Implementation of BPaL in the United States: Experience using a novel all-oral treatment regimen for treatment of rifampin-resistant or rifampin-intolerant TB disease
Haley CA , Schechter MC , Ashkin D , Peloquin CA , Cegielski JP , Andrino BB , Burgos M , Caloia LA , Chen L , Colon-Semidey A , DeSilva MB , Dhanireddy S , Dorman SE , Dworkin FF , Hammond-Epstein H , Easton AV , Gaensbauer JT , Ghassemieh B , Gomez ME , Horne D , Jasuja S , Jones BA , Kaplan LJ , Khan AE , Kracen E , Labuda S , Landers KM , Lardizabal AA , Lasley MT , Letzer DM , Lopes VK , Lubelchek RJ , Macias CP , Mihalyov A , Misch EA , Murray JA , Narita M , Nilsen DM , Ninneman MJ , Ogawa L , Oladele A , Overman M , Ray SM , Ritger KA , Rowlinson MC , Sabuwala N , Schiller TM , Schwartz LE , Spitters C , Thomson DB , Tresgallo RR , Valois P , Goswami ND . Clin Infect Dis 2023 77 (7) 1053-1062 BACKGROUND: Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons initiate treatment and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, six-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200 mg linezolid. After U.S. FDA approval in 2019, some U.S. clinicians rapidly implemented BPaL using an initial linezolid 600 mg dose adjusted by serum drug concentrations and clinical monitoring. METHODS: Data from U.S. patients treated with BPaL between 10/14/2019 and 4/30/2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider-driven, and most had linezolid adjusted by therapeutic drug monitoring (TDM). RESULTS: Of 70 patients starting BPaL, two changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and two of these 68 (2.9%) patients relapsed after completion. Using an initial 600 mg linezolid dose daily adjusted by TDM and careful clinical and laboratory monitoring for side effects, supportive care, and expert consultation throughout BPaL treatment, three (4.4%) patients with hematologic toxicity and four (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. CONCLUSIONS: BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in ATS/CDC/ERS/IDSA 2019 guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the U.S. is feasible. |
2022 American College of Rheumatology Guideline for exercise, rehabilitation, diet, and additional integrative interventions for rheumatoid arthritis
England BR , Smith BJ , Baker NA , Barton JL , Oatis CA , Guyatt G , Anandarajah A , Carandang K , Chan KK , Constien D , Davidson E , Dodge CV , Bemis-Dougherty A , Everett S , Fisher N , Fraenkel L , Goodman SM , Lewis J , Menzies V , Moreland LW , Navarro-Millan I , Patterson S , Phillips LR , Shah N , Singh N , White D , AlHeresh R , Barbour KE , Bye T , Guglielmo D , Haberman R , Johnson T , Kleiner A , Lane CY , Li LC , Master H , Pinto D , Poole JL , Steinbarger K , Sztubinski D , Thoma L , Tsaltskan V , Turgunbaev M , Wells C , Turner AS , Treadwell JR . Arthritis Care Res (Hoboken) 2023 75 (8) 1603-1615 OBJECTIVE: To develop initial American College of Rheumatology (ACR) guidelines on the use of exercise, rehabilitation, diet, and additional interventions in conjunction with disease-modifying antirheumatic drugs (DMARDs) as part of an integrative management approach for people with rheumatoid arthritis (RA). METHODS: An interprofessional guideline development group constructed clinically relevant Population, Intervention, Comparator, and Outcome (PICO) questions. A literature review team then completed a systematic literature review and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate the certainty of evidence. An interprofessional Voting Panel (n = 20 participants) that included 3 individuals with RA achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations. RESULTS: The Voting Panel achieved consensus on 28 recommendations for the use of integrative interventions in conjunction with DMARDs for the management of RA. Consistent engagement in exercise received a strong recommendation. Of 27 conditional recommendations, 4 pertained to exercise, 13 to rehabilitation, 3 to diet, and 7 to additional integrative interventions. These recommendations are specific to RA management, recognizing that other medical indications and general health benefits may exist for many of these interventions. CONCLUSION: This guideline provides initial ACR recommendations on integrative interventions for the management of RA to accompany DMARD treatments. The broad range of interventions included in these recommendations illustrates the importance of an interprofessional, team-based approach to RA management. The conditional nature of most recommendations requires clinicians to engage persons with RA in shared decision-making when applying these recommendations. |
Chemotherapy-induced PDL-1 expression in cancer-associated fibroblasts promotes chemoresistance in NSCLC
Heenatigala Palliyage G , Samart P , Bobbala S , Rojanasakul LW , Coyle J , Martin K , Callery PS , Rojanasakul Y . Lung Cancer 2023 181 107258 OBJECTIVES: A cure for cancer is out of reach for most patients due to chemoresistance. Cancer-associated fibroblasts (CAFs) play a vital role in cancer chemoresistance, but detailed understanding of the process particularly in chemoresistant lung cancer is lacking. In this study, we investigated programmed death-ligand 1 (PDL-1) as a potential biomarker for CAF-induced chemoresistance and evaluated its role and the underlying mechanisms of chemoresistance in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A systemic search of gene expression profiles of multiple tissues in NSCLC was carried out to determine the expression intensities of traditional fibroblast biomarkers and CAF-secreted protumorigenic cytokines. PDL-1 expression in CAFs was analyzed by ELISA, Western blotting, and flow cytometry. Human cytokine array was used to identify specific cytokines secreted from CAFs. Role of PDL-1 in NSCLC chemoresistance was assessed using CRISPR/Cas9 knockdown and various functional assays including MTT, cell invasion, sphere formation, and cell apoptosis. In vivo experiments were conducted using a co-implantation xenograft mouse model with live cell imaging and immunohistochemistry. RESULTS: We demonstrated that chemotherapy-stimulated CAFs promoted tumorigenic and stem cell-like properties of NSCLC cells, which contribute to their chemoresistance. Subsequently, we revealed that PDL-1 expression is upregulated in chemotherapy-treated CAFs and is associated with poor prognosis. Silencing PDL-1 expression suppressed CAFs' ability to promote stem cell-like properties and invasiveness of lung cancer cells, favoring chemoresistance. Mechanistically, an upregulation of PDL-1 in chemotherapy-treated CAFs led to an increase in hepatocyte growth factor (HGF) secretion, which stimulates cancer progression, cell invasion, and stemness of lung cancer cells, while inhibiting apoptosis. CONCLUSION: Our results show that PDL-1-positive CAFs modulate stem cell-like properties of NSCLC cells by secreting elevated HGF, thereby promoting chemoresistance. Our finding supports PDL-1 in CAFs as a chemotherapy response biomarker and as a drug delivery and therapeutic target for chemoresistant NSCLC. |
Changing severity and epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) in the United States after introduction of COVID-19 vaccines, March 2021-August 2022
Kojima N , Adams K , Self WH , Gaglani M , McNeal T , Ghamande S , Steingrub JS , Shapiro NI , Duggal A , Busse LW , Prekker ME , Peltan ID , Brown SM , Hager DN , Ali H , Gong MN , Mohamed A , Exline MC , Khan A , Wilson JG , Qadir N , Chang SY , Ginde AA , Withers CA , Mohr NM , Mallow C , Martin ET , Lauring AS , Johnson NJ , Casey JD , Stubblefield WB , Gibbs KW , Kwon JH , Baughman A , Chappell JD , Hart KW , Jones ID , Rhoads JP , Swan SA , Womack KN , Zhu Y , Surie D , McMorrow ML , Patel MM , Tenforde MW . Clin Infect Dis 2023 77 (4) 547-557 INTRODUCTION: Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies. METHODS: Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed. RESULTS: Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47-72), 47% were women, and 21% non-Hispanic Black. From the Alpha-predominant period (Mar-Jul 2021; N = 1312) to the Omicron BA.4/BA.5 sublineage-predominant period (Jun-Aug 2022; N = 1307): the percentage of patients who had ≥4 categories of underlying medical conditions increased from 11% to 21%; those vaccinated with at least a primary COVID-19 vaccine series increased from 7% to 67%; those ≥75 years old increased from 11% to 33%; those who did not receive any supplemental oxygen increased from 18% to 42%. Median (IQR) highest C-reactive protein and D-dimer concentration decreased from 42.0 mg/L (9.9-122.0) to 11.5 mg/L (2.7-42.8) and 3.1 mcg/mL (0.8-640.0) to 1.0 mcg/mL (0.5-2.2), respectively. In-hospital death peaked at 12% in the Delta-predominant period and declined to 4% during the BA.4/BA.5-predominant period. CONCLUSIONS: Compared to adults hospitalized during early COVID-19 variant periods, those hospitalized during Omicron-variant COVID-19 were older, had multiple co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death. |
Intravenous antimicrobial starts among hemodialysis patients in the National Healthcare Safety Network Dialysis Component, 2016-2020
Wilson WW , Gouin KA , Fike L , Apata IW , Bell JM , Edwards JR , Novosad S , Kabbani S . Kidney360 2023 4 (7) 971-975 NHSN total IV antimicrobial start rates for patients on hemodialysis decreased from 2016-2020, | but rates unsupported by NHSN surveillance documentation did not. | 80% of reporting hemodialysis facilities had ≥1 unsupported IV antimicrobial start and the | fraction of facilities with unsupported starts increased yearly. | Accurate reporting and timely review of antimicrobial data is critical to understanding | prescribing trends and practices in hemodialysis facilities. |
Narrowing the survival gap: Trends in survival of individuals with Down syndrome with and without congenital heart defects born 1979 - 2018
Wright LK , Stallings EB , Cragan JD , Pabst LJ , Alverson CJ , Oster ME . J Pediatr 2023 260 113523 OBJECTIVE: To evaluate the hypothesis that childhood survival for individuals with Down syndrome (DS) and congenital heart defects (CHDs) has improved in recent years, approaching survival of those with DS without CHDs. STUDY DESIGN: Individuals with DS born 1979-2018 were identified through the Metropolitan Atlanta Congenital Defects Program, a population-based birth defects surveillance system administered by the Centers for Disease Control and Prevention. Survival analysis was performed to evaluate predictors of mortality for those with DS. RESULTS: The cohort included 1,671 individuals with DS; 764 had associated CHDs. Five-year survival in those with DS with CHD improved steadily among individuals born in the 1980s through the 2010s (85% to 93%, p=0.01) but remained stable (96% to 95%, p=0.97) in those with DS without CHDs. The presence of a CHD was not associated with mortality through 5 years of age for those born 2010 or later (hazard ratio 2.63 [95% confidence interval 0.95 - 8.37]). In multivariable analyses, atrioventricular septal defects were associated with early (<1 year) and late (>5 year) mortality, while ventricular septal defects were associated with intermediate (1-5 years) mortality and atrial septal defects with late mortality, when adjusting for other risk factors. CONCLUSIONS: The gap in five-year survival between children with DS with and without CHDs has improved over the last four decades. Survival after 5 years remains lower for those with CHDs, although longer follow-up will be needed to determine if this difference lessens for those born in the more recent years. |
Factors associated with hospitalization with symptomatic coronavirus disease 2019 among pregnant individuals: A multicenter retrospective cohort study
Arriola CS , Li DK , Munoz F , Daugherty M , Doughty-Skierski C , Ellington S , Ferber J , Ferguson N , Greenberg M , Hadden L , Henderson JT , Irving SA , Juergens M , Kancharla V , Naleway AL , Newes-Adeyi G , Nicholson E , Odouli R , Reichle L , Sanyang M , Dawood FS . Open Forum Infect Dis 2022 9(7) (no pagination) Background: Pregnant individuals are at increased risk of coronavirus disease 2019 (COVID-19) hospitalization and death, and primary and booster COVID-19 vaccination is recommended for this population. Method(s): Among a cohort of pregnant individuals who received prenatal care at 3 healthcare systems in the United States, we estimated the cumulative incidence of hospitalization with symptomatic COVID-19 illness. We also identified factors associated with COVID-19 hospitalization using a multivariable Cox proportional hazards model with pregnancy weeks as the timescale and a time-varying adjustor that accounted for severe acute respiratory syndrome coronavirus 2 circulation; model covariates included site, age, race, ethnicity, insurance status, prepregnancy weight status, and selected underlying medical conditions. Data were collected primarily through medical record extraction. Result(s): Among 19 456 pregnant individuals with an estimated due date during 1 March 2020-28 February 2021, 75 (0.4%) were hospitalized with symptomatic COVID-19. Factors associated with hospitalization for symptomatic COVID-19 were Hispanic ethnicity (adjusted hazard ratio [aHR], 2.7 [95% confidence interval {CI}, 1.3-5.5]), Native Hawaiian or Pacific Islander race (aHR, 12 [95% CI, 3.2-45.5]), age <25 years (aHR, 3.1 [95% CI, 1.3-7.6]), prepregnancy obesity (aHR, 2.1 [95% CI, 1.1-3.9]), diagnosis of a metabolic disorder (aHR, 2.2 [95% CI, 1.2-3.8]), lung disease excluding asthma (aHR, 49 [95% CI, 28-84]), and cardiovascular disease (aHR, 2.6 [95% CI, 1.5-4.7]). Conclusion(s): Although hospitalization with symptomatic COVID-19 was uncommon, pregnant individuals should be aware of risk factors associated with severe illness when considering COVID-19 vaccination. Copyright © 2022 Published by Oxford University Press on behalf of Infectious Diseases Society of America. This work is written by (a) US Government employee(s) and is in the public domain in the US. |
