Characteristics and outcomes of a hospitalized cohort with reduced mortality from COVID-19, White Mountain apache tribal lands, April 1 - July 31, 2020.

BACKGROUND: Widespread transmission of COVID-19 continues to threaten public health, particularly of rural, American Indian communities. Although COVID-19 risk factors for severe disease and clinical characteristics are well described in the general population, there has been little shared on hospitalized American Indian populations. METHODS: In this observational study, we performed chart extractions on all persons hospitalized with COVID-19 from April 1 through July 31, 2020 among an exclusively American Indian population living on or near Tribal lands in eastern Arizona. We provide descriptive statistics for the cohort stratified by presentation, comparing those who self-presented or were referred by an outreach program. Exploratory analyses were performed to identify risk factors for morbidity and mortality. RESULTS: During the observation period, 2262 persons were diagnosed with COVID-19 and 490 (22%) were hospitalized. Hospitalized persons had a median age of 54 years; 92% had at least one comorbidity, 72% had greater than one comorbidity, and 60% had a BMI of > 30. Most persons required supplemental oxygen (83%), but the majority (62%) only required nasal cannula and only 11% were intubated. The case fatality rates were 1.7% for the population, 7.1% among hospitalizations, and 9.3% among hospitalized patients 50 years and older. All rates that are significantly lower than those reported nationally during the same period. CONCLUSIONS: We observed a cohort of American Indian patients hospitalized secondary to COVID-19 with greater number of comorbidities compared to the general population but with lower mortality rates. We posit that the primary driver of mortality reduction for this population and the hospitalized cohort was a community-based referral program that led to disproportionately lower fatality rates among the oldest persons.

Potential Benefits of Expanded Palivizumab in American Indian Children Under the Age of 2 Years.

Severe respiratory syncytial virus (RSV) infections disparately impact American Indian communities. We implemented a program that expanded palivizumab to all children under 2 years of age that led to significant reductions in RSV infections and hospitalizations for both high-risk and non-high-risk recipients in a rural American Indian community in Eastern Arizona.

Unique Genomic Epidemiology of COVID-19 in the White Mountain Apache Tribe, April to August 2020, Arizona.

The first case of coronavirus disease 2019 (COVID-19) within the White Mountain Apache Tribe (WMAT) in Arizona was diagnosed almost 1 month after community transmission was recognized in the state. Aggressive contact tracing allowed for robust genomic epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and subsequent phylogenetic analyses implicated only two virus introductions, which resulted in the spread of two unique viral lineages on the reservation. The phylogenies of these lineages reflect the nature of the introductions, the remoteness of the community, and the extraordinarily high attack rates. The timing and space-limited nature of the outbreaks validate the public health tracing efforts involved, which were illustrated by multiple short transmission chains over a period of several weeks, eventually resulting in extinction of the lineages. Comprehensive sampling and successful infection control efforts are illustrated in both the effective population size analyses and the limited mortality outcomes. The rapid spread and high attack rates of the two lineages may be due to a combination of sociological determinants of the WMAT and a seemingly enhanced transmissibility. The SARS-CoV-2 genomic epidemiology of the WMAT demonstrates a unique local history of the pandemic and highlights the extraordinary and successful efforts of their public health response. IMPORTANCE This article discusses the introduction and spread of two unique viral lineages of SARS-CoV-2 within the White Mountain Apache Tribe in Arizona. Both genomic sequencing and traditional epidemiological strategies (e.g., contract tracing) were used to understand the nature of the spread of both lineages. Beyond providing a robust genomic analysis of the epidemiology of the outbreaks, this work also highlights the successful efforts of the local public health response.

Point-of-care molecular diagnostics for the detection of group A Streptococcus in non-invasive skin and soft tissue infections: a validation study.

