Last data update: Jun 03, 2024. (Total: 46935 publications since 2009)
Records 1-30 (of 400 Records) |
Query Trace: Hill A [original query] |
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Comprehensive review of tinea capitis in adults: Epidemiology, risk factors, clinical presentations, and management
Hill RC , Gold JAW , Lipner SR . J Fungi (Basel) 2024 10 (5) Tinea capitis is a fungal infection of the scalp and hair caused by dermatophyte molds, that most often affects children and may also affect adults. Previous estimates suggest that between 3% and 11% of all tinea capitis cases worldwide occur in adults, although updated epidemiological studies are needed to reassess the prevalence of tinea capitis in adult populations specifically. Postmenopausal adult women are most often affected by tinea capitis, with African American or Black women particularly at risk. Adults who experience crowded living conditions, who live in close proximity to animals, who are immunosuppressed, and/or who live in households with affected children are at greatest risk of infection. Tinea capitis can be non-inflammatory or inflammatory in nature, and the subtype affects the extent and severity of clinical symptoms. Fungal culture and potassium hydroxide preparations are the most commonly used diagnostic tools. Trichoscopy, defined as dermoscopic imaging of the scalp and hair, is a useful adjunct to the physical examination. The mainstay of therapy is oral antifungal therapy, and topical therapy alone is not recommended. Since tinea capitis infection is uncommon in adults, there are no widely accepted treatment guidelines. Rather, the same medications used for tinea capitis infection among children are recommended for adults at varying doses, including griseofulvin, and terbinafine, and, less commonly, itraconazole and fluconazole. The prognosis for tinea capitis in adults is typically excellent when prompt and adequate treatment is administered; however, delayed diagnosis or inadequate treatment can result in scarring alopecia. Over the past decade, dermatophyte infections resistant to treatment with topical and oral antifungal agents have emerged. While tinea capitis infections resistant to antifungal therapy have been rarely reported to date, antifungal resistance is rising among superficial fungal infections in general, and antifungal stewardship is necessary to ensure that resistance to treatment does not develop among dermatophytes that cause tinea capitis. |
Changes in vaccine hesitancy among parents of children aged 6 months - 17 Years, National Immunization Surveys, 2019-2022
Vashist K , Yankey D , Elam-Evans LD , Mu Y , Valier MR , Pingali C , Hill HA , Santibanez TA , Singleton JA . Vaccine 2024 BACKGROUND: Vaccine hesitancy (VH) has been a major contributor to large outbreaks of vaccine-preventable diseases globally, including in the United States. METHODS: Data from the 2019-2022 National Immunization Surveys were analyzed to assess parental hesitancy toward routine vaccination of their children aged 6 months -17 years. Joinpoint regression was employed to investigate trends in VH from 2019 to 2022 nationally overall and among socio-demographic subgroups. Using logistic regression, the difference between the prevalence of VH before and after the authorization of the COVID-19 vaccine for children aged 6 months-4 years, 5-11 years, and 12-17 years was computed. Both unadjusted and adjusted estimates were reported. VH was also compared within each socio-demographic subgroup with a reference level, at two-time points- before and after the authorization of the COVID-19 vaccine for each age group. RESULTS: Overall, VH remained around 19.0 % from Q2 2019 to Q3 2022. Parents of non-Hispanic Black children had the largest average quarterly decrease in VH (β = -0.55; p < 0.05 by test for trend). After the authorization of the COVID-19 vaccine for children aged 6 months to 4 years, the adjusted percentage of children having parents that reported VH decreased by 2.2 (95 % CI: -3.9, -0.6) percentage points (pp) from 21.6 % to 19.4 %. Conversely, for children aged 5-11 years, VH increased by 1.2 (95 % CI: 0.2, 2.3) pp, from 19.8 % to 21.0 %. VH among parents of non-Hispanic Black children decreased after the authorization of the COVID-19 vaccine for adolescents aged 12-17 years but remained significantly higher compared to parents of non-Hispanic White children before and after authorization of the COVID-19 vaccine for all age groups. DISCUSSION: About 1 in 5 children had parents reporting VH from 2019 to 2022. Parental VH increased after the authorization of the COVID-19 vaccine for children aged 5-11 years and declined for children aged 6 months-4 years. |
Contemporary prestroke dual antiplatelet use and symptomatic intracerebral hemorrhage risk after thrombolysis
Peng TJ , Schwamm LH , Fonarow GC , Hassan AE , Hill M , Messé SR , Coronado F , Falcone GJ , Sharma R . JAMA Neurol 2024 IMPORTANCE: Intravenous alteplase (IV-tPA) can be administered to patients with acute ischemic stroke but is associated with symptomatic intracerebral hemorrhage (sICH). It is unclear if patients taking prestroke dual antiplatelet therapy (DAPT) are at higher risk of sICH. OBJECTIVE: To determine the associated risk of sICH in patients taking prestroke dual antiplatelet therapy receiving alteplase for acute ischemic stroke using propensity score matching analysis. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the American Heart Association and American Stroke Association Get With The Guidelines-Stroke (GWTG-Stroke) registry between 2013 and 2021. Data were obtained from hospitals in the GWTG-Stroke registry. This study included patients hospitalized with acute ischemic stroke and treated with IV-tPA. Data were analyzed from January 2013 to December 2021. EXPOSURES: Prestroke DAPT before treatment with IV-tPA for acute ischemic stroke. MAIN OUTCOME MEASURES: sICH, In-hospital death, discharge modified Rankin scale score, and other life-threatening systemic hemorrhages. RESULTS: Of 409 673 participants, 321 819 patients (mean [SD] age, 68.6 [15.1] years; 164 587 female [51.1%]) who were hospitalized with acute ischemic stroke and treated with IV-tPA were included in the analysis. The rate of sICH was 2.9% (5200 of 182 344), 3.8% (4457 of 117 670), and 4.1% (893 of 21 805) among patients treated with no antiplatelet therapy, single antiplatelet therapy (SAPT), and DAPT, respectively (P < .001). In adjusted analyses after propensity score subclassification, both SAPT (odds ratio [OR], 1.13; 95% CI, 1.07-1.19) and DAPT (OR, 1.28; 95% CI, 1.14-1.42) were associated with increased risks of sICH. Prestroke antiplatelet medications were associated with lower odds of discharge mRS score of 2 or less compared with no medication (SAPT OR, 0.92; 95% CI, 0.90-0.95; DAPT OR, 0.94; 95% CI, 0.88-0.98). Results of a subgroup analysis of patients taking DAPT exposed to aspirin-clopidogrel vs aspirin-ticagrelor combination therapy were not significant (OR, 1.35; 95% CI, 0.84-1.86). CONCLUSIONS AND RELEVANCE: Prestroke DAPT was associated with a significantly elevated risk of sICH among patients with ischemic stroke who were treated with thrombolysis; however, the absolute increase in risk was small. Patients exposed to antiplatelet medications did not have excess sICH compared with landmark trials, which demonstrated overall clinical benefit of thrombolysis therapy for acute ischemic stroke. |
Challenges of COVID-19 case forecasting in the US, 2020-2021
