Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-6 (of 6 Records) |
Query Trace: Mayfield K[original query] |
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Key considerations to improve the normalization, interpretation and reproducibility of morbidity data in mammalian models of viral disease
Belser JA , Kieran TJ , Mitchell ZA , Sun X , Mayfield K , Tumpey TM , Spengler JR , Maines TR . Dis Model Mech 2024 17 (3) Viral pathogenesis and therapeutic screening studies that utilize small mammalian models rely on the accurate quantification and interpretation of morbidity measurements, such as weight and body temperature, which can vary depending on the model, agent and/or experimental design used. As a result, morbidity-related data are frequently normalized within and across screening studies to aid with their interpretation. However, such data normalization can be performed in a variety of ways, leading to differences in conclusions drawn and making comparisons between studies challenging. Here, we discuss variability in the normalization, interpretation, and presentation of morbidity measurements for four model species frequently used to study a diverse range of human viral pathogens - mice, hamsters, guinea pigs and ferrets. We also analyze findings aggregated from influenza A virus-infected ferrets to contextualize this discussion. We focus on serially collected weight and temperature data to illustrate how the conclusions drawn from this information can vary depending on how raw data are collected, normalized and measured. Taken together, this work supports continued efforts in understanding how normalization affects the interpretation of morbidity data and highlights best practices to improve the interpretation and utility of these findings for extrapolation to public health contexts. |
Using regional sero-epidemiology SARS-CoV-2 Anti-S antibodies in the Dominican Republic to inform targeted public health response
Mario Martin B , Cadavid Restrepo A , Mayfield HJ , Then Paulino C , De St Aubin M , Duke W , Jarolim P , Zielinski Gutiérrez E , Skewes Ramm R , Dumas D , Garnier S , Etienne MC , Peña F , Abdalla G , Lopez B , de la Cruz L , Henríquez B , Baldwin M , Sartorius B , Kucharski A , Nilles EJ , Lau CL . Trop Med Infect Dis 2023 8 (11) Incidence of COVID-19 has been associated with sociodemographic factors. We investigated variations in SARS-CoV-2 seroprevalence at sub-national levels in the Dominican Republic and assessed potential factors influencing variation in regional-level seroprevalence. Data were collected in a three-stage cross-sectional national serosurvey from June to October 2021. Seroprevalence of antibodies against the SARS-CoV-2 spike protein (anti-S) was estimated and adjusted for selection probability, age, and sex. Multilevel logistic regression was used to estimate the effect of covariates on seropositivity for anti-S and correlates of 80% protection (PT(80)) against symptomatic infection for the ancestral and Delta strains. A total of 6683 participants from 134 clusters in all 10 regions were enrolled. Anti-S, PT80 for the ancestral and Delta strains odds ratio varied across regions, Enriquillo presented significant higher odds for all outcomes compared with Yuma. Compared to being unvaccinated, receiving ≥2 doses of COVID-19 vaccine was associated with a significantly higher odds of anti-S positivity (OR 85.94, [10.95-674.33]) and PT(80) for the ancestral (OR 4.78, [2.15-10.62]) and Delta strains (OR 3.08, [1.57-9.65]) nationally and also for each region. Our results can help inform regional-level public health response, such as strategies to increase vaccination coverage in areas with low population immunity against currently circulating strains. |
SARS-CoV-2 seroprevalence, cumulative infections, and immunity to symptomatic infection - A multistage national household survey and modelling study, Dominican Republic, June-October 2021.