BACKGROUND: Skin and soft tissue infections (SSTIs) are commonly caused by group A Streptococcus (GAS). Rapid molecular assays for detecting GAS in wounds would help with clinical management. This study assessed a point-of-care system for the detection of GAS in non-severe SSTIs in a Native American community in the Southwest. METHODS: Patients presenting with a new non-severe SSTI were eligible if a swab was collected. The swab was tested by traditional culture methods and using the cobas® Liat® point-of-care (POC) system and results were compared. RESULTS: 399 samples were included. The final result from the POC assay was positive for 52.0% of samples. Compared to culture, the POC assay had a sensitivity of 100% and specificity of 99.5%. CONCLUSIONS: The cobas® Liat® system accurately and efficiently identified GAS in non-severe SSTIs. Having a POC test available to rapidly identify or rule out GAS could help to minimize overuse of antibiotics.

Innovative and Integrated Contact Tracing: Indian Health Service, Arizona, December 2020-January 2021.

SARS-CoV-2 has exposed limitations of public health mitigation measures such as traditional case investigations and contact tracing. The Whiteriver Service Unit is a rural, acute care hospital on the Fort Apache Indian Reservation in Arizona with integrated health care delivery and public health services. During the first wave of COVID-19 cases in May-June 2020, we developed an innovative case investigation contact tracing approach that relied heavily on cross-trained personnel, in-person encounters, and baseline clinical evaluations. A second COVID-19 surge during December 13, 2020-January 31, 2021, caused incidence to peak at 413 cases per 100 000 community members. During that second surge, we investigated all 769 newly identified COVID-19 cases and notified 1911 (99.4%) of 1922 reported contacts. Median time interval from nasopharyngeal specimen collection to both case investigation and contact notification was 0 days (range, 0-5 days and 0-13 days, respectively). Our primary lesson was the importance of cross-trained personnel who integrated tasks along the testing-tracing continuum (eg, in-person interviews, prompt referral for additional testing and evaluation). These successive steps fed forward to identify new cases and their respective contacts. Our innovative community-based approach was both successful and efficient; our experience suggests that when adapted based on local needs, case investigation and contact tracing remain valuable and feasible public health tools, even in rural, resource-limited settings.

High-Risk Outreach for COVID-19 Mortality Reduction in an Indigenous Community.

Indigenous populations have been disproportionally affected by COVID-19, particularly those in rural and remote locations. Their unique environments and risk factors demand an equally unique public health response. Our rural Native American community experienced one of the highest prevalence outbreaks in the world, and we developed an aggressive management strategy that appears to have had a considerable effect on mortality reduction. The results have implications far beyond pandemic response, and have reframed how our community addresses several complicated health challenges. (Am J Public Health. 2021;111(11):1939-1941. https://doi.org/10.2105/AJPH.2021.306472).

Disparate Effects of Invasive Group A Streptococcus on Native Americans.

Active surveillance of invasive group A Streptococcus (iGAS) disease indicates that its incidence in the US general population is low, but limited studies show rates for American Indians and Alaska Natives (AI/AN) are severalfold higher. Major disparities in rates of iGAS exist between Indigenous and non-Indigenous populations of Australia, New Zealand, and Canada, but much less is understood about iGAS among AI/AN in the United States. Although complex host-pathogen interactions influence the rates of iGAS, including strain variation and virulence, the number and type of concurrent conditions, and socioeconomic status, the relative contribution of each remains unclear. We highlight the poor correlation between the substantial effect of iGAS among Indigenous persons in industrialized countries and the current understanding of factors that influence iGAS disease in these populations. Prospective, large-scale, population-based studies of iGAS are needed that include AI/AN as a necessary first step to understanding the effects of iGAS.

Prevalence and correlates of active syphilis and HIV co-Infection among sexually active persons aged 15-59 years in Zambia: Results from the Zambia Population-based HIV Impact Assessment (ZAMPHIA) 2016.

