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Article ; Online: The changing health impact of vaccines in the COVID-19 pandemic

Jamie A. Cohen / Robyn M. Stuart / Jasmina Panovska-Griffiths / Edinah Mudimu / Romesh G. Abeysuriya / Cliff C. Kerr / Michael Famulare / Daniel J. Klein

Cell Reports, Vol 42, Iss 4, Pp 112308- (2023)

A modeling study

2023

Abstract: Summary: Much of the world’s population had already been infected with COVID-19 by the time the Omicron variant emerged at the end of 2021, but the scale of the Omicron wave was larger than any that had come before or has happened since, and it left a ... ...

Abstract	Summary: Much of the world’s population had already been infected with COVID-19 by the time the Omicron variant emerged at the end of 2021, but the scale of the Omicron wave was larger than any that had come before or has happened since, and it left a global imprinting of immunity that changed the COVID-19 landscape. In this study, we simulate a South African population and demonstrate how population-level vaccine effectiveness and efficiency changed over the course of the first 2 years of the pandemic. We then introduce three hypothetical variants and evaluate the impact of vaccines with different properties. We find that variant-chasing vaccines have a narrow window of dominating pre-existing vaccines but that a variant-chasing vaccine strategy may have global utility, depending on the rate of spread from setting to setting. Next-generation vaccines might be able to overcome uncertainty in pace and degree of viral evolution.
Keywords	CP: Immunology ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Individual and community-level benefits of PrEP in western Kenya and South Africa

Edinah Mudimu / Kathryn Peebles / Zindoga Mukandavire / Emily Nightingale / Monisha Sharma / Graham F Medley / Daniel J Klein / Katharine Kripke / Anna Bershteyn

PLoS ONE, Vol 15, Iss 12, p e

Implications for population prioritization of PrEP provision.

2020 Volume 0244761

Abstract: Background Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV and has the potential to significantly impact the HIV epidemic. Given limited resources for HIV prevention, identifying PrEP provision strategies that maximize impact is ... ...

Abstract	Background Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV and has the potential to significantly impact the HIV epidemic. Given limited resources for HIV prevention, identifying PrEP provision strategies that maximize impact is critical. Methods We used a stochastic individual-based network model to evaluate the direct (infections prevented among PrEP users) and indirect (infections prevented among non-PrEP users as a result of PrEP) benefits of PrEP, the person-years of PrEP required to prevent one HIV infection, and the community-level impact of providing PrEP to populations defined by gender and age in western Kenya and South Africa. We examined sensitivity of results to scale-up of antiretroviral therapy (ART) and voluntary medical male circumcision (VMMC) by comparing two scenarios: maintaining current coverage ("status quo") and rapid scale-up to meet programmatic targets ("fast-track"). Results The community-level impact of PrEP was greatest among women aged 15-24 due to high incidence, while PrEP use among men aged 15-24 yielded the highest proportion of indirect infections prevented in the community. These indirect infections prevented continue to increase over time (western Kenya: 0.4-5.5 (status quo); 0.4-4.9 (fast-track); South Africa: 0.5-1.8 (status quo); 0.5-3.0 (fast-track)) relative to direct infections prevented among PrEP users. The number of person-years of PrEP needed to prevent one HIV infection was lower (59 western Kenya and 69 in South Africa in the status quo scenario; 201 western Kenya and 87 in South Africa in the fast-track scenario) when PrEP was provided only to women compared with only to men over time horizons of up to 5 years, as the indirect benefits of providing PrEP to men accrue in later years. Conclusions Providing PrEP to women aged 15-24 prevents the greatest number of HIV infections per person-year of PrEP, but PrEP provision for young men also provides indirect benefits to women and to the community overall. This finding supports existing policies that prioritize PrEP use for young women, while also illuminating the community-level benefits of PrEP availability for men when resources permit.
Keywords	Medicine ; R ; Science ; Q
Subject code	360
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Separatrix Algorithm for synthesis and analysis of stochastic simulations with applications in disease modeling.

