64 results on '"Pisanic, N"'
Search Results
2. Arsenic and Immune Response to Influenza Vaccination in Pregnant Women and Newborns
- Author
-
Heaney, C.D., primary, Smith, T.J., additional, Ali, H., additional, Alland, K., additional, Avolio, L.N., additional, Haque, R., additional, Pisanic, N., additional, Shaikh, S., additional, West, Jr., K.P., additional, and Labrique, A.B., additional
- Published
- 2020
- Full Text
- View/download PDF
3. Use of weekly mobile phone call-unit to screen pregnant women and their newborns for acute respiratory and gastrointestinal illness symptoms in rural Bangladesh
- Author
-
Avolio, L.N., primary, Pisanic, N., additional, Navas-Acien, A., additional, Alland, K., additional, Flora, M.S., additional, Haque, R., additional, Khanchon, A., additional, Lambrou, A., additional, Wu, L.S., additional, Labrique, A.B., additional, and Heaney, C.D., additional
- Published
- 2020
- Full Text
- View/download PDF
4. Antibiotic Resistance of Campylobacter Species in a Pediatric Cohort Study
- Author
-
Schiaffino Salazar, Francesca, Colston, J.M., Paredes-Olortegui, M., François, R., Pisanic, N., Burga, R., Peñataro-Yori, P., and Kosek, M.N.
- Subjects
Diarrhea ,chloramphenicol ,antibiotic resistance ,Microbial Sensitivity Tests ,purl.org/pe-repo/ocde/ford#3.03.08 [https] ,gentamicin ,Azithromycin ,Article ,Epidemiology and Surveillance ,Campylobacter jejuni ,quinolone ,ciprofloxacin ,Ciprofloxacin ,Drug Resistance, Bacterial ,Humans ,purl.org/pe-repo/ocde/ford#3.01.05 [https] ,antibiotic agent ,clavulanic acid ,amoxicillin plus clavulanic acid ,tetracycline ,azithromycin ,macrolide ,nalidixic acid ,Campylobacter ,Tetracycline ,cotrimoxazole ,MAL-ED ,Anti-Bacterial Agents ,Erythromycin ,ceftriaxone ,priority journal ,erythromycin ,ampicillin ,Iquitos - Abstract
The objective of this study was to determine the phenotypic patterns of antibiotic resistance and the epidemiology of drug-resistant Campylobacter spp. from a low-resource setting., The objective of this study was to determine the phenotypic patterns of antibiotic resistance and the epidemiology of drug-resistant Campylobacter spp. from a low-resource setting. A birth cohort of 303 patients was followed until 5 years of age. Stool samples from asymptomatic children (n = 10,008) and those with diarrhea (n = 3,175) were cultured for Campylobacter. Disk diffusion for ciprofloxacin (CIP), nalidixic acid (NAL), erythromycin (ERY), azithromycin (AZM), tetracycline (TE), gentamicin (GM), ampicillin (AMP), amoxicillin and clavulanic acid (AMC), ceftriaxone (CRO), chloramphenicol (C), and trimethoprim-sulfamethoxazole (TMS) was determined. Antibiotic resistances in Campylobacter jejuni and non-C. jejuni isolates from surveillance and diarrhea samples were compared, and the association between personal macrolide exposure and subsequent occurrence of a macrolide-resistant Campylobacter spp. was assessed. Of 917 Campylobacter isolates, 77.4% of C. jejuni isolates and 79.8% of non-C. jejuni isolates were resistant to ciprofloxacin, while 4.9% of C. jejuni isolates and 24.8% of non-C. jejuni isolates were not susceptible to azithromycin. Of the 303 children, 33.1% had been diagnosed with a Campylobacter strain nonsusceptible to both azithromycin and ciprofloxacin. Personal macrolide exposure did not affect the risk of macrolide-resistant Campylobacter. Amoxicillin and clavulanic acid (94.0%) was one of the antibiotics with the highest rates of susceptibility. There is a high incidence of quinolone- and macrolide-resistant Campylobacter infections in infants under 24 months of age. Given the lack of association between personal exposure to macrolides and a subsequent Campylobacter infection resistant to macrolides, there is a need to evaluate the source of multidrug-resistant (MDR) Campylobacter. This study provides compelling evidence to propose amoxicillin/clavulanic acid as a treatment for campylobacteriosis.
- Published
- 2019
5. Piloting the use of mobile devices in community-driven research to assess occupational and environmental exposures from industrial hog operations in rural eastern North Carolina, USA
- Author
-
Heaney C, McCormack M, Wiesner C, Coffman, Hall D, Rogers S, Pisanic N, Diener-West M, Davis M, and Rule A
- Subjects
Global and Planetary Change ,Geography ,Epidemiology ,business.industry ,Health, Toxicology and Mutagenesis ,Environmental resource management ,Public Health, Environmental and Occupational Health ,business ,Pollution ,Mobile device - Published
- 2019
6. Development of an oral fluid immunoassay to assess past and recent hepatitis E virus (HEV) infection
- Author
-
Pisanic, N, Rahman, A, Saha, SK, Labrique, AB, Nelson, KE, Granger, DA, Granger, SW, Detrick, B, and Heaney, CD
- Subjects
viruses ,virus diseases ,digestive system diseases - Abstract
Hepatitis E virus (HEV) infection causes significant morbidity and mortality worldwide, particularly among pregnant women. In clinical settings blood-based testing protocols are commonly used to diagnose HEV infection, but in community settings such invasive sampling can hinder study participation and limit discovery of the ecology and natural history of HEV infection. Oral fluid is a non-invasive biospecimen that can harbor pathogen-specific antibodies and has the potential to replace blood-based testing protocols.To develop an immunoassay to assess past and recent HEV infection that uses oral fluid instead of serum or plasma.The assay was validated using paired oral fluid and serum samples collected from 141 patients who presented either with (n=76) or without (n=65) symptoms of acute viral hepatitis at a clinical diagnostics center in Dhaka, Bangladesh. The sensitivity and specificity of the oral fluid-based immunoassay for HEV IgG (past HEV infection) and HEV IgA (recent HEV infection) antibodies was calculated in reference to Wantai's (Beijing Wantai) serum-based HEV enzyme-linked immunosorbent assay (ELISA) kits for IgG and IgM antibodies, respectively.The sensitivity and specificity of the oral fluid-based immunoassay for HEV-IgG antibodies were 98.7% and 98.4%, respectively. The sensitivity and specificity of the oral fluid-based immunoassay for HEV IgA were 89.5% and 98.3%, respectively.The high concordance of our non-invasive oral fluid-based immunoassays (HEV IgG and HEV IgA) with commercial high-performance serum HEV ELISA kits (IgG and IgM) means that population-based surveillance of past and recent HEV infection could be expanded to improve understanding of its ecology and natural history.
- Published
- 2017
7. The use of fixed-effects regression to assess work activities and protective measures associated with changes in respiratory function in a prospective industrial hog worker cohort, North Carolina, USA
- Author
-
Diener-West M, Hall D, Coffman, Davis M, Nadimpalli M, Pisanic N, Heaney C, and McCormack M
- Subjects
Global and Planetary Change ,Work activity ,Epidemiology ,business.industry ,Health, Toxicology and Mutagenesis ,Environmental health ,Cohort ,Public Health, Environmental and Occupational Health ,Medicine ,Respiratory function ,Fixed effects model ,business ,Pollution - Published
- 2019
8. Assessing Residential Exposure to Microbes from Industrial Hog Operations in Rural North Carolina: Methods and Lessons Learned
- Author
-
Coffman, Vanessa R., Hall, Devon J., Pisanic, Nora, Wiesner-Friedman, Corinne, Rogers, Shane, Rule, Ana, McCormack, Meredith, Diener-West, Marie, Davis, Meghan F., and Heaney, Christopher D.
- Published
- 2022
- Full Text
- View/download PDF
9. SARS-CoV-2 antibody prevalence by industry, workplace characteristics, and workplace infection prevention and control measures, North Carolina, USA, 2021 to 2022.
- Author
-
Gigot C, Pisanic N, Spicer K, Davis MF, Kruczynski K, Gregory Rivera M, Koehler K, Hall DJ Jr, Hall DJ, and Heaney CD
- Subjects
- Humans, North Carolina epidemiology, Male, Adult, Female, Middle Aged, Seroepidemiologic Studies, Prevalence, Industry statistics & numerical data, Immunoglobulin G blood, Occupational Exposure statistics & numerical data, Risk Factors, COVID-19 epidemiology, COVID-19 prevention & control, COVID-19 immunology, SARS-CoV-2 immunology, Workplace statistics & numerical data, Antibodies, Viral blood, Antibodies, Viral analysis
- Abstract
The COVID-19 pandemic has disproportionately affected workers in certain industries and occupations, and the workplace can be a high-risk setting for SARS-CoV-2 transmission. In this study, we measured SARS-CoV-2 antibody prevalence and identified work-related risk factors in a population primarily working at industrial livestock operations. We used a multiplex salivary SARS-CoV-2 IgG assay to determine infection-induced antibody prevalence among 236 adult (≥18 yr) North Carolina residents between February 2021 and August 2022. We used the National Institute for Occupational Safety and Health Industry and Occupation Computerized Coding System (NIOCCS) to classify employed participants' industry. Most participants (55%, 95% confidence interval [CI] 49% to 62%) were infection-induced IgG positive, including 71% (95% CI 60% to 83%) of animal slaughtering and processing industry workers, 1.5 to 4.3 times North Carolina general population infection-induced seroprevalence estimates during overlapping time periods. Considering self-reported diagnostic test positivity and vaccination history in addition to antibodies, the proportion of participants with evidence of prior infection increased slightly to 61% (95% CI 55% to 67%), including 75% (95% CI 64% to 87%) of animal slaughtering and processing workers. Participants with more than 1000 compared to 10 or fewer coworkers at their jobsite had higher odds of prior infection (adjusted odds ratio 4.5, 95% CI 1.0 to 21.0). This study contributes evidence of the severe and disproportionate impacts of COVID-19 on animal slaughtering and processing workers and workers in large congregate settings., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)
- Published
- 2024
- Full Text
- View/download PDF
10. Early, robust mucosal secretory IgA but not IgG response to SARS-CoV-2 spike in oral fluid is associated with faster viral clearance and COVID-19 symptom resolution.
- Author
-
Pisanic N, Antar AAR, Hetrich MK, Demko ZO, Zhang X, Spicer K, Kruczynski KL, Detrick B, Clarke W, Knoll MD, Thomas DL, Dawood FS, Veguilla V, Karron RA, Manabe YC, and Heaney CD
- Abstract
Background: High priority efforts are underway to support the development of novel mucosal COVID-19 vaccines, such as the US Government's Project NextGen and the Center for Epidemic Preparedness Innovations' goal to respond to the next pandemic with a new vaccine in 100 days. However, there is limited consensus about the complementary role of mucosal immunity in disease progression and how to evaluate immunogenicity of mucosal vaccines. This study investigated the role of oral mucosal antibody responses in viral clearance and COVID-19 symptom duration., Methods: Participants with PCR-confirmed SARS-CoV-2 infection provided oral fluid for testing with SARS-CoV-2 antibody multiplex assays, nasal swabs for RT-PCR and symptom information at up to eight follow-ups from April 2020 to February 2022., Results: High and moderate oral fluid anti-spike (S) secretory IgA (SIgA) post infection was associated with significantly faster viral clearance and symptom resolution across age groups with effect sizes equivalent to having COVID-19 vaccine immunity at the time of infection. Those with high and moderate anti-S SIgA cleared the virus 14 days (95% CI: 10-18) and recovered 9-10 days (95% CI: 6-14) earlier. Delayed and higher anti-S IgG was associated with significantly longer time to clearance and recovery. Experiencing symptoms longer than four weeks was associated with lower anti-RBD SIgA 15-30 days after infection onset (p<0.001)., Conclusion: Robust mucosal SIgA early post infection appears to support faster clearance of SARS-CoV-2 and recovery from COVID-19 symptoms. This research underscores the importance of harmonizing mucosal immune response assays to evaluate new mucosal vaccines., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)
- Published
- 2024
- Full Text
- View/download PDF
11. COVID-19 point-of-care tests can identify low-antibody individuals: In-depth immunoanalysis of boosting benefits in a healthy cohort.
- Author
-
Mallory M, Munt JE, Narowski TM, Castillo I, Cuadra E, Pisanic N, Fields P, Powers JM, Dickson A, Harris R, Wargowsky R, Moran S, Allabban A, Raphel K, McCaffrey TA, Brien JD, Heaney CD, Lafleur JE, Baric RS, and Premkumar L
- Subjects
- Humans, Immunization, Secondary, Female, Cohort Studies, Adult, Male, Immunity, Humoral, Middle Aged, T-Lymphocytes immunology, COVID-19 immunology, COVID-19 virology, COVID-19 diagnosis, COVID-19 prevention & control, Antibodies, Viral immunology, SARS-CoV-2 immunology, Point-of-Care Testing, COVID-19 Vaccines immunology
- Abstract
The recommended COVID-19 booster vaccine uptake is low. At-home lateral flow assay (LFA) antigen tests are widely accepted for detecting infection during the pandemic. Here, we present the feasibility and potential benefits of using LFA-based antibody tests as a means for individuals to detect inadequate immunity and make informed decisions about COVID-19 booster immunization. In a health care provider cohort, we investigated the changes in the breadth and depth of humoral and T cell immune responses following mRNA vaccination and boosting in LFA-positive and LFA-negative antibody groups. We show that negative LFA antibody tests closely reflect the lack of functional humoral immunity observed in a battery of sophisticated immune assays, while positive results do not necessarily reflect adequate immunity. After booster vaccination, both groups gain depth and breadth of systemic antibodies against evolving SARS-CoV-2 and related viruses. Our findings show that LFA-based antibody tests can alert individuals about inadequate immunity against COVID-19, thereby increasing booster shots and promoting herd immunity.