Lopez VK , Cramer EY , Pagano R , Drake JM , O'Dea EB , Adee M , Ayer T , Chhatwal J , Dalgic OO , Ladd MA , Linas BP , Mueller PP , Xiao J , Bracher J , Castro Rivadeneira AJ , Gerding A , Gneiting T , Huang Y , Jayawardena D , Kanji AH , Le K , Mühlemann A , Niemi J , Ray EL , Stark A , Wang Y , Wattanachit N , Zorn MW , Pei S , Shaman J , Yamana TK , Tarasewicz SR , Wilson DJ , Baccam S , Gurung H , Stage S , Suchoski B , Gao L , Gu Z , Kim M , Li X , Wang G , Wang L , Wang Y , Yu S , Gardner L , Jindal S , Marshall M , Nixon K , Dent J , Hill AL , Kaminsky J , Lee EC , Lemaitre JC , Lessler J , Smith CP , Truelove S , Kinsey M , Mullany LC , Rainwater-Lovett K , Shin L , Tallaksen K , Wilson S , Karlen D , Castro L , Fairchild G , Michaud I , Osthus D , Bian J , Cao W , Gao Z , Lavista Ferres J , Li C , Liu TY , Xie X , Zhang S , Zheng S , Chinazzi M , Davis JT , Mu K , Pastore YPiontti A , Vespignani A , Xiong X , Walraven R , Chen J , Gu Q , Wang L , Xu P , Zhang W , Zou D , Gibson GC , Sheldon D , Srivastava A , Adiga A , Hurt B , Kaur G , Lewis B , Marathe M , Peddireddy AS , Porebski P , Venkatramanan S , Wang L , Prasad PV , Walker JW , Webber AE , Slayton RB , Biggerstaff M , Reich NG , Johansson MA . PLoS Comput Biol 2024 20 (5) e1011200 During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making. |
Policy uptake and implementation of the RTS,S/AS01 malaria vaccine in sub-Saharan African countries: status 2 years following the WHO recommendation
Osoro CB , Ochodo E , Kwambai TK , Otieno JA , Were L , Sagam CK , Owino EJ , Kariuki S , Ter Kuile FO , Hill J . BMJ Glob Health 2024 9 (4) In October 2021, the WHO recommended the world's first malaria vaccine-RTS,S/AS01-to prevent malaria in children living in areas with moderate-to-high transmission in sub-Saharan Africa (SSA). A second malaria vaccine, R21/Matrix-M, was recommended for use in October 2023 and added to the WHO list of prequalified vaccines in December 2023. This study analysis assessed the country status of implementation and delivery strategies for RTS,S/AS01 by searching websites for national malaria policies, guidelines and related documents. Direct contact with individuals working in malaria programmes was made to obtain documents not publicly available. 10 countries had documents with information relating to malaria vaccine implementation, 7 referencing RTS,S/AS01 and 3 (Burkina Faso, Kenya and Nigeria) referencing RTS,S/AS01 and R21/Matrix-M. Five other countries reported plans for malaria vaccine roll-out without specifying which vaccine. Ghana, Kenya and Malawi, which piloted RTS,S/AS01, have now integrated the vaccine into routine immunisation services. Cameroon and Burkina Faso are the first countries outside the pilot countries to incorporate the vaccine into national immunisation services. Uganda plans a phased RTS,S/AS01 introduction, while Guinea plans to first pilot RTS,S/AS01 in five districts. The RTS,S/AS01 schedule varied by country, with the first dose administered at 5 or 6 months in all countries but the fourth dose at either 18, 22 or 24 months. SSA countries have shown widespread interest in rolling out the malaria vaccine, the Global Alliance for Vaccines and Immunization having approved financial support for 20 of 30 countries which applied as of March 2024. Limited availability of RTS,S/AS01 means that some approved countries will not receive the required doses. Vaccine availability and equity must be addressed even as R21/Matrix-M becomes available. |
Travel surveillance uncovers dengue virus dynamics and introductions in the Caribbean
Taylor-Salmon E , Hill V , Paul LM , Koch RT , Breban MI , Chaguza C , Sodeinde A , Warren JL , Bunch S , Cano N , Cone M , Eysoldt S , Garcia A , Gilles N , Hagy A , Heberlein L , Jaber R , Kassens E , Colarusso P , Davis A , Baudin S , Rico E , Mejía-Echeverri Á , Scott B , Stanek D , Zimler R , Muñoz-Jordán JL , Santiago GA , Adams LE , Paz-Bailey G , Spillane M , Katebi V , Paulino-Ramírez R , Mueses S , Peguero A , Sánchez N , Norman FF , Galán JC , Huits R , Hamer DH , Vogels CBF , Morrison A , Michael SF , Grubaugh ND . Nat Commun 2024 15 (1) 3508 Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region. |
HIV risk behaviour, viraemia, and transmission across HIV cascade stages including low-level viremia: Analysis of 14 cross-sectional population-based HIV Impact Assessment surveys in sub-Saharan Africa
Edun O , Okell L , Chun H , Bissek AZ , Ndongmo CB , Shang JD , Brou H , Ehui E , Ekra AK , Nuwagaba-Biribonwoha H , Dlamini SS , Ginindza C , Eshetu F , Misganie YG , Desta SL , Achia TNO , Aoko A , Jonnalagadda S , Wafula R , Asiimwe FM , Lecher S , Nkanaunena K , Nyangulu MK , Nyirenda R , Beukes A , Klemens JO , Taffa N , Abutu AA , Alagi M , Charurat ME , Dalhatu I , Aliyu G , Kamanzi C , Nyagatare C , Rwibasira GN , Jalloh MF , Maokola WM , Mgomella GS , Kirungi WL , Mwangi C , Nel JA , Minchella PA , Gonese G , Nasr MA , Bodika S , Mungai E , Patel HK , Sleeman K , Milligan K , Dirlikov E , Voetsch AC , Shiraishi RW , Imai-Eaton JW . PLOS Glob Public Health 2024 4 (4) e0003030 As antiretroviral treatment (ART) coverage for people living with HIV (PLHIV) increases, HIV programmes require up-to-date information about evolving HIV risk behaviour and transmission risk, including those with low-level viremia (LLV; >50 to ≤1000 copies/mL), to guide prevention priorities. We aimed to assess differences in sexual risk behaviours, distribution of viral load (VL) and proportion of transmission across PLHIV subgroups. We analysed data from Population-based HIV Impact Assessment surveys in 14 sub-Saharan African countries during 2015-2019. We estimated adjusted prevalence ratios (aPR) of self-reported HIV high-risk behaviour (multiple partners and condomless sex) across cascade stages via generalised estimation equations. We modelled the proportions of transmission from each subgroup using relative self-reported sexual risk, a Hill function for transmission rate by VL, and proportions within cascade stages from surveys and UNAIDS country estimates for 2010-2020. Compared to PLHIV with undetectable VL (≤50 copies/mL), undiagnosed PLHIV (aPR women: 1.28 [95% CI: 1.08-1.52]; men: 1.61 [1.33-1.95]) and men diagnosed but untreated (2.06 [1.52-2.78]) were more likely to self-report high-risk sex. High-risk behaviour was not significantly associated with LLV. Mean VL was similar among undiagnosed, diagnosed but untreated, and on ART but non-suppressed sub-groups. Across surveys, undiagnosed and diagnosed but untreated contributed most to transmission (40-91% and 1-41%, respectively), with less than 1% from those with LLV. Between 2010 and 2020, the proportion of transmission from individuals on ART but non-suppressed increased. In settings with high ART coverage, effective HIV testing, ART linkage, and retention remain priorities to reduce HIV transmission. Persons with LLV are an increasing share of PLHIV but their contribution to HIV transmission was small. Improving suppression among PLHIV on ART with VL ≥1000 copies/mL will become increasingly important. |
Comparison of tuberculin skin testing and interferon-γ release assays in predicting tuberculosis disease
Ayers T , Hill AN , Raykin J , Mohanty S , Belknap RW , Brostrom R , Khurana R , Lauzardo M , Miller TL , Narita M , Pettit AC , Pyan A , Salcedo KL , Polony A , Flood J . JAMA Netw Open 2024 7 (4) e244769 IMPORTANCE: Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown. OBJECTIVE: To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations. DESIGN, SETTING, AND PARTICIPANTS: This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023. EXPOSURES: At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment. MAIN OUTCOMES AND MEASURES: Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis. RESULTS: A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively). CONCLUSIONS AND RELEVANCE: In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB. |
