556 results found
Anderson RM, Vegvari C, Hollingsworth TD, et al., 2021, The SARS-CoV-2 pandemic: remaining uncertainties in our understanding of the epidemiology and transmission dynamics of the virus, and challenges to be overcome, Interface Focus, Vol: 11
<jats:p> Great progress has been made over the past 18 months in scientific understanding of the biology, epidemiology and pathogenesis of SARS-CoV-2. Extraordinary advances have been made in vaccine development and the execution of clinical trials of possible therapies. However, uncertainties remain, and this review assesses these in the context of virus transmission, epidemiology, control by social distancing measures and mass vaccination and the effect on all of these on emerging variants. We briefly review the current state of the global pandemic, focussing on what is, and what is not, well understood about the parameters that control viral transmission and make up the constituent parts of the basic reproductive number <jats:italic>R</jats:italic> <jats:sub>0</jats:sub> . Major areas of uncertainty include factors predisposing to asymptomatic infection, the population fraction that is asymptomatic, the infectiousness of asymptomatic compared to symptomatic individuals, the contribution of viral transmission of such individuals and what variables influence this. The duration of immunity post infection and post vaccination is also currently unknown, as is the phenotypic consequences of continual viral evolution and the emergence of many viral variants not just in one location, but globally, given the high connectivity between populations in the modern world. The pattern of spread of new variants is also examined. We review what can be learnt from contact tracing, household studies and whole-genome sequencing, regarding where people acquire infection, and how households are seeded with infection since they constitute a major location for viral transmission. We conclude by discussing the challenges to attaining herd immunity, given the uncertainty in the duration of vaccine-mediated immunity, the threat of continued evolution of the virus as demonstrated by the emergence and rapid spread of th
Hardwick RJ, Vegvari C, Collyer B, et al., 2021, Spatial scales in human movement between reservoirs of infection, JOURNAL OF THEORETICAL BIOLOGY, Vol: 524, ISSN: 0022-5193
Xin H, Li Y, Wu P, et al., 2021, Estimating the latent period of coronavirus disease 2019 (COVID-19), Clinical Infectious Diseases, ISSN: 1058-4838
<jats:title>Abstract</jats:title> <jats:p>Using detailed exposure information on COVID-19 cases, we estimated the mean latent period to be 5.5 days (95% confidence interval: 5.1-5.9 days), shorter than the mean incubation period (6.9 days). Laboratory testing may allow shorter quarantines since 95% of COVID-19 cases shed virus within 10.6 days (95%CI: 9.6-11.6) of infection.</jats:p>
Anderson RM, 2021, An urgent need: vaccines for neglected tropical diseases., Lancet Infect Dis
Chong NS, Smith SR, Werkman M, et al., 2021, Modelling the ability of mass drug administration to interrupt soil-transmitted helminth transmission: Community-based deworming in Kenya as a case study, PLOS NEGLECTED TROPICAL DISEASES, Vol: 15, ISSN: 1935-2735
Papaiakovou M, Littlewood TJ, Gasser RB, et al., 2021, How qPCR complements the WHO roadmap (2021-2030) for soil-transmitted helminths, TRENDS IN PARASITOLOGY, Vol: 37, Pages: 698-708, ISSN: 1471-4922
Ayabina D, Kura K, Toor J, et al., 2021, Maintaining low prevalence of Schistosoma mansoni: modelling the effect of less frequent treatment, Clinical Infectious Diseases, Vol: 72, Pages: S140-S145, ISSN: 1058-4838
BACKGROUND: The World Health Organization (WHO) previously set goals of controlling morbidity due to schistosomiasis by 2020 and attaining elimination as a public health problem (EPHP) by 2025 (now adjusted to 2030 in the new neglected tropical diseases roadmap). As these milestones are reached, it is important that programs reassess their treatment strategies to either maintain these goals or progress from morbidity control to EPHP and ultimately to interruption of transmission. In this study, we consider different mass drug administration (MDA) strategies to maintain the goals. METHODS: We use two independently developed individual-based stochastic models of schistosomiasis transmission to assess the optimal treatment strategy of a multi-year program to maintain the morbidity control and the EPHP goals. RESULTS: We find that in moderate prevalence settings, once the morbidity control and EPHP goals are reached, it may be possible to maintain the goals using less frequent MDAs than those that are required to achieve the goals. On the other hand, in some high transmission settings, if control efforts are reduced after achieving the goals, particularly the morbidity control goal, there is a high chance of recrudescence. CONCLUSIONS: To reduce the risk of recrudescence after the goals are achieved, programs have to re-evaluate their strategies and decide to either maintain these goals with reduced efforts where feasible or continue with at least the same efforts required to reach the goals.