- Published
- 2024
- Full Text
- View/download PDF
12. Exploring Natural Immune Responses to Shigella Exposure Using Multiplex Bead Assays on Dried Blood Spots in High-Burden Countries: Protocol From a Multisite Diarrhea Surveillance Study.
- Author
-
Benedicto-Matambo P, Avolio LN, Badji H, Batool R, Khanam F, Munga S, Tapia MD, Peñataro Yori P, Awuor AO, Ceesay BE, Cornick J, Cunliffe NA, Garcia Bardales PF, Heaney CD, Hotwani A, Ireen M, Taufiqul Islam M, Jallow O, Kaminski RW, Shapiama Lopez WV, Maiden V, Ikumapayi UN, Nyirenda R, Ochieng JB, Omore R, Paredes Olortegui M, Pavlinac PB, Pisanic N, Qadri F, Qureshi S, Rahman N, Rogawski McQuade ET, Schiaffino F, Secka O, Sonye C, Sultana S, Timite D, Traore A, Yousafzai MT, Taufiqur Rahman Bhuiyan M, Jahangir Hossain M, Jere KC, Kosek MN, Kotloff KL, Qamar FN, Sow SO, and Platts-Mills JA
- Abstract
Background: Molecular diagnostics on human fecal samples have identified a larger burden of shigellosis than previously appreciated by culture. Evidence of fold changes in immunoglobulin G (IgG) to conserved and type-specific Shigella antigens could be used to validate the molecular assignment of type-specific Shigella as the etiology of acute diarrhea and support polymerase chain reaction (PCR)-based microbiologic end points for vaccine trials., Methods: We will test dried blood spots collected at enrollment and 4 weeks later using bead-based immunoassays for IgG to invasion plasmid antigen B and type-specific lipopolysaccharide O-antigen for Shigella flexneri 1b, 2a, 3a, and 6 and Shigella sonnei in Shigella -positive cases and age-, site-, and season-matched test-negative controls from all sites in the Enterics for Global Health (EFGH) Shigella surveillance study. Fold antibody responses will be compared between culture-positive, culture-negative but PCR-attributable, and PCR-positive but not attributable cases and test-negative controls. Age- and site-specific seroprevalence distributions will be identified, and the association between baseline antibodies and Shigella attribution will be estimated., Conclusions: The integration of these assays into the EFGH study will help support PCR-based attribution of acute diarrhea to type-specific Shigella , describe the baseline seroprevalence of conserved and type-specific Shigella antibodies, and support correlates of protection for immunity to Shigella diarrhea. These insights can help support the development and evaluation of Shigella vaccine candidates., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
- Published
- 2024
- Full Text
- View/download PDF
13. SARS-CoV-2 antibody prevalence by industry, workplace characteristics, and workplace infection prevention and control measures, North Carolina, 2021 to 2022.
- Author
-
Gigot C, Pisanic N, Spicer K, Davis MF, Kruczynski K, Rivera MG, Koehler K, Hall DJ Jr, Hall DJ, and Heaney CD
- Abstract
Background: The COVID-19 pandemic has disproportionately affected workers in certain industries and occupations, and the workplace can be a high risk setting for SARS-CoV-2 transmission. In this study, we measured SARS-CoV-2 antibody prevalence and identified work-related risk factors in a population primarily working at industrial livestock operations., Methods: We used a multiplex salivary SARS-CoV-2 IgG antibody assay to determine infection-induced antibody prevalence among 236 adult (≥18 years) North Carolina residents between February 2021 and August 2022. We used the National Institute for Occupational Safety and Health Industry and Occupation Computerized Coding System (NIOCCS) to classify employed participants' industry and compared infection-induced IgG prevalence by participant industry and with the North Carolina general population. We also combined antibody results with reported SARS-CoV-2 molecular test positivity and vaccination history to identify evidence of prior infection. We used logistic regression to estimate odds ratios of prior infection by potential work-related risk factors, adjusting for industry and date., Results: Most participants (55%) were infection-induced IgG positive, including 71% of animal slaughtering and processing industry workers, which is 1.5 to 4.3 times higher compared to the North Carolina general population, as well as higher than molecularly-confirmed cases and the only other serology study we identified of animal slaughtering and processing workers. Considering questionnaire results in addition to antibodies, the proportion of participants with evidence of prior infection increased slightly, to 61%, including 75% of animal slaughtering and processing workers. Participants with more than 1000 compared to 10 or fewer coworkers at their jobsite had higher odds of prior infection (adjusted odds ratio [aOR] 4.5, 95% confidence interval [CI] 1.0 to 21.0)., Conclusions: This study contributes evidence of the severe and disproportionate impacts of COVID-19 on animal processing and essential workers and workers in large congregate settings. We also demonstrate the utility of combining non-invasive biomarker and questionnaire data for the study of workplace exposures., Competing Interests: Conflict of Interest The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
- Full Text
- View/download PDF
14. Application of machine learning models to identify serological predictors of COVID-19 severity and outcomes.
- Author
-
Klein S, Dhakal S, Yin A, Escarra-Senmarti M, Demko Z, Pisanic N, Johnston T, Trejo-Zambrano M, Kruczynski K, Lee J, Hardick J, Shea P, Shapiro J, Park HS, Parish M, Caputo C, Ganesan A, Mullapudi S, Gould S, Betenbaugh M, Pekosz A, Heaney CD, Antar A, Manabe Y, Cox A, Karaba A, Andrade F, and Zeger S
- Abstract
Critically ill people with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized. In 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma samples were collected at hospital enrollment and up to 3 months post-enrollment (MPE) to measure virus RNA, cytokines/chemokines, binding antibodies, ACE2 binding inhibition, and Fc effector antibody responses against SARS-CoV-2. The association of demographic variables and >20 serological antibody measures with intubation or death due to COVID-19 was determined using machine learning algorithms. Predictive models revealed that IgG binding and ACE2 binding inhibition responses at 1 MPE were positively and C1q complement activity at enrollment was negatively associated with an increased probability of intubation or death from COVID-19 within 3 MPE. Serological antibody measures were more predictive than demographic variables of intubation or death among COVID-19 patients., Competing Interests: Conflicts of interest The authors declare no conflicts of interest.
- Published
- 2023
- Full Text
- View/download PDF
15. Anthropometric measures and arsenic methylation among pregnant women in rural northern Bangladesh.
- Author
-
Smith TJS, Navas-Acien A, Baker S, Kok C, Kruczynski K, Avolio LN, Pisanic N, Randad PR, Fry RC, Goessler W, van Geen A, Buckley JP, Rahman MH, Ali H, Haque R, Shaikh S, Siddiqua TJ, Schulze K, West KP Jr, Labrique AB, and Heaney CD
- Subjects
- Adult, Humans, Female, Pregnancy, Methylation, Pregnant Women, Bangladesh, Cross-Sectional Studies, Environmental Exposure analysis, Arsenic analysis, Arsenicals
- Abstract
Introduction: Arsenic methylation converts inorganic arsenic (iAs) to monomethyl (MMA) and dimethyl (DMA) arsenic compounds. Body mass index (BMI) has been positively associated with arsenic methylation efficiency (higher DMA%) in adults, but evidence in pregnancy is inconsistent. We estimated associations between anthropometric measures and arsenic methylation among pregnant women in rural northern Bangladesh., Methods: We enrolled pregnant women (n = 784) (median [IQR] gestational week: 14 [13, 15]) in Gaibandha District, Bangladesh from 2018 to 2019. Anthropometric measures were BMI, subscapular and triceps skinfold thicknesses, and mid-upper arm circumference (MUAC), fat area (MUAFA), and muscle area (MUAMA). Arsenic methylation measures were urinary iAs, MMA, and DMA divided by their sum and multiplied by 100 (iAs%, MMA%, and DMA%), primary methylation index (MMA/iAs; PMI), and secondary methylation index (DMA/MMA; SMI). In complete cases (n = 765 [97.6%]), we fitted linear, beta, and Dirichlet regression models to estimate cross-sectional differences in iAs%, MMA%, DMA%, PMI, and SMI per IQR-unit difference in each anthropometric measure, adjusting for drinking water arsenic, age, gestational age, education, living standards index, and plasma folate, vitamin B12, and homocysteine., Results: Median (IQR) BMI, subscapular skinfold thickness, triceps skinfold thickness, MUAC, MUAFA, and MUAMA were 21.5 (19.4, 23.8) kg/m
2 , 17.9 (13.2, 24.2) mm, 14.2 (10.2, 18.7) mm, 25.9 (23.8, 28.0) cm, 15.3 (10.5, 20.3) cm2 , and 29.9 (25.6, 34.2) cm2 , respectively. Median (IQR) iAs%, MMA%, DMA%, PMI, and SMI were 12.0 (9.3, 15.2)%, 6.6 (5.3, 8.3)%, 81.0 (77.1, 84.6)%, 0.6 (0.4, 0.7), and 12.2 (9.3, 15.7), respectively. In both unadjusted and adjusted linear models, all anthropometric measures were negatively associated with iAs%, MMA%, and PMI and positively associated with DMA% and SMI. For example, fully adjusted mean differences (95% CI) in DMA% per IQR-unit difference in BMI, subscapular skinfolds thickness, triceps skinfold thickness, MUAC, MUAFA, and MUAMA were 1.72 (1.16, 2.28), 1.58 (0.95, 2.21), 1.74 (1.11, 2.37), 1.45 (0.85, 2.06), 1.70 (1.08, 2.31), and 0.70 (0.13, 1.27) pp, respectively., Conclusions: Anthropometric measures were positively associated with arsenic methylation efficiency among pregnant women in the early second trimester., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
16. Evaluating SARS-CoV-2 Saliva and Dried Blood Spot Surveillance Strategies in a Congregate Population.
- Author
-
Andronescu LR, Richard SA, Laing ED, Pisanic N, Coggins SA, Rivera MG, Kruczynski K, Saperstein AK, Modi J, Fraser JA, Shaikh S, Broder CC, Burgess TH, Heaney CD, Pollett SD, Millar E, Coles CL, and Simons MP
- Subjects
- Humans, Saliva, COVID-19 Testing, Clinical Laboratory Techniques, SARS-CoV-2, COVID-19 diagnosis, COVID-19 epidemiology
- Abstract
The optimal approach to COVID-19 surveillance in congregate populations remains unclear. Our study at the US Naval Academy in Annapolis, Maryland, USA, assessed the concordance of antibody prevalence in longitudinally collected dried blood spots and saliva in a setting of frequent PCR-based testing. Our findings highlight the utility of salivary-based surveillance.
- Published
- 2023
- Full Text
- View/download PDF
17. A Saliva-Based Serological and Behavioral Analysis of SARS-CoV-2 Antibody Prevalence in Howard County, Maryland.
- Author
-
Brown AC, Koshute PT, Cowley HP, Robinette MS, Gravelyn SR, Patel SV, Ju EY, Frommer CT, Zambidis AE, Schneider EJ, Zhao MY, Mugo BK, Clarke W, Kruczynski K, Pisanic N, Heaney CD, and Colella TA
- Subjects
- Humans, SARS-CoV-2, 2019-nCoV Vaccine mRNA-1273, BNT162 Vaccine, Maryland epidemiology, Cross-Sectional Studies, Prevalence, Saliva, Seroepidemiologic Studies, Antibodies, Viral, Immunoglobulin G, COVID-19 Vaccines, COVID-19 diagnosis, COVID-19 epidemiology
- Abstract
The objective of the study was to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in the Howard County, Maryland, general population and demographic subpopulations attributable to natural infection or coronavirus disease 2019 (COVID-19) vaccination and to identify self-reported social behaviors that may affect the likelihood of recent or past SARS-CoV-2 infection. A cross-sectional, saliva-based serological study of 2,880 residents of Howard County, Maryland, was carried out from July through September 2021. Natural SARS-CoV-2 infection prevalence was estimated by inferring infections among individuals according to anti-nucleocapsid immunoglobin G levels and calculating averages weighted by sample proportions of various demographics. Antibody levels between BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) recipients were compared. Antibody decay rate was calculated by fitting exponential decay curves to cross-sectional indirect immunoassay data. Regression analysis was carried out to identify demographic factors, social behaviors, and attitudes that may be linked to an increased likelihood of natural infection. The estimated overall prevalence of natural infection in Howard County, Maryland, was 11.9% (95% confidence interval, 9.2% to 15.1%), compared with 7% reported COVID-19 cases. Antibody prevalence indicating natural infection was highest among Hispanic and non-Hispanic Black participants and lowest among non-Hispanic White and non-Hispanic Asian participants. Participants from census tracts with lower average household income also had higher natural infection rates. After accounting for multiple comparisons and correlations between participants, none of the behavior or attitude factors had significant effects on natural infection. At the same time, recipients of the mRNA-1273 vaccine had higher antibody levels than those of BNT162b2 vaccine recipients. Older study participants had overall lower antibody levels compared with younger study participants. The true prevalence of SARS-CoV-2 infection is higher than the number of reported COVID-19 cases in Howard County, Maryland. A disproportionate impact of infection-induced SARS-CoV-2 positivity was observed across different ethnic/racial subpopulations and incomes, and differences in antibody levels across different demographics were identified. Taken together, this information may inform public health policy to protect vulnerable populations. IMPORTANCE We employed a highly innovative noninvasive multiplex oral fluid SARS-CoV-2 IgG assay to ascertain our seroprevalence estimates. This laboratory-developed test has been applied in NCI's SeroNet consortium, possesses high sensitivity and specificity according to FDA Emergency Use Authorization guidelines, correlates strongly with SARS-CoV-2 neutralizing antibody responses, and is Clinical Laboratory Improvement Amendments-approved by the Johns Hopkins Hospital Department of Pathology. It represents a broadly scalable public health tool to improve understanding of recent and past SARS-CoV-2 exposure and infection without drawing any blood. To our knowledge, this is the first application of a high-performance salivary SARS-CoV-2 IgG assay to estimate population-level seroprevalence, including identifying COVID-19 disparities. We also are the first to report differences in SARS-CoV-2 IgG responses by COVID-19 vaccine manufacturers (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]). Our findings demonstrate remarkable consistency with those of blood-based SARS-CoV-2 IgG assays in terms of differences in the magnitude of SARS-CoV-2 IgG responses between COVID-19 vaccines., Competing Interests: The authors declare no conflict of interest.