Correction and Republication: Symptoms of Depression, Anxiety, Post-Traumatic Stress Disorder, and Suicidal Ideation Among State, Tribal, Local, and Territorial Public Health Workers During the COVID-19 Pandemic - United States, March-April 2021
Bryant-Genevier J , Rao CY , Lopes-Cardozo B , Kone A , Rose C , Thomas I , Orquiola D , Lynfield R , Shah D , Freeman L , Becker S , Williams A , Gould DW , Tiesman H , Lloyd G , Hill L , Byrkit R . MMWR Morb Mortal Wkly Rep 12/28/2021 70 (48) 1679 On July 2, 2021, MMWR published “Symptoms of Depression, Anxiety, Post-Traumatic Stress Disorder, and Suicidal Ideation Among State, Tribal, Local, and Territorial Public Health Workers During the COVID-19 Pandemic — United States, March–April 2021” (1). On October 12, 2021, the authors informed MMWR that some data were inaccurate because 420 incomplete participant responses were incorrectly assigned scores for depression. This error resulted in a change in overall depression prevalence from 32.0% to 30.8%, and other similar changes in stratified prevalences of depression, prevalence ratios of depression, and the overall proportion of respondents who reported at least one mental health condition. The authors have corrected the MMWR report by excluding the 420 records from the depression analysis and confirmed that the interpretation and the conclusions of the original report were not affected by these corrections. MMWR has republished the report (2), which includes the original report with clearly marked corrections in supplementary materials. |
Disparities in tuberculosis incidence by race and ethnicity among the U.S.-born population in the United States, 2011 to 2021 : An analysis of national disease registry data
Li Y , Regan M , Swartwood NA , Barham T , Beeler Asay GR , Cohen T , Hill AN , Horsburgh CR Jr , Khan A , Marks SM , Myles RL , Salomon JA , Self JL , Menzies NA . Ann Intern Med 2024 BACKGROUND: Elevated tuberculosis (TB) incidence rates have recently been reported for racial/ethnic minority populations in the United States. Tracking such disparities is important for assessing progress toward national health equity goals and implementing change. OBJECTIVE: To quantify trends in racial/ethnic disparities in TB incidence among U.S.-born persons. DESIGN: Time-series analysis of national TB registry data for 2011 to 2021. SETTING: United States. PARTICIPANTS: U.S.-born persons stratified by race/ethnicity. MEASUREMENTS: TB incidence rates, incidence rate differences, and incidence rate ratios compared with non-Hispanic White persons; excess TB cases (calculated from incidence rate differences); and the index of disparity. Analyses were stratified by sex and by attribution of TB disease to recent transmission and were adjusted for age, year, and state of residence. RESULTS: In analyses of TB incidence rates for each racial/ethnic population compared with non-Hispanic White persons, incidence rate ratios were as high as 14.2 (95% CI, 13.0 to 15.5) among American Indian or Alaska Native (AI/AN) females. Relative disparities were greater for females, younger persons, and TB attributed to recent transmission. Absolute disparities were greater for males. Excess TB cases in 2011 to 2021 represented 69% (CI, 66% to 71%) and 62% (CI, 60% to 64%) of total cases for females and males, respectively. No evidence was found to indicate that incidence rate ratios decreased over time, and most relative disparity measures showed small, statistically nonsignificant increases. LIMITATION: Analyses assumed complete TB case diagnosis and self-report of race/ethnicity and were not adjusted for medical comorbidities or social determinants of health. CONCLUSION: There are persistent disparities in TB incidence by race/ethnicity. Relative disparities were greater for AI/AN persons, females, and younger persons, and absolute disparities were greater for males. Eliminating these disparities could reduce overall TB incidence by more than 60% among the U.S.-born population. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention. |
Detection of anatoxins in human urine by liquid chromatography triple quadrupole mass spectrometry and ELISA
Cunningham BR , Lagon SR , Bragg WA , Hill D , Hamelin EI . Toxins (Basel) 2024 16 (3) Harmful cyanobacterial blooms are becoming more common and persistent around the world. When in bloom, various cyanobacterial strains can produce anatoxins in high concentrations, which, unlike other cyanobacterial toxins, may be present in clear water. Potential human and animal exposures to anatoxins occur mainly through unintentional ingestion of contaminated algal mats and water. To address this public health threat, we developed and validated an LC-MS/MS method to detect anatoxins in human urine to confirm exposures. Pooled urine was fortified with anatoxin-a and dihydroanatoxin at concentrations from 10.0 to 500 ng/mL to create calibrators and quality control samples. Samples were diluted with isotopically labeled anatoxin and solvent prior to LC-MS/MS analysis. This method can accurately quantitate anatoxin-a with inter- and intraday accuracies ranging from 98.5 to 103% and relative standard deviations < 15%, which is within analytical guidelines for mass spectrometry methods. Additionally, this method qualitatively detects a common degradation product of anatoxin, dihydroanatoxin, above 10 ng/mL. We also evaluated a commercial anatoxin-a ELISA kit for potential diagnostic use; however, numerous false positives were detected from unexposed individual human urine samples. In conclusion, we have developed a method to detect anatoxins precisely and accurately in urine samples, addressing a public health area of concern, which can be applied to future exposure events. |
An environmental evaluation of urine-diverting dry toilets in Hiloweyn Camp, Dollo Ado, Ethiopia
Brown TW , Murphy JL , Akers P , Patrick M , Hill V , Mattioli M , Tsige Y , Adow A , Abdirashid M , Mohamed MN , Githiri D , Handzel T . Sci Total Environ 2024 926 171838 Safe and hygienic management of human waste is essential in humanitarian settings. Urine-diverting dry toilets (UDDTs) can enable this management in some humanitarian emergency settings. A seeded, longitudinal environmental study was conducted in Hiloweyn refugee camp, Dollo Ado, Ethiopia, to measure Escherichia coli and Ascaris suum ova inactivation within closed UDDT vaults and to document environmental conditions (temperature, moisture content, and pH) that could influence inactivation. Hiloweyn camp represented an optimal location for a desiccation-based sanitation technology such as the UDDT. E. coli and Ascaris ova inactivation was observed in UDDTs under warm, dry, alkaline conditions at 6, 9, and 12 months of storage; UDDTs with samples containing <1000 E. coli/g total solids increased from 30 % to 95 % over 12 months, and a >2.8-log(10) reduction in Ascaris ova viability was observed after 6 months. Additional laboratory-based studies were conducted to provide insights into the field study findings and study the impact of hydrated lime on E. coli and Ascaris ova inactivation. Results suggest that adding hydrated lime to elevate pH > 12 may increase inactivation and decrease storage time. Overall, UDDTs could contribute to the safe and hygienic management of human waste in comparable warm and dry humanitarian settings. |
