65 results on '"Nilles EJ"'
Search Results
2. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter-and intracontinental transmission events
- Author
-
Wong, VK, Baker, S, Pickard, DJ, Parkhill, J, Page, AJ, Feasey, NA, Kingsley, RA, Thomson, NR, Keane, JA, Weill, FX, Edwards, DJ, Hawkey, J, Harris, Mather, AE, Cain, AK, Hadfield, J, Hart, PJ, Thieu, NTV, Klemm, EJ, Glinos, DA, Breiman, RF, Watson, CH, Kariuki, S, Gordon, MA, Heyderman, RS, Okoro, C, Jacobs, J, Lunguya, O, Edmunds, WJ, Msefula, C, Chabalgoity, JA, Kama, M, Jenkins, K, Dutta, S, Marks, F, Campos, J, Thompson, C, Obaro, S, Maclennan, CA, Dolecek, C, Keddy, KH, Smith, AM, Parry, CM, Karkey, A, Mulholland, EK, Campbell, JI, Dongol, S, Basnyat, B, Dufour, M, Bandaranayake, D, Naseri, TT, Singh, SP, Hatta, M, Newton, P, Onsare, RS, Isaia, L, Dance, D, Davong, V, Thwaites, G, Wijedoru, L, Crump, JA, De Pinna, E, Nair, S, Nilles, EJ, Thanh, DP, Turner, P, Soeng, S, Valcanis, M, Powling, J, Dimovski, K, Hogg, G, Farrar, J, Holt, KE, and Dougan, G
- Subjects
3. Good health
3. Images in clinical medicine. Deep sulcus sign.
- Author
-
Sabbar S, Nilles EJ, Sabbar, Saweera, and Nilles, Eric James
- Published
- 2012
- Full Text
- View/download PDF
4. Convergence of SARS-CoV-2 spike antibody levels to a population immune setpoint.
- Author
-
Nilles EJ, Roberts K, de St Aubin M, Mayfield H, Restrepo AC, Garnier S, Abdalla G, Etienne MC, Duke W, Dumas D, Jarolim P, Oasan T, Peña F, Lopez B, Cruz L, Sanchez IM, Murray K, Baldwin M, Skewes-Ramm R, Paulino CT, Lau CL, and Kucharski A
- Abstract
Background: Individual immune responses to SARS-CoV-2 are well-studied, while the combined effect of these responses on population-level immune dynamics remains poorly understood. Given the key role of population immunity on pathogen transmission, delineation of the factors that drive population immune evolution has critical public health implications., Methods: We enrolled individuals 5 years and older selected using a multistage cluster survey approach in the Northwest and Southeast of the Dominican Republic. Paired blood samples were collected mid-pandemic (Aug 2021) and late pandemic (Nov 2022). We measured serum pan-immunoglobulin antibodies against the SARS-CoV-2 spike protein. Generalized Additive Models (GAMs) and random forest models were used to analyze the relationship between changes in antibody levels and various predictor variables. Principal component analysis and partial dependence plots further explored the relationships between predictors and antibody changes., Findings: We found a transformation in the distribution of antibody levels from an irregular to a normalized single peak Gaussian distribution that was driven by titre-dependent boosting. This led to the convergence of antibody levels around a common immune setpoint, irrespective of baseline titres and vaccination profile., Interpretation: Our results suggest that titre-dependent kinetics driven by widespread transmission direct the evolution of population immunity in a consistent manner. These findings have implications for targeted vaccination strategies and improved modeling of future transmission, providing a preliminary blueprint for understanding population immune dynamics that could guide public health and vaccine policy for SARS-CoV-2 and potentially other pathogens., Funding: The study was primarily funded by the Centers for Disease Control and Prevention grant U01GH002238 (EN). Salary support was provided by Wellcome Trust grant 206250/Z/17/Z (AK) and the Australian National Health and Medical Research Council Investigator grant APP1158469 (CLL)., Competing Interests: Declaration of interests EJN is the PI on a US Centers for Disease Control and Prevention (CDC) funded U01 award that funded the study. AK and CLL are co-investigators on the same award. DD, MdSA, SG, MCE, WD, GA, MB, and KWR have received salary support, consultancy fees, or travel paid through this award. BL is an employee of the US CDC. CTP, LC, IMS and RSR are employees of the Ministry of Ministry of Health and Social Assistance, Dominican Republic, that was subcontracted with funds from the US CDC award. AK is supported by the Wellcome Trust, UK. CLL is supported by the Australian National Health and Medical Research Council. CDC staff supported the design and manuscript editing. We declare no other competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
5. Hand hygiene perceptions, preferences, and practices among hospital staff in the Dominican Republic in the context of COVID-19: a qualitative study.
- Author
-
Craig CE, Schnorr CD, Then Paulino CJ, Payano EC, Guzmán PM, Ripkey C, de St Aubin M, Dumas D, Roberts KW, Duke W, Skewes-Ramm R, Lozier MJ, and Nilles EJ
- Abstract
Background: Proper hand hygiene (HH), which includes sanitizing with alcohol-based hand rub (ABHR) (or handwashing with soap and water if ABHR is unavailable), is key for preventing healthcare-associated infections (HCAI), including COVID-19. Understanding drivers of HH is key to improving adherence., Aim: This study aims to explore drivers and barriers to HH practice at two hospitals in the Dominican Republic in the context of the COVID-19 pandemic to inform development of HH behaviour change interventions., Methods: We conducted in-depth interviews with 20 hospital staff during September 2021. We used the COM-B (capability, opportunity, motivation, behaviour) model to explore HH experiences and preferences. Interviews were recorded, transcribed, coded, and analysed using a thematic approach., Results: A total of 11 parent codes and 27 sub-codes were identified, and 1145 coded segments were analysed. Use of handwashing with soap and water and/or sanitizing with ABHR was reported by all participants; handwashing was generally preferred. Participants expressed knowledge of proper HH methods (capability), but inconsistent supplies and lack of time presented HH challenges (opportunity). Interviewees described practicing HH to protect themselves and their families from COVID-19 and other infections (reflective motivation) or out of habit (automatic motivation)., Discussion: By understanding and addressing underlying factors affecting HH, hospitals can decrease the risk of HCAIs. Our findings suggest that interventions implemented to improve HH in these hospitals should target motivation and opportunity. These findings informed a multimodal intervention to increase ABHR access and implement message-tested communications campaigns; end-point assessments will provide insights into the intervention's impact.
- Published
- 2024
- Full Text
- View/download PDF
6. Using Regional Sero-Epidemiology SARS-CoV-2 Anti-S Antibodies in the Dominican Republic to Inform Targeted Public Health Response.
- Author
-
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, and Lau CL
- Abstract
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 PT80 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.- Published
- 2023
- Full Text
- View/download PDF
7. Monitoring Temporal Changes in SARS-CoV-2 Spike Antibody Levels and Variant-Specific Risk for Infection, Dominican Republic, March 2021-August 2022.
- Author
-
Nilles EJ, de St Aubin M, Dumas D, Duke W, Etienne MC, Abdalla G, Jarolim P, Oasan T, Garnier S, Iihoshi N, Lopez B, de la Cruz L, Puello YC, Baldwin M, Roberts KW, Peña F, Durski K, Sanchez IM, Gunter SM, Kneubehl AR, Murray KO, Lino A, Strobel S, Baez AA, Lau CL, Kucharski A, Gutiérrez EZ, Skewes-Ramm R, Vasquez M, and Paulino CT
- Subjects
- Humans, Dominican Republic epidemiology, Antibodies, Viral, Fever, Spike Glycoprotein, Coronavirus genetics, Antibodies, Neutralizing, SARS-CoV-2, COVID-19 epidemiology
- Abstract
To assess changes in SARS-CoV-2 spike binding antibody prevalence in the Dominican Republic and implications for immunologic protection against variants of concern, we prospectively enrolled 2,300 patients with undifferentiated febrile illnesses in a study during March 2021-August 2022. We tested serum samples for spike antibodies and tested nasopharyngeal samples for acute SARS-CoV-2 infection using a reverse transcription PCR nucleic acid amplification test. Geometric mean spike antibody titers increased from 6.6 (95% CI 5.1-8.7) binding antibody units (BAU)/mL during March-June 2021 to 1,332 (95% CI 1,055-1,682) BAU/mL during May-August 2022. Multivariable binomial odds ratios for acute infection were 0.55 (95% CI 0.40-0.74), 0.38 (95% CI 0.27-0.55), and 0.27 (95% CI 0.18-0.40) for the second, third, and fourth versus the first anti-spike quartile; findings were similar by viral strain. Combining serologic and virologic screening might enable monitoring of discrete population immunologic markers and their implications for emergent variant transmission.
- Published
- 2023
- Full Text
- View/download PDF
8. Diagnostic TR-FRET assays for detection of antibodies in patient samples.
- Author
-
Yue H, Nowak RP, Overwijn D, Payne NC, Fischinger S, Atyeo C, Lam EC, St Denis K, Brais LK, Konishi Y, Sklavenitis-Pistofidis R, Baden LR, Nilles EJ, Karlson EW, Yu XG, Li JZ, Woolley AE, Ghobrial IM, Meyerhardt JA, Balazs AB, Alter G, Mazitschek R, and Fischer ES
- Subjects
- Humans, Fluorescence Resonance Energy Transfer, Antibodies, Viral, Nucleocapsid, COVID-19 Testing, SARS-CoV-2, COVID-19 diagnosis
- Abstract
Serological assays are important diagnostic tools for surveying exposure to the pathogen, monitoring immune response post vaccination, and managing spread of the infectious agent among the population. Current serological laboratory assays are often limited because they require the use of specialized laboratory technology and/or work with a limited number of sample types. Here, we evaluate an alternative by developing time-resolved Förster resonance energy transfer (TR-FRET) homogeneous assays that exhibited exceptional versatility, scalability, and sensitivity and outperformed or matched currently used strategies in terms of sensitivity, specificity, and precision. We validated the performance of the assays measuring total immunoglobulin G (IgG) levels; antibodies against severe acute respiratory syndrome coronavirus (SARS-CoV) or Middle Eastern respiratory syndrome (MERS)-CoV spike (S) protein; and SARS-CoV-2 S and nucleocapsid (N) proteins and applied it to several large sample sets and real-world applications. We further established a TR-FRET-based ACE2-S competition assay to assess the neutralization propensity of the antibodies. Overall, these TR-FRET-based serological assays can be rapidly extended to other antigens and are compatible with commonly used plate readers., Competing Interests: E.S.F. is an equity holder and scientific advisor for Neomorph, Inc. (board member), Civetta Therapeutics, Proximity Therapeutics, Lighthorse Therapeutics, Avilar Therapeutics, and Photys Therapeutics and is a consultant to Novartis, Sanofi, AbbVie, Pfizer, Astellas, EcoR1 Capital, and Deerfield. The Fischer lab receives or has received research funding from Novartis, Ajax, Deerfield, and Astellas not related to this work. R.M. is a scientific advisory board (SAB) member and equity holder of Regenacy Pharmaceuticals, ERX Pharmaceuticals, and Frequency Therapeutics. H.Y., R.P.N., D.O., N.C.P., R.M., and E.S.F. are inventors on patent applications related to this work., (© 2023 The Author(s).)