- Published
- 2023
- Full Text
- View/download PDF
18. Longitudinal Analysis of Humoral and Cellular Immune Response Following SARS-CoV-2 Vaccination Supports Utilizing Point-Of-Care Tests to Enhance COVID-19 Booster Uptake.
- Author
-
Mallory M, Munt JE, Narowski TM, Castillo I, Cuadra E, Pisanic N, Fields P, Powers JM, Dickson A, Harris R, Wargowsky R, Moran S, Allabban A, Raphel K, McCaffrey TA, Brien JD, Heaney CD, Lafleur JE, Baric RS, and Premkumar L
- Abstract
Individuals with weaker neutralizing responses show reduced protection with SARS-CoV-2 variants. Booster vaccines are recommended for vaccinated individuals, but the uptake is low. We present the feasibility of utilizing point-of-care tests (POCT) to support evidence-based decision-making around COVID-19 booster vaccinations. Using infectious virus neutralization, ACE2 blocking, spike binding, and TCR sequencing assays, we investigated the dynamics of changes in the breadth and depth of blood and salivary antibodies as well as T-cell clonal response following mRNA vaccination in a cohort of healthcare providers. We evaluated the accuracy of two POCTs utilizing either blood or saliva to identify those in whom humoral immunity was inadequate. >4 months after two doses of mRNA vaccine, SARS-CoV-2 binding and neutralizing Abs (nAbs) and T-cell clones declined 40-80%, and 2/3rd lacked Omicron nAbs. After the third mRNA booster, binding and neutralizing Abs increased overall in the systemic compartment; notably, individuals with previously weak nAbs gained sharply. The third dose failed to stimulate secretory IgA, but salivary IgG closely tracked systemic IgG levels. Vaccine boosting increased Ab breadth against a divergent bat sarbecovirus, SHC014, although the TCR-beta sequence breadth was unchanged. Post 3rd booster dose, Ab avidity increased for the Wuhan and Delta strains, while avidity against Omicron and SHC014 increased to levels seen for Wuhan after the second dose. Negative results on POCTs strongly correlated with a lack of functional humoral immunity. The third booster dose helps vaccinees gain depth and breadth of systemic Abs against evolving SARS-CoV-2 and related viruses. Our findings show that POCTs are useful and easy-to-access tools to inform inadequate humoral immunity accurately. POCTs designed to match the circulating variants can help individuals with booster vaccine decisions and could serve as a population-level screening platform to preserve herd immunity., One Sentence Summary: SARS-CoV-2 point-of-care antibody tests are valuable and easy-to-access tools to inform inadequate humoral immunity and to support informed decision-making regarding the current and future booster vaccination.
- Published
- 2023
- Full Text
- View/download PDF
19. Modeling in higher dimensions to improve diagnostic testing accuracy: Theory and examples for multiplex saliva-based SARS-CoV-2 antibody assays.
- Author
-
Luke RA, Kearsley AJ, Pisanic N, Manabe YC, Thomas DL, Heaney CD, and Patrone PN
- Subjects
- Humans, Saliva, COVID-19 Testing, Diagnostic Techniques and Procedures, Antibodies, Viral, Sensitivity and Specificity, SARS-CoV-2, COVID-19 diagnosis
- Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has emphasized the importance and challenges of correctly interpreting antibody test results. Identification of positive and negative samples requires a classification strategy with low error rates, which is hard to achieve when the corresponding measurement values overlap. Additional uncertainty arises when classification schemes fail to account for complicated structure in data. We address these problems through a mathematical framework that combines high dimensional data modeling and optimal decision theory. Specifically, we show that appropriately increasing the dimension of data better separates positive and negative populations and reveals nuanced structure that can be described in terms of mathematical models. We combine these models with optimal decision theory to yield a classification scheme that better separates positive and negative samples relative to traditional methods such as confidence intervals (CIs) and receiver operating characteristics. We validate the usefulness of this approach in the context of a multiplex salivary SARS-CoV-2 immunoglobulin G assay dataset. This example illustrates how our analysis: (i) improves the assay accuracy, (e.g. lowers classification errors by up to 42% compared to CI methods); (ii) reduces the number of indeterminate samples when an inconclusive class is permissible, (e.g. by 40% compared to the original analysis of the example multiplex dataset) and (iii) decreases the number of antigens needed to classify samples. Our work showcases the power of mathematical modeling in diagnostic classification and highlights a method that can be adopted broadly in public health and clinical settings., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: RAL, AJK, NP, CDH, and PNP have no conflicts of interest to declare. YCM has received consulting fees from Abbott Diagnostics; served leadership or fiduciary roles in the Infectious Diseases Institute, Infectious Diseases Society of America, and WHOTDR; and her institution received reagents from Hologic, Chembio, Roche, Cepheid, and Becton-Dickinson for studies. DLT has received funds for Merck DSMB board membership, consulting fees and stock or stock option for Excision Bio, fees for expert testimony, honoraria for CME programs only, and royalties from UpToDate., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
- Published
- 2023
- Full Text
- View/download PDF
20. Methodological approaches to optimize multiplex oral fluid SARS-CoV-2 IgG assay performance and correlation with serologic and neutralizing antibody responses.
- Author
-
Pisanic N, Antar AAR, Kruczynski KL, Gregory Rivera M, Dhakal S, Spicer K, Randad PR, Pekosz A, Klein SL, Betenbaugh MJ, Detrick B, Clarke W, Thomas DL, Manabe YC, and Heaney CD
- Subjects
- Humans, Antibodies, Neutralizing, SARS-CoV-2, Antibodies, Viral, Immunoglobulin G, COVID-19 Testing, COVID-19 diagnosis, Blood Group Antigens
- Abstract
Background: Oral fluid (hereafter, saliva) is a non-invasive and attractive alternative to blood for SARS-CoV-2 IgG testing; however, the heterogeneity of saliva as a matrix poses challenges for immunoassay performance., Objectives: To optimize performance of a magnetic microparticle-based multiplex immunoassay (MIA) for SARS-CoV-2 IgG measurement in saliva, with consideration of: i) threshold setting and validation across different MIA bead batches; ii) sample qualification based on salivary total IgG concentration; iii) calibration to U.S. SARS-CoV-2 serological standard binding antibody units (BAU); and iv) correlations with blood-based SARS-CoV-2 serological and neutralizing antibody (nAb) assays., Methods: The salivary SARS-CoV-2 IgG MIA included 2 nucleocapsid (N), 3 receptor-binding domain (RBD), and 2 spike protein (S) antigens. Gingival crevicular fluid (GCF) swab saliva samples were collected before December 2019 (n = 555) and after molecular test-confirmed SARS-CoV-2 infection from 113 individuals (providing up to 5 repeated-measures; n = 398) and used to optimize and validate MIA performance (total n = 953). Combinations of IgG responses to N, RBD and S and total salivary IgG concentration (μg/mL) as a qualifier of nonreactive samples were optimized and validated, calibrated to the U.S. SARS-CoV-2 serological standard, and correlated with blood-based SARS-CoV-2 IgG ELISA and nAb assays., Results: The sum of signal to cutoff (S/Co) to all seven MIA SARS-CoV-2 antigens and disqualification of nonreactive saliva samples with ≤15 μg/mL total IgG led to correct classification of 62/62 positives (sensitivity [Se] = 100.0%; 95% confidence interval [CI] = 94.8%, 100.0%) and 108/109 negatives (specificity [Sp] = 99.1%; 95% CI = 97.3%, 100.0%) at 8-million beads coupling scale and 80/81 positives (Se = 98.8%; 95% CI = 93.3%, 100.0%] and 127/127 negatives (Sp = 100%; 95% CI = 97.1%, 100.0%) at 20-million beads coupling scale. Salivary SARS-CoV-2 IgG crossed the MIA cutoff of 0.1 BAU/mL on average 9 days post-COVID-19 symptom onset and peaked around day 30. Among n = 30 matched saliva and plasma samples, salivary SARS-CoV-2 MIA IgG levels correlated with corresponding-antigen plasma ELISA IgG (N: ρ = 0.76, RBD: ρ = 0.83, S: ρ = 0.82; all p < 0.001). Correlations of plasma SARS-CoV-2 nAb assay area under the curve (AUC) with salivary MIA IgG (N: ρ = 0.68, RBD: ρ = 0.78, S: ρ = 0.79; all p < 0.001) and with plasma ELISA IgG (N: ρ = 0.76, RBD: ρ = 0.79, S: ρ = 0.76; p < 0.001) were similar., Conclusions: A salivary SARS-CoV-2 IgG MIA produced consistently high Se (> 98.8%) and Sp (> 99.1%) across two bead coupling scales and correlations with nAb responses that were similar to blood-based SARS-CoV-2 IgG ELISA data. This non-invasive salivary SARS-CoV-2 IgG MIA could increase engagement of vulnerable populations and improve broad understanding of humoral immunity (kinetics and gaps) within the evolving context of booster vaccination, viral variants and waning immunity., (Copyright © 2023. Published by Elsevier B.V.)
- Published
- 2023
- Full Text
- View/download PDF
21. SARS-CoV-2 Antibody Prevalence among Industrial Livestock Operation Workers and Nearby Community Residents, North Carolina, 2021 to 2022.
- Author
-
Gigot C, Pisanic N, Kruczynski K, Gregory Rivera M, Spicer K, Kurowski KM, Randad P, Koehler K, Clarke WA, Holmes P, Hall DJ Jr, Hall DJ, and Heaney CD
- Subjects
- Animals, Humans, SARS-CoV-2, Livestock, Prevalence, North Carolina epidemiology, Seroepidemiologic Studies, COVID-19 Vaccines, Antibodies, Viral, Immunoglobulin G, COVID-19 epidemiology
- Abstract
Industrial livestock operations (ILOs), particularly processing facilities, emerged as centers of coronavirus disease 2019 (COVID-19) outbreaks in spring 2020. Confirmed cases of COVID-19 underestimate true prevalence. To investigate the prevalence of antibodies against SARS-CoV-2, we enrolled 279 participants in North Carolina from February 2021 to July 2022: 90 from households with at least one ILO worker (ILO), 97 from high-ILO intensity areas (ILO neighbors [ILON]), and 92 from metropolitan areas (metro). More metro (55.4%) compared to ILO (51.6%) and ILON participants (48.4%) completed the COVID-19 primary vaccination series; the median completion date was more than 4 months later for ILO compared to ILON and metro participants, although neither difference was statistically significant. Participants provided a saliva swab we analyzed for SARS-CoV-2 IgG using a multiplex immunoassay. The prevalence of infection-induced IgG (positive for nucleocapsid and receptor binding domain) was higher among ILO (63%) than ILON (42.9%) and metro (48.7%) participants (prevalence ratio [PR], 1.38; 95% confidence interval [CI], 1.06 to 1.80; reference category ILON and metro combined). The prevalence of infection-induced IgG was also higher among ILO participants than among an Atlanta health care worker cohort (PR, 2.45; 95% CI, 1.80 to 3.33) and a general population cohort in North Carolina (PRs, 6.37 to 10.67). The infection-induced IgG prevalence increased over the study period. Participants reporting not masking in public in the past 2 weeks had higher infection-induced IgG prevalence (78.6%) than participants reporting masking (49.3%) (PR, 1.59; 95% CI, 1.19 to 2.13). Lower education, more people per bedroom, Hispanic/Latino ethnicity, and more contact with people outside the home were also associated with higher infection-induced IgG prevalence. IMPORTANCE Few studies have measured COVID-19 seroprevalence in North Carolina, especially among rural, Black, and Hispanic/Latino communities that have been heavily affected. Antibody results show high rates of COVID-19 among industrial livestock operation workers and their household members. Antibody results add to evidence of health disparities related to COVID-19 by socioeconomic status and ethnicity. Associations between masking and physical distancing with antibody results also add to evidence of the effectiveness of these prevention strategies. Delays in the timing of receipt of COVID-19 vaccination reinforce the importance of dismantling vaccination barriers, especially for industrial livestock operation workers and their household members.
