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Article ; Online: Predicting vaccine effectiveness against severe COVID-19 over time and against variants

Deborah Cromer / Megan Steain / Arnold Reynaldi / Timothy E. Schlub / Shanchita R. Khan / Sarah C. Sasson / Stephen J. Kent / David S. Khoury / Miles P. Davenport

Nature Communications, Vol 14, Iss 1, Pp 1-

a meta-analysis

2023 Volume 9

Abstract: In this study, the authors perform a meta-analysis of COVID-19 vaccine effectiveness studies and compare observed protection against severe disease with model-based estimates of neutralising antibody titres. Their results show that SARS-CoV-2 antibody ... ...

Abstract	In this study, the authors perform a meta-analysis of COVID-19 vaccine effectiveness studies and compare observed protection against severe disease with model-based estimates of neutralising antibody titres. Their results show that SARS-CoV-2 antibody titres are predictive of protection against severe COVID-19 disease.
Keywords	Science ; Q
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evidence for exposure dependent carriage of malaria parasites across the dry season

Eva Stadler / Deborah Cromer / Samson Ogunlade / Aissata Ongoiba / Safiatou Doumbo / Kassoum Kayentao / Boubacar Traore / Peter D. Crompton / Silvia Portugal / Miles P. Davenport / David S. Khoury

Malaria Journal, Vol 22, Iss 1, Pp 1-

modelling analysis of longitudinal data

2023 Volume 13

Abstract: Abstract Background In malaria endemic regions, transmission of Plasmodium falciparum parasites is often seasonal with very low transmission during the dry season and high transmission in the wet season. Parasites survive the dry season within some ... ...

Abstract	Abstract Background In malaria endemic regions, transmission of Plasmodium falciparum parasites is often seasonal with very low transmission during the dry season and high transmission in the wet season. Parasites survive the dry season within some individuals who experience prolonged carriage of parasites and are thought to ‘seed’ infection in the next transmission season. Methods Dry season carriers and their role in the subsequent transmission season are characterized using a combination of mathematical simulations and data analysis of previously described data from a longitudinal study in Mali of individuals aged 3 months–12 years (n = 579). Results Simulating the life-history of individuals experiencing repeated exposure to infection predicts that dry season carriage is more likely in the oldest, most exposed and most immune individuals. This hypothesis is supported by the data from Mali, which shows that carriers are significantly older, experience a higher biting rate at the beginning of the transmission season and develop clinical malaria later than non-carriers. Further, since the most exposed individuals in a community are most likely to be dry season carriers, this is predicted to enable a more than twofold faster spread of parasites into the mosquito population at the start of the subsequent wet season. Conclusions Carriage of malaria parasites over the months-long dry season in Mali is most likely in the older, more exposed and more immune children. These children may act as super-spreaders facilitating the fast spread of parasites at the beginning of the next transmission season.
Keywords	Seasonal transmission ; Plasmodium falciparum ; Within-host model ; Parasite carriage ; Mali ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-term vaccination strategies to mitigate the impact of SARS-CoV-2 transmission

Alexandra B Hogan / Sean L Wu / Jaspreet Toor / Daniela Olivera Mesa / Patrick Doohan / Oliver J Watson / Peter Winskill / Giovanni Charles / Gregory Barnsley / Eleanor M Riley / David S Khoury / Neil M Ferguson / Azra C Ghani

PLoS Medicine, Vol 20, Iss 11, p e

A modelling study.

2023 Volume 1004195

Abstract: Background Vaccines have reduced severe disease and death from Coronavirus Disease 2019 (COVID-19). However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular ... ...