Vegvari C, Giardina F, Malizia V, et al., 2021, Impact of Key Assumptions About the Population Biology of Soil-Transmitted Helminths on the Sustainable Control of Morbidity, CLINICAL INFECTIOUS DISEASES, Vol: 72, Pages: S188-S194, ISSN: 1058-4838
Collyer BS, Anderson RM, 2021, Probability distributions of helminth parasite burdens within the human host population following repeated rounds of mass drug administration and their impact on the transmission breakpoint, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 18, ISSN: 1742-5689
Vegvari C, Giardina F, Bajaj S, et al., 2021, Deworming women of reproductive age during adolescence and pregnancy: what is the impact on morbidity from soil-transmitted helminths infection?, PARASITES & VECTORS, Vol: 14, ISSN: 1756-3305
Toor J, Adams ER, Aliee M, et al., 2021, Predicted impact of COVID-19 on neglected tropical disease programs and the opportunity for innovation, Clinical Infectious Diseases, Vol: 72, Pages: 1463-1466, ISSN: 1058-4838
Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases. Programs face a risk of resurgence, which will be fastest in high-transmission areas. Furthermore, of the mass drug administration diseases, schistosomiasis, STH, and trachoma are likely to encounter faster resurgence. The case-finding diseases (gambiense sleeping sickness and visceral leishmaniasis) are likely to have fewer cases being detected but may face an increasing underlying rate of new infections. However, once programs are able to resume, there are ways to mitigate the impact and accelerate progress towards the 2030 goals.
Ajjampur SSR, Kaliappan SP, Halliday KE, et al., 2021, Epidemiology of soil transmitted helminths and risk analysis of hookworm infections in the community: Results from the DeWorm3 Trial in southern India, PLOS NEGLECTED TROPICAL DISEASES, Vol: 15, ISSN: 1935-2735
Malizia V, Giardina F, Vegvari C, et al., 2021, Modelling the impact of COVID-19-related control programme interruptions on progress towards the WHO 2030 target for soil-transmitted helminths, Transactions of the Royal Society of Tropical Medicine and Hygiene, Vol: 115, Pages: 253-260, ISSN: 0035-9203
BACKGROUND: On 1 April 2020, the WHO recommended an interruption of all activities for the control of neglected tropical diseases, including soil-transmitted helminths (STH), in response to the COVID-19 pandemic. This paper investigates the impact of this disruption on the progress towards the WHO 2030 target for STH. METHODS: We used two stochastic individual-based models to simulate the impact of missing one or more preventive chemotherapy (PC) rounds in different endemicity settings. We also investigated the extent to which this impact can be lessened by mitigation strategies, such as semiannual or community-wide PC. RESULTS: Both models show that without a mitigation strategy, control programmes will catch up by 2030, assuming that coverage is maintained. The catch-up time can be up to 4.5 y after the start of the interruption. Mitigation strategies may reduce this time by up to 2 y and increase the probability of achieving the 2030 target. CONCLUSIONS: Although a PC interruption will only temporarily impact the progress towards the WHO 2030 target, programmes are encouraged to restart as soon as possible to minimise the impact on morbidity. The implementation of suitable mitigation strategies can turn the interruption into an opportunity to accelerate progress towards reaching the target.