Expert panel review of skin and hair dermatophytoses in an era of antifungal resistance
Hill RC , Caplan AS , Elewski B , Gold JAW , Lockhart SR , Smith DJ , Lipner SR . Am J Clin Dermatol 2024 Dermatophytoses are fungal infections of the skin, hair, and nails that affect approximately 25% of the global population. Occlusive clothing, living in a hot humid environment, poor hygiene, proximity to animals, and crowded living conditions are important risk factors. Dermatophyte infections are named for the anatomic area they infect, and include tinea corporis, cruris, capitis, barbae, faciei, pedis, and manuum. Tinea incognito describes steroid-modified tinea. In some patients, especially those who are immunosuppressed or who have a history of corticosteroid use, dermatophyte infections may spread to involve extensive skin areas, and, in rare cases, may extend to the dermis and hair follicle. Over the past decade, dermatophytoses cases not responding to standard of care therapy have been increasingly reported. These cases are especially prevalent in the Indian subcontinent, and Trichophyton indotineae has been identified as the causative species, generating concern regarding resistance to available antifungal therapies. Antifungal-resistant dermatophyte infections have been recently recognized in the United States. Antifungal resistance is now a global health concern. When feasible, mycological confirmation before starting treatment is considered best practice. To curb antifungal-resistant infections, it is necessary for physicians to maintain a high index of suspicion for resistant dermatophyte infections coupled with antifungal stewardship efforts. Furthermore, by forging partnerships with federal agencies, state and local public health agencies, professional societies, and academic institutions, dermatologists can lead efforts to prevent the spread of antifungal-resistant dermatophytes. |
Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis
Xie O , Morris JM , Hayes AJ , Towers RJ , Jespersen MG , Lees JA , Ben Zakour NL , Berking O , Baines SL , Carter GP , Tonkin-Hill G , Schrieber L , McIntyre L , Lacey JA , James TB , Sriprakash KS , Beatson SA , Hasegawa T , Giffard P , Steer AC , Batzloff MR , Beall BW , Pinho MD , Ramirez M , Bessen DE , Dougan G , Bentley SD , Walker MJ , Currie BJ , Tong SYC , McMillan DJ , Davies MR . Nat Commun 2024 15 (1) 2286 Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S. pyogenes. More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were shared across species. Assessing potential cross-protection from leading S. pyogenes vaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention. |
Procedural application of mode-of-action and human relevance analysis: styrene-induced lung tumors in mice
Frank EA , Meek MEB . Crit Rev Toxicol 2024 54 (2) 134-151 Risk assessment of human health hazards has traditionally relied on experiments that use animal models. Although exposure studies in rats and mice are a major basis for determining risk in many cases, observations made in animals do not always reflect health hazards in humans due to differences in biology. In this critical review, we use the mode-of-action (MOA) human relevance framework to assess the likelihood that bronchiolar lung tumors observed in mice chronically exposed to styrene represent a plausible tumor risk in humans. Using available datasets, we analyze the weight-of-evidence 1) that styrene-induced tumors in mice occur through a MOA based on metabolism of styrene by Cyp2F2; and 2) whether the hypothesized key event relationships are likely to occur in humans. This assessment describes how the five modified Hill causality considerations support that a Cyp2F2-dependent MOA causing lung tumors is active in mice, but only results in tumorigenicity in susceptible strains. Comparison of the key event relationships assessed in the mouse was compared to an analogous MOA hypothesis staged in the human lung. While some biological concordance was recognized between key events in mice and humans, the MOA as hypothesized in the mouse appears unlikely in humans due to quantitative differences in the metabolic capacity of the airways and qualitative uncertainties in the toxicological and prognostic concordance of pre-neoplastic and neoplastic lesions arising in either species. This analysis serves as a rigorous demonstration of the framework's utility in increasing transparency and consistency in evidence-based assessment of MOA hypotheses in toxicological models and determining relevance to human health. |
Integration of the RTS,S/AS01 malaria vaccine into the Essential Programme on Immunisation in western Kenya: a qualitative longitudinal study from the health system perspective
Hill J , Bange T , Hoyt J , Kariuki S , Jalloh MF , Webster J , Okello G . Lancet Glob Health 2024 BACKGROUND: Malaria accounts for over half a million child deaths annually. WHO recommends RTS,S/AS01 to prevent malaria in children living in moderate-to-high malaria transmission regions. We conducted a qualitative longitudinal study to investigate the contextual and dynamic factors shaping vaccine delivery and uptake during a pilot introduction in western Kenya. METHODS: The study was conducted between Oct 3, 2019, and Mar 24, 2022. We conducted participant and non-participant observations and in-depth interviews with health-care providers, health managers, and national policymakers at three timepoints using an iterative approach and observations of practices and processes of malaria vaccine delivery. Transcripts were coded by content analysis using the consolidated framework for implementation research, to which emerging themes were added deductively and categorised into challenges and opportunities. FINDINGS: We conducted 112 in-depth interviews with 60 participants (25 health-care providers, 27 managers, and eight policy makers). Health-care providers highlighted limitations in RTS,S/AS01 integration into routine immunisation services due to the concurrent pilot evaluation and temporary adaptations for health reporting. Initial challenges related to the complexity of the four-dose schedule (up to 24-months); however, self-efficacy increased over time as the health-care providers gained experience in vaccine delivery. Low uptake of the fourth dose remained a challenge. Health managers cited insufficient trained immunisation staff and inadequate funding for supervision. Confidence in the vaccine increased among all participant groups owing to reductions in malaria frequency and severity. INTERPRETATION: Integration of RTS,S/AS01 into immunisation services in western Kenya presented substantial operational challenges most of which were overcome in the first 2 years, providing important lessons for other countries. Programme expansion is feasible with intensive staff training and retention, enhanced supervision, and defaulter-tracing to ensure uptake of all doses. FUNDING: PATH via World Health Organization; Gavi, the Vaccine Alliance; The Global Fund; and Unitaid. |
Wilderness Medical Society clinical practice guidelines on water treatment for wilderness, international travel, and austere situations