Fluoroquinolone-resistant latent tuberculosis infection: A literature review and case series of 5 patients treated with linezolid monotherapy
Baker JJ , Nahar R , Petroelje BK , Goswami ND , Lardizabal AA . J Clin Tuberc Other Mycobact Dis 2023 32 100376 Latent tuberculosis infection (LTBI) constitutes an important public health problem because of risk of progression to TB disease. Effective treatment of multi-drug resistant (MDR) LTBI would prevent progression to MDR TB disease, which would improve patient and public health outcomes. The majority of MDR LTBI treatment studies have focused on the use of fluoroquinolone-based antibiotic regimens. Options for and experience in the treatment of fluoroquinolone-resistant MDR LTBI are limited in the published literature and not comprehensively addressed in current guidelines. In this review, we share our experience with the treatment of fluoroquinolone-resistant MDR LTBI with linezolid. We discuss treatment options for MDR TB that provide context for predicting effective MDR LTBI treatment, with a focus on the microbiologic and pharmacokinetic properties of linezolid that support its use. We then summarize the evidence for treatment of MDR LTBI. Finally, we present our experiences treating fluoroquinolone-resistant MDR LTBI with linezolid with an emphasis on dosing considerations to optimize efficacy and minimize potential toxicities. |
Tackling histoplasmosis infection in people living with HIV from Latin America: From diagnostic strategy to public health solutions
Cáceres DH , Gómez BL , Tobón Á M , Restrepo Á , Chiller T , Lindsley MD , Meis JF , Verweij PE . J Fungi (Basel) 2023 9 (5) Histoplasmosis, caused by the thermally dimorphic fungus Histoplasma spp., is a disease with a broad clinical spectrum, presenting from asymptomatic/flu-like symptoms to progressive disseminated disease in people with immunosuppression. In recent years, the concept of histoplasmosis as a disease restricted to the American continent has changed, as now histoplasmosis is reported in many regions around the world. In Latin America, histoplasmosis represents a threat, especially in people with advanced HIV disease (AHD). Diagnosis of histoplasmosis in people living with HIV (PLHIV) is challenging due to the low index of suspicion of the disease, non-specificity of signs and symptoms, and limited access to specific laboratory testing, while the diagnostic delay is significantly associated with mortality. In the last decade, novel diagnostic tests have been developed for the rapid detection of histoplasmosis, such as commercial kits for antigen detection. Furthermore, advocacy groups were created that presented histoplasmosis as a public health problem, with emphasis on patients at risk of progressive disseminated disease. This review aims to discuss the impact of histoplasmosis associated with AHD in Latin America and the strategies employed to tackle histoplasmosis, from the implementation of laboratory testing to disease advocacy and public health interventions. |
Systematic review and meta-analysis of the efficacy and effectiveness of pneumococcal vaccines in adults
Farrar JL , Childs L , Ouattara M , Akhter F , Britton A , Pilishvili T , Kobayashi M . Pathogens 2023 12 (5) New pneumococcal conjugate vaccines (PCVs), 15- and 20-valent (PCV15 and PCV20), have been licensed for use among U.S. adults based on safety and immunogenicity data compared with the previously recommended 13-valent PCV (PCV13) and 23-valent pneumococcal polysaccharide vaccines (PPSV23). We conducted a systematic review of the literature on PCV13 and PPSV23 efficacy (randomized controlled trials [RCTs]) or effectiveness (observational studies) against vaccine type (PCV13 type or PPSV23 type, respectively), invasive pneumococcal disease (IPD), and pneumococcal pneumonia (PP) in adults. We utilized the search strategy from a previous systematic review of the literature published during the period from January 2016 to April 2019, and updated the search through March 2022. The certainty of evidence was assessed using the Cochrane risk-of-bias 2.0 tool and the Newcastle-Ottawa scale. When feasible, meta-analyses were conducted. Of the 5085 titles identified, 19 studies were included. One RCT reported PCV13 efficacy of 75% (PCV13-type IPD) and 45% (PCV13-type PP). Three studies each reported PCV13 effectiveness against PCV13-type IPD (range 47% to 68%) and against PCV13-type PP (range 38% to 68%). The pooled PPSV23 effectiveness was 45% (95% CI: 37%, 51%) against PPSV23-type IPD (nine studies) and 18% (95% CI: -4%, 35%) against PPSV23-type PP (five studies). Despite the heterogeneity across studies, our findings suggest that PCV13 and PPSV23 protect against VT-IPD and VT-PP in adults. |
Identification of Trichomonas vaginalis 5-nitroimidazole resistance targets
Graves KJ , Reily C , Tiwari HK , Srinivasasainagendra V , Secor WE , Novak J , Muzny CA . Pathogens 2023 12 (5) Trichomonas vaginalis is the most common non-viral sexually transmitted infection. 5-nitroimidazoles are the only FDA-approved medications for T. vaginalis treatment. However, 5-nitroimidazole resistance has been increasingly recognized and may occur in up to 10% of infections. We aimed to delineate mechanisms of T. vaginalis resistance using transcriptome profiling of metronidazole (MTZ)-resistant and sensitive T. vaginalis clinical isolates. In vitro, 5-nitroimidazole susceptibility testing was performed to determine minimum lethal concentrations (MLCs) for T. vaginalis isolates obtained from women who had failed treatment (n = 4) or were successfully cured (n = 4). RNA sequencing, bioinformatics, and biostatistical analyses were performed to identify differentially expressed genes (DEGs) in the MTZ-resistant vs. sensitive T. vaginalis isolates. RNA sequencing identified 304 DEGs, 134 upregulated genes and 170 downregulated genes in the resistant isolates. Future studies with more T. vaginalis isolates with a broad range of MLCs are needed to determine which genes may represent the best alternative targets in drug-resistant strains. |
Risk factors for infection with influenza A(H3N2) virus on a US university campus, October-November 2021
Lewis NM , Delahoy MJ , Sumner KM , Lauring AS , Bendall EE , Mortenson L , Edwards E , Stamper A , Flannery B , Martin ET . Influenza Other Respir Viruses 2023 17 (5) e13151 BACKGROUND: Knowledge of the specific dynamics of influenza introduction and spread in university settings is limited. METHODS: Persons with acute respiratory illness symptoms received influenza testing by molecular assay during October 6-November 23, 2022. Viral sequencing and phylogenetic analysis were conducted on nasal swab samples from case-patients. Case-control analysis of a voluntary survey of persons tested was used to identify factors associated with influenza; logistic regression was conducted to calculate odds ratios and 95% CIs. A subset of case-patients tested during the first month of the outbreak was interviewed to identify sources of introduction and early spread. RESULTS: Among 3268 persons tested, 788 (24.1%) tested positive for influenza; 744 (22.8%) were included in the survey analysis. All 380 sequenced specimens were influenza A (H3N2) virus clade 3C.2a1b.2a.2, suggesting rapid transmission. Influenza (OR [95% CI]) was associated with indoor congregate dining (1.43 [1.002-2.03]), attending large gatherings indoors (1.83 [1.26-2.66]) or outdoors (2.33 [1.64-3.31]), and varied by residence type (apartment with ≥1 roommate: 2.93 [1.21-7.11], residence hall room alone: 4.18 [1.31-13.31], or with roommate: 6.09 [2.46-15.06], or fraternity/sorority house: 15.13 [4.30-53.21], all compared with single-dwelling apartment). Odds of influenza were lower among persons who left campus for ≥1 day during the week before their influenza test (0.49 [0.32-0.75]). Almost all early cases reported attending large events. CONCLUSIONS: Congregate living and activity settings on university campuses can lead to rapid spread of influenza following introduction. Isolating following a positive influenza test or administering antiviral medications to exposed persons may help mitigate outbreaks. |
Trends in patient's use of sexual health services during COVID-19 in a network of STD clinics, STD Surveillance Network, 2019- 2021
Llata E , Schumacher C , Grigorov I , Danforth B , Pathela P , Asbel L , Nguyen TQ , Berzkalns A , Kreisel KM . Sex Transm Dis 2023 50 (10) 692-698 BACKGROUND: The initial years of the COVID-19 pandemic disrupted sexual healthcare clinic's services. We describe use patterns by patient characteristics, and the use of telehealth (TH) services among a network of sexually transmitted disease (STD) clinics. METHODS: Data were collected using a survey to assess the impact of COVID-19 from March - December 2020 among seven jurisdictions who contribute STD visit-level data as part of the STD Surveillance Network. As a complement to the survey, retrospective data from January 2019 - December 2021 from these seven STD clinics in the same seven jurisdictions were examined for monthly utilization trends by overall visits, patient characteristics, and TH visits. RESULTS: Survey results indicated seven clinics prioritized patients for in-person visits and four jurisdictions reported urgent care centers were the most common referral location. In April 2020 (relative to April 2019) clinic visits and unique patients decreased by 68.0% and 75.8%, respectively. TH were documented in four clinics, beginning in March 2020, peaking in December 2020, and tapering until December 2021. We observed the number of clinic visits (-12.2%) and unique patients presenting for care (-27.2%)in December 2021 had yet to return to levels to that seen in December 2019. CONCLUSION: STD clinics showed fragility and resiliency in their adjustment to the pandemic; allowing for the continuation of services. Overall patient census has been slow to return to pre-pandemic levels, and many patients may still not be seeking timely care. This could result in missed opportunities to screen and treat STIs and increasing the possibility of harmful sequelae. |
Dynamic incidence of typhoid fever over a 10-year period (2010-2019) in Kibera, an urban informal settlement in Nairobi, Kenya
Ng'eno E , Lind M , Audi A , Ouma A , Oduor C , Munywoki PK , Agogo GO , Odongo G , Kiplangat S , Wamola N , Osita MP , Mugoh R , Ochieng C , Omballa V , Mogeni OD , Mikoleit M , Fields BS , Montgomery JM , Gauld J , Breiman RF , Juma B , Hunsperger E , Widdowson MA , Bigogo G , Mintz ED , Verani JR . Am J Trop Med Hyg 2023 109 (1) 22-31 Typhoid fever burden can vary over time. Long-term data can inform prevention strategies; however, such data are lacking in many African settings. We reexamined typhoid fever incidence and antimicrobial resistance (AMR) over a 10-year period in Kibera, a densely populated urban informal settlement where a high burden has been previously described. We used data from the Population Based Infectious Diseases Surveillance platform to estimate crude and adjusted incidence rates and prevalence of AMR in nearly 26,000 individuals of all ages. Demographic and healthcare-seeking information was collected through household visits. Blood cultures were processed for patients with acute fever or lower respiratory infection. Between 2010 and 2019, 16,437 participants were eligible for blood culture and 11,848 (72.1%) had a culture performed. Among 11,417 noncontaminated cultures (96.4%), 237 grew Salmonella enterica serovar Typhi (2.1%). Overall crude and adjusted incidences were 95 and 188 cases per 100,000 person-years of observation (pyo), respectively. Annual crude incidence varied from 144 to 233 between 2010 and 2012 and from 9 to 55 between 2013 and 2018 and reached 130 per 100,000 pyo in 2019. Children 5-9 years old had the highest overall incidence (crude, 208; adjusted, 359 per 100,000 pyo). Among isolates tested, 156 of 217 were multidrug resistant (resistant to chloramphenicol, ampicillin, and trimethoprim/sulfamethoxazole [71.9%]) and 6 of 223 were resistant to ciprofloxacin (2.7%). Typhoid fever incidence resurged in 2019 after a prolonged period of low rates, with the highest incidence among children. Typhoid fever control measures, including vaccines, could reduce morbidity in this setting. |
Single high-dose of liposomal amphotericin B in HIV/AIDS-related disseminated histoplasmosis: A randomized trial