Kura K, Ayabina D, Toor J, et al., 2021, Disruptions to schistosomiasis programmes due to COVID-19: an analysis of potential impact and mitigation strategies., Transactions of the Royal Society of Tropical Medicine and Hygiene, Vol: 115, Pages: 236-244, ISSN: 0035-9203
BACKGROUND: The 2030 goal for schistosomiasis is elimination as a public health problem (EPHP), with mass drug administration (MDA) of praziquantel to school-age children (SAC) as a central pillar of the strategy. However, due to coronavirus disease 2019, many mass treatment campaigns for schistosomiasis have been halted, with uncertain implications for the programmes. METHODS: We use mathematical modelling to explore how postponement of MDA and various mitigation strategies affect achievement of the EPHP goal for Schistosoma mansoni and S. haematobium. RESULTS: For both S. mansoni and S. haematobium in moderate- and some high-prevalence settings, the disruption may delay the goal by up to 2 y. In some high-prevalence settings, EPHP is not achievable with current strategies and so the disruption will not impact this. Here, increasing SAC coverage and treating adults can achieve the goal. The impact of MDA disruption and the appropriate mitigation strategy varies according to the baseline prevalence prior to treatment, the burden of infection in adults and the stage of the programme. CONCLUSIONS: Schistosomiasis MDA programmes in medium- and high-prevalence areas should restart as soon as is feasible and mitigation strategies may be required in some settings.
Hardwick RJ, Werkman M, Truscott JE, et al., 2021, Stochastic challenges to interrupting helminth transmission., Epidemics, Vol: 34
Predicting the effect of different programmes designed to control both the morbidity induced by helminth infections and parasite transmission is greatly facilitated by the use of mathematical models of transmission and control impact. In such models, it is essential to account for the many sources of uncertainty - natural, or otherwise - to ensure robustness in prediction and to accurately depict variation around an expected outcome. In this paper, we investigate how well the standard deterministic models match the predictions made using individual-based stochastic simulations. We also explore how well concepts which derive from deterministic models, such as 'breakpoints' in transmission, apply in the stochastic world. Employing an individual-based stochastic model framework we also investigate how transmission and control are affected by the migration of infected people into a defined community. To give our study focus we consider the control of soil-transmitted helminths (STH) by mass drug administration (MDA), though our methodology is readily applicable to the other helminth species such as the schistosome parasites and the filarial worms. We show it is possible to theoretically define a 'stochastic breakpoint' where much noise surrounds the expected deterministic breakpoint. We also discuss the concept of the 'interruption of transmission' independent of the 'breakpoint' concept where analyses of model behaviour illustrate the current limitations of deterministic models to account for the 'fade-out' or transmission extinction behaviour in simulations. Our analysis of migration confirms a relationship between the critical infected human migration rate scale (i.e., order of magnitude) per unit of time and the death rate of infective stages that are released into the free-living environment. This relationship is shown to determine the likelihood that control activities aim at chemotherapeutic treatment of the human host will eliminate transmission. The development
Vikentjeva M, Geller J, Remm J, et al., 2021, Forecasting the effectiveness of the DeWorm3 trial in interrupting the transmission of soil-transmitted helminths in three study sites in Benin, India and Malawi, Parasites and Vectors, Vol: 14, ISSN: 1756-3305
BackgroundThe DeWorm3 project is an ongoing cluster-randomised trial assessing the feasibility of interrupting the transmission of soil-transmitted helminths (STH) through mass drug administration (MDA) using study sites in India, Malawi and Benin. In this article, we describe an approach which uses a combination of statistical and mathematical methods to forecast the outcome of the trial with respect to its stated goal of reducing the prevalence of infection to below 2%.MethodsOur approach is first to define the local patterns of transmission within each study site, which is achieved by statistical inference of key epidemiological parameters using the baseline epidemiological measures of age-related prevalence and intensity of STH infection which have been collected by the DeWorm3 trials team. We use these inferred parameters to calibrate an individual-based stochastic simulation of the trial at the cluster and study site level, which is subsequently run to forecast the future prevalence of STH infections. The simulator takes into account both the uncertainties in parameter estimation and the variability inherent in epidemiological and demographic processes in the simulator. We interpret the forecast results from our simulation with reference to the stated goal of the DeWorm3 trial, to achieve a target of ≤2%prevalence at a point 24 months post-cessation of MDA.ResultsSimulated output predicts that the two arms will be distinguishable from each other in all three country sites at the study end point. In India and Malawi, measured prevalence in the intervention arm is below the threshold with a high probability (90% and 95%, respectively), but in Benin the heterogeneity between clusters prevents the arm prevalence from being reduced below the threshold value. At the level of individual study arms within each site, heterogeneity among clusters leads to a very low probability of achieving complete elimination in an intervention arm, yielding a post-study scenario w