OBJECTIVES: The main objectives of the study are to estimate HIV prevalence, active syphilis prevalence, and correlates of co-infection with HIV in Zambia, among recently sexually active individuals aged 15 to 59 years old. METHODS: We used data from the 2016 Zambia Population-based HIV Impact Assessment (ZAMPHIA), a national household survey that included biomarker testing for HIV and syphilis. Chembio DPP® Syphilis Screen and Confirm Assay was used to distinguish between active and older syphilis infections. This is the first time Chembio DPP® has been used in a national survey. Log-binominal modelling was utilized to understand the risk of acquiring HIV/active syphilis co-infection using select socio-demographic and sexual behavior variables. Multivariable analysis compared those with co-infection and those with no infection. All reported results account for the complex survey design and are weighted. RESULTS: A total of 19,114 individuals aged 15-59 years responded to the individual interview and had a valid syphilis and/or HIV test. The prevalence for those sexually active in the 12 months preceding ZAMPHIA 2016 was 3.5% and 13% for active syphilis and HIV, respectively. The prevalence of HIV/active syphilis co-infection was 1.5%. Factors associated with higher prevalence of co-infection versus no infection among females included, but were not limited to, those living in urban areas (adjusted prevalence ratio (aPR) = 3.0, 95% CI = 1.8, 4.8), those had sexual intercourse before age 15 years (aPR = 1.8, 95% CI = 1.1, 2.9), and those who had two or more sexual partners in the 12 months preceding the survey (aPR = 2.7, 95% CI = 1.6, 4.7). CONCLUSION: These findings show high prevalence for both mono-infection with HIV and syphilis, as well as co-infection with HIV/active syphilis in Zambia. There is a need for better screening and partner services, particularly among those engaging in high-risk sexual behaviors (e.g., engaging in transactional sex).

High Burden of Staphylococcus aureus Among Native American Individuals on the White Mountain Apache Tribal Lands.

BACKGROUND: This study was done to determine the burden of invasive Staphylococcus aureus on the White Mountain Apache Tribal lands. METHODS: Active population and laboratory-based surveillance for invasive S aureus infections was conducted from May 2016 to April 2018. A case was defined as a Native American individual living on or around the White Mountain Apache Tribal lands with S aureus isolated from a normally sterile body site. RESULTS: Fifty-three cases were identified. Most cases were adults (90.6%) and had ≥1 underlying medical condition (86.8%), the most common of which were diabetes (49.1%) and obesity (41.5%). A total of 26.4% cases were categorized as community acquired. Most infections were methicillin-resistant (75.5%). A total of 7.5% of cases required amputation, and 7.7% of cases died within 30 days of initial culture. The incidence of invasive S aureus was 156.3 per 100 000 persons. The age-adjusted incidence of invasive methicillin-resistant S aureus was 138.2 per 100 000 persons. CONCLUSIONS: This community has a disproportionately high burden of invasive methicillin-resistant S aureus compared with the general US population. Interventions are urgently needed to reduce the morbidity and mortality associated with these infections.

Congenital Toxoplasmosis.

Toxoplasmosis is caused by infection with the parasite Toxoplasma gondii. It is one of the most common parasitic infections in humans and is most typically asymptomatic. However, primary infection in a pregnant woman can cause severe and disabling disease in the developing fetus. Recent developments have included increased understanding of the role of parasite genotype in determining infectivity and disease severity. Risk factors for acquisition of infection have been better defined, and the important role of foodborne transmission has been further delineated. In addition, strategies have emerged to decrease mother-to-child transmission through prompt identification of acutely infected pregnant women followed by appropriate treatment. Refined diagnostic tools, particularly the addition of immunoglobulin G avidity testing, allow for more accurate timing of maternal infection and hence better decision making during pregnancy. Congenitally infected children can be treated, beginning in utero and continuing through the first year of life, to ameliorate the severity of disease. However, despite these many advances in our understanding of congenital toxoplasmosis prevention and treatment, significant areas of study remain: we need better drugs, well defined strategies for screening of pregnant women, improved food safety, and improved diagnostic tests.