Pasqualotto AC , Dalla Lana D , Godoy CSM , Leitão Tdmjs , Bay MB , Damasceno LS , Soares RBA , Kist R , Silva LR , Wiltgen D , Melo M , Guimarães TF , Guimarães MR , Vechi HT , de Mesquita JRL , Monteiro GRG , Adenis A , Bahr NC , Spec A , Boulware DR , Israelski D , Chiller T , Falci DR . Clin Infect Dis 2023 77 (8) 1126-1132 BACKGROUND: Histoplasmosis is a major AIDS-defining illness in Latin America. Liposomal amphotericin B (L-AmB) is the drug of choice for treatment, but access is restricted due to the high drug and hospitalization costs of the conventional long regimens. METHODS: Prospective randomized multicenter open-label trial of one or two-dose induction therapy with L-AmB versus control for disseminated histoplasmosis in AIDS, followed by oral itraconazole therapy. We randomized subjects to: (i) Single dose 10 mg/kg of L-AmB; (ii) 10 mg/kg of L-AmB on D1, and 5 mg/kg of L-AmB on D3; (iii) 3 mg/kg of L-AmB daily for 2 weeks (control). The primary outcome was clinical response (resolution of fever and signs/symptoms attributable to histoplasmosis) at day 14. RESULTS: A total of 118 subjects were randomizedMedian CD4+ counts and clinical presentations were similar between arms. Infusion-related toxicity, kidney toxicity at multiple time-points and frequency of anemia, hypokalemia, hypomagnesemia, and liver toxicity were similar. Day 14 clinical response was 84% for Single-dose L-AmB, 69% Two-dose L-AmB, and 74% Control arm (p=0.69). Overall survival on D14 was 89.0% (34/38) for Single-dose L-AmB, 78.0% (29/37) for Two-dose L-AmB, and 92.1% (35/38) for Control arm (p=0.82). CONCLUSIONS: One day induction therapy with 10 mg/kg of L-AmB in AIDS-related histoplasmosis was safe. Although clinical response may be non-inferior to standard L-AmB therapy, a confirmatory phase III clinical trial is needed. A single induction dose would markedly reduce drug-acquisition costs (>4-fold) and markedly shorten and simplify treatment, which are key points in terms of increased access. |
Potential for recurrent mpox outbreaks among gay, bisexual, and other men who have sex with men - United States, 2023
Pollock ED , Clay PA , Keen A , Currie DW , Carter RJ , Quilter LAS , Gundlapalli AV , Mermin J , Spicknall IH . MMWR Morb Mortal Wkly Rep 2023 72 (21) 568-573 More than 30,000 monkeypox (mpox) cases have been diagnosed in the United States since May 2022, primarily among gay, bisexual, and other men who have sex with men (MSM) (1,2). In recent months, diagnoses have declined to one case per day on average. However, mpox vaccination coverage varies regionally, suggesting variable potential risk for mpox outbreak recurrence (3). CDC simulated dynamic network models representing sexual behavior among MSM to estimate the risk for and potential size of recurrent mpox outbreaks at the jurisdiction level for 2023 and to evaluate the benefits of vaccination for preparedness against mpox reintroduction. The risk for outbreak recurrence after mpox reintroduction is linearly (inversely) related to the proportion of MSM who have some form of protective immunity: the higher the population prevalence of immunity (from vaccination or natural infection), the lower the likelihood of recurrence in that jurisdiction across all immunity levels modeled. In contrast, the size of a potential recurrent outbreak might have thresholds: very small recurrences are predicted for jurisdictions with mpox immunity of 50%-100%; exponentially increasing sizes of recurrences are predicted for jurisdictions with 25%-50% immunity; and linearly increasing sizes of recurrences are predicted for jurisdictions with <25% immunity. Among the 50 jurisdictions examined, 15 are predicted to be at minimal risk for recurrence because of their high levels of population immunity. This analysis underscores the ongoing need for accessible and sustained mpox vaccination to decrease the risk for and potential size of future mpox recurrences. |
Urban and rural mpox incidence among persons aged 15-64 years - United States, May 10-December 31, 2022
Zelaya CE , Smith BP , Riser AP , Hong J , Distler S , O'Connor S , Belay E , Shoeb M , Waltenburg MA , Negron ME , Ellington S . MMWR Morb Mortal Wkly Rep 2023 72 (21) 574-578 During May 10-December 31, 2022, a total of 29,980 confirmed and probable(†) U.S. monkeypox (mpox) cases were reported to CDC, predominantly in cisgender adult men reporting recent same-gender sexual partners (1). Urban-rural differences in health (2) and diagnosis of HIV (3,4) and other sexually transmitted infections (5) are well documented nationally. This report describes urban-rural differences in mpox incidence (cases per 100,000 population) among persons aged 15-64 years, by gender and race and ethnicity. Urbanicity was assessed using the 2013 National Center for Health Statistics (NCHS) Urban-Rural Classification Scheme for Counties (2). Substantial differences in incidence by urbanicity, gender, and race and ethnicity were observed; most (71.0%) cases occurred in persons residing in large central urban areas. Among the cases in large central urban areas, most (95.7%) were in cisgender men. The overall incidence of mpox in the United States was 13.5 per 100,000 persons aged 15-64 years and peaked in August in both urban and rural areas. Among cisgender men, incidence in rural areas was approximately 4% that in large central urban areas (risk ratio [RR] = 0.04). Among cisgender women, incidence in rural areas was approximately 11% that in large central urban areas (RR = 0.11). In both urban and rural areas, incidence among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) persons was consistently higher than that among non-Hispanic White (White) persons; RRs between Black and White persons were highest in rural areas. Support and maintenance of mpox surveillance and prevention efforts including vaccinations should focus on urban areas with the highest incidence of mpox during the 2022 outbreak; however, surveillance and prevention efforts should include all genders, persons of color, and persons residing in both urban and rural areas who are at increased risk for mpox. |
Achieving HIV epidemic control and improving maternal healthcare services with community-based HIV service delivery in Zambia: Mixed-methods assessment of the SMACHT Project
Claassen CW , Kafunda I , Mwango L , Shiyanda S , Stoebenau K , Gekanju-Toeque M , Lindsay B , Adebayo O , Sinjani M , Kaayunga C , Wa Banza PK , Mweebo K , Kancheya N , Musokotwane K , Mwila A , Monze N , Nichols BE , Blanco N , Lavoie MC , Watson DC , Hachaambwa L , Sheneberger R . AIDS Behav 2023 27 (11) 3571-3583 Novel community-based approaches are needed to achieve and sustain HIV epidemic control in Zambia. Under the Stop Mother and Child HIV Transmission (SMACHT) project, the Community HIV Epidemic Control (CHEC) differentiated service delivery model used community health workers to support HIV testing, ART linkage, viral suppression, and prevention of mother-to-child transmission (MTCT). A multi-methods assessment included programmatic data analysis from April 2015 to September 2020, and qualitative interviews from February to March 2020. CHEC provided HIV testing services to 1,379,387 clients; 46,138 were newly identified as HIV-positive (3.3% yield), with 41,366 (90%) linked to ART. By 2020, 91% (60,694/66,841) of clients on ART were virally suppressed. Qualitatively, healthcare workers and clients benefitted from CHEC, with provision of confidential services, health facility decongestion, and increased HIV care uptake and retention. Community-based models can increase uptake of HIV testing and linkage to care, and help achieve epidemic control and elimination of MTCT. |
Severity outcomes among adult patients with primary immunodeficiency and COVID-19 seen in emergency departments, United States, April 2020-August 2021
Drzymalla E , Moonesinghe R , Kolor K , Khoury MJ , Schieber L , Gundlapalli AV . J Clin Med 2023 12 (10) Primary immunodeficiencies (PIs) are a group of diseases that increase susceptibility to infectious diseases. Few studies have examined the relationship between PI and COVID-19 outcomes. In this study, we used Premier Healthcare Database, which contains information on inpatient discharges, to analyze COVID-19 outcomes among 853 adult PI and 1,197,430 non-PI patients who visited the emergency department. Hospitalization, intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and death had higher odds in PI patients than in non-PI patients (hospitalization aOR: 2.36, 95% CI: 1.87-2.98; ICU admission aOR: 1.53, 95% CI: 1.19-1.96; IMV aOR: 1.41, 95% CI: 1.15-1.72; death aOR: 1.37, 95% CI: 1.08-1.74), and PI patients spent on average 1.91 more days in the hospital than non-PI patients when adjusted for age, sex, race/ethnicity, and chronic conditions associated with severe COVID-19. Of the largest four PI groups, selective deficiency of the immunoglobulin G subclass had the highest hospitalization frequency (75.2%). This large study of United States PI patients provides real-world evidence that PI is a risk factor for adverse COVID-19 outcomes. |
Public health evaluation of PFAS exposures and breastfeeding: A systematic literature review
Hoadley L , Watters M , Rogers R , Siegmann Werner L , Markiewicz KV , Forrester T , McLanahan ED . Toxicol Sci 2023 194 (2) 121-137 Per- and polyfluoroalkyl substances (PFAS) are a class of man-made chemicals that are persistent in the environment. They can be transferred across the placenta to fetuses and through human milk to infants. The American Academy of Pediatrics advises that the benefits of breastfeeding infants outweigh the potential risks of harm from environmental chemicals in "nearly every circumstance." However, there are few chemical-specific summaries of the potential harms of exposure to PFAS during the neonatal period through breastfeeding. This systematic review explores whether exposure to PFAS through breastfeeding is associated with adverse health outcomes among infants and children using evidence from human and animal studies. Systematic searches identified 4,297 unique records from 7 databases. The review included 37 total articles, including 9 animal studies and 1 human study measuring the direct contribution of exposure of the infant or pup through milk for any health outcome. Animal studies provided evidence of associations between exposure to PFOA through breastfeeding and reduced early life body weight gain, mammary gland development and thyroid hormone levels. They also provided limited evidence of associations between PFOS exposure through breastfeeding with reduced early life body weight gain and cellular changes in the hippocampus. The direct relevance of any of these outcomes to human health is uncertain, and it is possible that many adverse health effects of exposure through breastfeeding have not yet been studied. This review documents the current state of science and highlights the need for future research to guide clinicians making recommendations on infant feeding. |
Community-facing toxicokineticmodels to estimate PFAS serum levels based on life history and drinking water exposures
Lynch MT , Lay CR , Sokolinski S , Antezana A , Ghio C , Chiu WA , Rogers R . Environ Int 2023 176 107974 BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are drinking water contaminants. Tools to assess the potential body burden associated with drinking PFAS-contaminated water may be helpful for public health assessment of exposed communities. METHODS: We implemented a suite of one-compartment toxicokinetic models using extensively calibrated toxicokinetic parameters (half-life and volume of distribution). We implemented the models both in the R programming language for research purposes, and as a web estimator for the general public (built in typescript.js). These models simulate exposure to PFAS water concentrations for individuals with varying characteristics such as age, sex, weight, and breastfeeding history. The models account for variability and uncertainty in parameter inputs to produce Monte Carlo-based estimates of serum concentration. For children, the models additionally account for gestational exposure, lactational exposure, and potential exposure through formula feeding. For adults who have borne children, the models account for clearance through birth and breastfeeding. We ran simulations of individuals with known PFAS water and serum concentrations to evaluate the model. We then compared the predicted serum PFAS concentrations to measured data. RESULTS: The models accurately estimate individual-level serum levels for each PFAS for most adults within ½ order of magnitude. We found that the models somewhat overestimated serum concentrations for children in the tested locations, and that these overestimates are generally within an order of magnitude. DISCUSSION: This paper presents scientifically robust models that allow users to estimate serum PFAS concentrations based on known PFAS water concentrations and physiologic information. However, accuracy in historical water concentration inputs, exposure from non-drinking water sources, and life-history characteristics of individuals present a complex problem for individual estimation. Additional refinements to the model suite to improve the prediction of individual results may consist of including duration of exposure and additional life-history characteristics. |
Greener residential environment is associated with increased bacterial diversity in outdoor ambient air