- Published
- 2023
- Full Text
- View/download PDF
9. Tracking immune correlates of protection for emerging SARS-CoV-2 variants.
- Author
-
Nilles EJ, Paulino CT, de St Aubin M, Duke W, Jarolim P, Sanchez IM, Murray KO, Lau CL, Gutiérrez EZ, Ramm RS, Vasquez M, and Kucharski A
- Subjects
- Humans, SARS-CoV-2, COVID-19
- Abstract
Competing Interests: EJN is the Principal Investigator on a US Centers for Disease Control and Prevention (CDC)-funded U01 award that funded the study, and CLL, AK, MdSA, WD, and MV have received salary support, consultancy fees, or travel paid through this award. EZG is an employee of the US CDC. CTP, IMS, and RSR are employees of the Ministry of Health and Social Assistance, Dominican Republic, that was subcontracted with funds from the US CDC award. AK is supported by the Wellcome Trust, UK. PJ and KOM declare no competing interests. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US CDC.
- Published
- 2023
- Full Text
- View/download PDF
10. SARS-CoV-2 seroprevalence, cumulative infections, and immunity to symptomatic infection - A multistage national household survey and modelling study, Dominican Republic, June-October 2021.
- Author
-
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, and Lau CL
- Abstract
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., Competing Interests: E.J.N. is the PI on a US CDC funded U01 award that funded the study, and C.L.L., A.K., D.D., M.d.S.A., A.C.R., H.M., S.G., M.C.E., W.D., N.I., G.A., B.H., K.D., M.B., E.F., and L.I. have received salaries, consultancy fees, or travel paid through this award. E.Z.G., B.L., and A.E.-B. are employees of the US CDC. B.H., C.T., L.C., F.P., and R.S.-R. are employees of the Ministry of Ministry of Health and Social Assistance, Dominican Republic, that was subcontracted with funds from the US CDC award. A.K. and E.F. are supported by the Welcome Trust, UK. D.B. had a patent for COVID-19 vaccine licensed to Janssen. We declare no other competing interests., (© 2022 The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
11. Humanitarian Training With Virtual Simulation During a Pandemic.
- Author
-
Kivlehan SM, Tenney K, Plasmati S, Bollettino V, Farineau K, Nilles EJ, Gottlieb G, and Kayden SR
- Subjects
- Humans, Pandemics, COVID-19 epidemiology, Simulation Training
- Abstract
There is an ongoing and established need for humanitarian training and professionalization. The coronavirus disease 2019 (COVID-19) pandemic disrupted training programs designed to accomplish this goal, including the Humanitarian Response Intensive Course, which includes a 3-d immersive simulation to prepare humanitarian workers for future field work. To provide program continuity, the 3-d simulation was quickly adapted to a virtual format using a combination of video conferencing, short messaging service, and cloud-based file storage software. Participants were geographically dispersed and participated virtually. Learning objectives were preserved, while some components not amenable to a virtual format were removed.A virtual humanitarian training simulation is a feasible, acceptable, and affordable alternative to an in-person simulation. Participants were engaged and experienced minimal technological disruptions. The majority of students believed the format met or exceeded expectations. However, feedback also emphasized the importance of providing sufficient time for team collaboration and deliverable preparation in the simulation schedule. The virtual format was more affordable than the traditional in-person simulation, and diverse expert faculty who could not have attended in-person were able to participate. This format could be used to overcome other barriers to in-person simulation training, including geographic, financial, time, or security.
- Published
- 2022
- Full Text
- View/download PDF
12. Longitudinal SARS-CoV-2 Nucleocapsid Antibody Kinetics, Seroreversion, and Implications for Seroepidemiologic Studies.
- Author
-
Loesche M, Karlson EW, Talabi O, Zhou G, Boutin N, Atchley R, Loevinsohn G, Chang JBP, Hasdianda MA, Okenla A, Sampson E, Schram H, Magsipoc K, Goodman K, Donahue L, MacGowan M, Novack LA, Jarolim P, Baden LR, and Nilles EJ
- Subjects
- Antibodies, Viral, Coronavirus Nucleocapsid Proteins immunology, Humans, Kinetics, Nucleocapsid, Phosphoproteins immunology, Seroepidemiologic Studies, COVID-19 epidemiology, SARS-CoV-2
- Abstract
Given widespread use of spike antibody in generating coronavirus disease vaccines, SARS-CoV-2 nucleocapsid antibodies are increasingly used to indicate previous infection in serologic surveys. However, longitudinal kinetics and seroreversion are poorly defined. We found substantial seroreversion of nucleocapsid total immunoglobulin, underscoring the need to account for seroreversion in seroepidemiologic studies.
- Published
- 2022
- Full Text
- View/download PDF
13. mRNA-1273 and BNT162b2 COVID-19 vaccines elicit antibodies with differences in Fc-mediated effector functions.
- Author
-
Kaplonek P, Cizmeci D, Fischinger S, Collier AR, Suscovich T, Linde C, Broge T, Mann C, Amanat F, Dayal D, Rhee J, de St Aubin M, Nilles EJ, Musk ER, Menon AS, Saphire EO, Krammer F, Lauffenburger DA, Barouch DH, and Alter G
- Subjects
- 2019-nCoV Vaccine mRNA-1273, Antibodies, Neutralizing, Antibodies, Viral, BNT162 Vaccine, Humans, SARS-CoV-2, Spike Glycoprotein, Coronavirus genetics, Vaccination, Vaccines, Synthetic, mRNA Vaccines, COVID-19 prevention & control, COVID-19 Vaccines
- Abstract
The successful development of several coronavirus disease 2019 (COVID-19) vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants that are able to evade vaccine-induced neutralizing antibodies, real-world vaccine efficacy has begun to show differences across the two approved mRNA platforms, BNT162b2 and mRNA-1273; these findings suggest that subtle variation in immune responses induced by the BNT162b2 and mRNA-1273 vaccines may confer differential protection. Given our emerging appreciation for the importance of additional antibody functions beyond neutralization, we profiled the postboost binding and functional capacity of humoral immune responses induced by the BNT162b2 and mRNA-1273 vaccines in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to variants of concern. However, differences emerged across epitope-specific responses, with higher concentrations of receptor binding domain (RBD)- and N-terminal domain-specific IgA observed in recipients of mRNA-1273. Antibodies eliciting neutrophil phagocytosis and natural killer cell activation were also increased in mRNA-1273 vaccine recipients as compared to BNT162b2 recipients. RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector functions induced across the mRNA vaccines. These data provide insights into potential differences in protective immunity conferred by these vaccines.
- Published
- 2022
- Full Text
- View/download PDF
14. Serological Markers of SARS-CoV-2 Reinfection.
- Author
-
Siddiqui SM, Bowman KA, Zhu AL, Fischinger S, Beger S, Maron JS, Bartsch YC, Atyeo C, Gorman MJ, Yanis A, Hultquist JF, Lorenzo-Redondo R, Ozer EA, Simons LM, Talj R, Rankin DA, Chapman L, Meade K, Steinhart J, Mullane S, Siebert S, Streeck H, Sabeti P, Halasa N, Musk ER, Barouch DH, Menon AS, Nilles EJ, Lauffenburger DA, and Alter G
- Subjects
- Animals, Humans, Macaca mulatta, SARS-CoV-2, Immunoglobulin G, Antibodies, Viral, Antibodies, Neutralizing, Reinfection, COVID-19
- Abstract
As public health guidelines throughout the world have relaxed in response to vaccination campaigns against SARS-CoV-2, it is likely that SARS-CoV-2 will remain endemic, fueled by the rise of more infectious SARS-CoV-2 variants. Moreover, in the setting of waning natural and vaccine immunity, reinfections have emerged across the globe, even among previously infected and vaccinated individuals. As such, the ability to detect reexposure to and reinfection by SARS-CoV-2 is a key component for global protection against this virus and, more importantly, against the potential emergence of vaccine escape mutations. Accordingly, there is a strong and continued need for the development and deployment of simple methods to detect emerging hot spots of reinfection to inform targeted pandemic response and containment, including targeted and specific deployment of vaccine booster campaigns. In this study, we identify simple, rapid immune biomarkers of reinfection in rhesus macaques, including IgG3 antibody levels against nucleocapsid and FcγR2A receptor binding activity of anti-RBD antibodies, that are recapitulated in human reinfection cases. As such, this cross-species analysis underscores the potential utility of simple antibody titers and function as price-effective and scalable markers of reinfection to provide increased resolution and resilience against new outbreaks. IMPORTANCE As public health and social distancing guidelines loosen in the setting of waning global natural and vaccine immunity, a deeper understanding of the immunological response to reexposure and reinfection to this highly contagious pathogen is necessary to maintain public health. Viral sequencing analysis provides a robust but unrealistic means to monitor reinfection globally. The identification of scalable pathogen-specific biomarkers of reexposure and reinfection, however, could significantly accelerate our capacity to monitor the spread of the virus through naive and experienced hosts, providing key insights into mechanisms of disease attenuation. Using a nonhuman primate model of controlled SARS-CoV-2 reexposure, we deeply probed the humoral immune response following rechallenge with various doses of viral inocula. We identified virus-specific humoral biomarkers of reinfection, with significant increases in antibody titer and function upon rechallenge across a range of humoral features, including IgG1 to the receptor binding domain of the spike protein of SARS-CoV-2 (RBD), IgG3 to the nucleocapsid protein (N), and FcγR2A receptor binding to anti-RBD antibodies. These features not only differentiated primary infection from reexposure and reinfection in monkeys but also were recapitulated in a sequencing-confirmed reinfection patient and in a cohort of putatively reinfected humans that evolved a PCR-positive test in spite of preexisting seropositivity. As such, this cross-species analysis using a controlled primate model and human cohorts reveals increases in antibody titers as promising cross-validated serological markers of reinfection and reexposure.