Daniel J Klein / Michael Baym / Philip Eckhoff

PLoS ONE, Vol 9, Iss 7, p e

2014 Volume 103467

Abstract: Decision makers in epidemiology and other disciplines are faced with the daunting challenge of designing interventions that will be successful with high probability and robust against a multitude of uncertainties. To facilitate the decision making ... ...

Abstract	Decision makers in epidemiology and other disciplines are faced with the daunting challenge of designing interventions that will be successful with high probability and robust against a multitude of uncertainties. To facilitate the decision making process in the context of a goal-oriented objective (e.g., eradicate polio by [Formula: see text]), stochastic models can be used to map the probability of achieving the goal as a function of parameters. Each run of a stochastic model can be viewed as a Bernoulli trial in which "success" is returned if and only if the goal is achieved in simulation. However, each run can take a significant amount of time to complete, and many replicates are required to characterize each point in parameter space, so specialized algorithms are required to locate desirable interventions. To address this need, we present the Separatrix Algorithm, which strategically locates parameter combinations that are expected to achieve the goal with a user-specified probability of success (e.g. 95%). Technically, the algorithm iteratively combines density-corrected binary kernel regression with a novel information-gathering experiment design to produce results that are asymptotically correct and work well in practice. The Separatrix Algorithm is demonstrated on several test problems, and on a detailed individual-based simulation of malaria.
Keywords	Medicine ; R ; Science ; Q
Subject code	006
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Controlling COVID-19 via test-trace-quarantine

Cliff C. Kerr / Dina Mistry / Robyn M. Stuart / Katherine Rosenfeld / Gregory R. Hart / Rafael C. Núñez / Jamie A. Cohen / Prashanth Selvaraj / Romesh G. Abeysuriya / Michał Jastrzębski / Lauren George / Brittany Hagedorn / Jasmina Panovska-Griffiths / Meaghan Fagalde / Jeffrey Duchin / Michael Famulare / Daniel J. Klein

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 12

Abstract: Initial COVID-19 containment in the United States focused on limiting mobility, including school and workplace closures, with enormous societal and economic costs. Here, the authors demonstrate the feasibility of a test-trace-quarantine strategy using an ...

Abstract	Initial COVID-19 containment in the United States focused on limiting mobility, including school and workplace closures, with enormous societal and economic costs. Here, the authors demonstrate the feasibility of a test-trace-quarantine strategy using an agent-based model and detailed data on the Seattle region.
Keywords	Science ; Q
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The emerging health impact of voluntary medical male circumcision in Zimbabwe

Jessica B McGillen / John Stover / Daniel J Klein / Sinokuthemba Xaba / Getrude Ncube / Mutsa Mhangara / Geraldine N Chipendo / Isaac Taramusi / Leo Beacroft / Timothy B Hallett / Patrick Odawo / Rumbidzai Manzou / Eline L Korenromp

PLoS ONE, Vol 13, Iss 7, p e

An evaluation using three epidemiological models.

2018 Volume 0199453

Abstract: Background Zimbabwe adopted voluntary medical male circumcision (VMMC) as a priority HIV prevention strategy in 2007 and began implementation in 2009. We evaluated the costs and impact of this VMMC program to date and in future. Methods Three ... ...