- Published
- 2023
- Full Text
- View/download PDF
22. The Pregnancy, Arsenic, and Immune Response (PAIR) Study in rural northern Bangladesh.
- Author
-
Avolio LN, Smith TJS, Navas-Acien A, Kruczynski K, Pisanic N, Randad PR, Detrick B, Fry RC, van Geen A, Goessler W, Karron RA, Klein SL, Ogburn EL, Wills-Karp M, Alland K, Ayesha K, Dyer B, Islam MT, Oguntade HA, Rahman MH, Ali H, Haque R, Shaikh S, Schulze KJ, Muraduzzaman AKM, Alamgir ASM, Flora MS, West KP Jr, Labrique AB, and Heaney CD
- Subjects
- Infant, Newborn, Infant, Pregnancy, Female, Humans, Prospective Studies, Bangladesh epidemiology, Water, Micronutrients, Immunity, Arsenic, Influenza, Human epidemiology, Influenza, Human prevention & control
- Abstract
Background: Arsenic exposure and micronutrient deficiencies may alter immune reactivity to influenza vaccination in pregnant women, transplacental transfer of maternal antibodies to the foetus, and maternal and infant acute morbidity., Objectives: The Pregnancy, Arsenic, and Immune Response (PAIR) Study was designed to assess whether arsenic exposure and micronutrient deficiencies alter maternal and newborn immunity and acute morbidity following maternal seasonal influenza vaccination during pregnancy., Population: The PAIR Study recruited pregnant women across a large rural study area in Gaibandha District, northern Bangladesh, 2018-2019., Design: Prospective, longitudinal pregnancy and birth cohort., Methods: We conducted home visits to enrol pregnant women in the late first or early second trimester (11-17 weeks of gestational age). Women received a quadrivalent seasonal inactivated influenza vaccine at enrolment. Follow-up included up to 13 visits between enrolment and 3 months postpartum. Arsenic was measured in drinking water and maternal urine. Micronutrient deficiencies were assessed using plasma biomarkers. Vaccine-specific antibody titres were measured in maternal and infant serum. Weekly telephone surveillance ascertained acute morbidity symptoms in women and infants., Preliminary Results: We enrolled 784 pregnant women between October 2018 and March 2019. Of 784 women who enrolled, 736 (93.9%) delivered live births and 551 (70.3%) completed follow-up visits to 3 months postpartum. Arsenic was detected (≥0.02 μg/L) in 99.7% of water specimens collected from participants at enrolment. The medians (interquartile ranges) of water and urinary arsenic at enrolment were 5.1 (0.5, 25.1) μg/L and 33.1 (19.6, 56.5) μg/L, respectively. Water and urinary arsenic were strongly correlated (Spearman's ⍴ = 0.72) among women with water arsenic ≥ median but weakly correlated (⍴ = 0.17) among women with water arsenic < median., Conclusions: The PAIR Study is well positioned to examine the effects of low-moderate arsenic exposure and micronutrient deficiencies on immune outcomes in women and infants., Registration: NCT03930017., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
23. Methodological approaches to optimize multiplex oral fluid SARS-CoV-2 IgG assay performance and correlation with serologic and neutralizing antibody responses.
- Author
-
Pisanic N, Antar AAR, Kruczynski K, Rivera MG, Dhakal S, Spicer K, Randad PR, Pekosz A, Klein SL, Betenbaugh MJ, Detrick B, Clarke W, Thomas DL, Manabe YC, and Heaney CD
- Abstract
Background: Oral fluid (hereafter, saliva) is a non-invasive and attractive alternative to blood for SARS-CoV-2 IgG testing; however, the heterogeneity of saliva as a matrix poses challenges for immunoassay performance., Objectives: To optimize performance of a magnetic microparticle-based multiplex immunoassay (MIA) for SARS-CoV-2 IgG measurement in saliva, with consideration of: i) threshold setting and validation across different MIA bead batches; ii) sample qualification based on salivary total IgG concentration; iii) calibration to U.S. SARS-CoV-2 serological standard binding antibody units (BAU); and iv) correlations with blood-based SARS-CoV-2 serological and neutralizing antibody (nAb) assays., Methods: The salivary SARS-CoV-2 IgG MIA included 2 nucleocapsid (N), 3 receptor-binding domain (RBD), and 2 spike protein (S) antigens. Gingival crevicular fluid (GCF) swab saliva samples were collected before December, 2019 (n=555) and after molecular test-confirmed SARS-CoV-2 infection from 113 individuals (providing up to 5 repeated-measures; n=398) and used to optimize and validate MIA performance (total n=953). Combinations of IgG responses to N, RBD and S and total salivary IgG concentration (μg/mL) as a qualifier of nonreactive samples were optimized and validated, calibrated to the U.S. SARS-CoV-2 serological standard, and correlated with blood-based SARS-CoV-2 IgG ELISA and nAb assays., Results: The sum of signal to cutoff (S/Co) to all seven MIA SARS-CoV-2 antigens and disqualification of nonreactive saliva samples with ≤15 μg/mL total IgG led to correct classification of 62/62 positives (sensitivity [Se]=100.0%; 95% confidence interval [CI]=94.8%, 100.0%) and 108/109 negatives (specificity [Sp]=99.1%; 95% CI=97.3%, 100.0%) at 8-million beads coupling scale and 80/81 positives (Se=98.8%; 95% CI=93.3%, 100.0%] and 127/127 negatives (Sp=100%; 95% CI=97.1%, 100.0%) at 20-million beads coupling scale. Salivary SARS-CoV-2 IgG crossed the MIA cutoff of 0.1 BAU/mL on average 9 days post-COVID-19 symptom onset and peaked around day 30. Among n=30 matched saliva and plasma samples, salivary SARS-CoV-2 MIA IgG levels correlated with corresponding-antigen plasma ELISA IgG (N: ρ=0.67, RBD: ρ=0.76, S: ρ=0.82; all p <0.0001). Correlations of plasma SARS-CoV-2 nAb assay area under the curve (AUC) with salivary MIA IgG (N: ρ=0.68, RBD: ρ=0.78, S: ρ=0.79; all p <0.0001) and with plasma ELISA IgG (N: ρ=0.76, RBD: ρ=0.79, S: ρ=0.76; p <0.0001) were similar., Conclusions: A salivary SARS-CoV-2 IgG MIA produced consistently high Se (>98.8%) and Sp (>99.1%) across two bead coupling scales and correlations with nAb responses that were similar to blood-based SARS-CoV-2 IgG ELISA data. This non-invasive salivary SARS-CoV-2 IgG MIA could increase engagement of vulnerable populations and improve broad understanding of humoral immunity (kinetics and gaps) within the evolving context of booster vaccination, viral variants and waning immunity.
- Published
- 2022
- Full Text
- View/download PDF
24. Reconsideration of Antinucleocapsid IgG Antibody as a Marker of SARS-CoV-2 Infection Postvaccination for Mild COVID-19 Patients.
- Author
-
Dhakal S, Yu T, Yin A, Pisanic N, Demko ZO, Antar AAR, Cox AL, Heaney CD, Manabe YC, and Klein SL
- Abstract
Antinucleocapsid (anti-N) immunoglobulin G antibody responses were lower in plasma and oral fluid after severe acute respiratory syndrome coronavirus 2 infection in vaccinated patients compared with patients infected before vaccination or infected without vaccination. This raises questions about the long-term use of anti-N antibodies as a marker for natural infection for surveillance., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)
- Published
- 2022
- Full Text
- View/download PDF
25. Optimal decision theory for diagnostic testing: Minimizing indeterminate classes with applications to saliva-based SARS-CoV-2 antibody assays.
- Author
-
Patrone PN, Bedekar P, Pisanic N, Manabe YC, Thomas DL, Heaney CD, and Kearsley AJ
- Subjects
- Antibodies, Viral, COVID-19 Testing, Decision Theory, Humans, Saliva, COVID-19 diagnosis, SARS-CoV-2
- Abstract
In diagnostic testing, establishing an indeterminate class is an effective way to identify samples that cannot be accurately classified. However, such approaches also make testing less efficient and must be balanced against overall assay performance. We address this problem by reformulating data classification in terms of a constrained optimization problem that (i) minimizes the probability of labeling samples as indeterminate while (ii) ensuring that the remaining ones are classified with an average target accuracy X. We show that the solution to this problem is expressed in terms of a bathtub-type principle that holds out those samples with the lowest local accuracy up to an X-dependent threshold. To illustrate the usefulness of this analysis, we apply it to a multiplex, saliva-based SARS-CoV-2 antibody assay and demonstrate up to a 30 % reduction in the number of indeterminate samples relative to more traditional approaches., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)
- Published
- 2022
- Full Text
- View/download PDF
26. The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization.
- Author
-
Karger AB, Brien JD, Christen JM, Dhakal S, Kemp TJ, Klein SL, Pinto LA, Premkumar L, Roback JD, Binder RA, Boehme KW, Boppana S, Cordon-Cardo C, Crawford JM, Daiss JL, Dupuis AP 2nd, Espino AM, Firpo-Betancourt A, Forconi C, Forrest JC, Girardin RC, Granger DA, Granger SW, Haddad NS, Heaney CD, Hunt DT, Kennedy JL, King CL, Krammer F, Kruczynski K, LaBaer J, Lee FE, Lee WT, Liu SL, Lozanski G, Lucas T, Mendu DR, Moormann AM, Murugan V, Okoye NC, Pantoja P, Payne AF, Park J, Pinninti S, Pinto AK, Pisanic N, Qiu J, Sariol CA, Simon V, Song L, Steffen TL, Stone ET, Styer LM, Suthar MS, Thomas SN, Thyagarajan B, Wajnberg A, Yates JL, and Sobhani K
- Subjects
- Antibodies, Viral, COVID-19 Testing, Humans, SARS-CoV-2, Serologic Tests methods, COVID-19 diagnosis
- Abstract
In October 2020, the National Cancer Institute (NCI) Serological Sciences Network (SeroNet) was established to study the immune response to COVID-19, and "to develop, validate, improve, and implement serological testing and associated technologies" (https://www.cancer.gov/research/key-initiatives/covid-19/coronavirus-research-initiatives/serological-sciences-network). SeroNet is comprised of 25 participating research institutions partnering with the Frederick National Laboratory for Cancer Research (FNLCR) and the SeroNet Coordinating Center. Since its inception, SeroNet has supported collaborative development and sharing of COVID-19 serological assay procedures and has set forth plans for assay harmonization. To facilitate collaboration and procedure sharing, a detailed survey was sent to collate comprehensive assay details and performance metrics on COVID-19 serological assays within SeroNet. In addition, FNLCR established a protocol to calibrate SeroNet serological assays to reference standards, such as the U.S. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology standard reference material and first WHO international standard (IS) for anti-SARS-CoV-2 immunoglobulin (20/136), to facilitate harmonization of assay reporting units and cross-comparison of study data. SeroNet institutions reported development of a total of 27 enzyme-linked immunosorbent assay (ELISA) methods, 13 multiplex assays, and 9 neutralization assays and use of 12 different commercial serological methods. FNLCR developed a standardized protocol for SeroNet institutions to calibrate these diverse serological assays to reference standards. In conclusion, SeroNet institutions have established a diverse array of COVID-19 serological assays to study the immune response to SARS-CoV-2 and vaccines. Calibration of SeroNet serological assays to harmonize results reporting will facilitate future pooled data analyses and study cross-comparisons. IMPORTANCE SeroNet institutions have developed or implemented 61 diverse COVID-19 serological assays and are collaboratively working to harmonize these assays using reference materials to establish standardized reporting units. This will facilitate clinical interpretation of serology results and cross-comparison of research data.
- Published
- 2022
- Full Text
- View/download PDF
27. Modeling in higher dimensions to improve diagnostic testing accuracy: theory and examples for multiplex saliva-based SARS-CoV-2 antibody assays.
- Author
-
Luke RA, Kearsley AJ, Pisanic N, Manabe YC, Thomas DL, Heaney CD, and Patrone PN
- Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has emphasized the importance and challenges of correctly interpreting antibody test results. Identification of positive and negative samples requires a classification strategy with low error rates, which is hard to achieve when the corresponding measurement values overlap. Additional uncertainty arises when classification schemes fail to account for complicated structure in data. We address these problems through a mathematical framework that combines high dimensional data modeling and optimal decision theory. Specifically, we show that appropriately increasing the dimension of data better separates positive and negative populations and reveals nuanced structure that can be described in terms of mathematical models. We combine these models with optimal decision theory to yield a classification scheme that better separates positive and negative samples relative to traditional methods such as confidence intervals (CIs) and receiver operating characteristics. We validate the usefulness of this approach in the context of a multiplex salivary SARS-CoV-2 immunoglobulin G assay dataset. This example illustrates how our analysis: (i) improves the assay accuracy (e.g. lowers classification errors by up to 42 % compared to CI methods); (ii) reduces the number of indeterminate samples when an inconclusive class is permissible (e.g. by 40 % compared to the original analysis of the example multiplex dataset); and (iii) decreases the number of antigens needed to classify samples. Our work showcases the power of mathematical modeling in diagnostic classification and highlights a method that can be adopted broadly in public health and clinical settings.
- Published
- 2022
28. Evaluating immunity to SARS-CoV-2 in nursing home residents using saliva IgG.
- Author
-
Katz MJ, Heaney CD, Pisanic N, Smith L, Bigelow BF, Sheikh F, Boudreau A, Kruczynski K, Hsu YJ, Salinas AB, Cosgrove SE, and Rock C
- Subjects
- Aged, COVID-19 epidemiology, COVID-19 Vaccines administration & dosage, Female, Humans, Male, Nursing Homes, SARS-CoV-2, Seroepidemiologic Studies, United States epidemiology, Antibodies, Viral immunology, COVID-19 immunology, COVID-19 prevention & control, COVID-19 Vaccines immunology, Immunoglobulin G immunology, Saliva immunology
- Abstract
Background: SARS-CoV-2 circulating variants coupled with waning immunity pose a significant threat to the long-term care (LTC) population. Our objective was to measure salivary IgG antibodies in residents and staff of an LTC facility to (1) evaluate IgG response in saliva post-natural infection and vaccination and (2) assess its feasibility to describe the seroprevalence over time., Methods: We performed salivary IgG sampling of all residents and staff who agreed to test in a 150-bed skilled nursing facility during three seroprevalence surveys between October 2020 and February 2021. The facility had SARS-CoV-2 outbreaks in May 2020 and November 2020, when 45 of 138 and 37 of 125 residents were infected, respectively; they offered two Federal vaccine clinics in January 2021. We evaluated quantitative IgG in saliva to the Nucleocapsid (N), Spike (S), and Receptor-binding domain (RBD) Antigens of SARS-CoV-2 over time post-infection and post-vaccination., Results: One hundred twenty-four residents and 28 staff underwent saliva serologic testing on one or more survey visits. Over three surveys, the SARS-CoV-2 seroprevalence at the facility was 49%, 64%, and 81%, respectively. IgG to S, RBD, and N Antigens all increased post infection. Post vaccination, the infection naïve group did not have a detectable N IgG level, and N IgG levels for the previously infected did not increase post vaccination (p < 0.001). Fully vaccinated subjects with prior COVID-19 infection had significantly higher RBD and S IgG responses compared with those who were infection-naïve prior to vaccination (p < 0.001 for both)., Conclusions: Positive SARS-COV-2 IgG in saliva was concordant with prior infection (Anti N, S, RBD) and vaccination (Anti S, RBD) and remained above positivity threshold for up to 9 months from infection. Salivary sampling is a non-invasive method of tracking immunity and differentiating between prior infection and vaccination to inform the need for boosters in LTC residents and staff., (© 2022 The American Geriatrics Society.)