Extended-Spectrum ß-Lactamase-Producing Enterobacteriaceae Infections in Children: A Two-Center Case-Case-Control Study of Risk Factors and Outcomes in Chicago, Illinois.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae infections are an emerging problem in children. We sought to identify risk factors and describe outcomes associated with pediatric ESBL-producing bacterial infections at 2 hospitals in Chicago, IL from 2008 to 2011. METHODS: A case-case-control study of children aged 0-17 years was conducted. Cases of Escherichia coli, Klebsiella, and Proteus spp. ESBL-producing bacterial infections (n = 30) were compared to uninfected controls and in parallel, cases of non-ESBL-producing bacterial infections (n = 30) were compared to uninfected controls (n = 60). We then qualitatively compared these results. RESULTS: Median age of cases was 1.06 years; 62% of isolates were from urine, and 60% were E. coli. By multivariable analysis, ESBL cases were 5.7 and 3.3 times more likely to have gastrointestinal (P = .001; 95% confidence interval [CI] 1.9-17.0) and neurologic (P = .001; 95% CI 1.1-3.7) comorbidities, respectively, than controls; non-ESBL cases were also more likely to have gastrointestinal comorbidities than controls (P = .014; odds ratio 3.6; 95% CI 1.2-10.1). Study period prevalence remained stable (1.7%). Most (60%) infections occurred in the intensive care unit; however, 30% of children presented in the outpatient setting. Seventy-seven percent of isolates were multidrug resistant (ie, resistant to ≥3 antibiotic classes). Recurrence of infection occurred in 17% of ESBL cases. Crude mortality rates (7%) did not differ between cases and controls. CONCLUSIONS: The incidence of pediatric infection due to ESBL-positive Enterobacteriaceae was stable at 2 large tertiary-care medical centers over a 4-year period. Multidrug resistance in pediatric ESBL isolates is common. Risk factors for infection due to ESBL-producing bacteria include neurologic medical conditions.

Immunogenicity of Licensed Influenza A (H1N1) 2009 Monovalent Vaccines in HIV-Infected Children and Youth.

BACKGROUND: With the emergence of pandemic influenza A (pH1N1) in 2009, children and youth infected with human immunodeficiency virus (HIV) were vulnerable because of immunologic impairment and the greater virulence of this infection in young persons. METHODS: A multicenter study of the immunogenicity of 3 licensed influenza A (H1N1) monovalent vaccines (1 live attenuated and 2 inactivated) was conducted in children and youth with perinatal HIV infection, most of whom were receiving ≥3 antiretroviral drugs, had CD4% ≥15, and plasma HIV RNA levels <400 copies/mL. Serum hemagglutinin inhibition assay (HAI) antibody levels were measured and correlated with baseline demographic and clinical variables. RESULTS: One hundred forty-nine subjects were enrolled at 26 sites in the United States and Puerto Rico. Over 40% had baseline HAI titers ≥40. For subjects aged 6 months to <10 years, 79% and 68%, respectively, achieved a ≥40- and ≥4-fold rise in HAI titers after the second dose of vaccine. Three weeks after a single immunization with an inactivated vaccine, similar immunogenicity results were achieved in youth aged 10-24 years. With multivariable analysis, only Hispanic ethnicity and CD4% ≥15 were associated with achieving both HAI titer ≥40- and ≥4-fold rise in titer. CONCLUSIONS: Although licensed pH1N1 vaccines produced HAI titers that were considered to be protective in the majority of HIV-infected children and youth, the proportion with titers ≥40- and ≥4-fold rise in titer was lower than expected for children without HIV infection. Vaccine immunogenicity was lower in HIV-infected children and youth with evidence of immune suppression.

Macrolide treatment failure in streptococcal pharyngitis resulting in acute rheumatic fever.