Abstract	Background Zimbabwe adopted voluntary medical male circumcision (VMMC) as a priority HIV prevention strategy in 2007 and began implementation in 2009. We evaluated the costs and impact of this VMMC program to date and in future. Methods Three mathematical models describing Zimbabwe's HIV epidemic and program evolution were calibrated to household survey data on prevalence and risk behaviors, with circumcision coverage calibrated to program-reported VMMCs. We compared trends in new infections and costs to a counterfactual without VMMC. Input assumptions were agreed in workshops with national stakeholders in 2015 and 2017. Results The VMMC program averted 2,600-12,200 infections (among men and women combined) by the end of 2016. This impact will grow as circumcised men are protected lifelong, and onward dynamic transmission effects, which protect women via reduced incidence and prevalence in their male partners, increase over time. If other prevention interventions remain at 2016 coverages, the VMMCs already performed will avert 24,400-69,800 infections (2.3-5% of all new infections) through 2030. If coverage targets are achieved by 2021 and maintained, the program will avert 108,000-171,000 infections (10-13% of all new infections) by 2030, costing $2,100-3,250 per infection averted relative to no VMMC. Annual savings from averted treatment needs will outweigh VMMC maintenance costs once coverage targets are reached. If Zimbabwe also achieves ambitious UNAIDS targets for scaling up treatment and prevention efforts, VMMC will reduce the HIV incidence remaining at 2030 by one-third, critically contributing to the UNAIDS goal of 90% incidence reduction. Conclusions VMMC can substantially impact Zimbabwe's HIV epidemic in the coming years; this investment will save costs in the longer term.
Keywords	Medicine ; R ; Science ; Q
Subject code	360
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Quantifying the impact of expanded age group campaigns for polio eradication.

Bradley G Wagner / Matthew R Behrend / Daniel J Klein / Alexander M Upfill-Brown / Philip A Eckhoff / Hao Hu

PLoS ONE, Vol 9, Iss 12, p e

2014 Volume 113538

Abstract: A priority of the Global Polio Eradication Initiative (GPEI) 2013-2018 strategic plan is to evaluate the potential impact on polio eradication resulting from expanding one or more Supplementary Immunization Activities (SIAs) to children beyond age five- ... ...

Abstract	A priority of the Global Polio Eradication Initiative (GPEI) 2013-2018 strategic plan is to evaluate the potential impact on polio eradication resulting from expanding one or more Supplementary Immunization Activities (SIAs) to children beyond age five-years in polio endemic countries. It has been hypothesized that such expanded age group (EAG) campaigns could accelerate polio eradication by eliminating immunity gaps in older children that may have resulted from past periods of low vaccination coverage. Using an individual-based mathematical model, we quantified the impact of EAG campaigns in terms of probability of elimination, reduction in polio transmission and age stratified immunity levels. The model was specifically calibrated to seroprevalence data from a polio-endemic region: Zaria, Nigeria. We compared the impact of EAG campaigns, which depend only on age, to more targeted interventions which focus on reaching missed populations. We found that EAG campaigns would not significantly improve prospects for polio eradication; the probability of elimination increased by 8% (from 24% at baseline to 32%) when expanding three annual SIAs to 5-14 year old children and by 18% when expanding all six annual SIAs. In contrast, expanding only two of the annual SIAs to target hard-to-reach populations at modest vaccination coverage-representing less than one tenth of additional vaccinations required for the six SIA EAG scenario-increased the probability of elimination by 55%. Implementation of EAG campaigns in polio endemic regions would not improve prospects for eradication. In endemic areas, vaccination campaigns which do not target missed populations will not benefit polio eradication efforts.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2014-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Estimating and mitigating the risk of COVID-19 epidemic rebound associated with reopening of international borders in Vietnam

Quang D Pham, MD / Robyn M Stuart, PhD / Thuong V Nguyen, MD / Quang C Luong, MD / Quang D Tran, PhD / Thai Q Pham, PhD / Lan T Phan, ProfPhD / Tan Q Dang, PhD / Duong N Tran, PhD / Hung T Do, PhD / Dina Mistry, PhD / Daniel J Klein, PhD / Romesh G Abeysuriya, PhD / Assaf P Oron, PhD / Cliff C Kerr, PhD

The Lancet Global Health, Vol 9, Iss 7, Pp e916-e

a modelling study

2021 Volume 924

Abstract: Summary: Background: Vietnam has emerged as one of the world's leading success stories in responding to COVID-19. After a prolonged period of little to no transmission, there was an outbreak of unknown source in July, 2020, in the Da Nang region, but the ...