- Published
- 2022
- Full Text
- View/download PDF
15. SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.
- Author
-
Finch E, Lowe R, Fischinger S, de St Aubin M, Siddiqui SM, Dayal D, Loesche MA, Rhee J, Beger S, Hu Y, Gluck MJ, Mormann B, Hasdianda MA, Musk ER, Alter G, Menon AS, Nilles EJ, and Kucharski AJ
- Subjects
- Adolescent, Adult, Aged, COVID-19 epidemiology, COVID-19 prevention & control, COVID-19 Nucleic Acid Testing, COVID-19 Serological Testing, Humans, Logistic Models, Middle Aged, Polymerase Chain Reaction, Prospective Studies, Reinfection prevention & control, SARS-CoV-2 immunology, Seroepidemiologic Studies, Time Factors, United States epidemiology, Workplace statistics & numerical data, Young Adult, Antibodies, Viral blood, COVID-19 immunology, Reinfection immunology
- Abstract
Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: GA is a founder of Seromyx Systems Inc., a company developing platform technology that describes the antibody immune response. GA’s interests were reviewed and are managed by Massachusetts General Hospital in accordance with their conflict-of-interest policies. MJG, SB, DD, YH, JR, EP, BM, ASM, and ERM are employees of Space Exploration Technologies Corp. All other authors have declared that no conflict of interest exists.
- Published
- 2022
- Full Text
- View/download PDF
16. mRNA-1273 vaccine-induced antibodies maintain Fc effector functions across SARS-CoV-2 variants of concern.
- Author
-
Kaplonek P, Fischinger S, Cizmeci D, Bartsch YC, Kang J, Burke JS, Shin SA, Dayal D, Martin P, Mann C, Amanat F, Julg B, Nilles EJ, Musk ER, Menon AS, Krammer F, Saphire EO, Andrea Carfi, and Alter G
- Subjects
- 2019-nCoV Vaccine mRNA-1273 administration & dosage, Adult, Antibodies, Neutralizing immunology, Cross Reactions immunology, Female, Host-Pathogen Interactions, Humans, Male, Middle Aged, Neutralization Tests, Protein Binding, Spike Glycoprotein, Coronavirus immunology, Vaccination, Young Adult, 2019-nCoV Vaccine mRNA-1273 immunology, Antibodies, Viral immunology, COVID-19 metabolism, COVID-19 prevention & control, Receptors, Fc metabolism, SARS-CoV-2 immunology
- Abstract
SARS-CoV-2 mRNA vaccines confer robust protection against COVID-19, but the emergence of variants has generated concerns regarding the protective efficacy of the currently approved vaccines, which lose neutralizing potency against some variants. Emerging data suggest that antibody functions beyond neutralization may contribute to protection from the disease, but little is known about SARS-CoV-2 antibody effector functions. Here, we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA-1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOCs). Although the neutralizing responses to VOCs decreased in both groups, the Fc-mediated responses were distinct. In convalescent individuals, although antibodies exhibited robust binding to VOCs, they showed compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies also bound robustly to VOCs but continued to interact with Fc-receptors and mediate antibody effector functions. These data point to a resilience in the mRNA-vaccine-induced humoral immune response that may continue to offer protection from SARS-CoV-2 VOCs independent of neutralization., Competing Interests: Declaration of interests G.A. is the founder of Seromyx Systems Inc. A.C. is an employee of Moderna Inc. D.D., P.M., A.S.M., and E.R.M. are employees of Space Exploration Technologies Corp. All other authors have declared no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
17. Epidemiological and Immunological Features of Obesity and SARS-CoV-2.
- Author
-
Nilles EJ, Siddiqui SM, Fischinger S, Bartsch YC, de St Aubin M, Zhou G, Gluck MJ, Berger S, Rhee J, Petersen E, Mormann B, Loesche M, Hu Y, Chen Z, Yu J, Gebre M, Atyeo C, Gorman MJ, Zhu AL, Burke J, Slein M, Hasdianda MA, Jambaulikar G, Boyer EW, Sabeti PC, Barouch DH, Julg B, Kucharski AJ, Musk ER, Lauffenburger DA, Alter G, and Menon AS
- Subjects
- Adolescent, Adult, Age Factors, Body Mass Index, COVID-19 epidemiology, COVID-19 physiopathology, Female, Humans, Immunoglobulin G blood, Male, Middle Aged, Risk Factors, SARS-CoV-2 immunology, Young Adult, Antibodies, Viral blood, COVID-19 complications, COVID-19 immunology, Obesity complications, Obesity immunology, Spike Glycoprotein, Coronavirus immunology
- Abstract
Obesity is a key correlate of severe SARS-CoV-2 outcomes while the role of obesity on risk of SARS-CoV-2 infection, symptom phenotype, and immune response remain poorly defined. We examined data from a prospective SARS-CoV-2 cohort study to address these questions. Serostatus, body mass index, demographics, comorbidities, and prior COVID-19 compatible symptoms were assessed at baseline and serostatus and symptoms monthly thereafter. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Our results from a large prospective SARS-CoV-2 cohort study indicate symptom phenotype is strongly influenced by obesity among younger but not older age groups; we did not identify evidence to suggest obese individuals are at higher risk of SARS-CoV-2 infection; and remarkably homogenous immune activity across BMI categories suggests immune protection across these groups may be similar.
- Published
- 2021
- Full Text
- View/download PDF
18. Evaluation of Three Commercial and Two Non-Commercial Immunoassays for the Detection of Prior Infection to SARS-CoV-2.
- Author
-
Nilles EJ, Karlson EW, Norman M, Gilboa T, Fischinger S, Atyeo C, Zhou G, Bennett CL, Tolan NV, Oganezova K, Walt DR, Alter G, Simmons DP, Schur P, Jarolim P, Woolley AE, and Baden LR
- Subjects
- Antibodies, Viral, COVID-19 Serological Testing, Humans, Immunoassay, Immunoglobulin G, Immunoglobulin M, Sensitivity and Specificity, COVID-19, SARS-CoV-2
- Abstract
Background: Serological testing provides a record of prior infection with SARS-CoV-2, but assay performance requires independent assessment., Methods: We evaluated 3 commercial (Roche Diagnostics pan-IG, and Epitope Diagnostics IgM and IgG) and 2 non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 1083 unique samples that included 251 PCR-positive and 832 prepandemic samples., Results: The Roche assay registered the highest specificity 99.6% (3/832 false positives), the Ragon/MGH assay 99.5% (4/832), the primary Simoa assay model 99.0% (8/832), and the Epitope IgG and IgM 99.0% (8/830) and 99.5% (4/830), respectively. Overall sensitivities for the Simoa, Roche pan-IG, Epitope IgG, Ragon/MGH IgG, and Epitope IgM were 92.0%, 82.9%, 82.5%, 64.5% and 47.0%, respectively. The Simoa immunoassay demonstrated the highest sensitivity among samples stratified by days postsymptom onset (PSO), <8 days PSO (57.69%) 8-14 days PSO (93.51%), 15-21 days PSO (100%), and > 21 days PSO (95.18%)., Conclusions: All assays demonstrated high to very high specificities while sensitivities were variable across assays., (© American Association for Clinical Chemistry 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
- View/download PDF
19. Early cross-coronavirus reactive signatures of humoral immunity against COVID-19.
- Author
-
Kaplonek P, Wang C, Bartsch Y, Fischinger S, Gorman MJ, Bowman K, Kang J, Dayal D, Martin P, Nowak RP, Villani AC, Hsieh CL, Charland NC, Gonye ALK, Gushterova I, Khanna HK, LaSalle TJ, Lavin-Parsons KM, Lilley BM, Lodenstein CL, Manakongtreecheep K, Margolin JD, McKaig BN, Rojas-Lopez M, Russo BC, Sharma N, Tantivit J, Thomas MF, Sade-Feldman M, Feldman J, Julg B, Nilles EJ, Musk ER, Menon AS, Fischer ES, McLellan JS, Schmidt A, Goldberg MB, Filbin MR, Hacohen N, Lauffenburger DA, and Alter G
- Subjects
- Adolescent, Cohort Studies, Coronavirus OC43, Human immunology, Disease Progression, Humans, Immunoglobulin Class Switching, Receptors, Fc immunology, Spike Glycoprotein, Coronavirus immunology, Survivors, Young Adult, COVID-19 immunology, Cross Reactions, Immunity, Humoral, SARS-CoV-2 immunology
- Abstract
The introduction of vaccines has inspired hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against SARS-CoV-2, thus we profiled the earliest humoral signatures in a large cohort of acutely ill (survivors and nonsurvivors) and mild or asymptomatic individuals with COVID-19. Although a SARS-CoV-2–specific immune response evolved rapidly in survivors of COVID-19, nonsurvivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibodies. Given the conservation of S2 across β-coronaviruses, we found that the early development of SARS-CoV-2–specific immunity occurred in tandem with preexisting common β-coronavirus OC43 humoral immunity in survivors, which was also selectively expanded in individuals that develop a paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.
- Published
- 2021
- Full Text
- View/download PDF
20. Subtle immunological differences in mRNA-1273 and BNT162b2 COVID-19 vaccine induced Fc-functional profiles.
- Author
-
Kaplonek P, Cizmeci D, Fischinger S, Collier AR, Suscovich T, Linde C, Broge T, Mann C, Amanat F, Dayal D, Rhee J, de St Aubin M, Nilles EJ, Musk ER, Menon AS, Saphire EO, Krammer F, Lauffenburger DA, Barouch DH, and Alter G
- Abstract
The successful development of several COVID-19 vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants, able to evade vaccine induced neutralizing antibodies, real world vaccine efficacy has begun to show differences across the mRNA platforms, suggesting that subtle variation in immune responses induced by the BNT162b2 and mRNA1273 vaccines may provide differential protection. Given our emerging appreciation for the importance of additional antibody functions, beyond neutralization, here we profiled the postboost binding and functional capacity of the humoral response induced by the BNT162b2 and mRNA-1273 in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to WT SARS-CoV-2 and VOCs. However, differences emerged across epitopespecific responses, with higher RBD- and NTD-specific IgA, as well as functional antibodies (ADNP and ADNK) in mRNA-1273 vaccine recipients. Additionally, RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector function induced across the mRNA vaccines, providing novel insights into potential differences in protective immunity generated across these vaccines in the setting of newly emerging VOCs.
- Published
- 2021
- Full Text
- View/download PDF
21. Early cross-coronavirus reactive signatures of protective humoral immunity against COVID-19.
- Author
-
Kaplonek P, Wang C, Bartsch Y, Fischinger S, Gorman MJ, Bowman K, Kang J, Dayal D, Martin P, Nowak R, Hsieh CL, Feldman J, Julg B, Nilles EJ, Musk ER, Menon AS, Fischer ES, McLellan JS, Schmidt A, Goldberg MB, Filbin M, Hacohen N, Lauffenburger DA, and Alter G
- Abstract
The introduction of vaccines has inspired new hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against COVID-19, thus we profiled the earliest humoral signatures in a large cohort of severe and asymptomatic COVID-19 individuals. While a SARS-CoV-2-specific immune response evolved rapidly in survivors of COVID-19, non-survivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibody evolution. Given the conservation of S2 across β-coronaviruses, we found the early development of SARS-CoV-2-specific immunity occurred in tandem with pre-existing common β-coronavirus OC43 humoral immunity in survivors, which was selectively also expanded in individuals that develop paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.