Styles JN , Egorov AI , Griffin SM , Klein J , Scott JW , Sams EA , Hudgens E , Mugford C , Stewart JR , Lu K , Jaspers I , Keely SP , Brinkman NE , Arnold JW , Wade TJ . Sci Total Environ 2023 880 163266 In urban areas, exposure to greenspace has been found to be beneficial to human health. The biodiversity hypothesis proposed that exposure to diverse ambient microbes in greener areas may be one pathway leading to health benefits such as improved immune system functioning, reduced systemic inflammation, and ultimately reduced morbidity and mortality. Previous studies observed differences in ambient outdoor bacterial diversity between areas of high and low vegetated land cover but didn't focus on residential environments which are important to human health. This research examined the relationship between vegetated land and tree cover near residence and outdoor ambient air bacterial diversity and composition. We used a filter and pump system to collect ambient bacteria samples outside residences in the Raleigh-Durham-Chapel Hill metropolitan area and identified bacteria by 16S rRNA amplicon sequencing. Geospatial quantification of total vegetated land or tree cover was conducted within 500 m of each residence. Shannon's diversity index and weighted UniFrac distances were calculated to measure α (within-sample) and β (between-sample) diversity, respectively. Linear regression for α-diversity and permutational analysis of variance (PERMANOVA) for β-diversity were used to model relationships between vegetated land and tree cover and bacterial diversity. Data analysis included 73 ambient air samples collected near 69 residences. Analysis of β-diversity demonstrated differences in ambient air microbiome composition between areas of high and low vegetated land (p = 0.03) and tree cover (p = 0.07). These relationships remained consistent among quintiles of vegetated land (p = 0.03) and tree cover (p = 0.008) and continuous measures of vegetated land (p = 0.03) and tree cover (p = 0.03). Increased vegetated land and tree cover were also associated with increased ambient microbiome α-diversity (p = 0.06 and p = 0.03, respectively). To our knowledge, this is the first study to demonstrate associations between vegetated land and tree cover and the ambient air microbiome's diversity and composition in the residential ecosystem. |
Per- and polyfluoroalkyl substances (PFAS) mixture during pregnancy and postpartum weight retention in the New Hampshire Birth Cohort Study (NHBCS)
Wang Y , Howe C , Gallagher LG , Botelho JC , Calafat AM , Karagas MR , Romano ME . Toxics 2023 11 (5) Per- and polyfluoroalkyl substances (PFAS), widely used in industrial and consumer products, are suspected metabolic disruptors. We examined the association between a PFAS mixture during pregnancy and postpartum weight retention in 482 participants from the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate, perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate, were quantified in maternal plasma collected at ~28 gestational weeks. Postpartum weight change was calculated as the difference between self-reported weight from a postpartum survey administered in 2020 and pre-pregnancy weight abstracted from medical records. Associations between PFAS and postpartum weight change were examined using Bayesian kernel machine regression and multivariable linear regression, adjusting for demographic, reproductive, dietary, and physical activity factors; gestational week of blood sample collection; and enrollment year. PFOS, PFOA, and PFNA were positively associated with postpartum weight retention, and associations were stronger among participants with a higher pre-pregnancy body mass index. A doubling of PFOS, PFOA, and PFNA concentrations was associated with a 1.76 kg (95%CI: 0.31, 3.22), 1.39 kg (-0.27, 3.04), and 1.04 kg (-0.19, 2.28) greater postpartum weight retention, respectively, among participants who had obesity/overweight prior to pregnancy. Prenatal PFAS exposure may be associated with increased postpartum weight retention. |
Using testing history to estimate HIV incidence in mothers living in resource-limited settings: Maximizing efficiency of a community health survey in Mozambique
Augusto O , Fernández-Luis S , Fuente-Soro L , Nhampossa T , Lopez-Varela E , Nhacolo A , Bernardo E , Guambe H , Tibana K , Juga AJC , Cowan JG , Urso M , Naniche D . PLOS Glob Public Health 2023 3 (5) e0001628 Obtaining rapid and accurate HIV incidence estimates is challenging because of the need for long-term follow-up for a large cohort. We estimated HIV incidence among women who recently delivered in southern Mozambique by leveraging data available in routine health cards. A cross-sectional household HIV-testing survey was conducted from October 2017 to April 2018 among mothers of children born in the previous four years in the Manhiça Health Demographic Surveillance System area. Randomly-selected mother-child pairs were invited to participate and asked to present documentation of their last HIV test result. HIV-testing was offered to mothers with no prior HIV-testing history, or with negative HIV results obtained over three months ago. HIV incidence was estimated as the number of mothers newly diagnosed with HIV per total person-years, among mothers with a prior documented HIV-negative test. Among 5000 mother-child pairs randomly selected, 3069 were interviewed, and 2221 reported a previous HIV-negative test. From this group, we included 1714 mothers who had taken a new HIV test during the survey. Most of mothers included (83.3%,1428/1714) had a previous documented HIV test result and date. Median time from last test to survey was 15.5 months (IQR:8.0-25.9). A total of 57 new HIV infections were detected over 2530.27 person-years of follow-up. The estimated HIV incidence was 2.25 (95% CI: 1.74-2.92) per 100 person-years. Estimating HIV incidence among women who recently delivered using a community HIV-focused survey coupled with previous HIV-testing history based on patients' clinical documents is an achievable strategy. |
Foodborne illness outbreaks at retail food establishments - National Environmental Assessment Reporting System, 25 state and local health departments, 2017-2019
Moritz ED , Ebrahim-Zadeh SD , Wittry B , Holst MM , Daise B , Zern A , Taylor T , Kramer A , Brown LG . MMWR Surveill Summ 2023 72 (6) 1-11 PROBLEM/CONDITION: Each year, state and local public health departments report hundreds of foodborne illness outbreaks associated with retail food establishments (e.g., restaurants or caterers) to CDC. Typically, investigations involve epidemiology, laboratory, and environmental health components. Health departments voluntarily report epidemiologic and laboratory data from their foodborne illness outbreak investigations to CDC through the National Outbreak Reporting System (NORS); however, minimal environmental health data from outbreak investigations are reported to NORS. This report summarizes environmental health data collected during outbreak investigations and reported to the National Environmental Assessment Reporting System (NEARS). PERIOD COVERED: 2017-2019. DESCRIPTION OF SYSTEM: In 2014, CDC launched NEARS to complement NORS surveillance and to use these data to enhance prevention efforts. State and local health departments voluntarily enter data from their foodborne illness outbreak investigations of retail food establishments into NEARS. These data include characteristics of foodborne illness outbreaks (e.g., etiologic agent and factors contributing to the outbreak), characteristics of establishments with outbreaks (e.g., number of meals served daily), and food safety policies in these establishments (e.g., ill worker policy requirements). NEARS is the only available data source that collects environmental characteristics of retail establishments with foodborne illness outbreaks. RESULTS: During 2017-2019, a total of 800 foodborne illness outbreaks associated with 875 retail food establishments were reported to NEARS by 25 state and local health departments. Among outbreaks with a confirmed or suspected agent (555 of 800 [69.4%]), the most common pathogens were norovirus and Salmonella, accounting for 47.0% and 18.6% of outbreaks, respectively. Contributing factors were identified in 62.5% of outbreaks. Approximately 40% of outbreaks with identified contributing factors had at least one reported factor associated with food contamination by an ill or infectious food worker. Investigators conducted an interview with an establishment manager in 679 (84.9%) outbreaks. Of the 725 managers interviewed, most (91.7%) said their establishment had a policy requiring food workers to notify their manager when they were ill, and 66.0% also said these policies were written. Only 23.0% said their policy listed all five illness symptoms workers needed to notify managers about (i.e., vomiting, diarrhea, jaundice, sore throat with fever, and lesion with pus). Most (85.5%) said that their establishment had a policy restricting or excluding ill workers from working, and 62.4% said these policies were written. Only 17.8% said their policy listed all five illness symptoms that would require restriction or exclusion from work. Only 16.1% of establishments with outbreaks had policies addressing all four components relating to ill or infectious workers (i.e., policy requires workers to notify a manager when they are ill, policy specifies all five illness symptoms workers need to notify managers about, policy restricts or excludes ill workers from working, and policy specifies all five illness symptoms requiring restriction or exclusion from work). INTERPRETATION: Norovirus was the most commonly identified cause of outbreaks reported to NEARS, and contamination of food by ill or infectious food workers contributed to approximately 40% of outbreaks with identified contributing factors. These findings are consistent with findings from other national outbreak data sets and highlight the role of ill workers in foodborne illness outbreaks. Although a majority of managers reported their establishment had an ill worker policy, often these policies were missing components intended to reduce foodborne illness risk. Contamination of food by ill or infectious food workers is an important cause of outbreaks; therefore, the content and enforcement of existing policies might need to be re-examined and refined. PUBLIC HEALTH ACTION: Retail food establishments can reduce viral foodborne illness outbreaks by protecting food from contamination through proper hand hygiene and excluding ill or infectious workers from working. Development and implementation of policies that prevent contamination of food by workers are important to foodborne outbreak reduction. NEARS data can help identify gaps in food safety policies and practices, particularly those concerning ill workers. Future analyses of stratified data linking specific outbreak agents and foods with outbreak contributing factors can help guide the development of effective prevention approaches by describing how establishments' characteristics and food safety policies and practices relate to foodborne illness outbreaks. |
Attitudes, beliefs, and perceptions associated with mask wearing within four racial and ethnic groups early in the COVID-19 pandemic
Earle-Richardson G , Nestor C , Fisher KA , Soelaeman RH , Calanan RM , Yee D , Craig C , Reese P , Prue CE . J Racial Ethn Health Disparities 2023 1-15 BACKGROUND: While previous studies have identified a range of factors associated with mask wearing in the US, little is known about drivers of mask-wearing among racial and ethnic minority groups. This analysis assessed whether factors positively associated with wearing a mask early in the pandemic differed between participants grouped by race/ethnicity (Hispanic, non-Hispanic Black, non-Hispanic Asian, and non-Hispanic White). METHOD: Data were obtained from a US internet panel survey of 3217 respondents during May-November 2020 (weighted by race/ethnicity, age, gender, and education to the US national population). Within each of the four available racial/ethnic groups, crude and adjusted odds ratios (COR and AOR) were calculated using logistic regression to assess factors positively associated with wearing a mask. Adjusted models were controlled for age, gender, education, county COVID-19 case count, presence of a state-issued mask mandate, and interview month. RESULTS: The following variables were most strongly positively associated with mask wearing (p<0.05) in each racial/ethnic group: Hispanic-seeing others wearing masks (AOR: 6.7), importance of wearing a mask combined with social distancing (AOR: 3.0); non-Hispanic Black-belief that wearing a mask would protect others from coronavirus (AOR: 5.1), reporting hearing that one should wear a mask (AOR: 3.6); non-Hispanic Asian-belief that people important to them believe they should wear a mask (COR: 5.1, not statistically significant); and non-Hispanic White-seeing others wearing masks (AOR: 3.1), importance of wearing a mask (AOR: 2.3). CONCLUSION: Public health efforts to encourage mask wearing should consider the diversity of behavioral influences within different population groups. |
A new type 2 diabetes microsimulation model to estimate long-term health outcomes, costs, and cost-effectiveness