Abstract	Summary: Background: Vietnam has emerged as one of the world's leading success stories in responding to COVID-19. After a prolonged period of little to no transmission, there was an outbreak of unknown source in July, 2020, in the Da Nang region, but the outbreak was quickly suppressed. We aimed to use epidemiological, behavioural, demographic, and policy data from the COVID-19 outbreak in Da Nang to calibrate an agent-based model of COVID-19 transmission for Vietnam, and to estimate the risk of future outbreaks associated with reopening of international borders in the country. Methods: For this modelling study, we used comprehensive data from June 15 to Oct 15, 2020, on testing, COVID-19 cases, and quarantine breaches within an agent-based model of SARS-CoV-2 transmission to model a COVID-19 outbreak in Da Nang in July, 2020. We applied this model to quantify the risk of future outbreaks in Vietnam in the 3 months after the reopening of international borders, under different behavioural scenarios, policy responses (ie, closure of workplaces and schools), and ongoing testing. Findings: We estimated that the outbreak in Da Nang between July and August, 2020, resulted in substantial community transmission, and that higher levels of symptomatic testing could have mitigated this transmission. We estimated that the outbreak peaked on Aug 2, 2020, with an estimated 1060 active infections (95% projection interval 890–1280). If the population of Vietnam remains highly compliant with mask-wearing policies, our projections indicate that the epidemic would remain under control even if a small but steady flow of imported infections escaped quarantine into the community. However, if complacency increases and testing rates are relatively low (10% of symptomatic individuals are tested), the epidemic could rebound again, resulting in an estimated 2100 infections (95% projected interval 1050–3610) in 3 months. These outcomes could be mitigated if the behaviour of the general population responds dynamically to increases in ...
Keywords	Public aspects of medicine ; RA1-1270
Subject code	333
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Covasim

Cliff C Kerr / Robyn M Stuart / Dina Mistry / Romesh G Abeysuriya / Katherine Rosenfeld / Gregory R Hart / Rafael C Núñez / Jamie A Cohen / Prashanth Selvaraj / Brittany Hagedorn / Lauren George / Michał Jastrzębski / Amanda S Izzo / Greer Fowler / Anna Palmer / Dominic Delport / Nick Scott / Sherrie L Kelly / Caroline S Bennette /

Bradley G Wagner / Stewart T Chang / Assaf P Oron / Edward A Wenger / Jasmina Panovska-Griffiths / Michael Famulare / Daniel J Klein

PLoS Computational Biology, Vol 17, Iss 7, p e

An agent-based model of COVID-19 dynamics and interventions.

2021 Volume 1009149

Abstract: The COVID-19 pandemic has created an urgent need for models that can project epidemic trends, explore intervention scenarios, and estimate resource needs. Here we describe the methodology of Covasim (COVID-19 Agent-based Simulator), an open-source model ... ...

Abstract	The COVID-19 pandemic has created an urgent need for models that can project epidemic trends, explore intervention scenarios, and estimate resource needs. Here we describe the methodology of Covasim (COVID-19 Agent-based Simulator), an open-source model developed to help address these questions. Covasim includes country-specific demographic information on age structure and population size; realistic transmission networks in different social layers, including households, schools, workplaces, long-term care facilities, and communities; age-specific disease outcomes; and intrahost viral dynamics, including viral-load-based transmissibility. Covasim also supports an extensive set of interventions, including non-pharmaceutical interventions, such as physical distancing and protective equipment; pharmaceutical interventions, including vaccination; and testing interventions, such as symptomatic and asymptomatic testing, isolation, contact tracing, and quarantine. These interventions can incorporate the effects of delays, loss-to-follow-up, micro-targeting, and other factors. Implemented in pure Python, Covasim has been designed with equal emphasis on performance, ease of use, and flexibility: realistic and highly customized scenarios can be run on a standard laptop in under a minute. In collaboration with local health agencies and policymakers, Covasim has already been applied to examine epidemic dynamics and inform policy decisions in more than a dozen countries in Africa, Asia-Pacific, Europe, and North America.
Keywords	Biology (General) ; QH301-705.5
Subject code	360
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Assessment of epidemic projections using recent HIV survey data in South Africa