Backer HD , Derlet RW , Hill VR . Wilderness Environ Med 2023 10806032231218722 To provide guidance to medical providers, wilderness users, and travelers, the Wilderness Medical Society convened an expert panel to develop evidence-based guidelines for treating water in situations where the potability of available water is not assured, including wilderness and international travel, areas impacted by disaster, and other areas without adequate sanitation. The guidelines present the available methods for reducing or eliminating microbiological contamination of water for individuals, groups, or households; evaluation of their effectiveness; and practical considerations. The evidence base includes both laboratory and clinical publications. The panel graded the recommendations based on the quality of supporting evidence and the balance between benefits and risks/burdens according to the criteria published by the American College of Chest Physicians. |
Ethnic and racial differences in self-reported symptoms, health status, activity level, and missed work at 3 and 6 months following SARS-CoV-2 infection
O'Laughlin KN , Klabbers RE , Ebna Mannan I , Gentile NL , Geyer RE , Zheng Z , Yu H , Li SX , Chan KCG , Spatz ES , Wang RC , L'Hommedieu M , Weinstein RA , Plumb ID , Gottlieb M , Huebinger RM , Hagen M , Elmore JG , Hill MJ , Kelly M , McDonald S , Rising KL , Rodriguez RM , Venkatesh A , Idris AH , Santangelo M , Koo K , Saydah S , Nichol G , Stephens KA . Front Public Health 2023 11 1324636 INTRODUCTION: Data on ethnic and racial differences in symptoms and health-related impacts following SARS-CoV-2 infection are limited. We aimed to estimate the ethnic and racial differences in symptoms and health-related impacts 3 and 6 months after the first SARS-CoV-2 infection. METHODS: Participants included adults with SARS-CoV-2 infection enrolled in a prospective multicenter US study between 12/11/2020 and 7/4/2022 as the primary cohort of interest, as well as a SARS-CoV-2-negative cohort to account for non-SARS-CoV-2-infection impacts, who completed enrollment and 3-month surveys (N = 3,161; 2,402 SARS-CoV-2-positive, 759 SARS-CoV-2-negative). Marginal odds ratios were estimated using GEE logistic regression for individual symptoms, health status, activity level, and missed work 3 and 6 months after COVID-19 illness, comparing each ethnicity or race to the referent group (non-Hispanic or white), adjusting for demographic factors, social determinants of health, substance use, pre-existing health conditions, SARS-CoV-2 infection status, COVID-19 vaccination status, and survey time point, with interactions between ethnicity or race and time point, ethnicity or race and SARS-CoV-2 infection status, and SARS-CoV-2 infection status and time point. RESULTS: Following SARS-CoV-2 infection, the majority of symptoms were similar over time between ethnic and racial groups. At 3 months, Hispanic participants were more likely than non-Hispanic participants to report fair/poor health (OR: 1.94; 95%CI: 1.36-2.78) and reduced activity (somewhat less, OR: 1.47; 95%CI: 1.06-2.02; much less, OR: 2.23; 95%CI: 1.38-3.61). At 6 months, differences by ethnicity were not present. At 3 months, Other/Multiple race participants were more likely than white participants to report fair/poor health (OR: 1.90; 95% CI: 1.25-2.88), reduced activity (somewhat less, OR: 1.72; 95%CI: 1.21-2.46; much less, OR: 2.08; 95%CI: 1.18-3.65). At 6 months, Asian participants were more likely than white participants to report fair/poor health (OR: 1.88; 95%CI: 1.13-3.12); Black participants reported more missed work (OR, 2.83; 95%CI: 1.60-5.00); and Other/Multiple race participants reported more fair/poor health (OR: 1.83; 95%CI: 1.10-3.05), reduced activity (somewhat less, OR: 1.60; 95%CI: 1.02-2.51; much less, OR: 2.49; 95%CI: 1.40-4.44), and more missed work (OR: 2.25; 95%CI: 1.27-3.98). DISCUSSION: Awareness of ethnic and racial differences in outcomes following SARS-CoV-2 infection may inform clinical and public health efforts to advance health equity in long-term outcomes. |
Introduction and spread of Dengue virus 3, Florida, USA, May 2022-April 2023
Jones FK , Morrison AM , Santiago GA , Rysava K , Zimler RA , Heberlein LA , Kopp E , Saunders KE , Baudin S , Rico E , Mejía-Echeverri Á , Taylor-Salmon E , Hill V , Breban MI , Vogels CBF , Grubaugh ND , Paul LM , Michael SF , Johansson MA , Adams LE , Munoz-Jordan J , Paz-Bailey G , Stanek DR . Emerg Infect Dis 2024 30 (2) 376-379 During May 2022-April 2023, dengue virus serotype 3 was identified among 601 travel-associated and 61 locally acquired dengue cases in Florida, USA. All 203 sequenced genomes belonged to the same genotype III lineage and revealed potential transmission chains in which most locally acquired cases occurred shortly after introduction, with little sustained transmission. |
The role of funded partnerships in working towards decreasing COVID-19 vaccination disparities, United States, March 2021-December 2022
Fiebelkorn AP , Adelsberg S , Anthony R , Ashenafi S , Asif AF , Azzarelli M , Bailey T , Boddie TT , Boyer AP , Bungum NW , Burstin H , Burton JL , Casey DM , Chaumont Menendez C , Courtot B , Cronin K , Dowdell C , Downey LH , Fields M , Fitzsimmons T , Frank A , Gustafson E , Gutierrez-Nkomo M , Harris BL , Hill J , Holmes K , Huerta Migus L , Jacob Kuttothara J , Johns N , Johnson J , Kelsey A , Kingangi L , Landrum CM , Lee JT , Martinez PD , Medina Martínez G , Nicholls R , Nilson JR , Ohiaeri N , Pegram L , Perkins C , Piasecki AM , Pindyck T , Price S , Rodgers MS , Roney H , Schultz EM , Sobczyk E , Thierry JM , Toledo C , Weiss NE , Wiatr-Rodriguez A , Williams L , Yang C , Yao A , Zajac J . Vaccine 2024 During the COVID-19 vaccination rollout from March 2021- December 2022, the Centers for Disease Control and Prevention funded 110 primary and 1051 subrecipient partners at the national, state, local, and community-based level to improve COVID-19 vaccination access, confidence, demand, delivery, and equity in the United States. The partners implemented evidence-based strategies among racial and ethnic minority populations, rural populations, older adults, people with disabilities, people with chronic illness, people experiencing homelessness, and other groups disproportionately impacted by COVID-19. CDC also expanded existing partnerships with healthcare professional societies and other core public health partners, as well as developed innovative partnerships with organizations new to vaccination, including museums and libraries. Partners brought COVID-19 vaccine education into farm fields, local fairs, churches, community centers, barber and beauty shops, and, when possible, partnered with local healthcare providers to administer COVID-19 vaccines. Inclusive, hyper-localized outreach through partnerships with community-based organizations, faith-based organizations, vaccination providers, and local health departments was critical to increasing COVID-19 vaccine access and building a broad network of trusted messengers that promoted vaccine confidence. Data from monthly and quarterly REDCap reports and monthly partner calls showed that through these partnerships, more than 295,000 community-level spokespersons were trained as trusted messengers and more than 2.1 million COVID-19 vaccinations were administered at new or existing vaccination sites. More than 535,035 healthcare personnel were reached through outreach strategies. Quality improvement interventions were implemented in healthcare systems, long-term care settings, and community health centers resulting in changes to the clinical workflow to incorporate COVID-19 vaccine assessments, recommendations, and administration or referrals into routine office visits. Funded partners' activities improved COVID-19 vaccine access and addressed community concerns among racial and ethnic minority groups, as well as among people with barriers to vaccination due to chronic illness or disability, older age, lower income, or other factors. |