Hoerger TJ , Hilscher R , Neuwahl S , Kaufmann MB , Shao H , Laxy M , Cheng YJ , Benoit S , Chen H , Anderson A , Craven T , Yang W , Cintina I , Staimez L , Zhang P . Value Health 2023 26 (9) 1372-1380 OBJECTIVE: To develop a microsimulation model to estimate the health effects, costs, and cost-effectiveness of public health and clinical interventions for preventing/managing type 2 diabetes. METHODS: We combined newly developed equations for complications, mortality, risk factor progression, patient utility, and cost-all based on U.S. studies-in a microsimulation model. We performed internal and external validation of the model. To demonstrate the model's utility, we predicted remaining life-years, quality-adjusted life-years (QALYs), and lifetime medical cost for a representative cohort of 10,000 U.S. adults with type 2 diabetes. We then estimated the cost-effectiveness of reducing HbA1c from 9% to 7% among adults with type 2 diabetes, using low-cost, generic, oral medications. RESULTS: The model performed well in internal validation; the average absolute difference between simulated and observed incidence for 17 complications was less than 8%. In external validation, the model was better at predicting outcomes in clinical trials than in observational studies. The cohort of U.S. adults with type 2 diabetes was projected to have an average of 19.95 remaining life-years (from mean age 61), incur $187,729 in discounted medical costs, and accrue 8.79 discounted QALYs. The intervention to reduce HbA1c increased medical costs by $1,256 and QALYs by 0.39, yielding an incremental cost-effectiveness ratio of $9,103 per QALY. CONCLUSIONS: Using equations exclusively derived from U.S. studies, this new microsimulation model achieves good prediction accuracy in U.S. POPULATIONS: The model can be used to estimate the long-term health impact, costs, and cost-effectiveness of interventions for type 2 diabetes in the United States. |
Evaluation of the impact of guideline communication from the Centers for Disease Control and Prevention and the Centers for Medicare and Medicaid Services among US healthcare providers: COVID-19 prevention counselling guidance
Taylor MM , Deb A , Frazier B , Lueken JR , Das M , Molke J , Fitzgerald E , Ullian T , Nair R , Couch M , Turbyfill C , Horter L , Joshi C , DeLuca N . Nurs Open 2023 10 (11) 7437-7445 AIM: To evaluate healthcare provider awareness and uptake of the Centers for Medicare & Medicaid Services (CMS) billing for coronavirus disease 2019 (COVID-19) prevention counselling and the delivery of prevention counselling to patients awaiting severe acute respiratory syndrome coronavirus 2 test results. DESIGN: Cross sectional survey of US-based healthcare providers in February 2021. METHODS: Analysis of associations with healthcare provider-reported awareness of CMS prevention counselling guidance and billing with provider type, specialty, and work setting. RESULTS: A total of 1919 healthcare providers responded to the survey. Overall, 38% (726/1919) of providers reported awareness of available CMS reimbursement for COVID-19 patient counselling and 29% (465/1614) of CMS billing-eligible providers reported billing for this counselling. Among physicians, those aware of CMS guidance were significantly more likely to bill (58%) versus those unaware (10%). Among RNSights respondents eligible for CMS billing (n = 114), 31% of those aware of the guidance reported billing as compared to 0% of those not aware. |
Racial and ethnic differences in timing of diagnosis and clinical services received in Duchenne muscular dystrophy
Mann JR , Zhang Y , McDermott S , Wang Y , Cai B , Conway KM , Paramsothy P , Royer J , Venkatesh S , Howard JF Jr , Ciafaloni E . Neuroepidemiology 2023 57 (2) 90-99 INTRODUCTION: Racial/ethnic differences in diagnostic and treatment services have been identified for a range of health conditions and outcomes. The current study aimed to analyze whether there are racial/ethnic differences in the timing of diagnostic testing and treatments for males with Duchenne muscular dystrophy (DMD). METHODS: Diagnostic and clinical data for male individuals with DMD born during 1990-2010 were analyzed from eight sites (Arizona, Colorado, Georgia, Iowa, Piedmont Region of North Carolina, Western New York, South Carolina, and Utah) of the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Seven milestones related to diagnosis/treatment experiences were selected as outcomes. Times to each milestone were estimated and compared by four racial/ethnic groups using Kaplan-Meier estimation and Cox proportional-hazards models. Times between initial evaluation or diagnostic testing and later milestones were also compared by race/ethnicity. RESULTS: We identified 682 males with definite or probable DMD of whom 61.7% were non-Hispanic white, 20.5% Hispanic, 10.6% other, and 7.2% non-Hispanic black. Seven milestone events were studied (initial evaluation, first neurology/neuromuscular visit, diagnosis, corticosteroid treatment first offered, corticosteroid treatment started, first electrocardiogram or echocardiogram, and first pulmonary function test). The first five milestone events occurred at an older age for non-Hispanic black individuals compared to non-Hispanic white individuals. Time to first offering of corticosteroids and initiation of corticosteroid therapy was later for Hispanic individuals compared to non-Hispanic white individuals. When accounting for timing of initial evaluation/diagnosis, offering of corticosteroids continued to occur later, but first pulmonary testing occurred earlier, among Hispanic individuals compared to non-Hispanic whites. No significant delays remained for non-Hispanic black individuals after accounting for later initial evaluation/diagnosis. CONCLUSION: We described racial/ethnic differences in ages at selected diagnostic and treatment milestones. The most notable differences were significant delays for five of seven milestones in non-Hispanic black individuals, which appeared to be attributable to later initial evaluation/diagnosis. Findings for Hispanic individuals were less consistent. Efforts to address barriers to early evaluation and diagnosis for non-Hispanic black children with DMD may promote more timely initiation of recommended disease monitoring and interventions. |
Engaging transgender women in HIV research in South Africa
van der Merwe LLA , Cloete A , Savva H , Skinner D , November G , Fisher ZZ . BMC Public Health 2023 23 (1) 990 The Botshelo Ba Trans study was the first HIV bio-behavioral survey conducted with transgender women in South Africa. Engaging research with marginalized communities requires clear points of entry, reference points for understanding the internal culture, and establishing trust and understanding. The community-based participatory research approach guided the development and implementation of this study. We conducted a rapid qualitative and pre-surveillance formative assessment between August 2017 to January 2018 and a bio-behavioral survey between July 2018 and March 2019. At the start, a Steering Committee, comprising primarily of transgender women, was established and subsequently provided substantial input into the mixed methods study conducted in Buffalo City, Cape Town, and Johannesburg. Key to the study's success was building trust and establishing ownership of the survey by transgender women recognized as expert knowledge holders. Thus, a community-based participatory research-informed approach enhanced the validity of the data and ensured that we addressed relevant issues. |
COVID-19 vaccine perceptions among ebola-affected communities in North Kivu, Democratic Republic of the Congo, 2021
Garbern SC , Perera SM , Mbong EN , Kulkarni S , Fleming MK , Ombeni AB , Muhayangabo RF , Tchoualeu DD , Kallay R , Song E , Powell J , Gainey M , Glenn B , Gao H , Mutumwa RM , Mustafa SHB , Abad N , Soke GN , Prybylski D , Doshi RH , Fukunaga R , Levine AC . Vaccines (Basel) 2023 11 (5) Populations affected by humanitarian crises and emerging infectious disease outbreaks may have unique concerns and experiences that influence their perceptions toward vaccines. In March 2021, we conducted a survey to examine the perceptions toward COVID-19 vaccines and identify the factors associated with vaccine intention among 631 community members (CMs) and 438 healthcare workers (HCWs) affected by the 2018-2020 Ebola Virus Disease outbreak in North Kivu, Democratic Republic of the Congo. A multivariable logistic regression was used to identify correlates of vaccine intention. Most HCWs (81.7%) and 53.6% of CMs felt at risk of contracting COVID-19; however, vaccine intention was low (27.6% CMs; 39.7% HCWs). In both groups, the perceived risk of contracting COVID-19, general vaccine confidence, and male sex were associated with the intention to get vaccinated, with security concerns preventing vaccine access being negatively associated. Among CMs, getting the Ebola vaccine was associated with the intention to get vaccinated (RR 1.43, 95% CI 1.05-1.94). Among HCWs, concerns about new vaccines' safety and side effects (OR 0.72, 95% CI 0.57-0.91), religion's influence on health decisions (OR 0.45, 95% CI 0.34-0.61), security concerns (OR 0.52, 95% CI 0.37-0.74), and governmental distrust (OR 0.50, 95% CI 0.35-0.70) were negatively associated with vaccine perceptions. Enhanced community engagement and communication that address this population's concerns could help improve vaccine perceptions and vaccination decisions. These findings could facilitate the success of vaccine campaigns in North Kivu and similar settings. |
Estimates of bivalent mRNA vaccine durability in preventing COVID-19-associated hospitalization and critical illness among adults with and without immunocompromising conditions - VISION Network, September 2022-April 2023
Link-Gelles R , Weber ZA , Reese SE , Payne AB , Gaglani M , Adams K , Kharbanda AB , Natarajan K , DeSilva MB , Dascomb K , Irving SA , Klein NP , Grannis SJ , Ong TC , Embi PJ , Dunne MM , Dickerson M , McEvoy C , Arndorfer J , Naleway AL , Goddard K , Dixon BE , Griggs EP , Hansen J , Valvi N , Najdowski M , Timbol J , Rogerson C , Fireman B , Fadel WF , Patel P , Ray CS , Wiegand R , Ball S , Tenforde MW . MMWR Morb Mortal Wkly Rep 2023 72 (21) 579-588 On September 1, 2022, CDC's Advisory Committee on Immunization Practices (ACIP) recommended a single bivalent mRNA COVID-19 booster dose for persons aged ≥12 years who had completed at least a monovalent primary series. Early vaccine effectiveness (VE) estimates among adults aged ≥18 years showed receipt of a bivalent booster dose provided additional protection against COVID-19-associated emergency department and urgent care visits and hospitalizations compared with that in persons who had received only monovalent vaccine doses (1); however, insufficient time had elapsed since bivalent vaccine authorization to assess the durability of this protection. The VISION Network* assessed VE against COVID-19-associated hospitalizations by time since bivalent vaccine receipt during September 13, 2022-April 21, 2023, among adults aged ≥18 years with and without immunocompromising conditions. During the first 7-59 days after vaccination, compared with no vaccination, VE for receipt of a bivalent vaccine dose among adults aged ≥18 years was 62% (95% CI = 57%-67%) among adults without immunocompromising conditions and 28% (95% CI = 10%-42%) among adults with immunocompromising conditions. Among adults without immunocompromising conditions, VE declined to 24% (95% CI = 12%-33%) among those aged ≥18 years by 120-179 days after vaccination. VE was generally lower for adults with immunocompromising conditions. A bivalent booster dose provided the highest protection, and protection was sustained through at least 179 days against critical outcomes, including intensive care unit (ICU) admission or in-hospital death. These data support updated recommendations allowing additional optional bivalent COVID-19 vaccine doses for certain high-risk populations. All eligible persons should stay up to date with recommended COVID-19 vaccines. |
COVID-19 vaccine safety inquiries to the Centers For Disease Control And Prevention Immunization Safety Office
Miller ER , Moro PL , Shimabukuro TT , Carlock G , Davis SN , Freeborn EM , Roberts AL , Gee J , Taylor AW , Gallego R , Suragh T , Su JR . Vaccine 2023 BACKGROUND: Following the authorization and recommendations for use of the U.S. COVID-19 vaccines, the Centers for Disease Control and Prevention (CDC)'s Immunization Safety Office (ISO) responded to inquiries and questions from public health officials, healthcare providers, and the general public on COVID-19 vaccine safety. METHODS: We describe COVID-19 vaccine safety inquiries, by topic, received and addressed by ISO from December 1, 2020-August 31, 2022. RESULTS: Of the 1978 COVID-19 vaccine-related inquiries received, 1655 specifically involved vaccine safety topics. The most frequently asked-about topics included deaths following vaccination, myocarditis, pregnancy, and reproductive health outcomes, understanding or interpreting data from the Vaccine Adverse Event Reporting System (VAERS), and thrombosis with thrombocytopenia syndrome. CONCLUSIONS: Inquiries about vaccine safety generally reflect issues that receive media attention. ISO will continue to monitor vaccine safety inquiries and provide accurate and timely information to healthcare providers, public health officials, and the general public. |
Community dialogue meetings among district leaders improved their willingness to receive COVID-19 vaccines in Western Uganda, May 2021