- Published
- 2022
- Full Text
- View/download PDF
29. Comparative performance of multiplex salivary and commercially available serologic assays to detect SARS-CoV-2 IgG and neutralization titers.
- Author
-
Heaney CD, Pisanic N, Randad PR, Kruczynski K, Howard T, Zhu X, Littlefield K, Patel EU, Shrestha R, Laeyendecker O, Shoham S, Sullivan D, Gebo K, Hanley D, Redd AD, Quinn TC, Casadevall A, Zenilman JM, Pekosz A, Bloch EM, and Tobian AAR
- Subjects
- Humans, Immunization, Passive, Immunoglobulin G isolation & purification, SARS-CoV-2, Sensitivity and Specificity, Seroepidemiologic Studies, Spike Glycoprotein, Coronavirus immunology, COVID-19 Serotherapy, Antibodies, Neutralizing isolation & purification, Antibodies, Viral isolation & purification, COVID-19 immunology, COVID-19 Serological Testing methods
- Abstract
Oral fluid (hereafter saliva) offers a non-invasive sampling method for detection of SARS-CoV-2 antibodies. However, data comparing performance of salivary tests against commercially-available serologic and neutralizing antibody (nAb) assays are lacking. This study compared the performance of a laboratory-developed multiplex salivary SARS-CoV-2 IgG assay targeting antibodies to nucleocapsid (N), receptor binding domain (RBD) and spike (S) antigens to three commercially-available SARS-CoV-2 serologic enzyme immunoassays (EIAs) (Ortho Vitros, Euroimmun, and BioRad) and nAb. Paired saliva and plasma samples were collected from 101 eligible COVID-19 convalescent plasma (CCP) donors >14 days since PCR+ confirmed diagnosis. Concordance was evaluated using positive (PPA) and negative (NPA) percent agreement, and Cohen's kappa coefficient. The range between salivary and plasma EIAs for SARS-CoV-2-specific N was PPA: 54.4-92.1% and NPA: 69.2-91.7%, for RBD was PPA: 89.9-100% and NPA: 50.0-84.6%, and for S was PPA: 50.6-96.6% and NPA: 50.0-100%. Compared to a plasma nAb assay, the multiplex salivary assay PPA ranged from 62.3% (N) and 98.6% (RBD) and NPA ranged from 18.8% (RBD) to 96.9% (S). Combinations of N, RBD, and S and a summary algorithmic index of all three (N/RBD/S) in saliva produced ranges of PPA: 87.6-98.9% and NPA: 50-91.7% with the three EIAs and ranges of PPA: 88.4-98.6% and NPA: 21.9-34.4% with the nAb assay. A multiplex salivary SARS-CoV-2 IgG assay demonstrated variable, but comparable performance to three commercially-available plasma EIAs and a nAb assay, and may be a viable alternative to assist in monitoring population-based seroprevalence and vaccine antibody response., (Copyright © 2021. Published by Elsevier B.V.)
- Published
- 2021
- Full Text
- View/download PDF
30. Application of SARS-CoV-2 Serology to Address Public Health Priorities.
- Author
-
Sherman AC, Smith T, Zhu Y, Taibl K, Howard-Anderson J, Landay T, Pisanic N, Kleinhenz J, Simon TW, Espinoza D, Edupuganti N, Hammond S, Rouphael N, Shen H, Fairley JK, Edupuganti S, Cardona-Ospina JA, Rodriguez-Morales AJ, Premkumar L, Wrammert J, Tarleton R, Fridkin S, Heaney CD, Scherer EM, and Collins MH
- Subjects
- Antibodies, Viral, Health Priorities, Humans, Sensitivity and Specificity, COVID-19, SARS-CoV-2
- Abstract
Background: Antibodies against SARS-CoV-2 can be detected by various testing platforms, but a detailed understanding of assay performance is critical. Methods: We developed and validated a simple enzyme-linked immunosorbent assay (ELISA) to detect IgG binding to the receptor-binding domain (RBD) of SARS-CoV-2, which was then applied for surveillance. ELISA results were compared to a set of complimentary serologic assays using a large panel of clinical research samples. Results: The RBD ELISA exhibited robust performance in ROC curve analysis (AUC> 0.99; Se = 89%, Sp = 99.3%). Antibodies were detected in 23/353 (6.5%) healthcare workers, 6/9 RT-PCR-confirmed mild COVID-19 cases, and 0/30 non-COVID-19 cases from an ambulatory site. RBD ELISA showed a positive correlation with neutralizing activity ( p = <0.0001, R
2 = 0.26). Conclusions: We applied a validated SARS-CoV-2-specific IgG ELISA in multiple contexts and performed orthogonal testing on samples. This study demonstrates the utility of a simple serologic assay for detecting prior SARS-CoV-2 infection, particularly as a tool for efficiently testing large numbers of samples as in population surveillance. Our work also highlights that precise understanding of SARS-CoV-2 infection and immunity at the individual level, particularly with wide availability of vaccination, may be improved by orthogonal testing and/or more complex assays such as multiplex bead assays., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sherman, Smith, Zhu, Taibl, Howard-Anderson, Landay, Pisanic, Kleinhenz, Simon, Espinoza, Edupuganti, Hammond, Rouphael, Shen, Fairley, Edupuganti, Cardona-Ospina, Rodriguez-Morales, Premkumar, Wrammert, Tarleton, Fridkin, Heaney, Scherer and Collins.)- Published
- 2021
- Full Text
- View/download PDF
31. Personal protective equipment use during industrial hog operation work activities and acute lung function changes in a prospective worker cohort, North Carolina 2014-2015.
- Author
-
Coffman VR, Hall DJ, Pisanic N, Nadimpalli M, McCormack M, Diener-West M, Davis MF, and Heaney CD
- Subjects
- Animals, Cross-Sectional Studies, Lung, North Carolina, Prospective Studies, Swine, Occupational Exposure, Personal Protective Equipment
- Abstract
Introduction: Occupational activities related to industrial hog operation (IHO) worker lung function are not well defined. Therefore, we aimed to identify IHO work activities associated with diminished respiratory function and the effectiveness, if any, of personal protective equipment (PPE) use on IHOs., Methods: From 2014 to 2015, 103 IHO workers were enrolled and followed for 16 weeks. At each biweekly visit, work activities and PPE use were self-reported via questionnaire and lung function measurements were collected via spirometry. Generalized linear and linear fixed-effects models were fitted to cross-sectional and longitudinal data., Results: Increasing years worked on an IHO were associated with diminished lung function, but baseline and longitudinal work activities were largely inconsistent in direction and magnitude. Unexpectedly, a -0.3 L (95% confidence interval: -0.6, -0.04) difference in forced expiratory volume in the first second (FEV
1 ) was estimated when workers wore PPE consistently (≥80% of the time at work) versus those weeks they did not. In post-hoc analyses, we found that coveralls and facemasks were worn less consistently when workers experienced worse barn conditions and had more contact with pigs, but coveralls were worn more consistently as cleaning activities increased., Conclusions: Similar to past studies, baseline estimates were likely obscured by healthy worker effect bias, but showed decrements in worker lung function as years of work increased. A challenge to disentangling the effect of work activities on lung function was the discovery that IHO workers used PPE differently according to the work task. These data suggest that interventions may be targeted toward improving barn conditions so that workers can consistently utilize IHO-provided PPE., (© 2021 Wiley Periodicals LLC.)- Published
- 2021
- Full Text
- View/download PDF
32. Self-reported work activities, eye, nose, and throat symptoms, and respiratory health outcomes among an industrial hog operation worker cohort, North Carolina, USA.
- Author
-
Coffman VR, Hall DJ, Pisanic N, Love DC, Nadimpalli M, McCormack M, Diener-West M, Davis MF, and Heaney CD
- Subjects
- Adult, Air Pollutants, Occupational analysis, Animals, Eye Diseases epidemiology, Eye Diseases etiology, Eye Diseases prevention & control, Female, Hand Disinfection, Humans, Livestock, Male, North Carolina epidemiology, Nose Diseases epidemiology, Nose Diseases etiology, Nose Diseases prevention & control, Occupational Diseases etiology, Occupational Diseases prevention & control, Occupational Exposure prevention & control, Odds Ratio, Outcome Assessment, Health Care, Personal Protective Equipment statistics & numerical data, Pharyngitis epidemiology, Pharyngitis etiology, Pharyngitis prevention & control, Respiratory Tract Diseases etiology, Respiratory Tract Diseases prevention & control, Self Report, Swine, Air Pollutants, Occupational adverse effects, Animal Husbandry, Occupational Diseases epidemiology, Occupational Exposure adverse effects, Respiratory Tract Diseases epidemiology
- Abstract
Introduction: Respiratory disease among industrial hog operation (IHO) workers is well documented; however, it remains unclear whether specific work activities are more harmful and if personal protective equipment (PPE), as used by workers, can reduce adverse health outcomes., Methods: IHO workers (n = 103) completed baseline and up to eight bi-weekly study visits. Workers reported typical (baseline) and transient (bi-weekly) work activities, PPE use, and physical health symptoms. Baseline and longitudinal associations were assessed using generalized logistic and fixed-effects logistic regression models, respectively., Results: At baseline, reports of ever versus never drawing pig blood, applying pesticides, and increasing years worked at any IHO were positively associated with reports of eye, nose, and/or throat irritation. Over time, transient exposures, associated with dustiness in barns, cleaning of barns, and pig contact were associated with increased odds of sneezing, headache, and eye or nose irritation, particularly in the highest categories of exposure. When PPE was used, workers had lower odds of symptoms interfering with sleep (odds ratio [OR]: 0.1; 95% confidence interval [CI]: 0.01-0.8), and eye or nose irritation (OR: 0.1; 95% CI: 0.02-0.9). Similarly, when they washed their hands eight times or more per shift (median frequency) versus less frequently, the odds of any respiratory symptom were reduced (OR: 0.3; 95% CI: 0.1-0.8)., Conclusions: In this healthy volunteer worker population, increasingly unfavorable IHO activities were associated with self-reported eye, nose, throat, and respiratory health symptoms. Strong protective associations were seen between PPE use and handwashing and the odds of symptoms, warranting further investigation., (© 2021 Wiley Periodicals LLC.)
- Published
- 2021
- Full Text
- View/download PDF
33. Delayed Rise of Oral Fluid Antibodies, Elevated BMI, and Absence of Early Fever Correlate With Longer Time to SARS-CoV-2 RNA Clearance in a Longitudinally Sampled Cohort of COVID-19 Outpatients.
- Author
-
Antar AAR, Yu T, Pisanic N, Azamfirei R, Tornheim JA, Brown DM, Kruczynski K, Hardick JP, Sewell T, Jang M, Church T, Walch SN, Reuland C, Bachu VS, Littlefield K, Park HS, Ursin RL, Ganesan A, Kusemiju O, Barnaba B, Charles C, Prizzi M, Johnstone JR, Payton C, Dai W, Fuchs J, Massaccesi G, Armstrong DT, Townsend JL, Keller SC, Demko ZO, Hu C, Wang MC, Sauer LM, Mostafa HH, Keruly JC, Mehta SH, Klein SL, Cox AL, Pekosz A, Heaney CD, Thomas DL, Blair PW, and Manabe YC
- Abstract
Background: Sustained molecular detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the upper respiratory tract (URT) in mild to moderate coronavirus disease 2019 (COVID-19) is common. We sought to identify host and immune determinants of prolonged SARS-CoV-2 RNA detection., Methods: Ninety-five symptomatic outpatients self-collected midturbinate nasal, oropharyngeal (OP), and gingival crevicular fluid (oral fluid) samples at home and in a research clinic a median of 6 times over 1-3 months. Samples were tested for viral RNA, virus culture, and SARS-CoV-2 and other human coronavirus antibodies, and associations were estimated using Cox proportional hazards models., Results: Viral RNA clearance, as measured by SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR), in 507 URT samples occurred a median (interquartile range) 33.5 (17-63.5) days post-symptom onset. Sixteen nasal-OP samples collected 2-11 days post-symptom onset were virus culture positive out of 183 RT-PCR-positive samples tested. All participants but 1 with positive virus culture were negative for concomitant oral fluid anti-SARS-CoV-2 antibodies. The mean time to first antibody detection in oral fluid was 8-13 days post-symptom onset. A longer time to first detection of oral fluid anti-SARS-CoV-2 S antibodies (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.92-0.99; P = .020) and body mass index (BMI) ≥25 kg/m
2 (aHR, 0.37; 95% CI, 0.18-0.78; P = .009) were independently associated with a longer time to SARS-CoV-2 viral RNA clearance. Fever as 1 of first 3 COVID-19 symptoms correlated with shorter time to viral RNA clearance (aHR, 2.06; 95% CI, 1.02-4.18; P = .044)., Conclusions: We demonstrate that delayed rise of oral fluid SARS-CoV-2-specific antibodies, elevated BMI, and absence of early fever are independently associated with delayed URT viral RNA clearance., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)- Published
- 2021
- Full Text
- View/download PDF
34. Transmission of Antimicrobial-Resistant Staphylococcus aureus Clonal Complex 9 between Pigs and Humans, United States.