- Published
- 2021
- Full Text
- View/download PDF
22. Interactions between timing and transmissibility explain diverse flavivirus dynamics in Fiji.
- Author
-
Henderson AD, Kama M, Aubry M, Hue S, Teissier A, Naivalu T, Bechu VD, Kailawadoko J, Rabukawaqa I, Sahukhan A, Hibberd ML, Nilles EJ, Funk S, Whitworth J, Watson CH, Lau CL, Edmunds WJ, Cao-Lormeau VM, and Kucharski AJ
- Subjects
- Animals, Culicidae, Dengue transmission, Dengue Virus, Disease Outbreaks, Epidemics, Fiji epidemiology, Flavivirus, Humans, Mosquito Vectors virology, Seasons, Zika Virus, Zika Virus Infection epidemiology, Zika Virus Infection transmission, Flavivirus Infections epidemiology, Flavivirus Infections transmission
- Abstract
Zika virus (ZIKV) has caused large, brief outbreaks in isolated populations, however ZIKV can also persist at low levels over multiple years. The reasons for these diverse transmission dynamics remain poorly understood. In Fiji, which has experienced multiple large single-season dengue epidemics, there was evidence of multi-year transmission of ZIKV between 2013 and 2017. To identify factors that could explain these differences in dynamics between closely related mosquito-borne flaviviruses, we jointly fit a transmission dynamic model to surveillance, serological and molecular data. We estimate that the observed dynamics of ZIKV were the result of two key factors: strong seasonal effects, which created an ecologically optimal time of year for outbreaks; and introduction of ZIKV after this optimal time, which allowed ZIKV transmission to persist over multiple seasons. The ability to jointly fit to multiple data sources could help identify a similar range of possible outbreak dynamics in other settings.
- Published
- 2021
- Full Text
- View/download PDF
23. Humoral signatures of protective and pathological SARS-CoV-2 infection in children.
- Author
-
Bartsch YC, Wang C, Zohar T, Fischinger S, Atyeo C, Burke JS, Kang J, Edlow AG, Fasano A, Baden LR, Nilles EJ, Woolley AE, Karlson EW, Hopke AR, Irimia D, Fischer ES, Ryan ET, Charles RC, Julg BD, Lauffenburger DA, Yonker LM, and Alter G
- Subjects
- Adolescent, Adult, Age of Onset, Aged, Antibodies, Neutralizing analysis, Antibodies, Neutralizing blood, Antibodies, Viral analysis, Asymptomatic Infections, COVID-19 blood, COVID-19 pathology, Carrier State blood, Carrier State epidemiology, Child, Child, Preschool, Cohort Studies, Female, Humans, Immunity physiology, Immunoglobulin A blood, Immunoglobulin G blood, Infant, Infant, Newborn, Male, Middle Aged, Pandemics, Severity of Illness Index, Systemic Inflammatory Response Syndrome blood, Systemic Inflammatory Response Syndrome epidemiology, Young Adult, Antibodies, Viral blood, COVID-19 epidemiology, SARS-CoV-2 immunology
- Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of multisystem inflammatory syndrome in children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into coronavirus disease 2019 (COVID-19) pathogenesis. Using systems serology, in this study we observed in 25 children with acute mild COVID-19 a functional phagocyte and complement-activating IgG response to SARS-CoV-2, similar to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil responses were significantly expanded in adults with severe disease. Moreover, weeks after the resolution of SARS-CoV-2 infection, children who develop MIS-C maintained highly inflammatory monocyte-activating SARS-CoV-2 IgG antibodies, distinguishable from acute disease in children but with antibody levels similar to those in convalescent adults. Collectively, these data provide unique insights into the potential mechanisms of IgG and IgA that might underlie differential disease severity as well as unexpected complications in children infected with SARS-CoV-2.
- Published
- 2021
- Full Text
- View/download PDF
24. Discrete SARS-CoV-2 antibody titers track with functional humoral stability.
- Author
-
Bartsch YC, Fischinger S, Siddiqui SM, Chen Z, Yu J, Gebre M, Atyeo C, Gorman MJ, Zhu AL, Kang J, Burke JS, Slein M, Gluck MJ, Beger S, Hu Y, Rhee J, Petersen E, Mormann B, Aubin MS, Hasdianda MA, Jambaulikar G, Boyer EW, Sabeti PC, Barouch DH, Julg BD, Musk ER, Menon AS, Lauffenburger DA, Nilles EJ, and Alter G
- Subjects
- Adolescent, Adult, Aged, Antibodies, Neutralizing blood, Antibodies, Neutralizing immunology, Antibodies, Viral blood, COVID-19 blood, Female, Humans, Immunity, Humoral immunology, Immunoglobulin G immunology, Male, Middle Aged, Spike Glycoprotein, Coronavirus immunology, T-Lymphocytes immunology, Viral Vaccines immunology, Young Adult, Antibodies, Viral immunology, COVID-19 immunology, SARS-CoV-2 immunology
- Abstract
Antibodies serve as biomarkers of infection, but if sustained can confer long-term immunity. Yet, for most clinically approved vaccines, binding antibody titers only serve as a surrogate of protection. Instead, the ability of vaccine induced antibodies to neutralize or mediate Fc-effector functions is mechanistically linked to protection. While evidence has begun to point to persisting antibody responses among SARS-CoV-2 infected individuals, cases of re-infection have begun to emerge, calling the protective nature of humoral immunity against this highly infectious pathogen into question. Using a community-based surveillance study, we aimed to define the relationship between titers and functional antibody activity to SARS-CoV-2 over time. Here we report significant heterogeneity, but limited decay, across antibody titers amongst 120 identified seroconverters, most of whom had asymptomatic infection. Notably, neutralization, Fc-function, and SARS-CoV-2 specific T cell responses were only observed in subjects that elicited RBD-specific antibody titers above a threshold. The findings point to a switch-like relationship between observed antibody titer and function, where a distinct threshold of activity-defined by the level of antibodies-is required to elicit vigorous humoral and cellular response. This response activity level may be essential for durable protection, potentially explaining why re-infections occur with SARS-CoV-2 and other common coronaviruses.
- Published
- 2021
- Full Text
- View/download PDF
25. Epidemiological and immunological features of obesity and SARS-CoV-2.
- Author
-
Nilles EJ, Siddiqui SM, Fischinger S, Bartsch YC, de Saint Aubin M, Zhou G, Gluck MJ, Berger S, Rhee J, Petersen E, Mormann B, Loesche M, Chen Z, Yu J, Gebre M, Atyeo C, Gorman MJ, Lee Zhu A, Burke J, Slein M, Hasdianda MA, Jambaulikar G, Boyer E, Sabeti P, Barouch DH, Julg BD, Kucharski AJ, Musk ER, Lauffenburger DA, Alter G, and Menon AS
- Abstract
Obesity is a key correlate of severe SARS-CoV-2 outcomes while the role of obesity on risk of SARS-CoV-2 infection, symptom phenotype, and immune response are poorly defined. We examined data from a prospective SARS-CoV-2 cohort study to address these questions. Serostatus, body mass index, demographics, comorbidities, and prior COVID-19 compatible symptoms were assessed at baseline and serostatus and symptoms monthly thereafter. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Our results from a large prospective SARS-CoV-2 cohort study indicate symptom phenotype is strongly influenced by obesity among younger but not older age groups; we did not identify evidence to suggest obese individuals are at higher risk of SARS-CoV-2 infection; and, remarkably homogenous immune activity across BMI categories suggests natural- and vaccine-induced protection may be similar across these groups.
- Published
- 2020
- Full Text
- View/download PDF
26. Using serological data to understand unobserved SARS-CoV-2 risk in health-care settings.
- Author
-
Kucharski AJ and Nilles EJ
- Subjects
- Delivery of Health Care, Health, Humans, Pandemics, COVID-19, Coronavirus Infections epidemiology, SARS-CoV-2
- Published
- 2020
- Full Text
- View/download PDF
27. SARS-CoV-2 Serosurvey in Addis Ababa, Ethiopia.
- Author
-
Kempen JH, Abashawl A, Suga HK, Nigussie Difabachew M, Kempen CJ, Tesfaye Debele M, Menkir AA, Assefa MT, Asfaw EH, Habtegabriel LB, Sitotaw Addisie Y, Nilles EJ, and Longenecker JC
- Subjects
- Adult, Betacoronavirus, COVID-19, Coronavirus Infections diagnosis, Ethiopia epidemiology, Female, Humans, Male, Pandemics, Pneumonia, Viral diagnosis, Population Surveillance, Prevalence, SARS-CoV-2, Coronavirus Infections epidemiology, Pneumonia, Viral epidemiology, Seroepidemiologic Studies
- Abstract
In a serosurvey of asymptomatic people from the general population recruited from a clinical laboratory in May 2020 in Addis Ababa, Ethiopia, three of 99 persons tested positive for SARS-CoV-2 IgG (3.0%, 95% binomial exact confidence interval: 0.6-8.6%). Taking into account pretest probability and the sampling scheme, the range of plausible population prevalence values was approximately 1.0-8.4%. These results suggest that a larger number of people have been infected than the counts detected by surveillance to date; nevertheless, the results suggest the large majority of the general population in Addis Ababa currently is susceptible to COVID-19.
- Published
- 2020
- Full Text
- View/download PDF
28. Rapid 'mix and read' assay for scalable detection of SARS-CoV-2 antibodies in patient plasma.
- Author
-
Yue H, Nowak RP, Overwijn D, Payne NC, Fischinger S, Atyeo C, Baden LR, Nilles EJ, Karlson EW, Yu XG, Li JZ, Alter G, Mazitschek R, and Fischer ES
- Abstract
The human beta coronavirus SARS-CoV-2, causative virus of COVID-19, has infected more than 15 million people globally and continues to spread. Widespread, population level testing to detect active and past infections is critical to curb the COVID-19 pandemic. Antibody (serological) testing is the only option for detecting past infections outside the narrow window accessible to nucleic acid-based tests. However, currently available serological assays commonly lack scalability. Here, we describe the development of a rapid homogenous serological assay for the detection of antibodies to SARS-CoV-2 in patient plasma. We show that the fluorescence-based assay accurately detects seroconversion in COVID-19 patients from less than 1 microliter of plasma. Using a cohort of samples from COVID-19 infected or healthy individuals, we demonstrate detection with 100% sensitivity and specificity. This assay addresses an important need for a robust, low barrier to implementation, and scalable serological assay with complementary strengths to currently available serological platforms.