Nilles EJ , Paulino CT , de St Aubin M , Restrepo AC , Mayfield H , Dumas D , Finch E , Garnier S , Etienne MC , Iselin L , Duke W , Jarolim P , Oasan T , Yu J , Wan H , Peña F , Iihoshi N , Abdalla G , Lopez B , Cruz L , Henríquez B , Espinosa-Bode A , Puello YC , Durski K , Baldwin M , Baez AA , Merchant RC , Barouch DH , Skewes-Ramm R , Gutiérrez EZ , Kucharski A , Lau CL . Lancet Reg Health Am 2022 16 100390 BACKGROUND: Population-level SARS-CoV-2 immunological protection is poorly understood but can guide vaccination and non-pharmaceutical intervention priorities. Our objective was to characterise cumulative infections and immunological protection in the Dominican Republic. METHODS: Household members ≥5 years were enrolled in a three-stage national household cluster serosurvey in the Dominican Republic. We measured pan-immunoglobulin antibodies against the SARS-CoV-2 spike (anti-S) and nucleocapsid glycoproteins, and pseudovirus neutralising activity against the ancestral and B.1.617.2 (Delta) strains. Seroprevalence and cumulative prior infections were weighted and adjusted for assay performance and seroreversion. Binary classification machine learning methods and pseudovirus neutralising correlates of protection were used to estimate 50% and 80% protection against symptomatic infection. FINDINGS: Between 30 Jun and 12 Oct 2021 we enrolled 6683 individuals from 3832 households. We estimate that 85.0% (CI 82.1-88.0) of the ≥5 years population had been immunologically exposed and 77.5% (CI 71.3-83) had been previously infected. Protective immunity sufficient to provide at least 50% protection against symptomatic SARS-CoV-2 infection was estimated in 78.1% (CI 74.3-82) and 66.3% (CI 62.8-70) of the population for the ancestral and Delta strains respectively. Younger (5-14 years, OR 0.47 [CI 0.36-0.61]) and older (≥75-years, 0.40 [CI 0.28-0.56]) age, working outdoors (0.53 [0.39-0.73]), smoking (0.66 [0.52-0.84]), urban setting (1.30 [1.14-1.49]), and three vs no vaccine doses (18.41 [10.69-35.04]) were associated with 50% protection against the ancestral strain. INTERPRETATION: Cumulative infections substantially exceeded prior estimates and overall immunological exposure was high. After controlling for confounders, markedly lower immunological protection was observed to the ancestral and Delta strains across certain subgroups, findings that can guide public health interventions and may be generalisable to other settings and viral strains. FUNDING: This study was funded by the US CDC. |
Developmental Monitoring and Referral for Low-Income Children Served by WIC: Program Development and Implementation Outcomes
Farmer JE , Falk LW , Clark MJ , Mayfield WA , Green KK . Matern Child Health J 2022 26 (2) 230-241 OBJECTIVE: To develop, implement, and assess implementation outcomes for a developmental monitoring and referral program for children in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). METHODS: Based on Centers for Disease Control and Prevention's Learn the Signs. Act Early. campaign, the program was developed and replicated in two phases at 20 demographically diverse WIC clinics in eastern Missouri. Parents were asked to complete developmental milestone checklists for their children, ages 2months to 4years, during WIC eligibility recertification visits; WIC staff referred children with potential concerns to their healthcare providers for developmental screening. WIC staff surveys and focus groups were used to assess initial implementation outcomes. RESULTS: In both phases, all surveyed staff (n=46) agreed the program was easy to use. Most (80%) agreed that checklists fit easily into clinic workflow and required5min to complete. Staff (55%) indicated using checklists with75% of their clients. 92% or more reported referring one or more children with potential developmental concerns. According to 80% of staff, parents indicated checklists helped them learn about development and planned to share them with healthcare providers. During thesecond phase, 18 of 20 staff surveyed indicated the program helped them learn when to refer children and how to support parents, and 19 felt the program promoted healthy development. Focus groups supported survey findings, and all clinics planned to sustain the program. CONCLUSIONS: Initial implementation outcomes supported this approach to developmental monitoring and referral in WIC. The program has potential to help low-income parents identify possible concerns and access support. |