- Author
-
Randad PR, Larsen J, Kaya H, Pisanic N, Ordak C, Price LB, Aziz M, Nadimpalli ML, Rhodes S, Stewart JR, Love DC, Mohr D, Davis MF, Miller LS, Hall D, Carroll KC, Perl TM, and Heaney CD
- Subjects
- Animal Husbandry, Animals, Anti-Bacterial Agents, Humans, Livestock, North Carolina, Phylogeny, Staphylococcus aureus, Swine, United States, Methicillin-Resistant Staphylococcus aureus, Staphylococcal Infections
- Abstract
Transmission of livestock-associated Staphylococcus aureus clonal complex 9 (LA-SA CC9) between pigs raised on industrial hog operations (IHOs) and humans in the United States is poorly understood. We analyzed whole-genome sequences from 32 international S. aureus CC9 isolates and 49 LA-SA CC9 isolates from IHO pigs and humans who work on or live near IHOs in 10 pig-producing counties in North Carolina, USA. Bioinformatic analysis of sequence data from the 81 isolates demonstrated 3 major LA-SA CC9 clades. North Carolina isolates all fell within a single clade (C3). High-resolution phylogenetic analysis of C3 revealed 2 subclades of intermingled IHO pig and human isolates differing by 0-34 single-nucleotide polymorphisms. Our findings suggest that LA-SA CC9 from pigs and humans share a common source and provide evidence of transmission of antimicrobial-resistant LA-SA CC9 between IHO pigs and humans who work on or live near IHOs in North Carolina.
- Published
- 2021
- Full Text
- View/download PDF
35. Associations among Household Animal Ownership, Infrastructure, and Hygiene Characteristics with Source Attribution of Household Fecal Contamination in Peri-Urban Communities of Iquitos, Peru.
- Author
-
Schiaffino F, Rengifo Trigoso D, Colston JM, Paredes Olortegui M, Shapiama Lopez WV, Garcia Bardales PF, Pisanic N, Davis MF, Penataro Yori P, and Kosek MN
- Subjects
- Animals, Chickens, Dogs, Environmental Monitoring, Humans, Ownership, Peru, Water Microbiology, Water Pollution, Water Supply, Animal Husbandry, Environmental Microbiology standards, Feces, Housing, Hygiene, Sanitation
- Abstract
Using previously validated microbial source tracking markers, we detected and quantified fecal contamination from avian species and avian exposure, dogs, and humans on household cooking tables and floors. The association among contamination, infrastructure, and socioeconomic covariates was assessed using simple and multiple ordinal logistic regressions. The presence of Campylobacter spp. in surface samples was linked to avian markers. Using molecular methods, animal feces were detected in 75.0% and human feces in 20.2% of 104 households. Floors were more contaminated than tables as detected by the avian marker Av4143 , dog marker Bactcan , and human marker Bachum . Wood tables were consistently more contaminated than non-wood surfaces, specifically with the mitochondrial avian markers ND5 and CytB, fecal marker Av4143, and canine marker Bactcan . Final multivariable models with socioeconomic and infrastructure characteristics included as covariates indicate that detection of avian feces and avian exposure was associated with the presence of chickens, maternal age, and length of tenancy, whereas detection of human markers was associated with unimproved water source. Detection of Campylobacter in surface samples was associated with the avian fecal marker Av4143. We highlight the critical need to detect and measure the burden of animal fecal waste when evaluating household water, hygiene, and sanitation interventions, and the possibility of decreasing risk of exposure through the modification of surfaces to permit more effective household disinfection practices. Animals may be a more important source of household fecal contamination than humans in many low-resource settings, although interventions have historically focused almost exclusively on managing human waste.
- Published
- 2021
- Full Text
- View/download PDF
36. COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva.
- Author
-
Pisanic N, Randad PR, Kruczynski K, Manabe YC, Thomas DL, Pekosz A, Klein SL, Betenbaugh MJ, Clarke WA, Laeyendecker O, Caturegli PP, Larman HB, Detrick B, Fairley JK, Sherman AC, Rouphael N, Edupuganti S, Granger DA, Granger SW, Collins MH, and Heaney CD
- Subjects
- COVID-19 Nucleic Acid Testing methods, Coronavirus Nucleocapsid Proteins immunology, Female, Humans, Immunoglobulin A blood, Immunoglobulin G blood, Immunoglobulin M blood, Male, Spike Glycoprotein, Coronavirus immunology, Antibodies, Viral analysis, Antibodies, Viral blood, COVID-19 diagnosis, SARS-CoV-2 immunology, Saliva immunology
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses ( n = 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing., (Copyright © 2020 American Society for Microbiology.)
- Published
- 2020
- Full Text
- View/download PDF
37. Validation of microbial source tracking markers for the attribution of fecal contamination in indoor-household environments of the Peruvian Amazon.
- Author
-
Schiaffino F, Pisanic N, Colston JM, Rengifo D, Paredes Olortegui M, Shapiama V, Peñataro Yori P, Heaney CD, Davis MF, and Kosek MN
- Subjects
- Animals, Biomarkers, Cats, Dogs, Feces, Guinea Pigs, Humans, Peru, Rats, Water Microbiology, Water Pollution analysis, Chickens, Environmental Monitoring
- Abstract
The performance of eight microbial source tracking (MST) markers was evaluated in a low-resource, tropical community located in Iquitos, Peru. Fecal samples from humans, dogs, cats, rats, goats, buffalos, guinea-pigs, chickens, ducks, pigeons, and parrots were collected (n = 117). All samples were tested with human (BacHum, HF183-Taqman), dog (BactCan), pig (Pig-2-Bac), and avian (LA35, Av4143, ND5, cytB) markers using quantitative PCR (qPCR). Internal validity metrics were calculated using all animal fecal samples, as well as animal fecal samples contextually relevant for the Peruvian Amazon. Overall, Pig-2-Bac performed best, with 100% sensitivity and 88.5% specificity to detect the correct fecal source. Human-associated markers showed a sensitivity of 80.0% and 76.7%, and specificity of 66.2% and 67.6%. When limiting the analysis to contextually relevant animal fecal samples for the Peruvian Amazon, Av143 surpassed cytB with 95.7% sensitivity and 81.8% specificity. BactCan demonstrated 100% sensitivity and 47.4% specificity. The gene copy number detected by BacHum and HF183-Taqman were positively correlated (Pearson's correlation coefficient: 0.785), as well as avian markers cytB with Av4143 (Pearson's correlation coefficient: 0.508) and nd5 (Pearson's correlation coefficient: 0.949). These findings suggest that markers such as Av4143, Pig2Bac, cytb and BacHum have acceptable performance to be impactful in source attribution studies for zoonotic enteric disease transmission in this and similar low-resource communities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
38. The use of personal protective equipment during common industrial hog operation work activities and acute lung function changes in a prospective worker cohort, North Carolina, USA.
- Author
-
Coffman VR, Hall DJ, Pisanic N, Nadimpalli M, McCormack M, Diener-West M, Davis MF, and Heaney CD
- Abstract
Introduction: As occupational activities related to acute industrial hog operation (IHO) worker lung function are not well defined, we aimed to identify IHO work activities associated with diminished respiratory function and the effectiveness, if any, of personal protective equipment (PPE) on IHOs., Methods: From 2014-2015, 103 IHO workers were enrolled and followed for 16 weeks. At each bi-weekly visit, lung function measurements were collected via spirometry and work activities and PPE use were self-reported via questionnaire. Generalized linear and linear fixed-effects models were fitted to cross-sectional and longitudinal data., Results: At baseline, increasing years worked on an IHO were associated with diminished lung function, but other activities were less consistent in direction and magnitude. In longitudinal models, only reports of working in feeding/finisher barns, showed a consistent association. However, a -0.3 L (95% confidence interval: -0.6, -0.04) difference in FEV
1 was estimated when workers wore PPE consistently versus those weeks they did not. In post-hoc analyses, we found that coveralls and facemasks were worn less consistently when workers experienced worse barn conditions and had more contact with pigs, but coveralls were worn more consistently as cleaning activities increased., Conclusions: Similar to past studies, baseline estimates were likely obscured by healthy worker bias. Also making it challenging to disentangle the effect of work activities on lung function was the discovery that IHO workers used PPE differently according to work task. These data suggest that interventions may be targeted toward improving barn conditions so that workers can consistently utilize IHO-provided PPE., Key Messages: What is already known about this subject?: Working on industrial hog operations may be deleterious to long- and short-term respiratory health due to airborne bacteria, endotoxin, hazardous gases, dust, and dander in barns. In efficacy studies PPE has been shown to be protective, but studies have shown that PPE utilization among hog workers has historically been sub-optimal. What are the new findings?: As barn conditions worsened and contact with pigs increased, workers in this cohort reported wearing coveralls and face masks less often; however, they reported increased PPE use as they conducted more cleaning activities at work. During weeks when workers wore PPE their lung function declined, a possible cause being the improper use of the equipment leading to a false sense of protection or re-exposure to hazardous contaminants. How might this impact on policy or clinical practice in the foreseeable future?: Given COVID-19, the H1N1 "swine flu" pandemic, our knowledge of antimicrobial resistant pathogens, and increasing awareness about how food systems are linked to the spread of emerging infectious diseases, occupational health intervention research and workplace policies may focus on creating barn environments that are more conducive to PPE use which could help protect workers and consequently the community.- Published
- 2020
- Full Text
- View/download PDF
39. COVID-19 serology at population scale: SARS-CoV-2-specific antibody responses in saliva.
- Author
-
Randad PR, Pisanic N, Kruczynski K, Manabe YC, Thomas D, Pekosz A, Klein SL, Betenbaugh MJ, Clarke WA, Laeyendecker O, Caturegli PP, Larman HB, Detrick B, Fairley JK, Sherman AC, Rouphael N, Edupuganti S, Granger DA, Granger SW, Collins M, and Heaney CD
- Abstract
Non-invasive SARS-CoV-2 antibody testing is urgently needed to estimate the incidence and prevalence of SARS-CoV-2 infection at the general population level. Precise knowledge of population immunity could allow government bodies to make informed decisions about how and when to relax stay-at-home directives and to reopen the economy. We hypothesized that salivary antibodies to SARS-CoV-2 could serve as a non-invasive alternative to serological testing for widespread monitoring of SARS-CoV-2 infection throughout the population. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology and tested 167 saliva and 324 serum samples, including 134 and 118 negative saliva and serum samples, respectively, collected before the COVID-19 pandemic, and 33 saliva and 206 serum samples from participants with RT-PCR-confirmed SARS-CoV-2 infection. We evaluated the correlation of results obtained in saliva vs. serum and determined the sensitivity and specificity for each diagnostic media, stratified by antibody isotype, for detection of SARS-CoV-2 infection based on COVID-19 case designation for all specimens. Matched serum and saliva SARS-CoV-2 antigen-specific IgG responses were significantly correlated. Within the 10-plex SARS-CoV-2 panel, the salivary anti-nucleocapsid (N) protein IgG response resulted in the highest sensitivity for detecting prior SARS-CoV-2 infection (100% sensitivity at ≥10 days post-SARS-CoV-2 symptom onset). The salivary anti-receptor binding domain (RBD) IgG response resulted in 100% specificity. Among individuals with SARS-CoV-2 infection confirmed with RT-PCR, the temporal kinetics of IgG, IgA, and IgM in saliva were consistent with those observed in serum. SARS-CoV-2 appears to trigger a humoral immune response resulting in the almost simultaneous rise of IgG, IgM and IgA levels both in serum and in saliva, mirroring responses consistent with the stimulation of existing, cross-reactive B cells. SARS-CoV-2 antibody testing in saliva can play a critically important role in large-scale "sero"-surveillance to address key public health priorities and guide policy and decision-making for COVID-19., Competing Interests: Conflict of interest In the interest of full disclosure, D.A.G. is founder and Chief Scientific and Strategy Advisor at Salimetrics, LLC and Salivabio, LLC and these relationships are managed by the policies of the committees on conflict of interest at Johns Hopkins School of Medicine and the University of California at Irvine. N.R. received funds from Sanofi Pasteur, Quidel, Merck and Pfizer.
- Published
- 2020
- Full Text
- View/download PDF
40. Effects of Child and Maternal Histo-Blood Group Antigen Status on Symptomatic and Asymptomatic Enteric Infections in Early Childhood.