Abstract	Background Vaccines have reduced severe disease and death from Coronavirus Disease 2019 (COVID-19). However, with evidence of waning efficacy coupled with continued evolution of the virus, health programmes need to evaluate the requirement for regular booster doses, considering their impact and cost-effectiveness in the face of ongoing transmission and substantial infection-induced immunity. Methods and findings We developed a combined immunological-transmission model parameterised with data on transmissibility, severity, and vaccine effectiveness. We simulated Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission and vaccine rollout in characteristic global settings with different population age-structures, contact patterns, health system capacities, prior transmission, and vaccine uptake. We quantified the impact of future vaccine booster dose strategies with both ancestral and variant-adapted vaccine products, while considering the potential future emergence of new variants with modified transmission, immune escape, and severity properties. We found that regular boosting of the oldest age group (75+) is an efficient strategy, although large numbers of hospitalisations and deaths could be averted by extending vaccination to younger age groups. In countries with low vaccine coverage and high infection-derived immunity, boosting older at-risk groups was more effective than continuing primary vaccination into younger ages in our model. Our study is limited by uncertainty in key parameters, including the long-term durability of vaccine and infection-induced immunity as well as uncertainty in the future evolution of the virus. Conclusions Our modelling suggests that regular boosting of the high-risk population remains an important tool to reduce morbidity and mortality from current and future SARS-CoV-2 variants. Our results suggest that focusing vaccination in the highest-risk cohorts will be the most efficient (and hence cost-effective) strategy to reduce morbidity and mortality.
Keywords	Medicine ; R
Subject code	910
Language	English
Publishing date	2023-11-01T00:00:00Z
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 and preventing Plasmodium vivax recurrences in primaquine-untreated pregnant women

Rodrigo M Corder / Antonio C P de Lima / David S Khoury / Steffen S Docken / Miles P Davenport / Marcelo U Ferreira

PLoS Neglected Tropical Diseases, Vol 14, Iss 7, p e

An observational and modeling study in Brazil.

2020 Volume 0008526

Abstract: Each year, 4.3 million pregnant women are exposed to malaria risk in Latin America and the Caribbean. Plasmodium vivax causes 76% of the regional malaria burden and appears to be less affected than P. falciparum by current elimination efforts. This is in ...

Abstract	Each year, 4.3 million pregnant women are exposed to malaria risk in Latin America and the Caribbean. Plasmodium vivax causes 76% of the regional malaria burden and appears to be less affected than P. falciparum by current elimination efforts. This is in part due to the parasite's ability to stay dormant in the liver and originate relapses within months after a single mosquito inoculation. Primaquine (PQ) is routinely combined with chloroquine (CQ) or other schizontocidal drugs to supress P. vivax relapses and reduce the risk of late blood-stage recrudescences of parasites with low-grade CQ resistance. However, PQ is contraindicated for pregnant women, who remain at increased risk of repeated infections following CQ-only treatment. Here we apply a mathematical model to time-to-recurrence data from Juruá Valley, Brazil's main malaria transmission hotspot, to quantify the extra burden of parasite recurrences attributable to PQ ineligibility in pregnant women. The model accounts for competing risks, since relapses and late recrudescences (that may be at least partially prevented by PQ) and new infections (that are not affected by PQ use) all contribute to recurrences. We compare recurrence rates observed after primary P. vivax infections in 158 pregnant women treated with CQ only and 316 P. vivax infections in non-pregnant control women, matched for age, date of infection, and place of residence, who were administered a standard CQ-PQ combination. We estimate that, once infected with P. vivax, 23% of the pregnant women have one or more vivax malaria recurrences over the next 12 weeks; 86% of these early P. vivax recurrences are attributable to relapses or late recrudescences, rather than new infections that could be prevented by reducing malaria exposure during pregnancy. Model simulations indicate that weekly CQ chemoprophylaxis extending over 4 to 12 weeks, starting after the first vivax malaria episode diagnosed in pregnancy, might reduce the risk of P. vivax recurrences over the next 12 months by 20% to 65%. We ...
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2020-07-01T00:00:00Z
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: Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting

Deborah Cromer, PhD / Megan Steain, PhD / Arnold Reynaldi, PhD / Timothy E Schlub, PhD / Adam K Wheatley, PhD / Jennifer A Juno, PhD / Stephen J Kent, MD / James A Triccas, PhD / David S Khoury, PhD / Miles P Davenport, DPhil

The Lancet Microbe, Vol 3, Iss 1, Pp e52-e

a meta-analysis

2022 Volume 61

Abstract: Summary: Background: Several SARS-CoV-2 variants of concern have been identified that partly escape serum neutralisation elicited by current vaccines. Studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with ...