Nsubuga EJ , Fitzmaurice AG , Komakech A , Odoi TD , Kadobera D , Bulage L , Kwesiga B , Elyanu PJ , Ario AR , Harris JR . BMC Public Health 2023 23 (1) 969 BACKGROUND: Widespread COVID-19 vaccine uptake can facilitate epidemic control. A February 2021 study in Uganda suggested that public vaccine uptake would follow uptake among leaders. In May 2021, Baylor Uganda led community dialogue meetings with district leaders from Western Uganda to promote vaccine uptake. We assessed the effect of these meetings on the leaders' COVID-19 risk perception, vaccine concerns, perception of vaccine benefits and access, and willingness to receive COVID-19 vaccine. METHODS: All departmental district leaders in the 17 districts in Western Uganda, were invited to the meetings, which lasted approximately four hours. Printed reference materials about COVID-19 and COVID-19 vaccines were provided to attendees at the start of the meetings. The same topics were discussed in all meetings. Before and after the meetings, leaders completed self-administered questionnaires with questions on a five-point Likert Scale about risk perception, vaccine concerns, perceived vaccine benefits, vaccine access, and willingness to receive the vaccine. We analyzed the findings using Wilcoxon's signed-rank test. RESULTS: Among 268 attendees, 164 (61%) completed the pre- and post-meeting questionnaires, 56 (21%) declined to complete the questionnaires due to time constraints and 48 (18%) were already vaccinated. Among the 164, the median COVID-19 risk perception scores changed from 3 (neutral) pre-meeting to 5 (strong agreement with being at high risk) post-meeting (p < 0.001). Vaccine concern scores reduced, with medians changing from 4 (worried about vaccine side effects) pre-meeting to 2 (not worried) post-meeting (p < 0.001). Median scores regarding perceived COVID-19 vaccine benefits changed from 3 (neutral) pre-meeting to 5 (very beneficial) post-meeting (p < 0.001). The median scores for perceived vaccine access increased from 3 (neutral) pre-meeting to 5 (very accessible) post-meeting (p < 0.001). The median scores for willingness to receive the vaccine changed from 3 (neutral) pre-meeting to 5 (strong willingness) post-meeting (p < 0.001). CONCLUSION: COVID-19 dialogue meetings led to district leaders' increased risk perception, reduced concerns, and improvement in perceived vaccine benefits, vaccine access, and willingness to receive the COVID-19 vaccine. These could potentially influence public vaccine uptake if leaders are vaccinated publicly as a result. Broader use of such meetings with leaders could increase vaccine uptake among themselves and the community. |
Prior SARS-CoV-2 infection and COVID-19 vaccine effectiveness against outpatient illness during widespread circulation of SARS-CoV-2 Omicron variant, US Flu VE network
Tartof SY , Xie F , Yadav R , Wernli KJ , Martin ET , Belongia EA , Gaglani M , Zimmerman RK , Talbot HK , Thornburg N , Flannery B . Influenza Other Respir Viruses 2023 17 (5) e13143 BACKGROUND: We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI). METHODS: During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARS-CoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status. RESULTS: Four hundred fifty-five (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%-99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%-76%) against Omicron; VE against Delta could not be estimated. CONCLUSIONS: Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants. |
Impact and effectiveness of Rotavin-M1 under conditions of routine use in two provinces in Vietnam, 20162021, an observational and casecontrol study
VanTrang N , Tate JE , PhuongMai LT , Vu TD , Quyet NT , ThiLe LK , ThiChu MN , NgocTran MP , ThiPham TP , Nguyen HT , Hien ND , Jiang B , Yen C , Tran DN , Anh DD , Parashar UD , Anh LT , Thanh VD , Sanh LV , DieuThuy DT , Trang DC , Phong NQ , Truong DH , Tai TV , Dung PV , Van DV . Lancet Reg Health West Pac 2023 Background: Half of diarrhea hospitalizations in children aged <5 years in Vietnam are due to rotavirus. Following introduction of a locally developed and licensed oral rotavirus vaccine, Rotavin-M1, into the routine immunization program in two Vietnamese provinces, Nam Dinh and TT Hue, we describe changes in rotavirus positivity among children hospitalized for diarrhea and calculate vaccine effectiveness against moderate-to-severe rotavirus hospitalizations. Methods: Active rotavirus surveillance among children <5 years began in December 2016 at sentinel hospitals in districts where rotavirus vaccine was introduced in December 2017. To estimate reductions in rotavirus detection, we calculated risk ratios comparing rotavirus positivity pre- and post-vaccine introduction. We used a test-negative casecontrol design to calculate vaccine effectiveness. Findings: From December 2016 to May 2021, 7228 children <5 years hospitalized for diarrhea were enrolled. Following introduction, Rotavin-M1 coverage was 77% (1066/1377) in Nam Dinh and 42% (203/489) in TT Hue. In Nam Dinh, rotavirus positivity among children <5 years significantly declined by 40.6% (95% CI: 34.8%45.8%) during the three-year post-vaccine introduction period. In TT Hue, no change in rotavirus positivity was observed. Among children aged 623 months, a 2-dose series of Rotavin-M1 was 57% (95% CI: 39%70%) effective against moderate-to-severe rotavirus hospitalizations. Interpretation: Higher vaccination coverage in Nam Dinh than TT Hue likely contributed to substantial declines in rotavirus positivity observed in Nam Dinh following rotavirus vaccine introduction. Robust vaccine effectiveness was observed through the second year of life. National rotavirus vaccine introduction with high coverage may have substantial impact on reducing rotavirus disease burden in Vietnam. Funding: Bill and Melinda Gates Foundation. 2023 |
Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination
Zhou ZH , Cortese MM , Fang JL , Wood R , Hummell DS , Risma KA , Norton AE , KuKuruga M , Kirshner S , Rabin RL , Agarabi C , Staat MA , Halasa N , Ware RE , Stahl A , McMahon M , Browning P , Maniatis P , Bolcen S , Edwards KM , Su JR , Dharmarajan S , Forshee R , Broder KR , Anderson S , Kozlowski S . Vaccine 2023 BACKGROUND: The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms. METHODS: Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020-March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination ("controls") were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay (DCBA). Anti-PEG IgG and IgM were measured using two different assays: DCBA and a PEGylated-polystyrene bead assay. Laboratorians were blinded to case/control status. RESULTS: All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65 %) were hospitalized and 7 (35 %) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10 %) case-patients vs 8 of 30 (27 %) controls (p = 0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0 %) vs 1 of 30 (3 %) controls (p >n 0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats. CONCLUSION: Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination. |
Impact and effectiveness of Rotavin-M1 under conditions of routine use in two provinces in Vietnam, 2016-2021, an observational and case-control study
Van Trang N , Tate JE , Phuong Mai LT , Vu TD , Quyet NT , Thi Le LK , Thi Chu MN , Ngoc Tran MP , Thi Pham TP , Nguyen HT , Hien ND , Jiang B , Yen C , Tran DN , Anh DD , Parashar UD , Anh LT , Thanh VD , Sanh LV , Dieu Thuy DT , Trang DC , Phong NQ , Truong DH , Tai TV , Dung PV , Van DV . Lancet Reg Health West Pac 2023 37 100789 Background: Half of diarrhea hospitalizations in children aged <5 years in Vietnam are due to rotavirus. Following introduction of a locally developed and licensed oral rotavirus vaccine, Rotavin-M1, into the routine immunization program in two Vietnamese provinces, Nam Dinh and TT Hue, we describe changes in rotavirus positivity among children hospitalized for diarrhea and calculate vaccine effectiveness against moderate-to-severe rotavirus hospitalizations. Methods: Active rotavirus surveillance among children <5 years began in December 2016 at sentinel hospitals in districts where rotavirus vaccine was introduced in December 2017. To estimate reductions in rotavirus detection, we calculated risk ratios comparing rotavirus positivity pre- and post-vaccine introduction. We used a test-negative case–control design to calculate vaccine effectiveness. Findings: From December 2016 to May 2021, 7228 children <5 years hospitalized for diarrhea were enrolled. Following introduction, Rotavin-M1 coverage was 77% (1066/1377) in Nam Dinh and 42% (203/489) in TT Hue. In Nam Dinh, rotavirus positivity among children <5 years significantly declined by 40.6% (95% CI: 34.8%–45.8%) during the three-year post-vaccine introduction period. In TT Hue, no change in rotavirus positivity was observed. Among children aged 6–23 months, a 2-dose series of Rotavin-M1 was 57% (95% CI: 39%–70%) effective against moderate-to-severe rotavirus hospitalizations. Interpretation: Higher vaccination coverage in Nam Dinh than TT Hue likely contributed to substantial declines in rotavirus positivity observed in Nam Dinh following rotavirus vaccine introduction. Robust vaccine effectiveness was observed through the second year of life. National rotavirus vaccine introduction with high coverage may have substantial impact on reducing rotavirus disease burden in Vietnam. Funding: Bill and Melinda Gates Foundation. © 2023 |
From paper files to web-based application for data-driven monitoring of HIV programs: Nigeria's journey to a national data repository for decision-making and patient care
Dalhatu I , Aniekwe C , Bashorun A , Abdulkadir A , Dirlikov E , Ohakanu S , Adedokun O , Oladipo A , Jahun I , Murie L , Yoon S , Abdu-Aguye MG , Sylvanus A , Indyer S , Abbas I , Bello M , Nalda N , Alagi M , Odafe S , Adebajo S , Ogorry O , Akpu M , Okoye I , Kakanfo K , Onovo AA , Ashefor G , Nzelu C , Ikpeazu A , Aliyu G , Ellerbrock T , Boyd M , Stafford KA , Swaminathan M . Methods Inf Med 2023 62 130-139 BACKGROUND: Timely and reliable data are crucial for clinical, epidemiologic, and program management decision making. Electronic health information systems provide platforms for managing large longitudinal patient records. Nigeria implemented the National Data Repository (NDR) to create a central data warehouse of all people living with human immunodeficiency virus (PLHIV) while providing useful functionalities to aid decision making at different levels of program implementation. OBJECTIVE: We describe the Nigeria NDR and its development process, including its use for surveillance, research, and national HIV program monitoring toward achieving HIV epidemic control. METHODS: Stakeholder engagement meetings were held in 2013 to gather information on data elements and vocabulary standards for reporting patient-level information, technical infrastructure, human capacity requirements, and information flow. Findings from these meetings guided the development of the NDR. An implementation guide provided common terminologies and data reporting structures for data exchange between the NDR and the electronic medical record (EMR) systems. Data from the EMR were encoded in extensible markup language and sent to the NDR over secure hypertext transfer protocol after going through a series of validation processes. RESULTS: By June 30, 2021, the NDR had up-to-date records of 1,477,064 (94.4%) patients receiving HIV treatment across 1,985 health facilities, of which 1,266,512 (85.7%) patient records had fingerprint template data to support unique patient identification and record linkage to prevent registration of the same patient under different identities. Data from the NDR was used to support HIV program monitoring, case-based surveillance and production of products like the monthly lists of patients who have treatment interruptions and dashboards for monitoring HIV test and start. CONCLUSION: The NDR enabled the availability of reliable and timely data for surveillance, research, and HIV program monitoring to guide program improvements to accelerate progress toward epidemic control. |
Web-based social networks of individuals with adverse childhood experiences: Quantitative study
Cao Y , Rajendran S , Sundararajan P , Law R , Bacon S , Sumner SA , Masuda N . J Med Internet Res 2023 25 e45171 BACKGROUND: Adverse childhood experiences (ACEs), which include abuse and neglect and various household challenges such as exposure to intimate partner violence and substance use in the home, can have negative impacts on the lifelong health of affected individuals. Among various strategies for mitigating the adverse effects of ACEs is to enhance connectedness and social support for those who have experienced them. However, how the social networks of those who experienced ACEs differ from the social networks of those who did not is poorly understood. OBJECTIVE: In this study, we used Reddit and Twitter data to investigate and compare social networks between individuals with and without ACE exposure. METHODS: We first used a neural network classifier to identify the presence or absence of public ACE disclosures in social media posts. We then analyzed egocentric social networks comparing individuals with self-reported ACEs with those with no reported history. RESULTS: We found that, although individuals reporting ACEs had fewer total followers in web-based social networks, they had higher reciprocity in following behavior (ie, mutual following with other users), a higher tendency to follow and be followed by other individuals with ACEs, and a higher tendency to follow back individuals with ACEs rather than individuals without ACEs. CONCLUSIONS: These results imply that individuals with ACEs may try to actively connect with others who have similar previous traumatic experiences as a positive connection and coping strategy. Supportive interpersonal connections on the web for individuals with ACEs appear to be a prevalent behavior and may be a way to enhance social connectedness and resilience in those who have experienced ACEs. |