- Author
-
Colston JM, Francois R, Pisanic N, Peñataro Yori P, McCormick BJJ, Olortegui MP, Gazi MA, Svensen E, Ahmed MMM, Mduma E, Liu J, Houpt ER, Klapheke R, Schwarz JW, Atmar RL, Black RE, and Kosek MN
- Subjects
- Asymptomatic Infections, Child, Preschool, Diarrhea immunology, Diarrhea microbiology, Diarrhea virology, Feces microbiology, Feces virology, Female, Gastrointestinal Diseases microbiology, Gastrointestinal Diseases virology, Humans, Male, Mother-Child Relations, Mothers, Risk Factors, Blood Group Antigens immunology, Gastrointestinal Diseases immunology
- Abstract
Background: Histo-blood group antigens (HBGAs) such as fucosyltransferase (FUT)2 and 3 may act as innate host factors that differentially influence susceptibility of individuals and their offspring to pediatric enteric infections., Methods: In 3 community-based birth cohorts, FUT2 and FUT3 statuses were ascertained for mother-child dyads. Quantitative polymerase chain reaction panels tested 3663 diarrheal and 18 148 asymptomatic stool samples for 29 enteropathogens. Cumulative diarrhea and infection incidence were compared by child (n = 520) and mothers' (n = 519) HBGA status and hazard ratios (HRs) derived for all-cause diarrhea and specific enteropathogens., Results: Children of secretor (FUT2 positive) mothers had a 38% increased adjusted risk of all-cause diarrhea (HR = 1.38; 95% confidence interval (CI), 1.15-1.66) and significantly reduced time to first diarrheal episode. Child FUT2 and FUT3 positivity reduced the risk for all-cause diarrhea by 29% (HR = 0.81; 95% CI, 0.71-0.93) and 27% (HR = 0.83; 95% CI, 0.74-0.92), respectively. Strong associations between HBGAs and pathogen-specific infection and diarrhea were observed, particularly for noroviruses, rotaviruses, enterotoxigenic Escherichia coli, and Campylobacter jejuni/coli., Conclusions: Histo-blood group antigens affect incidence of all-cause diarrhea and enteric infections at magnitudes comparable to many common disease control interventions. Studies measuring impacts of interventions on childhood enteric disease should account for both child and mothers' HBGA status., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Published
- 2019
- Full Text
- View/download PDF
41. Minimally Invasive Saliva Testing to Monitor Norovirus Infection in Community Settings.
- Author
-
Pisanic N, Ballard SB, Colquechagua FD, François R, Exum N, Yori PP, Schwab KJ, Granger DA, Detrick B, Olortegui MP, Mayta H, Sánchez GJ, Gilman RH, Heaney CD, Vinjé J, and Kosek MN
- Subjects
- Antibodies, Viral immunology, Caliciviridae Infections epidemiology, Caliciviridae Infections virology, Case-Control Studies, Child, Preschool, Feces virology, Humans, Immunoglobulin G immunology, Norovirus genetics, Norovirus immunology, Peru epidemiology, ROC Curve, Reverse Transcriptase Polymerase Chain Reaction, Saliva immunology, Sensitivity and Specificity, Caliciviridae Infections diagnosis, Saliva virology
- Abstract
Background: Norovirus is a leading cause of acute gastroenteritis worldwide. Routine norovirus diagnosis requires stool collection. The goal of this study was to develop and validate a noninvasive method to diagnose norovirus to complement stool diagnostics and to facilitate studies on transmission., Methods: A multiplex immunoassay to measure salivary immunoglobulin G (IgG) responses to 5 common norovirus genotypes (GI.1, GII.2, GII.4, GII.6, and GII.17) was developed. The assay was validated using acute and convalescent saliva samples collected from Peruvian children <5 years of age with polymerase chain reaction (PCR)-diagnosed norovirus infections (n = 175) and controls (n = 32). The assay sensitivity and specificity were calculated to determine infection status based on fold rise of salivary norovirus genotype-specific IgG using norovirus genotype from stool as reference., Results: The salivary assay detected recent norovirus infections and correctly assigned the infecting genotype. Sensitivity was 71% and specificity was 96% across the evaluated genotypes compared to PCR-diagnosed norovirus infection., Conclusions: This saliva-based assay will be a useful tool to monitor norovirus transmission in high-risk settings such as daycare centers or hospitals. Cross-reactivity is limited between the tested genotypes, which represent the most commonly circulating genotypes., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Published
- 2019
- Full Text
- View/download PDF
42. Probable transmission of hepatitis E virus (HEV) via transfusion in the United States.
- Author
-
Ticehurst JR, Pisanic N, Forman MS, Ordak C, Heaney CD, Ong E, Linnen JM, Ness PM, Guo N, Shan H, and Nelson KE
- Subjects
- Blood Donors, Enzyme-Linked Immunosorbent Assay, Female, Hepatitis E virus genetics, Humans, Male, RNA, Viral genetics, United States, Blood Transfusion statistics & numerical data, Hepatitis E transmission, Hepatitis E virus pathogenicity
- Abstract
Background: Hepatitis E virus (HEV) can inapparently infect blood donors. To assess transfusion transmission of HEV in the United States, which has not been documented, a donor-recipient repository was evaluated., Study Design and Methods: To identify donations that contained HEV RNA and were linked to patient-recipients with antibody evidence of HEV exposure, we assayed samples from the Retrovirus Epidemiology Donor Study (REDS) Allogeneic Donor and Recipient repository that represents 13,201 linked donations and 3384 transfused patients. Posttransfusion samples, determined to contain IgG anti-HEV by enzyme-linked immunosorbent assay, were reassayed along with corresponding pretransfusion samples for seroconversion (incident exposure) or at least fourfold IgG anti-HEV increase (reexposure). HEV-exposed patients were linked to donations in which HEV RNA was then detected by reverse-transcription quantitative polymerase chain reaction, confirmed by transcription-mediated amplification, and phylogenetically analyzed as subgenomic cDNA sequences., Results: Among all patients, 19 of 1036 (1.8%) who had IgG anti-HEV before transfusion were reexposed; 40 of 2348 (1.7%) without pretransfusion IgG anti-HEV seroconverted. These 59 patients were linked to 257 donations, 1 of which was positive by reverse-transcription quantitative polymerase chain reaction and transcription-mediated amplification. Plasma from this donation contained 5.5 log IU/mL of HEV RNA that grouped with HEV genotype 3, clade 3abchij. The patient-recipient of RBCs from this donation had a greater than eightfold IgG increase; however, clinical data are unavailable., Conclusions: This is the first report of probable HEV transmission via transfusion in the United States, although it has been frequently observed in Europe and Japan. Additional data on the magnitude of the risk in the United States are needed., (© 2019 AABB.)
- Published
- 2019
- Full Text
- View/download PDF
43. Face Mask Use and Persistence of Livestock-associated Staphylococcus aureus Nasal Carriage among Industrial Hog Operation Workers and Household Contacts, USA.
- Author
-
Nadimpalli ML, Stewart JR, Pierce E, Pisanic N, Love DC, Hall D, Larsen J, Carroll KC, Tekle T, Perl TM, and Heaney CD
- Subjects
- Adolescent, Adult, Animal Husbandry, Animals, Drug Resistance, Bacterial, Family Characteristics, Female, Humans, Male, Methicillin-Resistant Staphylococcus aureus isolation & purification, Middle Aged, North Carolina epidemiology, Occupational Exposure prevention & control, Protective Clothing, Staphylococcal Infections epidemiology, Swine, Tetracycline pharmacology, Masks, Nasal Cavity microbiology, Occupational Exposure statistics & numerical data, Staphylococcus aureus isolation & purification
- Abstract
Background: Industrial hog operation (IHO) workers may persistently carry antibiotic-resistant, livestock-associated Staphylococcus aureus in their nasal cavities. It is unclear whether IHO work activities can alter IHO workers' and their household members' exposure to these bacteria., Objective: Our objective was to investigate the relationship of IHO work activities with persistence of antibiotic-resistant, livestock-associated S. aureus nasal carriage among IHO workers and their household members., Methods: At biweekly intervals over 4 months, IHO workers and their household members completed questionnaires and provided nasal swabs that were assessed for S. aureus , multidrug-resistant S. aureus (MDRSA), and livestock-associated markers (tetracycline resistance, scn absence, spa type). We examined the association between transient and habitual IHO work activities and S. aureus nasal carriage outcomes., Results: One hundred one IHO workers and 79 household members completed 1,456 study visits. Face mask use (each 25% increase) was associated with reduced odds of nasal carriage of MDRSA (odds ratio [OR]: 0.65 [95% confidence interval (CI): 0.46, 0.92], tetracycline-resistant S. aureus [OR = 0.74 (95% CI: 0.56, 0.97)], and S. aureus clonal complex (CC) 398/CC9 [OR = 0.77 (95% CI: 0.60, 0.99)]. IHO workers who ever (vs. never) gave pigs injections had higher odds of these outcomes. Among household members, living with an IHO worker who consistently ([Formula: see text] of the time) versus sometimes or never used a face mask was associated with reduced odds of carrying scn -negative S. aureus , tetracycline-resistant S. aureus , and S. aureus CC398/CC9 (OR range: 0.12-0.20, all [Formula: see text]), and consistent IHO worker coveralls use was associated with reduced odds of household member MDRSA carriage only. Living with an IHO worker who habitually had contact with [Formula: see text] hogs (vs. [Formula: see text]) was associated with higher odds of household member livestock-associated S. aureus carriage., Conclusions: Consistent face mask use was associated with reduced exposure to antibiotic-resistant, livestock-associated S. aureus among IHO workers and their household members. https://doi.org/10.1289/EHP3453.
- Published
- 2018
- Full Text
- View/download PDF
44. Occurrence of Staphylococcus aureus in swine and swine workplace environments on industrial and antibiotic-free hog operations in North Carolina, USA: A One Health pilot study.
- Author
-
Davis MF, Pisanic N, Rhodes SM, Brown A, Keller H, Nadimpalli M, Christ A, Ludwig S, Ordak C, Spicer K, Love DC, Larsen J, Wright A, Blacklin S, Flowers B, Stewart J, Sexton KG, Rule AM, and Heaney CD
- Subjects
- Animal Husbandry, Animals, Anti-Bacterial Agents, Humans, North Carolina, Occupational Exposure, Pilot Projects, Staphylococcus aureus, Swine metabolism, Methicillin-Resistant Staphylococcus aureus isolation & purification, One Health, Staphylococcal Infections veterinary, Workplace
- Abstract
Occupational exposure to swine has been associated with increased Staphylococcus aureus carriage, including antimicrobial-resistant strains, and increased risk of infections. To characterize animal and environmental routes of worker exposure, we optimized methods to identify S. aureus on operations that raise swine in confinement with antibiotics (industrial hog operation: IHO) versus on pasture without antibiotics (antibiotic-free hog operation: AFHO). We associated findings from tested swine and environmental samples with those from personal inhalable air samplers on worker surrogates at one IHO and three AFHOs in North Carolina using a new One Health approach. We determined swine S. aureus carriage status by collecting swab samples from multiple anatomical sites, and we determined environmental positivity for airborne bioaerosols with inhalable and impinger samplers and a single-stage impactor (ambient air) cross-sectionally. All samples were analyzed for S. aureus, and isolates were tested for antimicrobial susceptibility, absence of scn (livestock marker), and spa type. Seventeen of twenty (85%) swine sampled at the one IHO carried S. aureus at >1 anatomical sites compared to none of 30 (0%) swine sampled at the three AFHOs. All S. aureus isolates recovered from IHO swine and air samples were scn negative and spa type t337; almost all isolates (62/63) were multidrug resistant. S. aureus was recovered from eight of 14 (67%) ambient air and two (100%) worker surrogate personal air samples at the one IHO, whereas no S. aureus isolates were recovered from 19 ambient and six personal air samples at the three AFHOs. Personal worker surrogate inhalable sample findings were consistent with both swine and ambient air data, indicating the potential for workplace exposure. IHO swine and the one IHO environment could be a source of potential pathogen exposure to workers, as supported by the detection of multidrug-resistant S. aureus (MDRSA) with livestock-associated spa type t337 among swine, worker surrogate personal air samplers and environmental air samples at the one IHO but none of the three AFHOs sampled in this study. Concurrent sampling of swine, personal swine worker surrogate air, and ambient airborne dust demonstrated that IHO workers may be exposed through both direct (animal contact) and indirect (airborne) routes of transmission. Investigation of the effectiveness of contact and respiratory protections is warranted to prevent IHO worker exposure to multidrug-resistant livestock-associated S. aureus and other pathogens., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
45. The other Campylobacters: Not innocent bystanders in endemic diarrhea and dysentery in children in low-income settings.