Naegleria fowleri detected in Grand Teton National Park Hot Springs
Barnhart EP , Kinsey SM , Wright PR , Caldwell SL , Hill V , Kahler A , Mattioli M , Cornman RS , Iwanowicz D , Eddy Z , Halonen S , Mueller R , Peyton BM , Puzon GJ . ACS ES and T Water 2023 The free-living thermophilic amoeba Naegleria fowleri (N. fowleri) causes the highly fatal disease primary amoebic meningoencephalitis. The environmental conditions that are favorable to the growth and proliferation of N. fowleri are not well-defined, especially in northern regions of the United States. In this study, we used culture-based methods and multiple molecular approaches to detect and analyzeN. fowleri and other Naegleria spp. in water, sediment, and biofilm samples from five hot spring sites in Grand Teton National Park, Wyoming, U.S.A. These results provide the first detections of N. fowleri in Grand Teton National Park and provide new insights into the distribution of pathogenic N. fowleri and other nonpathogenic Naegleria spp. in natural thermal water systems in northern latitudes. © 2024 The Authors. Published by American Chemical Society. |
Chemoprevention for malaria with monthly intermittent preventive treatment with dihydroartemisinin-piperaquine in pregnant women living with HIV on daily co-trimoxazole in Kenya and Malawi: a randomised, double-blind, placebo-controlled trial
Barsosio HC , Madanitsa M , Ondieki ED , Dodd J , Onyango ED , Otieno K , Wang D , Hill J , Mwapasa V , Phiri KS , Maleta K , Taegtmeyer M , Kariuki S , Schmiegelow C , Gutman JR , Ter Kuile FO . Lancet 2024 403 (10424) 365-378 BACKGROUND: The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of Plasmodium falciparum to the antifolate sulfadoxine-pyrimethamine. We assessed whether addition of monthly dihydroartemisinin-piperaquine to daily co-trimoxazole is more effective at preventing malaria infection than monthly placebo plus daily co-trimoxazole in pregnant women living with HIV. METHODS: We did an individually randomised, two-arm, placebo-controlled trial in areas with high-grade sulfadoxine-pyrimethamine resistance in Kenya and Malawi. Pregnant women living with HIV on dolutegravir-based combination antiretroviral therapy (cART) who had singleton pregnancies between 16 weeks' and 28 weeks' gestation were randomly assigned (1:1) by computer-generated block randomisation, stratified by site and HIV status (known positive vs newly diagnosed), to daily co-trimoxazole plus monthly dihydroartemisinin-piperaquine (three tablets of 40 mg dihydroartemisinin and 320 mg piperaquine given daily for 3 days) or daily co-trimoxazole plus monthly placebo. Daily co-trimoxazole consisted of one tablet of 160 mg sulfamethoxazole and 800 mg trimethoprim. The primary endpoint was the incidence of Plasmodium infection detected in the peripheral (maternal) or placental (maternal) blood or tissue by PCR, microscopy, rapid diagnostic test, or placental histology (active infection) from 2 weeks after the first dose of dihydroartemisinin-piperaquine or placebo to delivery. Log-binomial regression was used for binary outcomes, and Poisson regression for count outcomes. The primary analysis was by modified intention to treat, consisting of all randomised eligible participants with primary endpoint data. The safety analysis included all women who received at least one dose of study drug. All investigators, laboratory staff, data analysts, and participants were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, NCT04158713. FINDINGS: From Nov 11, 2019, to Aug 3, 2021, 904 women were enrolled and randomly assigned to co-trimoxazole plus dihydroartemisinin-piperaquine (n=448) or co-trimoxazole plus placebo (n=456), of whom 895 (99%) contributed to the primary analysis (co-trimoxazole plus dihydroartemisinin-piperaquine, n=443; co-trimoxazole plus placebo, n=452). The cumulative risk of any malaria infection during pregnancy or delivery was lower in the co-trimoxazole plus dihydroartemisinin-piperaquine group than in the co-trimoxazole plus placebo group (31 [7%] of 443 women vs 70 [15%] of 452 women, risk ratio 0·45, 95% CI 0·30-0·67; p=0·0001). The incidence of any malaria infection during pregnancy or delivery was 25·4 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 77·3 per 100 person-years in the co-trimoxazole plus placebo group (incidence rate ratio 0·32, 95% CI 0·22-0·47, p<0·0001). The number needed to treat to avert one malaria infection per pregnancy was 7 (95% CI 5-10). The incidence of serious adverse events was similar between groups in mothers (17·7 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group [23 events] vs 17·8 per 100 person-years in the co-trimoxazole group [25 events]) and infants (45·4 per 100 person-years [23 events] vs 40·2 per 100 person-years [21 events]). Nausea within the first 4 days after the start of treatment was reported by 29 (7%) of 446 women in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 12 (3%) of 445 women in the co-trimoxazole plus placebo group. The risk of adverse pregnancy outcomes did not differ between groups. INTERPRETATION: Addition of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine to the standard of care with daily unsupervised co-trimoxazole in areas of high antifolate resistance substantially improves malaria chemoprevention in pregnant women living with HIV on dolutegravir-based cART and should be considered for policy. FUNDING: European and Developing Countries Clinical Trials Partnership 2; UK Joint Global Health Trials Scheme (UK Foreign, Commonwealth and Development Office; Medical Research Council; National Institute for Health Research; Wellcome); and Swedish International Development Cooperation Agency. |
Cost-effectiveness of expanded latent TB infection testing and treatment: Lynn City, Massachusetts, USA
Beeler Asay GR , Woodruff R , Sanderson DM , Fisher CF , Marks SM , Green VD , Tibbs AM , Hill AN , Haptu HH , McManus D , Paradise RK , Auguste-Nelson C , Cochran JJ . Int J Tuberc Lung Dis 2024 28 (1) 21-28 BACKGROUND: Between October 2016 and March 2019, Lynn Community Health Center in Massachusetts implemented a targeted latent TB infection testing and treatment (TTT) program, increasing testing from a baseline of 1,200 patients tested to an average of 3,531 patients tested, or 9% of the population per year.METHODS: We compared pre-implementation TTT, represented by the first two quarters of implementation data, to TTT, represented by 12 quarters of data. Time, diagnostic, and laboratory resources were estimated using micro-costing. Other cost and testing data were obtained from the electronic health record, pharmaceutical claims, and published reimbursement rates. A Markov cohort model estimated future health outcomes and cost-effectiveness from a societal perspective in 2020 US dollars. Monte Carlo simulation generated 95% uncertainty intervals.RESULTS: The TTT program exhibited extended dominance over baseline pre-intervention testing and had an incremental cost-effectiveness ratio (ICER) of US$52,603 (US$22,008â-"US$95,360). When compared to baseline pre-TTT testing, the TTT program averted an estimated additional 7.12 TB cases, 3.49 hospitalizations, and 0.16 deaths per lifetime cohort each year.CONCLUSIONS: TTT was more cost-effective than baseline pre-implementation testing. Lynn Community Health Centerâ-™s experience can help inform other clinics considering expanding latent TB infection testing. |
Racial and ethnic disparities in diagnosis and treatment outcomes among US-born people diagnosed with tuberculosis, 2003-19: an analysis of national surveillance data