Abstract	Summary: Background: Several SARS-CoV-2 variants of concern have been identified that partly escape serum neutralisation elicited by current vaccines. Studies have also shown that vaccines demonstrate reduced protection against symptomatic infection with SARS-CoV-2 variants. We explored whether in-vitro neutralisation titres remain predictive of vaccine protection from infection with SARS-CoV-2 variants. Methods: In this meta-analysis, we analysed published data from 24 identified studies on in-vitro neutralisation and clinical protection to understand the loss of neutralisation to existing SARS-CoV-2 variants of concern. We integrated the results of this analysis into our existing statistical model relating in-vitro neutralisation to protection (parameterised on data from ancestral virus infection) to estimate vaccine efficacy against SARS-CoV-2 variants. We also analysed data on boosting of vaccine responses and use the model to predict the impact of booster vaccination on protection against SARS-CoV-2 variants. Findings: The neutralising activity against the ancestral SARS-CoV-2 was highly predictive of neutralisation of variants of concern. Decreases in neutralisation titre to the alpha (1·6-fold), beta (8·8-fold), gamma (3·5-fold), and delta (3·9-fold) variants (compared to the ancestral virus) were not significantly different between different vaccines. Neutralisation remained strongly correlated with protection from symptomatic infection with SARS-CoV-2 variants of concern (rS=0·81, p=0·0005) and the existing model remained predictive of vaccine efficacy against variants of concern once decreases in neutralisation to the variants of concern were incorporated. Modelling of predicted vaccine efficacy against variants over time suggested that protection against symptomatic infection might decrease below 50% within the first year after vaccination for some vaccines. Boosting of previously infected individuals with existing vaccines (which target ancestral virus) is predicted to provide a higher degree of protection from infection with variants of concern than primary vaccination schedules alone. Interpretation: In-vitro neutralisation titres remain a correlate of protection from SARS-CoV-2 variants and modelling of the effects of waning immunity predicts a loss of protection to the variants after vaccination. However, booster vaccination with current vaccines should enable higher neutralisation to SARS-CoV-2 variants than is achieved with primary vaccination, which is predicted to provide robust protection from severe infection outcomes with the current SARS-CoV-2 variants of concern, at least in the medium term. Funding: The National Health and Medical Research Council (Australia), the Medical Research Future Fund (Australia), and the Victorian Government.
Keywords	Medicine (General) ; R5-920 ; Microbiology ; QR1-502
Subject code	570
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Similarly efficacious anti-malarial drugs SJ733 and pyronaridine differ in their ability to remove circulating parasites in mice

Arya SheelaNair / Aleksandra S. Romanczuk / Rosemary A. Aogo / Rohit Nemai Haldar / Lianne I. M. Lansink / Deborah Cromer / Yandira G. Salinas / R. Kiplin Guy / James S. McCarthy / Miles P. Davenport / Ashraful Haque / David S. Khoury

Malaria Journal, Vol 21, Iss 1, Pp 1-

2022 Volume 10

Abstract: Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating ... ...

Abstract	Abstract Background Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the “parasite clearance curve”, has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation. Methods In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine were compared against sodium artesunate in mice infected with Plasmodium berghei (strain ANKA). To measure each compound’s capacity for pRBC removal in vivo, flow cytometric monitoring of a single cohort of fluorescently-labelled pRBC was employed, and combined with ex vivo parasite culture to assess parasite maturation and replication. Results These three compounds were found to be similarly efficacious in controlling established infection by reducing overall parasitaemia. While sodium artesunate acted relatively consistently across the life-stages, single-dose SJ733 elicited a biphasic effect, triggering rapid, partly phagocyte-dependent removal of trophozoites and schizonts, followed by arrest of residual ring-stages. In contrast, pyronaridine abrogated maturation of younger parasites, with less pronounced effects on mature parasites, while modestly increasing pRBC removal. Conclusions Anti-malarials SJ733 and pyronaridine, though similarly efficacious in reducing overall parasitaemia in mice, differed markedly in their capacity to arrest replication and remove pRBC from circulation. Thus, similar parasite clearance curves can result for anti-malarials with distinct capacities to inhibit, kill and clear parasites.
Keywords	SJ733 ; Pyronaridine ; Artesunate ; Plasmodium berghei ; Parasite clearance ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
Subject code	572
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Population heterogeneity in Plasmodium vivax relapse risk.

Eva Stadler / Deborah Cromer / Somya Mehra / Adeshina I Adekunle / Jennifer A Flegg / Nicholas M Anstey / James A Watson / Cindy S Chu / Ivo Mueller / Leanne J Robinson / Timothy E Schlub / Miles P Davenport / David S Khoury

PLoS Neglected Tropical Diseases, Vol 16, Iss 12, p e

2022 Volume 0010990

Abstract: A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation ... ...