- Author
-
François R, Yori PP, Rouhani S, Siguas Salas M, Paredes Olortegui M, Rengifo Trigoso D, Pisanic N, Burga R, Meza R, Meza Sanchez G, Gregory MJ, Houpt ER, Platts-Mills JA, and Kosek MN
- Subjects
- Biomarkers analysis, Campylobacter classification, Campylobacter genetics, Campylobacter isolation & purification, Campylobacter Infections diagnosis, Campylobacter coli pathogenicity, Campylobacter jejuni pathogenicity, Case-Control Studies, Child, Preschool, Cohort Studies, Coinfection diagnosis, Coinfection microbiology, DNA, Bacterial analysis, Dysentery, Bacillary diagnosis, Dysentery, Bacillary epidemiology, Feces microbiology, Female, Humans, Infant, Infant, Newborn, Intestines injuries, Intestines microbiology, Male, Odds Ratio, Peru epidemiology, Poverty, Prevalence, RNA, Ribosomal, 16S genetics, Shigella genetics, Shigella isolation & purification, Shigella pathogenicity, Campylobacter pathogenicity, Campylobacter Infections epidemiology, Campylobacter Infections microbiology, Diarrhea epidemiology, Diarrhea microbiology, Dysentery epidemiology, Dysentery microbiology
- Abstract
Background: Campylobacter is one of the main causes of gastroenteritis worldwide. Most of the current knowledge about the epidemiology of this food-borne infection concerns two species, C. coli and C. jejuni. Recent studies conducted in developing countries and using novel diagnostic techniques have generated evidence of the increasing burden and importance of other Campylobacter species, i.e. non-C. coli/jejuni. We performed a nested case-control study to compare the prevalence of C. coli/jejuni and other Campylobacter in children with clinical dysentery and severe diarrhea as well as without diarrhea to better understand the clinical importance of infections with Campylobacter species other than C. coli/jejuni., Methodology/principal Findings: Our nested case-control study of 439 stool samples included dysenteric stools, stools collected during severe diarrhea episodes, and asymptomatic stools which were systematically selected to be representative of clinical phenotypes from 9,160 stools collected during a birth cohort study of 201 children followed until two years of age. Other Campylobacter accounted for 76.4% of the 216 Campylobacter detections by qPCR and were more prevalent than C. coli/jejuni across all clinical groups. Other Campylobacter were also more prevalent than C. coli/jejuni across all age groups, with older children bearing a higher burden of other Campylobacter. Biomarkers of intestinal inflammation and injury (methylene blue, fecal occult test, myeloperoxidase or MPO) showed a strong association with dysentery, but mixed results with infection. MPO levels were generally higher among children infected with C. coli/jejuni, but Shigella-infected children suffering from dysentery recorded the highest levels (26,224 ng/mL); the lowest levels (10,625 ng/mL) were among asymptomatic children infected with other Campylobacter. Adjusting for age, sex, and Shigella infection, dysentery was significantly associated with C. coli/jejuni but not with other Campylobacter, whereas severe diarrhea was significantly associated with both C. coli/jejuni and other Campylobacter. Compared to asymptomatic children, children suffering from dysentery had a 14.6 odds of C. coli/jejuni infection (p-value < 0.001, 95% CI 5.5-38.7) but were equally likely to have other Campylobacter infections-odds ratio of 1.3 (0.434, 0.7-2.4). Children suffering from severe diarrhea were more likely than asymptomatic children to test positive for both C. coli/jejuni and other Campylobacter-OR of 2.8 (0.034, 1.1-7.1) and 1.9 (0.018, 1.1-3.1), respectively. Compared to the Campylobacter-free group, the odds of all diarrhea given C. coli/jejuni infection and other Campylobacter infection were 8.8 (<0.001, 3.0-25.7) and 2.4 (0.002, 1.4-4.2), respectively. Eliminating other Campylobacter in this population would eliminate 24.9% of the diarrhea cases, which is almost twice the population attributable fraction of 15.1% due to C. coli/jejuni., Conclusions/significance: Eighty-seven percent of the dysentery and 59.5% of the severe diarrhea samples were positive for Campylobacter, Shigella, or both, emphasizing the importance of targeting these pathogens to limit the impact of dysentery and severe diarrhea in children. Notably, the higher prevalence of other Campylobacter compared to C. coli/jejuni, their increasing burden during early childhood, and their association with severe diarrhea highlight the importance of these non-C. coli/jejuni Campylobacter species and suggest a need to clarify their importance in the etiology of clinical disease across different epidemiological contexts.
- Published
- 2018
- Full Text
- View/download PDF
46. Development of an oral fluid immunoassay to assess past and recent hepatitis E virus (HEV) infection.
- Author
-
Pisanic N, Rahman A, Saha SK, Labrique AB, Nelson KE, Granger DA, Granger SW, Detrick B, and Heaney CD
- Subjects
- Adult, Bangladesh epidemiology, Biomarkers analysis, Case-Control Studies, Enzyme-Linked Immunosorbent Assay, Female, Hepatitis E epidemiology, Hepatitis E immunology, Hepatitis E virology, Humans, Immunoglobulin G blood, Immunoglobulin M blood, Male, Middle Aged, Predictive Value of Tests, Prevalence, Reproducibility of Results, Serologic Tests, Young Adult, Antibodies, Viral analysis, Hepatitis E diagnosis, Hepatitis E virus immunology, Immunoassay methods, Immunoglobulin A analysis, Immunoglobulin G analysis, Saliva virology
- Abstract
Background: Hepatitis E virus (HEV) infection causes significant morbidity and mortality worldwide, particularly among pregnant women. In clinical settings blood-based testing protocols are commonly used to diagnose HEV infection, but in community settings such invasive sampling can hinder study participation and limit discovery of the ecology and natural history of HEV infection. Oral fluid is a non-invasive biospecimen that can harbor pathogen-specific antibodies and has the potential to replace blood-based testing protocols., Objectives: To develop an immunoassay to assess past and recent HEV infection that uses oral fluid instead of serum or plasma., Methods: The assay was validated using paired oral fluid and serum samples collected from 141 patients who presented either with (n=76) or without (n=65) symptoms of acute viral hepatitis at a clinical diagnostics center in Dhaka, Bangladesh. The sensitivity and specificity of the oral fluid-based immunoassay for HEV IgG (past HEV infection) and HEV IgA (recent HEV infection) antibodies was calculated in reference to Wantai's (Beijing Wantai) serum-based HEV enzyme-linked immunosorbent assay (ELISA) kits for IgG and IgM antibodies, respectively., Results: The sensitivity and specificity of the oral fluid-based immunoassay for HEV-IgG antibodies were 98.7% and 98.4%, respectively. The sensitivity and specificity of the oral fluid-based immunoassay for HEV IgA were 89.5% and 98.3%, respectively., Conclusions: The high concordance of our non-invasive oral fluid-based immunoassays (HEV IgG and HEV IgA) with commercial high-performance serum HEV ELISA kits (IgG and IgM) means that population-based surveillance of past and recent HEV infection could be expanded to improve understanding of its ecology and natural history., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
47. The Prevalence of Antibiotic-Resistant Staphylococcus aureus Nasal Carriage among Industrial Hog Operation Workers, Community Residents, and Children Living in Their Households: North Carolina, USA.
- Author
-
Hatcher SM, Rhodes SM, Stewart JR, Silbergeld E, Pisanic N, Larsen J, Jiang S, Krosche A, Hall D, Carroll KC, and Heaney CD
- Subjects
- Adult, Child, Humans, North Carolina epidemiology, Occupational Exposure statistics & numerical data, Prevalence, Staphylococcal Infections, Animal Husbandry statistics & numerical data, Drug Resistance, Bacterial genetics, Environmental Exposure statistics & numerical data, Methicillin-Resistant Staphylococcus aureus genetics
- Abstract
Background: Antibiotic use in industrial hog operations (IHOs) can support the emergence of antibiotic-resistant (ABR) Staphylococcus aureus . The extent of ABR S. aureus exposure in IHO workers and children living in their households remains unclear., Objective: We investigated ABR S. aureus nasal carriage prevalence among adults with versus without occupational exposure to IHOs and among children living in their households., Methods: In total, 198 IHO worker-child household pairs and 202 community referent (CR) adult-child household pairs completed a questionnaire and provided a nasal swab which was analyzed for S. aureus, methicillin-resistant S. aureus (MRSA), multidrug-resistant S. aureus (MDRSA), absence of scn (putative marker of livestock association), and spa type., Results: S. aureus nasal carriage prevalence was higher among IHO (53%) compared with CR (31%) adults [adjusted prevalence ratio (aPR): 1.40; 95% confidence interval (CI): 1.07, 1.83], but MRSA nasal carriage prevalence was uncommon (2-3%) in IHO and CR adults. MDRSA nasal carriage prevalence was similar among IHO workers and CR adults (12% vs. 8%; aPR: 1.14; 95% CI: 0.56, 2.29). Nasal carriage prevalence was higher among IHO compared with CR children for S. aureus (49% vs. 31%; aPR: 1.50; 95% CI: 1.13, 1.99), MRSA (14% vs. 6%; aPR: 2.37; 95% CI: 1.14, 4.92), and MDRSA (23% vs. 8%; aPR: 2.64; 95% CI: 1.47, 4.75). We also found suggestive evidence of a higher prevalence of S. aureus , MRSA, and MDRSA among children living with an IHO worker who did versus did not report taking personal protective equipment (PPE) home from the IHO. Livestock-associated S. aureus nasal carriage predominated among IHO workers., Conclusion: Our findings support the importance of further research on the prevalence and potential sources of exposure to ABR S. aureus among children living with IHO workers.
- Published
- 2017
- Full Text
- View/download PDF
48. Livestock-Associated, Antibiotic-Resistant Staphylococcus aureus Nasal Carriage and Recent Skin and Soft Tissue Infection among Industrial Hog Operation Workers.
- Author
-
Nadimpalli M, Stewart JR, Pierce E, Pisanic N, Love DC, Hall D, Larsen J, Carroll KC, Tekle T, Perl TM, and Heaney CD
- Subjects
- Adult, Animals, Family Characteristics, Female, Humans, Male, Prevalence, Risk Factors, Soft Tissue Infections epidemiology, Soft Tissue Infections microbiology, Staphylococcal Infections microbiology, Swine, Tetracycline pharmacology, Industry, Livestock microbiology, Methicillin-Resistant Staphylococcus aureus physiology, Nose microbiology, Occupational Exposure statistics & numerical data, Skin microbiology, Staphylococcal Infections epidemiology
- Abstract
Swine production work is a risk factor for nasal carriage of livestock-associated (LA-) Staphylococcus aureus and also for skin and soft tissue infection (SSTI). However, whether LA-S. aureus nasal carriage is associated with increased risk of SSTI remains unclear. We aimed to examine S. aureus nasal carriage and recent (≤3 months prior to enrollment) SSTI symptoms among industrial hog operation (IHO) workers and their household contacts. IHO workers and their household contacts provided a nasal swab and responded to a questionnaire assessing self-reported personal and occupational exposures and recent SSTI symptoms. Nasal swabs were analyzed for S. aureus, including methicillin-resistant S. aureus (MRSA), multidrug-resistant-S. aureus (MDRSA), absence of scn (livestock association), and spa type. S. aureus with at least one indicator of LA was observed among 19% of 103 IHO workers and 6% of 80 household members. Prevalence of recent SSTI was 6% among IHO workers and 11% among 54 minor household members (0/26 adult household members reported SSTI). Among IHO workers, nasal carriers of MDRSA and scn-negative S. aureus were 8.8 (95% CI: 1.8, 43.9) and 5.1 (95% CI: 1.2, 22.2) times as likely to report recent SSTI as non-carriers, respectively. In one household, both an IHO worker and child reported recent SSTI and carried the same S. aureus spa type (t4976) intranasally. Prevalence of scn-negative S. aureus (PR: 5.0, 95% CI: 1.2, 21.4) was elevated among IHO workers who reported never versus always wearing a face mask at work. Although few SSTI were reported, this study of IHO workers and their household contacts is the first to characterize a relation between nasal carriage of antibiotic-resistant LA-S. aureus and SSTI. The direction and temporality of this relation and IHO workers' use of face masks to prevent nasal carriage of these bacteria warrant further investigation., Competing Interests: DH is Program Manager and co-founder of the Rural Empowerment Association for Community Help (REACH), a 501(c)(3) not for profit organization located in Duplin County, North Carolina. DH is a complainant in a Title VI administrative complaint against the North Carolina Department of Environmental Quality related to its statewide hog operation lagoon and sprayfield liquid waste management permitting system. There is no potential personal financial gain from this administrative complaint, which is not directly related to the research described in this manuscript and is not a lawsuit or litigation. The other authors declare they have no actual or potential competing financial interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Published
- 2016
- Full Text
- View/download PDF
49. Use of Pathogen-Specific Antibody Biomarkers to Estimate Waterborne Infections in Population-Based Settings.
- Author
-
Exum NG, Pisanic N, Granger DA, Schwab KJ, Detrick B, Kosek M, Egorov AI, Griffin SM, and Heaney CD
- Subjects
- Humans, Incidence, Water Pollution, Waterborne Diseases transmission, Antibodies, Biomarkers blood, Water Microbiology, Waterborne Diseases epidemiology
- Abstract
Purpose of Review: This review discusses the utility of pathogen-specific antibody biomarkers for improving estimates of the population burden of waterborne infections, assessing the fraction of infections that can be prevented by specific water treatments, and understanding transmission routes and the natural history and ecology of disease in different populations (including asymptomatic infection rates)., Recent Findings: We review recent literature on the application of pathogen-specific antibody response data to estimate incidence and prevalence of acute infections and their utility to assess the contributions of waterborne transmission pathways. Advantages and technical challenges associated with the use of serum versus minimally invasive salivary antibody biomarkers in cross-sectional and prospective surveys are discussed. We highlight recent advances and challenges and outline future directions for research, development, and application of antibody-based and other immunological biomarkers of waterborne infections.
- Published
- 2016
- Full Text
- View/download PDF
50. Hepatitis E Virus Infection Among Solid Organ Transplant Recipients at a North American Transplant Center.
- Author
-
Sue PK, Pisanic N, Heaney CD, Forman M, Valsamakis A, Jackson AM, Ticehurst JR, Montgomery RA, Schwarz KB, Nelson KE, and Karnsakul W
- Abstract
Background. Autochthonous hepatitis E virus (HEV) infection has been reported in over 200 solid organ transplant (SOT) recipients since 2006, yet little is known about the burden of HEV among SOT recipients in North America. We performed a retrospective, cross-sectional study to investigate the prevalence and risk factors associated with HEV infection among SOT recipients at our institution. Methods. Children and adults (n = 311) who received allografts between 1988 and 2012 at the Johns Hopkins Hospital were assessed for evidence of HEV infection by testing posttransplantation serum samples for HEV antibody by enzyme immunoassay and HEV RNA by reverse transcription quantitative polymerase chain reaction. Individuals with evidence of posttransplant HEV infection (presence of anti-HEV immunoglobulin [Ig]M antibody, anti-HEV IgG seroconversion, or HEV RNA) were compared with individuals without evidence of infection and assessed for risk factors associated with infection. Results. Twelve individuals (4%) developed posttransplant HEV infection. Posttransplant HEV infection was associated with an increased risk for graft rejection (odds ratio, 14.2; P = .03). No individuals developed chronic infection. Conclusions. Solid organ transplant recipients in the United States are at risk for posttransplant HEV infection. Further studies are needed to characterize environmental risk factors and the risk of HEV infection after SOT in North America.
- Published
- 2016
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.