Regan M , Li Y , Swartwood NA , Barham T , Asay GRB , Cohen T , Hill AN , Horsburgh CR , Khan A , Marks SM , Myles RL , Salomon JA , Self JL , Menzies NA . Lancet Public Health 2024 9 (1) e47-e56 BACKGROUND: Persistent racial and ethnic disparities in tuberculosis incidence exist in the USA, however, less is known about disparities along the tuberculosis continuum of care. This study aimed to describe how race and ethnicity are associated with tuberculosis diagnosis and treatment outcomes. METHODS: In this analysis of national surveillance data, we extracted data from the US National Tuberculosis Surveillance System on US-born patients with tuberculosis during 2003-19. To estimate the association between race and ethnicity and tuberculosis diagnosis (diagnosis after death, cavitation, and sputum smear positivity) and treatment outcomes (treatment for more than 12 months, treatment discontinuation, and death during treatment), we fitted log-binomial regression models adjusting for calendar year, sex, age category, and regional division. Race and ethnicity were defined based on US Census Bureau classification as White, Black, Hispanic, Asian, American Indian or Alaska Native, Native Hawaiian or Pacific Islander, and people of other ethnicities. We quantified racial and ethnic disparities as adjusted relative risks (aRRs) using non-Hispanic White people as the reference group. We also calculated the Index of Disparity as a summary measure that quantifies the dispersion in a given outcome across all racial and ethnic groups, relative to the population mean. We estimated time trends in each outcome to evaluate whether disparities were closing or widening. FINDINGS: From 2003 to 2019, there were 72 809 US-born individuals diagnosed with tuberculosis disease of whom 72 369 (35·7% women and 64·3% men) could be included in analyses. We observed an overall higher risk of any adverse outcome (defined as diagnosis after death, treatment discontinuation, or death during treatment) for non-Hispanic Black people (aRR 1·27, 95% CI 1·22-1·32), Hispanic people (1·20, 1·14-1·27), and American Indian or Alaska Native people (1·24, 1·12-1·37), relative to non-Hispanic White people. The Index of Disparity for this summary outcome remained unchanged over the study period. INTERPRETATION: This study, based on national surveillance data, indicates racial and ethnic disparaties among US-born tuberculosis patients along the tuberculosis continuum of care. Initiatives are needed to reduce diagnostic delays and improve treatment outcomes for US-born racially marginalised people in the USA. FUNDING: US Centers for Disease Control and Prevention. |
Performance of established disease severity scores in predicting severe outcomes among adults hospitalized with influenza-FluSurv-NET, 2017-2018
Doyle JD , Garg S , O'Halloran AC , Grant L , Anderson EJ , Openo KP , Alden NB , Herlihy R , Meek J , Yousey-Hindes K , Monroe ML , Kim S , Lynfield R , McMahon M , Muse A , Spina N , Irizarry L , Torres S , Bennett NM , Gaitan MA , Hill M , Cummings CN , Reed C , Schaffner W , Talbot HK , Self WH , Williams D . Influenza Other Respir Viruses 2023 17 (12) e13228 BACKGROUND: Influenza is a substantial cause of annual morbidity and mortality; however, correctly identifying those patients at increased risk for severe disease is often challenging. Several severity indices have been developed; however, these scores have not been validated for use in patients with influenza. We evaluated the discrimination of three clinical disease severity scores in predicting severe influenza-associated outcomes. METHODS: We used data from the Influenza Hospitalization Surveillance Network to assess outcomes of patients hospitalized with influenza in the United States during the 2017-2018 influenza season. We computed patient scores at admission for three widely used disease severity scores: CURB-65, Quick Sepsis-Related Organ Failure Assessment (qSOFA), and the Pneumonia Severity Index (PSI). We then grouped patients with severe outcomes into four severity tiers, ranging from ICU admission to death, and calculated receiver operating characteristic (ROC) curves for each severity index in predicting these tiers of severe outcomes. RESULTS: Among 8252 patients included in this study, we found that all tested severity scores had higher discrimination for more severe outcomes, including death, and poorer discrimination for less severe outcomes, such as ICU admission. We observed the highest discrimination for PSI against in-hospital mortality, at 0.78. CONCLUSIONS: We observed low to moderate discrimination of all three scores in predicting severe outcomes among adults hospitalized with influenza. Given the substantial annual burden of influenza disease in the United States, identifying a prediction index for severe outcomes in adults requiring hospitalization with influenza would be beneficial for patient triage and clinical decision-making. |
Analysis of the yearly transition function in measles disease modeling
Davila-Payan CS , Hill A , Kayembe L , Alexander JP , Lynch M , Pallas SW . Stat Med 2023 Globally, there were an estimated 9.8 million measles cases and 207 500 measles deaths in 2019. As the effort to eliminate measles around the world continues, modeling remains a valuable tool for public health decision-makers and program implementers. This study presents a novel approach to the use of a yearly transition function that formulates mathematically the vaccine schedules for different age groups while accounting for the effects of the age of vaccination, the timing of vaccination, and disease seasonality on the yearly number of measles cases in a country. The methodology presented adds to an existing modeling framework and expands its analysis, making its utilization more adjustable for the user and contributing to its conceptual clarity. This article also adjusts for the temporal interaction between vaccination and exposure to disease, applying adjustments to estimated yearly counts of cases and the number of vaccines administered that increase population immunity. These new model features provide the ability to forecast and compare the effects of different vaccination timing scenarios and seasonality of transmission on the expected disease incidence. Although the work presented is applied to the example of measles, it has potential relevance to modeling other vaccine-preventable diseases. |
Evaluation of the US COVID-19 Scenario Modeling Hub for informing pandemic response under uncertainty
Howerton E , Contamin L , Mullany LC , Qin M , Reich NG , Bents S , Borchering RK , Jung SM , Loo SL , Smith CP , Levander J , Kerr J , Espino J , van Panhuis WG , Hochheiser H , Galanti M , Yamana T , Pei S , Shaman J , Rainwater-Lovett K , Kinsey M , Tallaksen K , Wilson S , Shin L , Lemaitre JC , Kaminsky J , Hulse JD , Lee EC , McKee CD , Hill A , Karlen D , Chinazzi M , Davis JT , Mu K , Xiong X , Pastore YPiontti A , Vespignani A , Rosenstrom ET , Ivy JS , Mayorga ME , Swann JL , España G , Cavany S , Moore S , Perkins A , Hladish T , Pillai A , Ben Toh K , Longini I Jr , Chen S , Paul R , Janies D , Thill JC , Bouchnita A , Bi K , Lachmann M , Fox SJ , Meyers LA , Srivastava A , Porebski P , Venkatramanan S , Adiga A , Lewis B , Klahn B , Outten J , Hurt B , Chen J , Mortveit H , Wilson A , Marathe M , Hoops S , Bhattacharya P , Machi D , Cadwell BL , Healy JM , Slayton RB , Johansson MA , Biggerstaff M , Truelove S , Runge MC , Shea K , Viboud C , Lessler J . Nat Commun 2023 14 (1) 7260 Our ability to forecast epidemics far into the future is constrained by the many complexities of disease systems. Realistic longer-term projections may, however, be possible under well-defined scenarios that specify the future state of critical epidemic drivers. Since December 2020, the U.S. COVID-19 Scenario Modeling Hub (SMH) has convened multiple modeling teams to make months ahead projections of SARS-CoV-2 burden, totaling nearly 1.8 million national and state-level projections. Here, we find SMH performance varied widely as a function of both scenario validity and model calibration. We show scenarios remained close to reality for 22 weeks on average before the arrival of unanticipated SARS-CoV-2 variants invalidated key assumptions. An ensemble of participating models that preserved variation between models (using the linear opinion pool method) was consistently more reliable than any single model in periods of valid scenario assumptions, while projection interval coverage was near target levels. SMH projections were used to guide pandemic response, illustrating the value of collaborative hubs for longer-term scenario projections. |