Hardwick RJ, Truscott JE, Oswald WE, et al., 2021, Individual adherence to mass drug administration in neglected tropical disease control: A probability model conditional on past behaviour, PLOS NEGLECTED TROPICAL DISEASES, Vol: 15, ISSN: 1935-2735
Anderson RM, Vegvari C, Truscott J, et al., 2020, Challenges in creating herd immunity to SARS-CoV-2 infection by mass vaccination, The Lancet, Vol: 396, Pages: 1614-1616, ISSN: 0140-6736
Kura K, Hardwick RJ, Truscott JE, et al., 2020, The impact of mass drug administration on Schistosoma haematobium infection: what is required to achieve morbidity control and elimination?, Parasites and Vectors, Vol: 13, Pages: 1-10, ISSN: 1756-3305
BACKGROUND: Schistosomiasis remains an endemic parasitic disease causing much morbidity and, in some cases, mortality. The World Health Organization (WHO) has outlined strategies and goals to combat the burden of disease caused by schistosomiasis. The first goal is morbidity control, which is defined by achieving less than 5% prevalence of heavy intensity infection in school-aged children (SAC). The second goal is elimination as a public health problem (EPHP), achieved when the prevalence of heavy intensity infection in SAC is reduced to less than 1%. Mass drug administration (MDA) of praziquantel is the main strategy for control. However, there is limited availability of praziquantel, particularly in Africa where there is high prevalence of infection. It is therefore important to explore whether the WHO goals can be achieved using the current guidelines for treatment based on targeting SAC and, in some cases, adults. Previous modelling work has largely focused on Schistosoma mansoni, which in advance cases can cause liver and spleen enlargement. There has been much less modelling of the transmission of Schistosoma haematobium, which in severe cases can cause kidney damage and bladder cancer. This lack of modelling has largely been driven by limited data availability and challenges in interpreting these data. RESULTS: In this paper, using an individual-based stochastic model and age-intensity profiles of S. haematobium from two different communities, we calculate the probability of achieving the morbidity and EPHP goals within 15 years of treatment under the current WHO treatment guidelines. We find that targeting SAC only can achieve the morbidity goal for all transmission settings, regardless of the burden of infection in adults. The EPHP goal can be achieved in low transmission settings, but in some moderate to high settings community-wide treatment is needed. CONCLUSIONS: We show that the key determinants of achieving the WHO goals are the precise form of the ag
Lochen A, Croucher N, Anderson R, 2020, Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency, Scientific Reports, Vol: 10, ISSN: 2045-2322
Streptococcus pneumoniae is a significant cause of otitis media, pneumonia, and meningitis. Only seven of the approximately 100 serotypes were initially included in the pneumococcal conjugate vaccine (PCV) in 2000 before it was expanded in subsequent years. Although the invasive pneumococcal disease (IPD) incidence due to vaccine serotypes (VT) has declined, partial replacement by non-vaccine serotypes (NVT) was observed following widespread vaccine uptake. We conducted a trend analysis assembling all the available evidence for PCV impact on European, North American and Australian national IPD. Significant effectiveness against VT IPD in infants was observed, although the impact on national IPD incidence varied internationally due to serotype replacement. Currently, NVT serotypes 8, 9N, 15A and 23B are increasing in the countries assessed, although a variety of other NVTs are affecting each country and age group. Despite these common emerging serotypes, there has not been a dominant IPD serotype post-vaccination as there was pre-vaccination (serotype 14) or post-PCV7 (serotype 19A), suggesting that future vaccines with additional serotypes will be less effective at targeting and reducing IPD in global populations than previous PCVs. The rise of diverse NVTs in all settings’ top-ranked IPD-causing serotypes emphasizes the urgent need for surveillance data on serotype distribution and serotype-specific invasiveness post-vaccination to facilitate decision making concerning both expanding current vaccination programmes and increasing vaccine valency.