- Published
- 2020
- Full Text
- View/download PDF
29. Tenacious Endemic Typhoid Fever in Samoa.
- Author
-
Sikorski MJ, Desai SN, Tupua S, Thomsen RE, Han J, Rambocus S, Nimarota-Brown S, Punimata L, Tusitala S, Sialeipata M, Hoffman SA, Tracy JK, Higginson EE, Tennant SM, Gauld JS, Klein DJ, Ballard SA, Robins-Browne RM, Dougan G, Nilles EJ, Howden BP, Crump JA, Naseri TK, and Levine MM
- Subjects
- Child, Child, Preschool, Humans, Infant, Salmonella typhi, Samoa, Vaccines, Conjugate, Typhoid Fever epidemiology, Typhoid-Paratyphoid Vaccines
- Abstract
Background: Typhoid fever has been endemic on the island nation of Samoa (2016 population, 195 979) since the 1960s and has persisted through 2019, despite economic development and improvements in water supply and sanitation., Methods: Salmonella enterica serovar Typhi isolates from the 2 hospitals with blood culture capability and matched patient demographic and clinical data from January 2008 through December 2019 were analyzed. Denominators to calculate incidence by island, region, and district came from 2011 and 2016 censuses and from 2017-2019 projections from Samoa's Bureau of Statistics. Data were analyzed to describe typhoid case burden and incidence from 2008 to 2019 by time, place, and person., Results: In sum, 53-193 blood culture-confirmed typhoid cases occurred annually from 2008 to 2019, without apparent seasonality. Typhoid incidence was low among children age < 48 months (17.6-27.8/105), rose progressively in ages 5-9 years (54.0/105), 10-19 years (60.7-63.4/105), and 20-34 years (61.0-79.3/105), and then tapered off; 93.6% of cases occurred among Samoans < 50 years of age. Most typhoid cases and the highest incidence occurred in Northwest Upolu, but Apia Urban Area (served by treated water supplies) also exhibited moderate incidence. The proportion of cases from short-cycle versus long-cycle transmission is unknown. Samoan S. Typhi are pansusceptible to traditional first-line antibiotics. Nevertheless, enhanced surveillance in 2019 detected 4 (2.9%) deaths among 140 cases., Conclusions: Typhoid has been endemic in Samoa in the period 2008-2019. Interventions, including mass vaccination with a Vi-conjugate vaccine coadministered with measles vaccine are planned., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Published
- 2020
- Full Text
- View/download PDF
30. First evidence of concurrent enzootic and endemic transmission of Ross River virus in the absence of marsupial reservoirs in Fiji.
- Author
-
Togami E, Gyawali N, Ong O, Kama M, Cao-Lormeau VM, Aubry M, Ko AI, Nilles EJ, Collins-Emerson JM, Devine GJ, Weinstein P, and Lau CL
- Subjects
- Alphavirus Infections epidemiology, Alphavirus Infections transmission, Animals, Cattle, Dogs, Female, Fiji epidemiology, Goats virology, Horses virology, Humans, Marsupialia, Mice, Pregnancy, Rats, Seroepidemiologic Studies, Swine virology, Alphavirus Infections veterinary, Ross River virus immunology
- Abstract
Background: Ross River virus (RRV) is a zoonotic alphavirus transmitted by several mosquito species. Until recently, endemic transmission was only considered possible in the presence of marsupial reservoirs., Methods: RRV seroprevalence was investigated in placental mammals (including horses, cows, goats, pigs, dogs, rats, and mice) in Fiji, where there are no marsupials. A total of 302 vertebrate serum samples were collected from 86 households from 10 communities in Western Fiji., Results: Neutralizing antibodies against RRV were detected in 28% to 100% of sera depending on the species, and neutralization was strong even at high dilutions., Conclusions: These results are unlikely to be due to cross-reactions. Chikungunya is the only other alphavirus known to be present in the Pacific Islands, but it rarely spills over into non-humans, even during epidemics. The study findings, together with a recent report of high RRV seroprevalence in humans, strongly suggest that RRV is circulating in Fiji in the absence of marsupial reservoirs. Considering that all non-human vertebrates present in Fiji are pan-global in distribution, RRV has the potential to further expand its geographic range. Further surveillance of RRV and access to RRV diagnostics will be critical for the early detection of emergence and outbreaks., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2020
- Full Text
- View/download PDF
31. Evaluation of two commercial and two non-commercial immunoassays for the detection of prior infection to SARS-CoV-2.
- Author
-
Nilles EJ, Karlson EW, Norman M, Gilboa T, Fischinger S, Atyeo C, Zhou G, Bennett CL, Tolan NV, Oganezova K, Walt DR, Alter G, Simmons DP, Schur P, Jarolim P, and Baden LR
- Abstract
Background Seroepidemiology is an important tool to characterize the epidemiology and immunobiology of SARS-CoV-2 but many immunoassays have not been externally validated raising questions about reliability of study findings. To ensure meaningful data, particularly in a low seroprevalence population, assays need to be rigorously characterized with high specificity. Methods We evaluated two commercial (Roche Diagnostics and Epitope Diagnostics IgM/IgG) and two non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 68 confirmed positive and 232 pre-pandemic negative controls. Sensitivity was stratified by time from symptom onset. The Simoa multiplex assay applied three pre-defined algorithm models to determine sample result. Results The Roche and Ragon/MGH IgG assays each registered 1/232 false positive, the primary Simoa model registered 2/232 false positives, and the Epitope registered 2/230 and 3/230 false positives for the IgG and IgM assays respectively. Sensitivity >21 days post symptom-onset was 100% for all assays except Epitope IgM, but lower and/or with greater variability between assays for samples collected 9-14 days (67-100%) and 15-21 days (69-100%) post-symptom onset. The Simoa and Epitope IgG assays demonstrated excellent sensitivity earlier in the disease course. The Roche and Ragon/MGH IgG assays were less sensitive during early disease, particularly among immunosuppressed individuals. Conclusions The Epitope IgG demonstrated good sensitivity and specificity. The Roche and Ragon/MGH IgG assays registered rare false positives with lower early sensitivity. The Simoa assay primary model had excellent sensitivity and few false positives.
- Published
- 2020
- Full Text
- View/download PDF
32. Dynamics of conflict during the Ebola outbreak in the Democratic Republic of the Congo 2018-2019.
- Author
-
Kraemer MUG, Pigott DM, Hill SC, Vanderslott S, Reiner RC Jr, Stasse S, Brownstein JS, Gutierrez B, Dennig F, Hay SI, Wint GRW, Pybus OG, Castro MC, Vinck P, Pham PN, Nilles EJ, and Cauchemez S
- Subjects
- Democratic Republic of the Congo epidemiology, Disease Outbreaks, Hemorrhagic Fever, Ebola mortality, History, 21st Century, Humans, Incidence, Survival Analysis, Hemorrhagic Fever, Ebola epidemiology
- Abstract
Background: The 2018-2019 Ebola virus disease (EVD) outbreak in North Kivu and Ituri provinces in the Democratic Republic of the Congo (DRC) is the largest ever recorded in the DRC. It has been declared a Public Health Emergency of International Concern. The outbreak emerged in a region of chronic conflict and insecurity, and directed attacks against health care workers may have interfered with disease response activities. Our study characterizes and quantifies the broader conflict dynamics over the course of the outbreak by pairing epidemiological and all available spatial conflict data., Methods: We build a set of conflict variables by mapping the spatial locations of all conflict events and their associated deaths in each of the affected health zones in North Kivu and Ituri, eastern DRC, before and during the outbreak. Using these data, we compare patterns of conflict before and during the outbreak in affected health zones and those not affected. We then test whether conflict is correlated with increased EVD transmission at the health zone level., Findings: The incidence of conflict events per capita is ~ 600 times more likely in Ituri and North Kivu than for the rest of the DRC. We identified 15 time periods of substantial uninterrupted transmission across 11 health zones and a total of 120 bi-weeks. We do not find significant short-term associations between the bi-week reproduction numbers and the number of conflicts. However, we do find that the incidence of conflict per capita was correlated with the incidence of EVD per capita at the health zone level for the entire outbreak (Pearson's r = 0.33, 95% CI 0.05-0.57). In the two provinces, the monthly number of conflict events also increased by a factor of 2.7 in Ebola-affected health zones (p value < 0.05) compared to 2.0 where no transmission was reported and 1.3 in the rest of the DRC, in the period between February 2019 and July 2019., Conclusion: We characterized the association between variables documenting broad conflict levels and EVD transmission. Such assessment is important to understand if and how such conflict variables could be used to inform the outbreak response. We found that while these variables can help characterize long-term challenges and susceptibilities of the different regions they provide little insight on the short-term dynamics of EVD transmission.
- Published
- 2020
- Full Text
- View/download PDF
33. Sustained Low-Level Transmission of Zika and Chikungunya Viruses after Emergence in the Fiji Islands.
- Author
-
Kama M, Aubry M, Naivalu T, Vanhomwegen J, Mariteragi-Helle T, Teissier A, Paoaafaite T, Hué S, Hibberd ML, Manuguerra JC, Christi K, Watson CH, Nilles EJ, Aaskov J, Lau CL, Musso D, Kucharski AJ, and Cao-Lormeau VM
- Subjects
- Chikungunya Fever virology, Disease Outbreaks, Female, Fiji epidemiology, Humans, Islands, Male, Phylogeny, Population Surveillance, Risk Factors, Sequence Analysis, DNA, Seroepidemiologic Studies, Viral Envelope Proteins genetics, Zika Virus Infection virology, Chikungunya Fever epidemiology, Chikungunya Fever transmission, Chikungunya virus classification, Chikungunya virus genetics, Zika Virus classification, Zika Virus genetics, Zika Virus Infection epidemiology, Zika Virus Infection transmission
- Abstract
Zika and chikungunya viruses were first detected in Fiji in 2015. Examining surveillance and phylogenetic and serologic data, we found evidence of low-level transmission of Zika and chikungunya viruses during 2013-2017, in contrast to the major outbreaks caused by closely related virus strains in other Pacific Island countries.
- Published
- 2019
- Full Text
- View/download PDF
34. Institutional trust and misinformation in the response to the 2018-19 Ebola outbreak in North Kivu, DR Congo: a population-based survey.