Abstract	A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P vivax endemic regions and are thought to be influenced by factors such as febrile infections which may cause temporary changes in hypnozoite activation leading to 'temporal heterogeneity' in reactivation risk. In addition, immunity and variation in exposure to infection may be longer-term characteristics of individuals that lead to 'population heterogeneity' in hypnozoite activation. We analyze data on risk of P vivax in two previously published data sets from Papua New Guinea and the Thailand-Myanmar border region. Modeling different mechanisms of reactivation risk, we find strong evidence for population heterogeneity, with 30% of patients having almost 70% of all P vivax infections. Model fitting and data analysis indicates that individual variation in relapse risk is a primary source of heterogeneity of P vivax risk of recurrences. Trial Registration: ClinicalTrials.gov NCT01640574, NCT01074905, NCT02143934.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2022-12-01T00:00:00Z
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: Modelling food and population dynamics in honey bee colonies.

David S Khoury / Andrew B Barron / Mary R Myerscough

PLoS ONE, Vol 8, Iss 5, p e

2013 Volume 59084

Abstract: Honey bees (Apis mellifera) are increasingly in demand as pollinators for various key agricultural food crops, but globally honey bee populations are in decline, and honey bee colony failure rates have increased. This scenario highlights a need to ... ...

Abstract	Honey bees (Apis mellifera) are increasingly in demand as pollinators for various key agricultural food crops, but globally honey bee populations are in decline, and honey bee colony failure rates have increased. This scenario highlights a need to understand the conditions in which colonies flourish and in which colonies fail. To aid this investigation we present a compartment model of bee population dynamics to explore how food availability and bee death rates interact to determine colony growth and development. Our model uses simple differential equations to represent the transitions of eggs laid by the queen to brood, then hive bees and finally forager bees, and the process of social inhibition that regulates the rate at which hive bees begin to forage. We assume that food availability can influence both the number of brood successfully reared to adulthood and the rate at which bees transition from hive duties to foraging. The model predicts complex interactions between food availability and forager death rates in shaping colony fate. Low death rates and high food availability results in stable bee populations at equilibrium (with population size strongly determined by forager death rate) but consistently increasing food reserves. At higher death rates food stores in a colony settle at a finite equilibrium reflecting the balance of food collection and food use. When forager death rates exceed a critical threshold the colony fails but residual food remains. Our model presents a simple mathematical framework for exploring the interactions of food and forager mortality on colony fate, and provides the mathematical basis for more involved simulation models of hive performance.
Keywords	Medicine ; R ; Science ; Q
Subject code	590
Language	English
Publishing date	2013-01-01T00:00:00Z
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: A quantitative model of honey bee colony population dynamics.

David S Khoury / Mary R Myerscough / Andrew B Barron

PLoS ONE, Vol 6, Iss 4, p e

2011 Volume 18491

Abstract: Since 2006 the rate of honey bee colony failure has increased significantly. As an aid to testing hypotheses for the causes of colony failure we have developed a compartment model of honey bee colony population dynamics to explore the impact of different ...

Abstract	Since 2006 the rate of honey bee colony failure has increased significantly. As an aid to testing hypotheses for the causes of colony failure we have developed a compartment model of honey bee colony population dynamics to explore the impact of different death rates of forager bees on colony growth and development. The model predicts a critical threshold forager death rate beneath which colonies regulate a stable population size. If death rates are sustained higher than this threshold rapid population decline is predicted and colony failure is inevitable. The model also predicts that high forager death rates draw hive bees into the foraging population at much younger ages than normal, which acts to accelerate colony failure. The model suggests that colony failure can be understood in terms of observed principles of honey bee population dynamics, and provides a theoretical framework for experimental investigation of the problem.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2011-04-01T00:00:00Z
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: Evolution of immune responses to SARS-CoV-2 in mild-moderate COVID-19

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

2021 Volume 11

Abstract: Longitudinal analyses are needed to show how the immune response to Sars-Cov-2 infection changes over time. Here, the authors use multiple strategies to profile the change in immune cell responses from patients with convalescent COVID-19 over the course ... ...

Abstract	Longitudinal analyses are needed to show how the immune response to Sars-Cov-2 infection changes over time. Here, the authors use multiple strategies to profile the change in immune cell responses from patients with convalescent COVID-19 over the course of ~5 months, showing that although neutralizing antibody responses drop off after ~4 months, B cell immune responses strengthen.
Keywords	Science ; Q
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Nature Portfolio
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