Oswald WE, Kepha S, Halliday KE, et al., 2020, Patterns of individual non-treatment during multiple rounds of mass drug administration for control of soil-transmitted helminths in the TUMIKIA trial, Kenya: a secondary longitudinal analysis, LANCET GLOBAL HEALTH, Vol: 8, Pages: E1418-E1426, ISSN: 2214-109X
Celma CC, Beard S, Douglas A, et al., 2020, Retrospective analysis on confirmation rates for referred positive rotavirus samples in England, 2016 to 2017: implications for diagnosis and surveillance, Eurosurveillance, Vol: 25, Pages: 1-8, ISSN: 1025-496X
BackgroundRapid diagnostic tests are commonly used by hospital laboratories in England to detect rotavirus (RV), and results are used to inform clinical management and support national surveillance of the infant rotavirus immunisation programme since 2013. In 2017, the Public Health England (PHE) national reference laboratory for enteric viruses observed that the presence of RV could not be confirmed by PCR in a proportion of RV-positive samples referred for confirmatory detection.AimWe aimed to compare the positivity rate of detection methods used by hospital laboratories with the PHE confirmatory test rate.MethodsRotavirus specimens testing positive at local hospital laboratories were re-tested at the PHE national reference laboratory using a PCR test. Confirmatory results were compared to original results from the PHE laboratory information management system.ResultsHospital laboratories screened 70.1% (2,608/3,721) of RV samples using immunochromatographic assay (IC) or rapid tests, 15.5% (578/3,721) using enzyme immunoassays (EIA) and 14.4% (535/3,721) using PCR. Overall, 1,011/3,721 (27.2%) locally RV-positive samples referred to PHE in 2016 and 2017 failed RV detection using the PHE reference laboratory PCR test. Confirmation rates were 66.9% (1,746/2,608) for the IC tests, 87.4% (505/578) for the EIA and 86.4% (465/535) for the PCR assays. Seasonal confirmation rate discrepancies were also evident for IC tests.ConclusionsThis report highlights high false positive rates with the most commonly used RV screening tests and emphasises the importance of implementing verified confirmatory tests for RV detections. This has implications for clinical diagnosis and national surveillance.
Collyer BS, Irvine MA, Hollingsworth TD, et al., 2020, Defining a prevalence level to describe the elimination of Lymphatic Filariasis (LF) transmission and designing monitoring & evaluating (M&E) programmes post the cessation of mass drug administration (MDA), PLoS Neglected Tropical Diseases, Vol: 14, Pages: 1-21, ISSN: 1935-2727
The global decline in prevalence of lymphatic filariasis has been one of the major successes of the WHO’s NTD programme. The recommended strategy of intensive, community-wide mass drug administration, aims to break localised transmission by either reducing the prevalence of microfilaria positive infections to below 1%, or antigen positive infections to below 2%. After the threshold is reached, and mass drug administration is stopped, geographically defined evaluation units must pass Transmission Assessment Surveys to demonstrate that transmission has been interrupted. In this study, we use an empirically parameterised stochastic transmission model to investigate the appropriateness of 1% microfilaria-positive prevalence as a stopping threshold, and statistically evaluate how well various monitoring prevalence-thresholds predict elimination or disease resurgence in the future by calculating their predictive value. Our results support the 1% filaremia prevalence target as appropriate stopping criteria. However, because at low prevalence-levels random events dominate the transmission dynamics, we find single prevalence measurements have poor predictive power for predicting resurgence, which suggests alternative criteria for restarting MDA may be beneficial.
