence schools were more likely to come from households allowing pigs to freely forage for food (OR 2.26, 95% CI 1.72-2.98) and lacking a toilet (OR 1.84, 95% CI 1.38-2.46). Children who were boarding at school were less likely to have received treatment for gastrointestinal worms (adjusted OR 0.58, 95% CI 0.42-0.80). CONCLUSIONS/SIGNIFICANCE: Our study indicates high prevalences of cysticercosis antibodies in young school aged children in rural China. While further studies to assess potential for school-based transmission are needed, school-based disease control may be an important intervention to ensure the health of vulnerable pediatric populations in T. solium endemic areas.

Reduction in bacterial contamination of hospital textiles by a novel silver-based laundry treatment.

Treating hospital patient textiles with ionic silver after each washing results in a significant decrease in microbial contamination. Although further study is needed to better understand the role textiles play in hospital-acquired infections and to quantify the influence of silver textile treatment on health care-associated infection risk and patient outcomes, ionic silver treatment of textiles may prove useful in hospital-acquired infection reduction strategies.

Increased Morbidity and Mortality in Domestic Animals Eating Dropped and Bitten Fruit in Bangladeshi Villages: Implications for Zoonotic Disease Transmission.

We used data on feeding practices and domestic animal health gathered from 207 Bangladeshi villages to identify any association between grazing dropped fruit found on the ground or owners directly feeding bat- or bird-bitten fruit and animal health. We compared mortality and morbidity in domestic animals using a mixed effects model controlling for village clustering, herd size, and proxy measures of household wealth. Thirty percent of household heads reported that their animals grazed on dropped fruit and 20% reported that they actively fed bitten fruit to their domestic herds. Household heads allowing their cattle to graze on dropped fruit were more likely to report an illness within their herd (adjusted prevalence ratio 1.17, 95% CI 1.02-1.31). Household heads directly feeding goats bitten fruit were more likely to report illness (adjusted prevalence ratio 1.35, 95% CI 1.16-1.57) and deaths (adjusted prevalence ratio 1.64, 95% CI 1.13-2.4). Reporting of illnesses and deaths among goats rose as the frequency of feeding bitten fruit increased. One possible explanation for this finding is the transmission of bat pathogens to domestic animals via bitten fruit consumption.

Rocky mountain spotted fever in the United States, 2000-2007: interpreting contemporary increases in incidence.

Rocky Mountain spotted fever (RMSF), a potentially fatal tick-borne infection caused by Rickettsia rickettsii, is considered a notifiable condition in the United States. During 2000 to 2007, the annual reported incidence of RMSF increased from 1.7 to 7 cases per million persons from 2000 to 2007, the highest rate ever recorded. American Indians had a significantly higher incidence than other race groups. Children 5-9 years of age appeared at highest risk for fatal outcome. Enzyme-linked immunosorbent assays became more widely available beginning in 2004 and were used to diagnose 38% of cases during 2005-2007. The proportion of cases classified as confirmed RMSF decreased from 15% in 2000 to 4% in 2007. Concomitantly, case fatality decreased from 2.2% to 0.3%. The decreasing proportion of confirmed cases and cases with fatal outcome suggests that changes in diagnostic and surveillance practices may be influencing the observed increase in reported incidence rates.

Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever.

BACKGROUND: Rickettsia parkeri rickettsiosis, a recently identified spotted fever transmitted by the Gulf Coast tick (Amblyomma maculatum), was first described in 2004. We summarize the clinical and epidemiological features of 12 patients in the United States with confirmed or probable disease attributable to R. parkeri and comment on distinctions between R. parkeri rickettsiosis and other United States rickettsioses. METHODS: Clinical specimens from patients in the United States who reside within the range of A. maculatum for whom an eschar or vesicular rash was described were evaluated by > or =1 laboratory assays at the Centers for Disease Control and Prevention (Atlanta, GA) to identify probable or confirmed infection with R. parkeri. RESULTS: During 1998-2007, clinical samples from 12 patients with illnesses epidemiologically and clinically compatible with R. parkeri rickettsiosis were submitted for diagnostic evaluation. Using indirect immunofluorescence antibody assays, immunohistochemistry, polymerase chain reaction assays, and cell culture isolation, we identified 6 confirmed and 6 probable cases of infection with R. parkeri. The aggregate clinical characteristics of these patients revealed a disease similar to but less severe than classically described Rocky Mountain spotted fever. CONCLUSIONS: Closer attention to the distinct clinical features of the various spotted fever syndromes that exist in the United States and other countries of the Western hemisphere, coupled with more frequent use of specific confirmatory assays, may unveil several unique diseases that have been identified collectively as Rocky Mountain spotted fever during the past century. Accurate assessments of these distinct infections will ultimately provide a more valid description of the currently recognized distribution, incidence, and case-fatality rate of Rocky Mountain spotted fever.