- Author
-
Vinck P, Pham PN, Bindu KK, Bedford J, and Nilles EJ
- Subjects
- Adolescent, Adult, Communication, Congo epidemiology, Disease Outbreaks prevention & control, Family Characteristics, Female, Health Knowledge, Attitudes, Practice, Hemorrhagic Fever, Ebola prevention & control, Humans, Male, Middle Aged, Patient Acceptance of Health Care statistics & numerical data, Surveys and Questionnaires, Trust, Young Adult, Disease Outbreaks statistics & numerical data, Hemorrhagic Fever, Ebola epidemiology, Hemorrhagic Fever, Ebola psychology, Patient Acceptance of Health Care psychology
- Abstract
Background: The current outbreak of Ebola in eastern DR Congo, beginning in 2018, emerged in a complex and violent political and security environment. Community-level prevention and outbreak control measures appear to be dependent on public trust in relevant authorities and information, but little scholarship has explored these issues. We aimed to investigate the role of trust and misinformation on individual preventive behaviours during an outbreak of Ebola virus disease (EVD)., Methods: We surveyed 961 adults between Sept 1 and Sept 16, 2018. We used a multistage sampling design in Beni and Butembo in North Kivu, DR Congo. Of 412 avenues and cells (the lowest administrative structures; 99 in Beni and 313 in Butembo), we randomly selected 30 in each city. In each avenue or cell, 16 households were selected using the WHO Expanded Programme on Immunization's random walk approach. In each household, one adult (aged ≥18 years) was randomly selected for interview. Standardised questionnaires were administered by experienced interviewers. We used multivariate models to examine the intermediate variables of interest, including institutional trust and belief in selected misinformation, with outcomes of interest related to EVD prevention behaviours., Findings: Among 961 respondents, 349 (31·9%, 95% CI 27·4-36·9) trusted that local authorities represent their interest. Belief in misinformation was widespread, with 230 (25·5%, 21·7-29·6) respondents believing that the Ebola outbreak was not real. Low institutional trust and belief in misinformation were associated with a decreased likelihood of adopting preventive behaviours, including acceptance of Ebola vaccines (odds ratio 0·22, 95% CI 0·21-0·22, and 1·40, 1·39-1·42) and seeking formal health care (0·06, 0·05-0·06, and 1·16, 1·15-1·17)., Interpretation: The findings underscore the practical implications of mistrust and misinformation for outbreak control. These factors are associated with low compliance with messages of social and behavioural change and refusal to seek formal medical care or accept vaccines, which in turn increases the risk of spread of EVD., Funding: The Harvard Humanitarian Initiative Innovation Fund., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
35. Ross River Virus Antibody Prevalence, Fiji Islands, 2013-2015.
- Author
-
Aubry M, Kama M, Vanhomwegen J, Teissier A, Mariteragi-Helle T, Hue S, Hibberd ML, Manuguerra JC, Christi K, Watson CH, Nilles EJ, Lau CL, Aaskov J, Musso D, Kucharski AJ, and Cao-Lormeau VM
- Subjects
- Alphavirus Infections blood, Alphavirus Infections epidemiology, Antibodies, Viral blood, Fiji epidemiology, Humans, Ross River virus isolation & purification, Seroepidemiologic Studies, Alphavirus Infections diagnosis, Ross River virus immunology
- Abstract
A unique outbreak of Ross River virus (RRV) infection was reported in Fiji in 1979. In 2013, RRV seroprevalence among residents was 46.5% (362/778). Of the residents who were seronegative in 2013 and retested in 2015, 10.9% (21/192) had seroconverted to RRV, suggesting ongoing endemic circulation of RRV in Fiji.
- Published
- 2019
- Full Text
- View/download PDF
36. Environmental health effects attributed to toxic and infectious agents following hurricanes, cyclones, flash floods and major hydrometeorological events.
- Author
-
Erickson TB, Brooks J, Nilles EJ, Pham PN, and Vinck P
- Subjects
- Animals, Cyclonic Storms, Disaster Planning, Environmental Exposure adverse effects, Floods, Humans, Climate Change, Disasters, Environmental Health
- Abstract
Extreme hydrometeorological events such as hurricanes and cyclones are increasing in frequency and intensity due to climate change and often associated with flash floods in coastal, urbanized and industrial areas. Preparedness and response measures need to concentrate on toxicological and infectious hazards, the potential impact on environmental health, and threat to human lives. The recognition of the danger of flood water after hurricanes is critical. Effective health management needs to consider the likelihood and specific risks of toxic agents present in waters contaminated by chemical spills, bio-toxins, waste, sewage, and water-borne pathogens. Despite significant progress in the ability to rapidly detect and test water for a wide range of chemicals and pathogens, there has been a lack of implementation to adapt toxicity measurements in the context of flash and hurricane-induced flooding. The aim of this review was to highlight the need to collect and analyze data on toxicity of flood waters to understand the risks and prepare vulnerable communities and first responders. It is proposed that new and routinely used technologies be employed during disaster response to rapidly assess toxicity and infectious disease threats, and subsequently take necessary remedial actions.
- Published
- 2019
- Full Text
- View/download PDF
37. Predictive risk mapping of an environmentally-driven infectious disease using spatial Bayesian networks: A case study of leptospirosis in Fiji.
- Author
-
Mayfield HJ, Smith CS, Lowry JH, Watson CH, Baker MG, Kama M, Nilles EJ, and Lau CL
- Subjects
- Animal Husbandry, Animals, Bayes Theorem, Fiji epidemiology, Humans, Livestock, Poverty, Risk Assessment, Rural Population, Seroepidemiologic Studies, Spatial Analysis, Urban Population, Environmental Exposure, Leptospirosis epidemiology, Leptospirosis transmission, Zoonoses epidemiology, Zoonoses transmission
- Abstract
Introduction: Leptospirosis is a zoonotic disease responsible for over 1 million severe cases and 60,000 deaths annually. The wide range of animal hosts and complex environmental drivers of transmission make targeted interventions challenging, particularly when restricted to regression-based analyses which have limited ability to deal with complexity. In Fiji, important environmental and socio-demographic factors include living in rural areas, poverty, and livestock exposure. This study aims to examine drivers of transmission under different scenarios of environmental and livestock exposures., Methods: Spatial Bayesian networks (SBN) were used to analyse the influence of livestock and poverty on the risk of leptospirosis infection in urban compared to rural areas. The SBN models used a combination of spatially-explicit field data from previous work and publically available census information. Predictive risk maps were produced for overall risk, and for scenarios related to poverty, livestock, and urban/rural setting., Results: While high, rather than low, commercial dairy farm density similarly increased the risk of infection in both urban (12% to 18%) and rural areas (70% to 79%), the presence of pigs in a village had different impact in rural (43% to 84%) compared with urban areas (4% to 24%). Areas with high poverty rates were predicted to have 26.6% and 18.0% higher probability of above average seroprevalence in rural and urban areas, respectively. In urban areas, this represents >300% difference between areas of low and high poverty, compared to 43% difference in rural areas., Conclusions: Our study demonstrates the use of SBN to provide valuable insights into the drivers of leptospirosis transmission under complex scenarios. By estimating the risk of leptospirosis infection under different scenarios, such as urban versus rural areas, these subgroups or areas can be targeted with more precise interventions that focus on the most relevant key drivers of infection., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
- Full Text
- View/download PDF
38. A Large Leptospirosis Outbreak following Successive Severe Floods in Fiji, 2012.
- Author
-
Togami E, Kama M, Goarant C, Craig SB, Lau C, Ritter JM, Imrie A, Ko AI, and Nilles EJ
- Subjects
- Enzyme-Linked Immunosorbent Assay, Fiji epidemiology, Humans, Incidence, Leptospira genetics, Leptospira immunology, Leptospirosis blood, Leptospirosis microbiology, Polymerase Chain Reaction, Rain, Retrospective Studies, Seasons, Antibodies, Bacterial blood, DNA, Bacterial genetics, Disease Outbreaks, Floods, Leptospira isolation & purification, Leptospirosis epidemiology
- Abstract
Severe flooding has been linked to outbreaks of leptospirosis. Two sequential extreme flood events in Western Fiji caused the largest outbreak of leptospirosis recorded in the South Pacific, with 1,217 total suspected cases, of which 314 were probable and confirmed. Most (83%) cases occurred within 6 weeks of the flood events, displaying a biphasic epidemic curve associated with the floods. Given the temporal proximity of cases to flooding events, most of the transmission appeared to occur during or immediately after the floods; therefore, prevention of exposure to contaminated environments is a priority in the immediate flood and post-flood period. In addition, genotyping studies suggest that multiple animal reservoirs were implicated in the outbreak, reaffirming the importance of integrated human and animal health strategies for leptospirosis control.
- Published
- 2018
- Full Text
- View/download PDF
39. Zika Virus Infection during Pregnancy and Effects on Early Childhood Development, French Polynesia, 2013-2016.
- Author
-
Subissi L, Dub T, Besnard M, Mariteragi-Helle T, Nhan T, Lutringer-Magnin D, Barboza P, Gurry C, Brindel P, Nilles EJ, Baud D, Merianos A, Musso D, Glynn JR, Dupuis G, Cao-Lormeau VM, Giard M, and Mallet HP
- Subjects
- Adult, Case-Control Studies, Child, Child, Preschool, Congenital Abnormalities epidemiology, Congenital Abnormalities etiology, Cross-Sectional Studies, Female, Geography, Medical, History, 21st Century, Humans, Infant, Male, Middle Aged, Odds Ratio, Patient Outcome Assessment, Polynesia epidemiology, Pregnancy, Pregnancy Complications, Infectious diagnosis, Pregnancy Complications, Infectious history, Public Health Surveillance, Young Adult, Zika Virus Infection diagnosis, Zika Virus Infection virology, Child Development, Maternal Exposure adverse effects, Pregnancy Complications, Infectious epidemiology, Pregnancy Complications, Infectious etiology, Prenatal Exposure Delayed Effects, Zika Virus, Zika Virus Infection complications, Zika Virus Infection epidemiology
- Abstract
Congenital Zika virus syndrome consists of a large spectrum of neurologic abnormalities seen in infants infected with Zika virus in utero. However, little is known about the effects of Zika virus intrauterine infection on the neurocognitive development of children born without birth defects. Using a case-control study design, we investigated the temporal association of a cluster of congenital defects with Zika virus infection. In a nested study, we also assessed the early childhood development of children recruited in the initial study as controls who were born without known birth defects,. We found evidence for an association of congenital defects with both maternal Zika virus seropositivity (time of infection unknown) and symptomatic Zika virus infection during pregnancy. Although the early childhood development assessment found no excess burden of developmental delay associated with maternal Zika virus infection, larger, longer-term studies are needed.
- Published
- 2018
- Full Text
- View/download PDF
40. Using paired serology and surveillance data to quantify dengue transmission and control during a large outbreak in Fiji.