Dr. Jeffrey W Eaton, PhD / Nicolas Bacaër, PhD / Anna Bershteyn, PhD / Valentina Cambiano, PhD / Anne Cori, PhD / Prof. Rob E Dorrington, MPhil / Prof. Christophe Fraser, PhD / Chaitra Gopalappa, PhD / Jan A C Hontelez, PhD / Leigh F Johnson, PhD / Daniel J Klein, PhD / Prof. Andrew N Phillips, PhD / Carel Pretorius, PhD / John Stover, MA / Prof. Thomas M Rehle, MD / Prof. Timothy B Hallett, PhD

The Lancet Global Health, Vol 3, Iss 10, Pp e598-e

a validation analysis of ten mathematical models of HIV epidemiology in the antiretroviral therapy era

2015 Volume 608

Abstract: Background: Mathematical models are widely used to simulate the effects of interventions to control HIV and to project future epidemiological trends and resource needs. We aimed to validate past model projections against data from a large household ... ...

Abstract	Background: Mathematical models are widely used to simulate the effects of interventions to control HIV and to project future epidemiological trends and resource needs. We aimed to validate past model projections against data from a large household survey done in South Africa in 2012. Methods: We compared ten model projections of HIV prevalence, HIV incidence, and antiretroviral therapy (ART) coverage for South Africa with estimates from national household survey data from 2012. Model projections for 2012 were made before the publication of the 2012 household survey. We compared adult (age 15–49 years) HIV prevalence in 2012, the change in prevalence between 2008 and 2012, and prevalence, incidence, and ART coverage by sex and by age groups between model projections and the 2012 household survey. Findings: All models projected lower prevalence estimates for 2012 than the survey estimate (18·8%), with eight models' central projections being below the survey 95% CI (17·5–20·3). Eight models projected that HIV prevalence would remain unchanged (n=5) or decline (n=3) between 2008 and 2012, whereas prevalence estimates from the household surveys increased from 16·9% in 2008 to 18·8% in 2012 (difference 1·9, 95% CI −0·1 to 3·9). Model projections accurately predicted the 1·6 percentage point prevalence decline (95% CI −0·3 to 3·5) in young adults aged 15–24 years, and the 2·2 percentage point (0·5 to 3·9) increase in those aged 50 years and older. Models accurately represented the number of adults on ART in 2012; six of ten models were within the survey 95% CI of 1·54–2·12 million. However, the differential ART coverage between women and men was not fully captured; all model projections of the sex ratio of women to men on ART were lower than the survey estimate of 2·22 (95% CI 1·73–2·71). Interpretation: Projections for overall declines in HIV epidemics during the ART era might have been optimistic. Future treatment and HIV prevention needs might be greater than previously forecasted. Additional data about service ...
Keywords	Public aspects of medicine ; RA1-1270
Subject code	310
Language	English
Publishing date	2015-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: HIV treatment as prevention

Jeffrey W Eaton / Leigh F Johnson / Joshua A Salomon / Till Bärnighausen / Eran Bendavid / Anna Bershteyn / David E Bloom / Valentina Cambiano / Christophe Fraser / Jan A C Hontelez / Salal Humair / Daniel J Klein / Elisa F Long / Andrew N Phillips / Carel Pretorius / John Stover / Edward A Wenger / Brian G Williams / Timothy B Hallett

PLoS Medicine, Vol 9, Iss 7, p e

systematic comparison of mathematical models of the potential impact of antiretroviral therapy on HIV incidence in South Africa.

2012 Volume 1001245

Abstract: Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and ...

Abstract	Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART.Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/µl and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results.Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all ...
Keywords	Medicine ; R
Subject code	306
Language	English
Publishing date	2012-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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