Formation of protein adducts with Hydroperoxy-PE electrophilic cleavage products during ferroptosis
Amoscato AA , Anthonymuthu T , Kapralov O , Sparvero LJ , Shrivastava IH , Mikulska-Ruminska K , Tyurin VA , Shvedova AA , Tyurina YY , Bahar I , Wenzel S , Bayir H , Kagan VE . Redox Biol 2023 63 102758 Ferroptosis is an iron dependent form of cell death, that is triggered by the discoordination of iron, lipids, and thiols. Its unique signature that distinguishes it from other forms of cell death is the formation and accumulation of lipid hydroperoxides, particularly oxidized forms of polyunsaturated phosphatidylethanolamines (PEs), which drives cell death. These readily undergo iron-catalyzed secondary free radical reactions leading to truncated products which retain the signature PE headgroup and which can readily react with nucleophilic moieties in proteins via their truncated electrophilic acyl chains. Using a redox lipidomics approach, we have identified oxidatively-truncated PE species (trPEox) in enzymatic and non-enzymatic model systems. Further, using a model peptide we demonstrate adduct formation with Cys as the preferred nucleophilic residue and PE(26:2) +2 oxygens, as one of the most reactive truncated PE-electrophiles produced. In cells stimulated to undergo ferroptosis we identified PE-truncated species with sn-2 truncations ranging from 5 to 9 carbons. Taking advantage of the free PE headgroup, we have developed a new technology using the lantibiotic duramycin, to enrich and identify the PE-lipoxidated proteins. Our results indicate that several dozens of proteins for each cell type, are PE-lipoxidated in HT-22, MLE, and H9c2 cells and M2 macrophages after they were induced to undergo ferroptosis. Pretreatment of cells with the strong nucleophile, 2-mercaptoethanol, prevented the formation of PE-lipoxidated proteins and blocked ferroptotic death. Finally, our docking simulations showed that the truncated PE species bound at least as good to several of the lantibiotic-identified proteins, as compared to the non-truncated parent molecule, stearoyl-arachidonoyl PE (SAPE), indicating that these oxidatively-truncated species favor/promote the formation of PEox-protein adducts. The identification of PEox-protein adducts during ferroptosis suggests that they are participants in the ferroptotic process preventable by 2-mercaptoethanol and may contribute to a point of no return in the ferroptotic death process. |
Considerations for endpoint titer determination in syphilis testing using newly marketed, automated rapid plasma reagin instruments
Shukla M , Pereira L , Sun Y , Fakile YF , Kersh EN , Cao W . Public Health Rep 2023 333549231176007 Syphilis is a sexually transmitted disease (STD) caused by the bacterium Treponema pallidum, subspecies pallidum (T. pallidum).1 The resurgence of syphilis in the last 2 decades is a major public health concern in the United States. In 2020, a total of 133 945 cases of all stages of syphilis were reported in the United States, an increase of more than 70% since 2015. The national rate of congenital syphilis has increased 254% since 2016. In 2020, a total of 2148 cases of congenital syphilis were reported, including 149 congenital syphilis–related stillbirths and infant deaths.2 However, syphilis diagnosis is still challenging, partially because of overlapping and ambiguous clinical presentation, particularly during early infection.3 For laboratory testing, darkfield microscopy examinations and direct molecular detection of T. pallidum from clinical specimens are definitive methods for diagnosing early syphilis, but both methods are currently not widely performed at local, reference, or public health laboratories and have challenges in identifying asymptomatic or early-stage infection without the presence of visible lesions for suitable specimen collection.4 Darkfield microscopy requires special equipment and experienced operators for reliable results.5 US Food and Drug Administration (FDA)–cleared molecular tests for syphilis are still not available, and laboratory-developed molecular tests are limited in availability. Therefore, serological tests that detect treponemal and nontreponemal antibodies remain the mainstay for routine laboratory diagnosis of active syphilis infection.6 |
Associations between knowledge of health risks and sugar-sweetened beverage intake among US adolescents
Park S , Lee SH , Merlo C , Blanck HM . Nutrients 2023 15 (10) BACKGROUND: Sugar-sweetened beverage (SSB) intake is associated with adverse health outcomes. OBJECTIVE: We examined associations between the knowledge of health risks related to SSB and SSB intake among adolescents. DESIGN: A cross-sectional study using 2021 YouthStyles survey data. PARTICIPANTS/SETTINGS: 831 US adolescents (12-17 years old). MAIN OUTCOME MEASURES: The outcome variable was SSB intake (none, 1-6 times/week, and ≥1 time/day). Exposure variables were knowledge of seven SSB-related health risks. STATISTICAL ANALYSES PERFORMED: Seven multinomial regressions were used to estimate adjusted odds ratios (AOR) for drinking SSB, according to knowledge of SSB-related health risks and after controlling for sociodemographics. RESULTS: Overall, 29% of adolescents consumed SSB ≥1 time/day. Although most adolescents identified cavities (75.4%), weight gain (74.6%), and diabetes (69.7%) as being related to drinking SSB, fewer adolescents identified related conditions such as high blood pressure (31.7%), high cholesterol (25.8%), heart disease (24.6%), and some cancers (18.0%). Compared to non-SSB consumers, drinking SSB ≥1 time/day was significantly higher among adolescents who lacked knowledge of associations between SSB intake and weight gain (AOR = 2.0), heart disease (AOR = 1.9), or some cancers (AOR = 2.3) after controlling for covariates. CONCLUSIONS: Among US adolescents, knowledge of SSB-related health risks varied by condition, ranging from 18% (some cancers) to 75% (cavities and weight gain). There were increased odds of drinking SSB among those unaware that weight gain, heart disease, and some cancers are associated with SSB intake. Intervention could evaluate whether increasing certain types of knowledge may influence youth SSB intake. |
Characteristics associated with being a high consumer of sweet foods and sugar-sweetened beverages among US adults during the COVID-19 pandemic, 2021
Park S , Lee SH , Blanck HM . Nutrients 2023 15 (10) BACKGROUND: The COVID-19 pandemic impacted some dietary habits of Americans. OBJECTIVE: We examined characteristics associated with a high intake of sweet foods and sugar-sweetened beverages (SSB) during the COVID-19 pandemic among US adults. DESIGN: This was a cross-sectional study. PARTICIPANTS/SETTINGS: The SummerStyles survey data were collected in 2021 among 4034 US adults (≥18 years). MAIN OUTCOME MEASURES: The frequencies were measured of consuming various sweet foods (chocolate/candy, doughnuts/sweet rolls/Danish/muffins/Pop-Tarts, cookies/cake/pie/brownies, and ice cream/frozen desserts) and SSB (regular sodas, sweetened coffee/tea drinks fruit drinks, sports drinks, and energy drinks) during the COVID-19 pandemic. The responses were categorized into 0, >0 to <1, 1 to <2, and ≥2 times/day. The descriptive variables were sociodemographics, food insecurity, weight status, metropolitan status, census regions, and eating habit changes during the COVID-19 pandemic. STATISTICAL ANALYSES PERFORMED: Multinomial regressions were used to estimate adjusted odds ratios (AOR) for being a high consumer of sweet foods and SSB after controlling for characteristics. RESULTS: During 2021, 15% of adults reported consuming sweet foods ≥2 times/day, and 30% reported drinking SSB ≥2 times/day. The factors that were significantly associated with greater odds of high sweet food intake (≥2 times/day) were lower household income (AOR = 1.53 for <$35,000 vs. ≥$100,000), often/sometimes experiencing food insecurity (AOR = 1.41 vs. never), and eating more sweet foods than usual since start of the pandemic (AOR = 2.47 vs. same as usual). The factors that were significantly associated with greater odds of high SSB intake (≥2 times/day) were males (AOR = 1.51), lower education (AOR = 1.98 for ≤high school; AOR = 1.33 for some college vs. college graduate), currently having children (AOR = 1.65), living in nonmetropolitan areas (AOR = 1.34), and drinking more SSB than usual since the pandemic began (AOR = 2.23 vs. same as usual). Younger age, Black race, and reductions in consumption during COVID-19 were related to lower sweet food and SSB intakes. CONCLUSIONS: Our findings, which identified high consumers of sweet foods or SSB, can be used to inform efforts to reduce consumers' added sugars intake during pandemic recovery and support their health. |
Comparison of the "tall and fall" versus "drop and drive" pitching styles: Analysis of Major League Baseball pitchers during a single season
Beaudry MF , Beaudry AG , Bradley JP , Haynes DE , Holland G , Edwards A , Baker BA , Jacobson BR , Chetlin RD . Orthop J Sports Med 2023 11 (5) 23259671231173691 BACKGROUND: Previous research has documented the proportion of "tall and fall" (TF) and "drop and drive" (DD) pitching styles among Major League Baseball (MLB) pitchers who underwent ulnar collateral ligament reconstruction (UCLR). The proportion of these 2 styles among all MLB pitchers remains unknown. PURPOSE: To determine the proportion of the TF and DD pitching styles in all rostered MLB pitchers during a single season as well as the proportion of TF and DD pitchers who sustained an upper extremity (UE) injury and those who underwent UCLR. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Pitcher demographic characteristics from the 2019 MLB season and pitching information were obtained via open-access sources. Two-dimensional video analysis was used to categorize the included pitchers into TF and DD groups. Statistical comparisons and contrasts were made using 2-tailed t tests, chi-square tests, and Pearson correlation analyses as appropriate. RESULTS: Of the 660 MLB rostered pitchers in 2019 (age, 27.39 ± 3.51 years; body mass index, 26.34 ± 2.47 kg/m(2); fastball velocity, 150.49 ± 3.99 kph [93.51 ± 2.48 mph]), 412 (62.4%) pitchers used the TF style and 248 (37.6%) pitchers used the DD style. Significantly more UE injuries were seen in the TF group compared with the DD group (112 vs 38 injuries, respectively; P < .001). Twelve pitchers underwent UCLR (TF, 10; DD, 2), representing a 1.8% UCLR rate among all pitchers. This was a second surgery for 2 pitchers, both of whom used the TF pitching style. Significantly more pitchers in the TF group than the DD group had undergone UCLR before 2019 (135 vs 56 pitchers, respectively; P = .005). CONCLUSION: The results of the present study demonstrated a higher prevalence of both UE injury and prior UCLR in TF pitchers. Further research is needed to explore the potential association between pitching style and UE injury. |
Ionizing radiation and solid cancer mortality among US nuclear facility workers
Kelly-Reif K , Bertke SJ , Daniels RD , Richardson DB , Schubauer-Berigan MK . Int J Epidemiol 2023 52 (4) 1015-1024 BACKGROUND: The risk of solid cancers from low-level protracted ionizing radiation is not well characterized. Nuclear workers provide valuable information on the effects of ionizing radiation in contemporary exposure scenarios relevant to workers and the public. METHODS: We evaluated the association between penetrating ionizing radiation exposure and solid cancer mortality among a pooled cohort of nuclear workers in the USA, with extended follow-up to examine cancers with long latencies. This analysis includes 101 363 workers from five nuclear facilities, with 12 069 solid cancer deaths between 1944 and 2016. The association between cumulative equivalent dose measured in sieverts (Sv) and solid cancer subtypes were modelled as the excess relative rate per Sv (ERR Sv-1) using Cox regression. RESULTS: For the association between ionizing radiation exposure and all solid cancer mortality we observed an elevated rate (ERR Sv-1=0.19; 95% CI: -0.10, 0.52), which was higher among a contemporary sub-cohort of workers first hired in 1960 or later (ERR Sv-1= 2.23; 95% CI: 1.13, 3.49). Similarly, we observed an elevated rate for lung cancer mortality (ERR Sv-1= 0.65; 95% CI: 0.09, 1.30) that was higher among contemporary hires (ERR Sv-1= 2.90; 95% CI: 1.00, 5.26). CONCLUSIONS: Although concerns remain about confounding, measurement error and precision, this analysis strengthens the evidence base indicating there are radiogenic risks for several solid cancer types. |
Trends in robotics research in occupational safety and health: A scientometric analysis and review