Thomas DX, Bajaj S, McRae-McKee K, et al., 2020, Association of TDP-43 proteinopathy, cerebral amyloid angiopathy, and Lewy bodies with cognitive impairment in individuals with or without Alzheimer's disease neuropathology, Scientific Reports, Vol: 10, ISSN: 2045-2322
Alzheimer's disease patients typically present with multiple co-morbid neuropathologies at autopsy, but the impact of these pathologies on cognitive impairment during life is poorly understood. In this study, we developed cognitive trajectories for patients with common co-pathologies in the presence and absence of Alzheimer's disease neuropathology. Cognitive trajectories were modelled in a Bayesian hierarchical regression framework to estimate the effects of each neuropathology on cognitive decline as assessed by the mini-mental state examination and the clinical dementia rating scale sum of boxes scores. We show that both TDP-43 proteinopathy and cerebral amyloid angiopathy associate with cognitive impairment of similar magnitude to that associated with Alzheimer's disease neuropathology. Within our study population, 63% of individuals given the 'gold-standard' neuropathological diagnosis of Alzheimer's disease in fact possessed either TDP-43 proteinopathy or cerebral amyloid angiopathy of sufficient severity to independently explain the majority of their cognitive impairment. This suggests that many individuals diagnosed with Alzheimer's disease may actually suffer from a mixed dementia, and therapeutics targeting only Alzheimer's disease-related processes may have severely limited efficacy in these co-morbid populations.
Anderson RM, Hollingsworth TD, Baggaley RF, et al., 2020, COVID-19 spread in the UK: the end of the beginning?, LANCET, Vol: 396, Pages: 587-590, ISSN: 0140-6736
Wolters FJ, Chibnik LB, Waziry R, et al., 2020, Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium, Neurology, Vol: 95, Pages: e519-e531, ISSN: 0028-3878
OBJECTIVE: To determine changes in the incidence of dementia between 1988 and 2015. METHODS: This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex. RESULTS: Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person-years in individuals aged 65-69 years to 65 per 1,000 person-years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% confidence interval [CI], 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] vs 8% [0%-15%]). CONCLUSION: The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations.
Dunn JC, Papaiakovou M, Han KT, et al., 2020, The increased sensitivity of qPCR in comparison to Kato-Katz is required for the accurate assessment of the prevalence of soil-transmitted helminth infection in settings that have received multiple rounds of mass drug administration, Parasites and Vectors, Vol: 13, Pages: 1-11, ISSN: 1756-3305
BackgroundThe most commonly used diagnostic tool for soil-transmitted helminths (STH) is the Kato-Katz (KK) thick smear technique. However, numerous studies have suggested that the sensitivity of KK can be problematic, especially in low prevalence and low intensity settings. An emerging alternative is quantitative polymerase chain reaction (qPCR).MethodsIn this study, both KK and qPCR were conducted on stool samples from 648 participants in an STH epidemiology study conducted in the delta region of Myanmar in June 2016.ResultsPrevalence of any STH was 20.68% by KK and 45.06% by qPCR. Prevalence of each individual STH was also higher by qPCR than KK, the biggest difference was for hookworm with an approximately 4-fold increase between the two diagnostic techniques. Prevalence of Ancylostoma ceylanicum, a parasite predominately found in dogs, was 4.63%, indicating that there is the possibility of zoonotic transmission in the study setting. In individuals with moderate to high intensity infections there is evidence for a linear relationship between eggs per gram (EPG) of faeces, derived from KK, and DNA copy number, derived from qPCR which is particularly strong for Ascaris lumbricoides.ConclusionsThe use of qPCR in low prevalence settings is important to accurately assess the epidemiological situation and plan control strategies for the ‘end game’. However, more work is required to accurately assess STH intensity from qPCR results and to reduce the cost of qPCR so that is widely accessible in STH endemic countries.