A three dose intramuscular schedule of anthrax vaccine adsorbed generates sustained humoral and cellular immune responses to protective antigen and provides long term protection against inhalation anthrax in rhesus macaques
Quinn CP , Sabourin CL , Niemuth NA , Li H , Semenova VA , Rudge TL , Mayfield HJ , Schiffer J , Mittler RS , Ibegbu CC , Wrammert J , Ahmed R , Brys AM , Hunt RE , Levesque D , Estep JE , Barnewall RE , Robinson DM , Plikaytis BD , Marano N . Clin Vaccine Immunol 2012 19 (11) 1730-45 A 3 dose (0, 1, 6 months) intramuscular (3-IM) priming series of a human dose (HuAVA) and dilutions up to 1:10 of anthrax vaccine adsorbed (AVA) provided statistically significant levels of protection (60-100%) against inhalation anthrax for up to 4 years in rhesus macaques.Serum anti-protective antigen (PA) IgG and lethal toxin neutralization activity (TNA) were detectable following a single injection of HuAVA or 1:5 AVA, or two injections of diluted vaccine (1:10, 1:20, 1:40 AVA). Anti-PA and TNA were highly correlated (overall r(2) = 0.89 for log(10) transformed data). Peak responses were at 6.5 months (mo). In general, with the exception of animals receiving 1:40 AVA, serum anti-PA and TNA responses remained significantly above control levels at 28.5mo (last time point measured for 1:20 AVA) and through 50.5mo in HuAVA, 1:5 and 1:10 AVA groups (p <0.05).PA-specific IFN-gamma and IL-4 CD4(+) cell frequencies and T cell stimulation indices were sustained to 50.5mo (last time point measured). PA-specific memory B cell frequencies were highly variable, but in general were detectable in PBMC by 2mo, significantly above controls by 7mo, and remained detectable in the HuAVA, 1:5 and 1:20 AVA groups to 42mo (last time point measured).HuAVA and diluted AVA elicited a combined Th1/Th2 response and robust immunological priming with sustained production of high avidity PA-specific functional antibody, long term immune cell competence and immunological memory (30mo for 1:20 AVA; 52mo for 1:10 AVA). Vaccinated animals surviving inhalation anthrax developed high magnitude anamnestic anti-PA IgG and TNA responses. |
Vaccination of Rhesus macaques with AVA produces a serum antibody response that effectively neutralizes receptor bound protective antigen in vitro
Clement KH , Rudge TL Jr , Mayfield HJ , Carlton LA , Hester A , Niemuth NA , Sabourin CL , Brys AM , Quinn CP . Clin Vaccine Immunol 2010 17 (11) 1753-62 Anthrax toxin (ATx) is comprised of binary exotoxins lethal toxin (LTx) and edema toxin (ETx). They have separate effector proteins (edema factor (EF) or lethal factor (LF)) and share the common binding protein Protective Antigen (PA). PA is the primary immunogen in current licensed vaccine "Anthrax Vaccine Adsorbed" (AVA, Biothrax(R)). AVA confers protective immunity by stimulating production of ATx neutralizing antibodies, which could block the intoxication process at several steps (binding of PA to target cells surface, furin cleavage, toxin complex formation, and binding/translocation of ATx into the cell. To evaluate ATx neutralization by anti-AVA antibodies, we developed two low-temperature LTx neutralization activity (TNA) assays that distinguish antibody blocking before and after binding of PA to target cells (non-complexed (NC) and receptor-bound (RB) TNAs). These assays were used to investigate anti-PA antibody responses in AVA-vaccinated Rhesus macaques (Macaca mulatta) that survived aerosol challenge with Bacillus anthracis Ames spores. Results showed that macaque anti-AVA sera neutralized LTx in vitro, even when PA was pre-bound to cells. Neutralization titers in surviving versus non-surviving animals and between pre-challenge versus post-challenge activity were highly correlated. These data demonstrate that AVA stimulates a myriad of antibodies that recognize multiple neutralizing epitopes, and confirm that change, loss, or occlusion of epitopes after PA is processed from PA83 to PA63 at the cell surface does not significantly affect in vitro neutralizing efficacy. Furthermore, these data support that full length PA83 monomer is an appropriate immunogen for inclusion in next-generation anthrax vaccines. |
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