- Author
-
Kucharski AJ, Kama M, Watson CH, Aubry M, Funk S, Henderson AD, Brady OJ, Vanhomwegen J, Manuguerra JC, Lau CL, Edmunds WJ, Aaskov J, Nilles EJ, Cao-Lormeau VM, Hué S, and Hibberd ML
- Subjects
- Adolescent, Adult, Aged, Child, Female, Fiji epidemiology, Humans, Immunity, Herd, Male, Middle Aged, Models, Theoretical, Risk Factors, Seasons, Young Adult, Antibodies, Viral blood, Dengue epidemiology, Dengue transmission, Disease Outbreaks, Disease Transmission, Infectious, Epidemiological Monitoring, Serologic Tests
- Abstract
Dengue is a major health burden, but it can be challenging to examine transmission and evaluate control measures because outbreaks depend on multiple factors, including human population structure, prior immunity and climate. We combined population-representative paired sera collected before and after the 2013/14 dengue-3 outbreak in Fiji with surveillance data to determine how such factors influence transmission and control in island settings. Our results suggested the 10-19 year-old age group had the highest risk of infection, but we did not find strong evidence that other demographic or environmental risk factors were linked to seroconversion. A mathematical model jointly fitted to surveillance and serological data suggested that herd immunity and seasonally varying transmission could not explain observed dynamics. However, the model showed evidence of an additional reduction in transmission coinciding with a vector clean-up campaign, which may have contributed to the decline in cases in the later stages of the outbreak., Competing Interests: AK, MK, CW, MA, SF, AH, OB, JV, JM, CL, WE, JA, EN, VC No competing interests declared, SH SH acknowledges the financial contribution of Janssen Sciences Ireland UC towards the research and completion of this work. MH MH acknowledges the financial contribution of Janssen Sciences Ireland UC towards the research and completion of this work., (© 2018, Kucharski et al.)
- Published
- 2018
- Full Text
- View/download PDF
41. Re-emergence of thiamine deficiency disease in the Pacific islands (2014-15): A case-control study.
- Author
-
Nilles EJ, Manaia A, Ruaia B, Huppatz C, Ward C, George P, Sies C, Cangiano A, Sejvar J, Reiffer A, and Tira T
- Subjects
- Adolescent, Adult, Case-Control Studies, Child, Child, Preschool, Epidemiological Monitoring, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Pacific Islands epidemiology, Risk Factors, Thiamine blood, Thiamine Deficiency blood, Thiamine Deficiency drug therapy, Young Adult, Chromium deficiency, Disease Outbreaks, Thiamine therapeutic use, Thiamine Deficiency epidemiology, Vitamin B Complex therapeutic use
- Abstract
Background: From late 2014 multiple atolls in Kiribati reported an unusual and sometimes fatal illness. We conducted an investigation to identify the etiology of the outbreak on the most severely affected atoll, Kuria, and identified thiamine deficiency disease as the cause. Thiamine deficiency disease has not been reported in the Pacific islands for >5 decades. We present the epidemiological, clinical, and laboratory findings of the investigation., Methodology/principal Findings: We initially conducted detailed interviews and examinations on previously identified cases to characterize the unknown illness and develop a case definition. Active and passive surveillance was then conducted to identify additional cases. A questionnaire to identify potential risk factors and blood samples to assay biochemical indices were collected from cases and asymptomatic controls. Thiamine hydrochloride treatment was implemented and the response to treatment was systematically monitored using a five-point visual analogue scale and by assessing resolution of previously abnormal neurological examination findings. Risk factors and biochemical results were assessed by univariate and multivariate analyses. 69 cases were identified on Kuria (7% attack rate) including 34 confirmed and 35 unconfirmed. Most were adults (median age 28 years [range 0-62]) and 83% were male. Seven adult males and two infants died (13% case fatality rate). Resolution of objective clinical signs (78%) or symptoms (94%) were identified within one week of starting treatment. Risk factors included having a friend with thiamine deficiency disease and drinking kava; drinking yeast alcohol reduced the risk of disease. Higher chromium (p<0·001) but not thiamine deficiency (p = 0·66) or other biochemical indices were associated with disease by univariate analyses. Chromium (p<0·001) and thiamine deficiency (p = 0·02) were associated with disease by multivariate analysis., Conclusions/significance: An outbreak of thiamine deficiency disease (beriberi) in Kiribati signals the re-emergence of a classic nutritional disease in the Pacific islands after five decades. Although treatment is safe and effective, the underlying reason for the re-emergence remains unknown. Chromium was highly and positively correlated with disease in this study raising questions about the potential role of factors other than thiamine in the biochemistry and pathophysiology of clinical disease., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
- Full Text
- View/download PDF
42. Methicillin resistant Staphylococcus Aureus in emergency department patients in the United Arab Emirates.
- Author
-
Al Jalaf M, Fadali H, Alanee R, Najjar F, Al Deesi Z, Seliem RM, and Nilles EJ
- Subjects
- Adolescent, Adult, Anti-Bacterial Agents administration & dosage, Community-Acquired Infections, Female, Humans, Male, Middle Aged, Prospective Studies, Risk Factors, Sex Factors, Soft Tissue Infections drug therapy, Soft Tissue Infections microbiology, Sports, Staphylococcal Skin Infections drug therapy, United Arab Emirates epidemiology, Young Adult, Emergency Service, Hospital statistics & numerical data, Methicillin-Resistant Staphylococcus aureus isolation & purification, Soft Tissue Infections epidemiology, Staphylococcal Infections epidemiology, Staphylococcal Skin Infections epidemiology
- Abstract
Background: Since the 1990s, community-associated methicillin resistant staphylococcus aureus (CA-MRSA) has emerged as an important global cause of skin and soft tissue infections. Little is known about the epidemiology of this pathogen in the Middle East., Methods: We conducted a prospective observational study in a single large teaching hospital in Dubai to identify the incidence of community-acquired methicillin resistant staphylococcus aureus (MRSA) among ambulatory patients presenting with purulent skin and soft tissue infections. We performed wound cultures and administered standard questionnaires to 100 cases presenting to the emergency department. Bivariate and multivariate analyses were performed to identify risk factors for MSRA versus other pathogens., Results: The prevalence of MRSA was 23% (18/78) among 78 culture-positive isolates and 29% (18/62) among Staphylococcus-positive isolates. 74% received antibiotics of which 4/74 (5%) received antibiotics appropriate for CA-MRSA infections. Multivariate adjusted analysis identified playing contact sports (OR 5.9 [95% CI 1.3-27.1]) and female sex (OR 6.3 [95% CI 1.6-24.8]) as independent risks for MRSA infection., Conclusions: This is the first study to describe the epidemiology of CA-MRSA in the ambulatory setting in the Middle East and demonstrates a substantial proportion of cases presenting with skin and soft tissue infections were CA-MRSA. Although most skin and soft tissue infections are abscesses for which the cornerstone of treatment is high quality incision and drainage, if adjunct antibiotics are prescribed in this setting, CA-MRSA-active antibiotics should be considered.
- Published
- 2018
- Full Text
- View/download PDF
43. Use of geographically weighted logistic regression to quantify spatial variation in the environmental and sociodemographic drivers of leptospirosis in Fiji: a modelling study.
- Author
-
Mayfield HJ, Lowry JH, Watson CH, Kama M, Nilles EJ, and Lau CL
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Agriculture, Child, Child, Preschool, Fiji epidemiology, Humans, Infant, Leptospirosis transmission, Logistic Models, Middle Aged, Poverty, Rain, Rural Population, Spatial Analysis, Spatial Regression, Young Adult, Leptospirosis epidemiology, Models, Statistical
- Abstract
Background: Leptospirosis is a globally important zoonotic disease, with complex exposure pathways that depend on interactions between human beings, animals, and the environment. Major drivers of outbreaks include flooding, urbanisation, poverty, and agricultural intensification. The intensity of these drivers and their relative importance vary between geographical areas; however, non-spatial regression methods are incapable of capturing the spatial variations. This study aimed to explore the use of geographically weighted logistic regression (GWLR) to provide insights into the ecoepidemiology of human leptospirosis in Fiji., Methods: We obtained field data from a cross-sectional community survey done in 2013 in the three main islands of Fiji. A blood sample obtained from each participant (aged 1-90 years) was tested for anti-Leptospira antibodies and household locations were recorded using GPS receivers. We used GWLR to quantify the spatial variation in the relative importance of five environmental and sociodemographic covariates (cattle density, distance to river, poverty rate, residential setting [urban or rural], and maximum rainfall in the wettest month) on leptospirosis transmission in Fiji. We developed two models, one using GWLR and one with standard logistic regression; for each model, the dependent variable was the presence or absence of anti-Leptospira antibodies. GWLR results were compared with results obtained with standard logistic regression, and used to produce a predictive risk map and maps showing the spatial variation in odds ratios (OR) for each covariate., Findings: The dataset contained location information for 2046 participants from 1922 households representing 81 communities. The Aikaike information criterion value of the GWLR model was 1935·2 compared with 1254·2 for the standard logistic regression model, indicating that the GWLR model was more efficient. Both models produced similar OR for the covariates, but GWLR also detected spatial variation in the effect of each covariate. Maximum rainfall had the least variation across space (median OR 1·30, IQR 1·27-1·35), and distance to river varied the most (1·45, 1·35-2·05). The predictive risk map indicated that the highest risk was in the interior of Viti Levu, and the agricultural region and southern end of Vanua Levu., Interpretation: GWLR provided a valuable method for modelling spatial heterogeneity of covariates for leptospirosis infection and their relative importance over space. Results of GWLR could be used to inform more place-specific interventions, particularly for diseases with strong environmental or sociodemographic drivers of transmission., Funding: WHO, Australian National Health & Medical Research Council, University of Queensland, UK Medical Research Council, Chadwick Trust., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
44. Facing the Shortage of IV Fluids - A Hospital-Based Oral Rehydration Strategy.
- Author
-
Patiño AM, Marsh RH, Nilles EJ, Baugh CW, Rouhani SA, and Kayden S
- Subjects
- Adult, Clinical Protocols, Humans, Infusions, Intravenous statistics & numerical data, Rehydration Solutions therapeutic use, Sodium Chloride therapeutic use, United States, Fluid Therapy methods, Rehydration Solutions supply & distribution, Sodium Chloride supply & distribution
- Published
- 2018
- Full Text
- View/download PDF
45. Role of Environmental Factors in Shaping Spatial Distribution of Salmonella enterica Serovar Typhi, Fiji.
- Author
-
de Alwis R, Watson C, Nikolay B, Lowry JH, Thieu NTV, Van TT, Ngoc DTT, Rawalai K, Taufa M, Coriakula J, Lau CL, Nilles EJ, Edmunds WJ, Kama M, Baker S, and Cano J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antibodies, Bacterial blood, Child, Child, Preschool, Cluster Analysis, Cross-Sectional Studies, Environmental Microbiology, Fiji epidemiology, Humans, Infant, Infant, Newborn, Middle Aged, Peptides, Cyclic, Risk Factors, Seroepidemiologic Studies, Salmonella typhi physiology, Typhoid Fever epidemiology, Typhoid Fever microbiology
- Abstract
Fiji recently experienced a sharp increase in reported typhoid fever cases. To investigate geographic distribution and environmental risk factors associated with Salmonella enterica serovar Typhi infection, we conducted a cross-sectional cluster survey with associated serologic testing for Vi capsular antigen-specific antibodies (a marker for exposure to Salmonella Typhi in Fiji in 2013. Hotspots with high seroprevalence of Vi-specific antibodies were identified in northeastern mainland Fiji. Risk for Vi seropositivity increased with increased annual rainfall (odds ratio [OR] 1.26/quintile increase, 95% CI 1.12-1.42), and decreased with increased distance from major rivers and creeks (OR 0.89/km increase, 95% CI 0.80-0.99) and distance to modeled flood-risk areas (OR 0.80/quintile increase, 95% CI 0.69-0.92) after being adjusted for age, typhoid fever vaccination, and home toilet type. Risk for exposure to Salmonella Typhi and its spatial distribution in Fiji are driven by environmental factors. Our findings can directly affect typhoid fever control efforts in Fiji.