RTS,S/AS01 malaria vaccine pilot implementation in western Kenya: a qualitative longitudinal study to understand immunisation barriers and optimise uptake
Hoyt J , Okello G , Bange T , Kariuki S , Jalloh MF , Webster J , Hill J . BMC Public Health 2023 23 (1) 2283 BACKGROUND: Malaria is a significant public health threat in sub-Saharan Africa, particularly among children. The RTS,S/AS01 malaria vaccine reduces the risk and severity of malaria in children. RTS,S/AS01 was piloted in three African countries, Ghana, Kenya and Malawi, to assess safety, feasibility and cost-effectiveness in real-world settings. A qualitative longitudinal study was conducted as part of the feasibility assessment. This analysis explores RTS,S/AS01 vaccination barriers and identifies potential motivators among caregivers in three sub-counties in western Kenya. METHODS: A cohort of 63 caregivers with a malaria vaccine eligible child was interviewed at three time points over 24 months. A sub-set of 11 caregivers whose eligible children were either partially or non-vaccinated were selected for this sub-analysis. The 5A Taxonomy for root causes of under-vaccination was used to organise the inductively-coded data into categories (awareness, acceptance, access, affordability, and activation) and identify the factors influencing uptake across caregivers. A trajectory analysis was conducted to understand changes in factors over time within each caregiver experience. Caregiver narratives are used to illustrate how the factors influencing uptake were interrelated and changed over time. RESULTS: Lack of awareness, previous negative experiences with routine childhood immunisations and the burden of getting to the health facility contributed to caregivers initially delaying uptake of the vaccine. Over time concerns about vaccine side effects diminished and anticipated vaccination benefits strongly motivated caregivers to vaccinate their children. Persistent health system barriers (e.g., healthcare provider strikes, vaccine stockouts, negative provider attitudes) meant some children missed the first-dose eligibility window by aging-out. CONCLUSIONS: Caregivers in this study believed the RTS,S/AS01 to be effective and were motivated to have their children vaccinated. Despite these positive perceptions of the malaria vaccine, uptake was substantially hindered by persistent health system constraints. Negative provider attitudes emerged as a powerful deterrent to attending immunisation services and hampered uptake of the vaccine. Strategies that focus on improving interpersonal communication skills among healthcare providers are needed. |
Vaccination coverage by age 24 months among children born in 2019 and 2020 - National Immunization Survey-Child, United States, 2020-2022
Hill HA , Yankey D , Elam-Evans LD , Chen M , Singleton JA . MMWR Morb Mortal Wkly Rep 2023 72 (44) 1190-1196 National Immunization Survey-Child data collected in 2022 were combined with data from previous years to assemble birth cohorts and assess coverage with routine vaccines by age 24 months by birth cohort. Overall, vaccination coverage was similar among children born during 2019-2020 compared with children born during 2017-2018, except that coverage with both the birth dose of hepatitis B vaccine and ≥1 dose of hepatitis A vaccine increased. Coverage was generally higher among non-Hispanic White (White) children (2-21 percentage points higher than coverage for non-Hispanic Black or African American, Hispanic or Latino, and non-Hispanic American Indian/Alaska Native [AI/AN] children), children living at or above poverty (3.5-22 percentage points higher than coverage for children living below the federal poverty level), privately insured children (2.4-38 percentage points higher than coverage for children with Medicaid, other insurance, or no insurance), and children in urban areas (3-16.5 percentage points higher than coverage for children living in rural areas). Coverage with the full series of Haemophilus influenzae type b conjugate vaccine was lower among AI/AN children compared with White children. Trends in vaccination coverage disparities across categories of race and ethnicity, health insurance status, poverty status, and urbanicity were evaluated for the 2016-2020 birth cohorts. Fewer than 5% of 168 trends examined were statistically significant, including six increases (widening of the coverage gap) and one decrease (narrowing of the gap). Analyses revealed a widening of the gap between children living at or above the poverty level (higher coverage) and those living below poverty (lower coverage), for several vaccines. Socioeconomic, demographic, and geographic disparities in vaccination coverage persist; addressing them is important to ensure protection for all children against vaccine-preventable disease. |
Adverse events among persons with TB using in-person vs. electronic directly observed therapy
Salerno MM , Burzynski J , Mangan JM , Hill A , deCastro BR , Goswami ND , Lam CK , Macaraig M , Schluger NW , Vernon AA . Int J Tuberc Lung Dis 2023 27 (11) 833-840 BACKGROUND: We evaluated patient safety within a randomized crossover trial comparing electronic directly observed therapy (eDOT) to in-person DOT (ipDOT) in persons undergoing TB treatment in New York City, NY, USA.METHODS: Participant symptoms, symptom severity, and clinical management were documented. We assessed adverse event reports (AERs) by DOT method during the two-period crossover. Using Cox proportional-hazards mixed-effects models, we estimated the adjusted hazard ratio (aHR) of participants reporting an adverse event (AE) vs. not reporting an AE.RESULTS: Of 211 participants, 57 (27.0%) reported AEs during the two-period crossover; of these, 54.4% (31/57) were reported while using eDOT vs. 45.6% (26/57) while using ipDOT. Controlling for study group and period, the aHR for eDOT vs. ipDOT was 0.98 (95% CI 0.49-1.93). Although statistically not significant, the wide confidence intervals suggest that a significant association cannot be entirely ruled out. Gastrointestinal symptoms were most frequently reported (42.1%, 24/57). AER types and severity did not differ significantly by DOT method. Days from symptom onset to medical attention was similar across DOT methods (median: 1.0 day, IQR 0.0-2.0). No participants switched DOT methods due to AERs or monitoring concerns.CONCLUSION: Further evaluation to ascertain whether AERs differ when patients use eDOT vs. ipDOT is warranted. |
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