Hadjichrysanthou C, Evans S, Bajaj S, et al., 2020, The dynamics of biomarkers across the clinical spectrum of Alzheimer's disease, Alzheimers Research & Therapy, Vol: 12, Pages: 1-16, ISSN: 1758-9193
BackgroundQuantifying changes in the levels of biological and cognitive markers prior to the clinical presentation of Alzheimer’s disease (AD) will provide a template for understanding the underlying aetiology of the clinical syndrome and, concomitantly, for improving early diagnosis, clinical trial recruitment and treatment assessment. This study aims to characterise continuous changes of such markers and determine their rate of change and temporal order throughout the AD continuum.MethodsThe methodology is founded on the development of stochastic models to estimate the expected time to reach different clinical disease states, for different risk groups, and synchronise short-term individual biomarker data onto a disease progression timeline. Twenty-seven markers are considered, including a range of cognitive scores, cerebrospinal (CSF) and plasma fluid proteins, and brain structural and molecular imaging measures. Data from 2014 participants in the Alzheimer’s Disease Neuroimaging Initiative database is utilised.ResultsThe model suggests that detectable memory dysfunction could occur up to three decades prior to the onset of dementia due to AD (ADem). This is closely followed by changes in amyloid-β CSF levels and the first cognitive decline, as assessed by sensitive measures. Hippocampal atrophy could be observed as early as the initial amyloid-β accumulation. Brain hypometabolism starts later, about 14 years before onset, along with changes in the levels of total and phosphorylated tau proteins. Loss of functional abilities occurs rapidly around ADem onset. Neurofilament light is the only protein with notable early changes in plasma levels. The rate of change varies, with CSF, memory, amyloid PET and brain structural measures exhibiting the highest rate before the onset of ADem, followed by a decline. The probability of progressing to a more severe clinical state increases almost exponentially with age. In accordance with previous stu
Toor J, Rollinson D, Turner HC, et al., 2020, Achieving elimination as a public health problem for schistosoma mansoni and S. haematobium: when is community-wide treatment required?, Journal of Infectious Diseases, Vol: 221, Pages: S525-S530, ISSN: 0022-1899
The World Health Organization (WHO) has set elimination as a public health problem (EPHP) as a goal for schistosomiasis. As the WHO treatment guidelines for schistosomiasis are currently under revision, we investigate whether school-based or community-wide treatment strategies are required for achieving the EPHP goal. In low- to moderate-transmission settings with good school enrolment, we find that school-based treatment is sufficient for achieving EPHP. However, community-wide treatment is projected to be necessary in certain high-transmission settings as well as settings with low school enrolment. Hence, the optimal treatment strategy depends on setting-specific factors such as the species present, prevalence prior to treatment, and the age profile of infection.
Kura K, Collyer BS, Toor J, et al., 2020, Policy implications of the potential use of a novel vaccine to prevent infection with Schistosoma mansoni with or without mass drug administration, Vaccine, Vol: 38, Pages: 4379-4386, ISSN: 0264-410X
Schistosomiasis is one of the most important neglected tropical diseases (NTDs) affecting millions of people in 79 different countries. The World Health Organization (WHO) has specified two control goals to be achieved by 2020 and 2025 - morbidity control and elimination as a public health problem (EPHP). Mass drug administration (MDA) is the main method for schistosomiasis control but it has sometimes proved difficult to both secure adequate supplies of the most efficacious drug praziquantel to treat the millions infected either annually or biannually, and to achieve high treatment coverage in targeted communities in regions of endemic infection. The development of alternative control methods remains a priority.In this paper, using stochastic individual-based models, we analyze whether the addition of a novel vaccine alone or in combination with drug treatment, is a more effective control strategy, in terms of achieving the WHO goals, as well as the time and costs to achieve these goals when compared to MDA alone. The key objective of our analyses is to help facilitate decision making for moving a promising candidate vaccine through the phase I, II and III trials in humans to a final product for use in resource poor settings.We find that in low to moderate transmission settings, both vaccination and MDA are highly likely to achieve the WHO goals within 15 years and are likely to be cost-effective. In high transmission settings, MDA alone is unable to achieve the goals, whereas vaccination is able to achieve both goals in combination with MDA. In these settings Vaccination is cost-effective, even for short duration vaccines, so long as vaccination costs up to US$7.60 per full course of vaccination. The public health value of the vaccine depends on the duration of vaccine protection, the baseline prevalence prior to vaccination and the WHO goal.
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