- Published
- 2018
- Full Text
- View/download PDF
46. Social mixing in Fiji: Who-eats-with-whom contact patterns and the implications of age and ethnic heterogeneity for disease dynamics in the Pacific Islands.
- Author
-
Watson CH, Coriakula J, Ngoc DTT, Flasche S, Kucharski AJ, Lau CL, Thieu NTV, le Polain de Waroux O, Rawalai K, Van TT, Taufa M, Baker S, Nilles EJ, Kama M, and Edmunds WJ
- Subjects
- Animals, Animals, Domestic, Contact Tracing, Fiji, Humans, Ownership, Pacific Islands, Age Factors, Eating, Ethnicity, Salmonella Infections transmission, Social Behavior
- Abstract
Empirical data on contact patterns can inform dynamic models of infectious disease transmission. Such information has not been widely reported from Pacific islands, nor strongly multi-ethnic settings, and few attempts have been made to quantify contact patterns relevant for the spread of gastrointestinal infections. As part of enteric fever investigations, we conducted a cross-sectional survey of the general public in Fiji, finding that within the 9,650 mealtime contacts reported by 1,814 participants, there was strong like-with-like mixing by age and ethnicity, with higher contact rates amongst iTaukei than non-iTaukei Fijians. Extra-domiciliary lunchtime contacts follow these mixing patterns, indicating the overall data do not simply reflect household structures. Inter-ethnic mixing was most common amongst school-age children. Serological responses indicative of recent Salmonella Typhi infection were found to be associated, after adjusting for age, with increased contact rates between meal-sharing iTaukei, with no association observed for other contact groups. Animal ownership and travel within the geographical division were common. These are novel data that identify ethnicity as an important social mixing variable, and use retrospective mealtime contacts as a socially acceptable metric of relevance to enteric, contact and respiratory diseases that can be collected in a single visit to participants. Application of these data to other island settings will enable communicable disease models to incorporate locally relevant mixing patterns in parameterisation.
- Published
- 2017
- Full Text
- View/download PDF
47. A cross-sectional seroepidemiological survey of typhoid fever in Fiji.
- Author
-
Watson CH, Baker S, Lau CL, Rawalai K, Taufa M, Coriakula J, Thieu NTV, Van TT, Ngoc DTT, Hens N, Lowry JH, de Alwis R, Cano J, Jenkins K, Mulholland EK, Nilles EJ, Kama M, and Edmunds WJ
- Subjects
- Adolescent, Adult, Age Distribution, Aged, Antibodies, Bacterial blood, Child, Child, Preschool, Cross-Sectional Studies, Demography, Female, Fiji epidemiology, Humans, Immunoglobulin G blood, Infant, Logistic Models, Male, Middle Aged, Multivariate Analysis, Odds Ratio, Salmonella typhi, Seroepidemiologic Studies, Sex Distribution, Socioeconomic Factors, Surveys and Questionnaires, Young Adult, Sanitation, Typhoid Fever epidemiology, Vaccination statistics & numerical data
- Abstract
Fiji, an upper-middle income state in the Pacific Ocean, has experienced an increase in confirmed case notifications of enteric fever caused by Salmonella enterica serovar Typhi (S. Typhi). To characterize the epidemiology of typhoid exposure, we conducted a cross-sectional sero-epidemiological survey measuring IgG against the Vi antigen of S. Typhi to estimate the effect of age, ethnicity, and other variables on seroprevalence. Epidemiologically relevant cut-off titres were established using a mixed model analysis of data from recovering culture-confirmed typhoid cases. We enrolled and assayed plasma of 1787 participants for anti-Vi IgG; 1,531 of these were resident in mainland areas that had not been previously vaccinated against S. Typhi (seropositivity 32.3% (95%CI 28.2 to 36.3%)), 256 were resident on Taveuni island, which had been previously vaccinated (seropositivity 71.5% (95%CI 62.1 to 80.9%)). The seroprevalence on the Fijian mainland is one to two orders of magnitude higher than expected from confirmed case surveillance incidence, suggesting substantial subclinical or otherwise unreported typhoid. We found no significant differences in seropositivity prevalences by ethnicity, which is in contrast to disease surveillance data in which the indigenous iTaukei Fijian population are disproportionately affected. Using multivariable logistic regression, seropositivity was associated with increased age (odds ratio 1.3 (95% CI 1.2 to 1.4) per 10 years), the presence of a pit latrine (OR 1.6, 95%CI 1.1 to 2.3) as opposed to a septic tank or piped sewer, and residence in settlements rather than residential housing or villages (OR 1.6, 95% CI 1.0 to 2.7). Increasing seropositivity with age is suggestive of low-level endemic transmission in Fiji. Improved sanitation where pit latrines are used and addressing potential transmission routes in settlements may reduce exposure to S. Typhi. Widespread unreported infection suggests there may be a role for typhoid vaccination in Fiji, in addition to public health management of cases and outbreaks.
- Published
- 2017
- Full Text
- View/download PDF
48. Epidemiological Investigation of a Diarrhea Outbreak in the South Pacific Island Nation of Tuvalu During a Severe La Niña-Associated Drought Emergency in 2011.
- Author
-
Emont JP, Ko AI, Homasi-Paelate A, Ituaso-Conway N, and Nilles EJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Case-Control Studies, Child, Child, Preschool, Climate Change, Droughts, Family Characteristics, Female, Hand Disinfection, Health Promotion, Humans, Hygiene, Infant, Infant, Newborn, Logistic Models, Male, Micronesia epidemiology, Middle Aged, Multivariate Analysis, Risk Factors, Young Adult, Diarrhea epidemiology, Disease Outbreaks, El Nino-Southern Oscillation
- Abstract
The association between heavy rainfall and an increased risk of diarrhea has been well established but less is known about the effect of drought on diarrhea transmission. In 2011, the Pacific island nation of Tuvalu experienced a concurrent severe La Niña-associated drought and large diarrhea outbreak. We conducted a field investigation in Tuvalu to identify factors that contributed to epidemic transmission in the context of a drought emergency. Peak case numbers coincided with the nadir of recorded monthly rainfall, the lowest recorded since 1930. Independent factors associated with increased risk of diarrhea were households with water tank levels below 20% (odds ratio [OR] = 2.31; 95% confidence interval = 1.16-4.60) and decreased handwashing frequency (OR = 3.00 [1.48-6.08]). The resolution of the outbreak occurred after implementation of a hygiene promotion campaign, despite persistent drought and limited water access. These findings are potentially important given projections that future climate change will cause more frequent and severe droughts.
- Published
- 2017
- Full Text
- View/download PDF
49. Investigation of a Guillain-Barré syndrome cluster in the Republic of Fiji.
- Author
-
Pastula DM, Khan AS, Sharp TM, Biaukula VL, Naivalu TK, Rafai E, Ermias Belay, Staples JE, Fischer M, Kosoy OI, Laven JJ, Bennett EJ, Jenney AWJ, Naidu RN, Lanciotti RS, Galloway RL, Nilles EJ, Sejvar JJ, and Kama M
- Subjects
- Adolescent, Adult, Age Factors, Case-Control Studies, Child, Child, Preschool, Dengue epidemiology, Dengue genetics, Female, Fiji epidemiology, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, Neurologic Examination, Young Adult, Dengue complications, Guillain-Barre Syndrome epidemiology, Guillain-Barre Syndrome etiology
- Abstract
Background: In 2014, we investigated a cluster of Guillain-Barre syndrome (GBS) in Fiji that occurred during a dengue epidemic. We designed a case-control study to determine the etiology., Methods: Cases were patients meeting Brighton Collaboration criteria for GBS with onset from February 2014 to May 2014. Controls were persons without symptoms of GBS who were matched by age group and location. We collected information on demographics and potential exposures. Serum samples were tested for evidence of recent arboviral or Leptospira spp. infections., Results: Nine cases of GBS were identified for an incidence of five cases per 100,000 population/year. Median age of cases was 27years (range: 0.8-52); five (56%) were male. Six (67%) reported an acute illness prior to GBS onset. Among the 9 cases and 28 controls enrolled, odds ratios for reported exposures or antibodies against various arboviruses or Leptospira spp. were not statistically significant., Conclusions: No clear etiologies were identified for this unusual GBS cluster. There was a temporal association between the GBS cluster and a dengue epidemic, but we were unable to substantiate an epidemiologic or laboratory association. Further study is needed to explore potential associations between arboviral infections and GBS., (Copyright © 2016. Published by Elsevier B.V.)
- Published
- 2017
- Full Text
- View/download PDF
50. Early warning epidemic surveillance in the Pacific island nations: an evaluation of the Pacific syndromic surveillance system.
- Author
-
Craig AT, Kama M, Samo M, Vaai S, Matanaicake J, Joshua C, Kolbe A, Durrheim DN, Paterson BJ, Biaukula V, and Nilles EJ
- Subjects
- Humans, Pacific Islands, Communicable Disease Control, Disease Outbreaks, Sentinel Surveillance
- Abstract
Objective: The Pacific Syndromic Surveillance System (PSSS), launched in 2010, provides a simple mechanism by which 121 sentinel surveillance sites in 21 Pacific island countries and areas perform routine indicator- and event-based surveillance for the early detection of infectious disease outbreaks. This evaluation aims to assess whether the PSSS is meeting its objectives, what progress has been made since a formative evaluation of the system was conducted in 2011, and provides recommendations to enhance the PSSS's performance in the future., Methods: Twenty-one informant interviews were conducted with national operators of the system and regional public health agencies that use information generated by it. Historic PSSS data were analysed to assess timeliness and completeness of reporting., Results: The system is simple, acceptable and useful for public health decision-makers. The PSSS has greatly enhanced Pacific island countries' ability to undertake early warning surveillance and has contributed to efforts to meet national surveillance-related International Health Regulation (2005) capacity development obligations. Despite this, issues with timeliness and completeness of reporting, data quality and system stability persist., Conclusion: A balance between maintaining the system's simplicity and technical advances will need to be found to ensure its long-term sustainability, given the low-resource context for which it is designed., (© 2016 John Wiley & Sons Ltd.)
- 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.