Macrolide resistance (MR) in group A Streptococcus (GAS) has been well documented in several countries and has become clinically significant since the large increases in macrolide usage during the 1970s. Macrolides are recommended as an alternative therapy for GAS pharyngitis, the most common cause of bacterial pharyngitis. Macrolide resistance has been associated with certain emm types, a sequence-based typing system of the hypervariable region of the GAS M-protein gene. Clinical failure of macrolide treatment of GAS infections can be associated with complications including acute rheumatic fever and rheumatic heart disease, the leading cause of acquired heart disease in children worldwide. Here we report 2 pediatric cases of MR and/or treatment failure in the treatment of GAS pharyngitis with the subsequent development of acute rheumatic fever. We also review the literature on worldwide MR rates, molecular classifications, and emm types, primarily associated with GAS pharyngeal isolates between the years of 2000 and 2010. The use of macrolides in the management of GAS pharyngitis should be limited to patients with significant penicillin allergy.

A multicenter retrospective study of childhood brucellosis in Chicago, Illinois from 1986 to 2008.

OBJECTIVES: To determine risk factors in children for the acquisition of Brucella, clinical presentation, treatment, and disease outcomes. METHODS: A retrospective multicenter chart review was undertaken of children identified with brucellosis from 1986 to 2008 at three tertiary care centers in Chicago, Illinois, USA. The charts were reviewed for data regarding risk factors for acquisition, clinical presentation, and outcomes. RESULTS: Twenty-one charts were available for review. The median age was 6.5 years (range 2-14 years); 62% were female. Ethnic background was 67% Hispanic and 24% Arabic. Risk factors included travel to an endemic area (86%), particularly Mexico, and consumption of unpasteurized milk products (76%). Common findings included fever (95%), bacteremia (86%), elevated liver transaminases (80%), constitutional symptoms (76%), splenomegaly (60%), and hepatomegaly (55%). Relapse occurred in three of six subjects started on single drug treatment, but in only one of 15 subjects who started on two or more drugs (p=0.053). No relapses occurred in children whose initial therapy included rifampin or those administered three-drug regimens. CONCLUSIONS: Brucella is an infrequent pathogen but should be considered in children with compatible epidemiologic and clinical characteristics. Blood cultures should be obtained, and initial therapy with two or more drugs may decrease the risk of relapse.

Efficacy of fluconazole prophylaxis for prevention of invasive fungal infection in extremely low birth weight infants.

BACKGROUND: Invasive fungal infections (IFI) are an important cause of late-onset disease in extremely low birth weight (ELBW) infants. Despite prior trials of fluconazole prophylaxis in neonates, application of this regimen remains controversial. Review of our neonatal intensive care unit aggregate annual number of fungal isolates from sterile sites in ELBW infants from 1997 to 2006 suggested a significant decrease following the institution of routine prophylactic fluconazole in February 2002. We undertook a retrospective study to document the efficacy and adverse effects of routine fluconazole prophylaxis. METHODS: ELBW infants admitted during 2000 to 2006 were divided into 2 groups: Control group-admitted before the institution of fluconazole prophylaxis, and Fluconazole group-admitted after institution of fluconazole prophylaxis. Primary outcome was the frequency of IFI. Secondary outcome was the frequency of cholestasis, which has been rarely reported with fluconazole use. RESULTS: Data were extracted from 262 infant records: control 99, fluconazole 163. Baseline demographics and potentially confounding variables differed between the 2 groups with greater birth weight, greater gestational age, shorter durations of ventilation and central catheter use, and earlier start of feeding in the control group, reflecting healthier control infants. Frequency of IFI was 7.1% in the control group versus 1.8% in the fluconazole group, P = 0.045. Logistic regression revealed that fluconazole prophylaxis was independently associated with a lower risk of IFI. There was no difference in the frequency of cholestasis between the control and fluconazole groups. CONCLUSIONS: Prophylactic administration of fluconazole to all ELBW infants was associated with significantly decreased rates of IFI without associated adverse effects.