Liang CJ , Cheng MH . Int J Environ Res Public Health 2023 20 (10) Robots have been deployed in workplaces to assist, work alongside, or collaborate with human workers on various tasks, which introduces new occupational safety and health hazards and requires research efforts to address these issues. This study investigated the research trends for robotic applications in occupational safety and health. The scientometric method was applied to quantitatively analyze the relationships between robotics applications in the literature. The keywords "robot", "occupational safety and health", and their variants were used to find relevant articles. A total of 137 relevant articles published during 2012-2022 were collected from the Scopus database for this analysis. Keyword co-occurrence, cluster, bibliographic coupling, and co-citation analyses were conducted using VOSviewer to determine the major research topics, keywords, co-authorship, and key publications. Robot safety, exoskeletons and work-related musculoskeletal disorders, human-robot collaboration, and monitoring were four popular research topics in the field. Finally, research gaps and future research directions were identified based on the analysis results, including additional efforts regarding warehousing, agriculture, mining, and construction robots research; personal protective equipment; and multi-robot collaboration. The major contributions of the study include identifying the current trends in the application of robotics in the occupational safety and health discipline and providing pathways for future research in this discipline. |
Development and implementation of clinical mentorship in Rwanda: successes and challenges
Sebeza J , Riedel DJ , Kiromera A , Lavoie MCC , Blanco N , Lascko T , Muhayimpundu R , Mtiro E , Placidie M , Savio HD , Baribwira C . J Public Health Afr 2023 13 (4) Rwanda has prioritized the decentralization and integration of HIV services over the past decade to ensure universal access to HIV services throughout the nation. Improving the capacity of healthcare providers to provide high-quality HIV prevention and treatment services was a crucial component of this process. In partnership with the authors, Rwanda's national health implementation agency developed a national clinical mentorship program from 2011 to 2017 to facilitate this transition. The Rwanda Clinical Mentorship Model aims to effectively manage HIV-infected patients across all levels of healthcare delivery, implement task shifting, and adhere to national guidelines. The clinical care of HIV-positive individuals was transferred from HIV specialists to family physicians and nurses. The facility team was trained, supervised, and mentored by a multidisciplinary team. Mentorship consisted of routine site visits during which clinical case reviews, clinical supervision teaching, and data reviews were conducted to assess the facility's performance and identify obstacles. Between 2012 and 2020, 5,774 healthcare professionals across the country received HIV testing and treatment training. This clinical mentoring has demonstrated a pragmatic, data-driven, and enduring strategy for enhancing clinical practice at all levels of care. A dedicated cadre of mentors is required to ensure the coordination and sustainability of this approach, according to one finding. The authors participated in accelerating the geographic and scope expansion of clinical mentoring in Rwanda. Developing a sustainable HIV clinical mentorship program in Rwanda requires long-term partnerships and evolving technical assistance. |
Public health and medical preparedness for mass casualties from the deliberate release of synthetic opioids
Cibulsky SM , Wille T , Funk R , Sokolowski D , Gagnon C , Lafontaine M , Brevett C , Jabbour R , Cox J , Russell DR , Jett DA , Thomas JD , Nelson LS . Front Public Health 2023 11 1158479 The large amounts of opioids and the emergence of increasingly potent illicitly manufactured synthetic opioids circulating in the unregulated drug supply in North America and Europe are fueling not only the ongoing public health crisis of overdose deaths but also raise the risk of another type of disaster: deliberate opioid release with the intention to cause mass harm. Synthetic opioids are highly potent, rapidly acting, can cause fatal ventilatory depression, are widely available, and have the potential to be disseminated for mass exposure, for example, if effectively formulated, via inhalation or ingestion. As in many other chemical incidents, the health consequences of a deliberate release of synthetic opioid would manifest quickly, within minutes. Such an incident is unlikely, but the consequences could be grave. Awareness of the risk of this type of incident and preparedness to respond are required to save lives and reduce illness. Coordinated planning across the entire local community emergency response system is also critical. The ability to rapidly recognize the opioid toxidrome, education on personal protective actions, and training in medical management of individuals experiencing an opioid overdose are key components of preparedness for an opioid mass casualty incident. |
Buprenorphine use and setting type among reproductive-aged women self-reporting nonmedical prescription opioid use
DeSisto CL , Terplan M , Kacha-Ochana A , Green JL , Mueller T , Cox S , Ko JY . J Subst Use Addict Treat 2023 155 209083 INTRODUCTION: Screening for opioid misuse and treatment for opioid use disorder are critical for reducing morbidity and mortality. We sought to understand the extent of self-reported past 30-day buprenorphine use in various settings among women of reproductive age with self-reported nonmedical prescription opioid use being assessed for substance use problems. METHODS: The study collected data from individuals being assessed for substance use problems using the Addiction Severity Index-Multimedia Version in 2018-2020. We stratified the sample of 10,196 women ages 12-55 self-reporting past 30-day nonmedical prescription opioid use by buprenorphine use and setting type. We categorized setting types as: buprenorphine in specialty addiction treatment, buprenorphine in office-based opioid treatment, and diverted buprenorphine. We included each woman's first intake assessment during the study period. The study assessed number of buprenorphine products, reasons for using buprenorphine, and sources of buprenorphine procurement. The study calculated frequency of reasons for using buprenorphine to treat opioid use disorder outside of a doctor-managed treatment, overall and by race/ethnicity. RESULTS: Overall, 25.5 % of the sample used buprenorphine in specialty addiction treatment, 6.1 % used buprenorphine prescribed in office-based treatment, 21.7 % used diverted buprenorphine, and 46.7 % reported no buprenorphine use during the past 30 days. Among women who reported using buprenorphine to treat opioid use disorder, but not as part of a doctor-managed treatment, 72.3 % could not find a provider or get into a treatment program, 21.8 % did not want to be part of a program or see a provider, and 6.0 % reported both; a higher proportion of American Indian/Alaska Native women (92.1 %) reported that they could not find a provider or get into a treatment program versus non-Hispanic White (78.0 %), non-Hispanic Black (76.0 %), and Hispanic (75.0 %) women. CONCLUSIONS: Appropriate screening for nonmedical prescription opioid use to assess need for treatment with medication for opioid use disorder is important for all women of reproductive age. Our data highlight opportunities to improve treatment program accessibility and availability and support the need to increase equitable access for all women. |
Evaluation of country infrastructure as an indirect measure of dog-mediated human rabies deaths
Bonaparte SC , Moodie J , Undurraga EA , Wallace RM . Front Vet Sci 2023 10 1147543 BACKGROUND: Rabies is a neglected disease, primarily due to poor detection stemming from limited surveillance and diagnostic capabilities in most countries. As a result, there is limited ability to monitor and evaluate country, regional, and global progress towards the WHO goal of eliminating human rabies deaths by 2030. There is a need for a low-cost, readily reproducible method of estimating rabies burden and elimination capacity in endemic countries. METHODS: Publicly available economic, environmental, political, social, public health, and One Health indicators were evaluated to identify variables with strong correlation to country-level rabies burden estimates. A novel index was developed to estimate infrastructural rabies elimination capacity and annual case-burden for dog-mediated rabies virus variant (DMRVV) endemic countries. FINDINGS: Five country-level indicators with superior explanatory value represent the novel "STOP-R index:" (1) literacy rate, (2) infant mortality rate, (3) electricity access, (4) political stability, and (5) presence/severity of natural hazards. Based on the STOP-R index, 40,111 (95% CI 25,854-74,344) global human rabies deaths are estimated to occur in 2022 among DMRVV-endemic countries and are projected to decrease to 32,349 (95% CI 21,110-57,019) in 2030. INTERPRETATION: The STOP-R index offers a unique means of addressing the data gap and monitoring progress towards eliminating dog-mediated human rabies deaths. Results presented here suggest that factors external to rabies programs influence the successes of rabies elimination, and it is now possible to identify countries exceeding or lagging in expected rabies control and elimination progress based on country infrastructure. |
Deer management generally reduces densities of nymphal Ixodes scapularis, but not prevalence of infection with Borrelia burgdorferi sensu stricto
Martin AM , Buttke D , Raphael J , Taylor K , Maes S , Parise CM , Ginsberg HS , Cross PC . Ticks Tick Borne Dis 2023 14 (5) 102202 Human Lyme disease-primarily caused by the bacterium Borrelia burgdorferi sensu stricto (s.s.) in North America-is the most common vector-borne disease in the United States. Research on risk mitigation strategies during the last three decades has emphasized methods to reduce densities of the primary vector in eastern North America, the blacklegged tick (Ixodes scapularis). Controlling white-tailed deer populations has been considered a potential method for reducing tick densities, as white-tailed deer are important hosts for blacklegged tick reproduction. However, the feasibility and efficacy of white-tailed deer management to impact acarological risk of encountering infected ticks (namely, density of host-seeking infected nymphs; DIN) is unclear. We investigated the effect of white-tailed deer density and management on the density of host-seeking nymphs and B. burgdorferi s.s. infection prevalence using surveillance data from eight national parks and park regions in the eastern United States from 2014-2022. We found that deer density was significantly positively correlated with the density of nymphs (nymph density increased by 49% with a 1 standard deviation increase in deer density) but was not strongly correlated with the prevalence of B. burgdorferi s.s. infection in nymphal ticks. Further, while white-tailed deer reduction efforts were followed by a decrease in the density of I. scapularis nymphs in parks, deer removal had variable effects on B. burgdorferi s.s. infection prevalence, with some parks experiencing slight declines and others slight increases in prevalence. Our findings suggest that managing white-tailed deer densities alone may not be effective in reducing DIN in all situations but may be a useful tool when implemented in integrated management regimes. |
A bioinformatics pipeline for a tick pathogen surveillance multiplex amplicon sequencing assay
Osikowicz LM , Hojgaard A , Maes S , Eisen RJ , Stenglein MD . Ticks Tick Borne Dis 2023 14 (5) 102207 The Centers for Disease Control and Prevention's national tick and tick-borne pathogen surveillance program collects information to better understand the regional distribution, prevalence, and exposure risk of host-seeking medically important ticks in the United States. A recently developed next generation sequencing (NGS) targeted multiplex PCR amplicon sequencing (MPAS) assay has enhanced the detection capabilities for Ixodes-associated human pathogens found in Ixodes scapularis and Ixodes pacificus ticks compared to the routinely used real-time PCR assay. To operationalize the MPAS assay for the large number of tick surveillance submissions processed each year, a reproducible high throughput bioinformatics pipeline is needed. We describe the development and validation of the MPAS pipeline, a bioinformatics pipeline that identifies and summarizes amplicon sequences produced by the MPAS assay. This pipeline is portable and reproducible across different computing environments, and flexible by allowing modifications to input parameters, assay primer and reference sequences. The automation of the summary report, BLAST report, and phylogenetic analysis reduces the amount of time needed for downstream analysis. To validate this pipeline, we compared the analysis of a MPAS assay dataset consisting of 175 I. scapularis nymphs with the MPAS pipeline and previously published results analyzed with a CLC Genomic Workbench workflow. The MPAS pipeline identified the same number of positive ticks for Anaplasma phagocytophilum and Babesia species as the original analysis, but the MPAS pipeline provided enhanced sequencing resolution of Borrelia burgdorferi sensu lato co-infected samples. The reproducibility, flexibility, analysis automation, and improved sequence resolution of the MPAS pipeline make it well suited for a high throughput tick pathogen surveillance program. |
Content Index (Achived Edition)
- Antimicrobial Resistance and Antibiotic Stewardship
- Chronic Diseases and Conditions
- Communicable Diseases
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- Informatics
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- Zoonotic and Vectorborne Diseases
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