546 results found
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., Trans R Soc Trop Med Hyg
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
Truscott JE, Hardwick RJ, Werkman M, 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., Parasit Vectors, Vol: 14
BACKGROUND: The 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%. METHODS: Our 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 [Formula: see text] prevalence at a point 24 months post-cessation of MDA. RESULTS: Simulated 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
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 Negl Trop Dis, Vol: 15
We present a general framework which describes the systematic (binary) scenario of individuals either taking treatment or not for any reason, over the course of mass drug administration (MDA)-which we refer to as 'adherence' and 'non-adherence'. The probability models developed can be informed by observed adherence behaviour as well as employed to explore how different patterns influence the impact of MDA programmes, by the use of mathematical models of transmission and control. We demonstrate the interpretative value of the developed probability model employing a dataset collected in the TUMIKIA project, a randomised trial of deworming strategies to control soil-transmitted helminths (STH) by MDA conducted in coastal Kenya. We stratify our analysis by age and sex, although the framework which we introduce here may be readily adapted to accommodate other stratifications. Our findings include the detection of specific patterns of non-adherence in all age groups to varying extents. This is particularly apparent in men of ages 30+. We then demonstrate the use of the probability model in stochastic individual-based simulations by running two example forecasts for the elimination of STH transmission employing MDA within the TUMIKIA trial setting with different adherence patterns. This suggested a substantial reduction in the probability of elimination (between 23-43%) when comparing observed adherence patterns with an assumption of independence, with important implications for programmes. The results here demonstrate the considerable impact and utility of considering non-adherence on the success of MDA programmes to control neglected tropical diseases (NTDs).
Malizia V, Giardina F, Vegvari C, et al., 2020, Modelling the impact of COVID-19-related control programme interruptions on progress towards the WHO 2030 target for soil-transmitted helminths., Trans R Soc Trop Med Hyg
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.
Anderson RM, Vegvari C, Truscott J, et al., 2020, Challenges in creating herd immunity to SARS-CoV-2 infection by mass vaccination, 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
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, ISSN: 1935-2735
Toor J, Adams ER, Aliee M, et al., 2020, Predicted impact of COVID-19 on neglected tropical disease programs and the opportunity for innovation, Clinical Infectious Diseases, 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.
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.
Werkman M, Wright JE, Truscott JE, et al., 2020, The impact of community-wide, mass drug administration on aggregation of soil-transmitted helminth infection in human host populations, Parasites and Vectors, Vol: 13, ISSN: 1756-3305
BackgroundSoil-transmitted helminths (STH) are intestinal parasites estimated to infect over 1.5 billion people. Current treatment programmes are aimed at morbidity control through school-based deworming programmes (targeting school-aged children, SAC) and treating women of reproductive age (WRA), as these two groups are believed to record the highest morbidity. More recently, however, the potential for interrupting transmission by treating entire communities has been receiving greater emphasis and the feasibility of such programmes are now under investigation in randomised clinical trials through the Bill & Melinda Gates Foundation funded DeWorm3 studies. Helminth parasites are known to be highly aggregated within human populations, with a small minority of individuals harbouring most worms. Empirical evidence from the TUMIKIA project in Kenya suggests that aggregation may increase significantly after anthelminthic treatment.MethodsA stochastic, age-structured, individual-based simulation model of parasite transmission is employed to better understand the factors that might induce this pattern. A simple probabilistic model based on compounded negative binomial distributions caused by age-dependencies in both treatment coverage and exposure to infection is also employed to further this understanding.ResultsBoth approaches confirm helminth aggregation is likely to increase post-mass drug administration as measured by a decrease in the value of the negative binomial aggregation parameter, k. Simple analytical models of distribution compounding describe the observed patterns well.ConclusionsThe helminth aggregation that was observed in the field was replicated with our stochastic individual-based model. Further work is required to generalise the probabilistic model to take account of the respective sensitivities of different diagnostics on the presence or absence of infection.
Vegvari C, Grad Y, White P, et al., 2020, Using rapid point-of-care tests to inform antibiotic choice to mitigate drug resistance in gonorrhoea, Eurosurveillance, ISSN: 1025-496X
Anderson RM, Heesterbeek H, Klinkenberg D, et al., 2020, How will country-based mitigation measures influence the course of the COVID-19 epidemic?, The Lancet, Vol: 395, Pages: 931-934, ISSN: 0140-6736
Hardwick RJ, Vegvari C, Truscott JE, et al., 2020, The 'breakpoint' of soil-transmitted helminths with infected human migration, JOURNAL OF THEORETICAL BIOLOGY, Vol: 486, ISSN: 0022-5193
Lochen A, Anderson RM, 2020, Dynamic transmission models and economic evaluations of pneumococcal conjugate vaccines: a quality appraisal and limitations, Clinical Microbiology and Infection, Vol: 26, Pages: 60-70, ISSN: 1198-743X
BackgroundOf over 90 serotypes of Streptococcus pneumoniae, only seven were included in the first pneumococcal conjugate vaccine (PCV). While PCV reduced the disease incidence, in part because of a herd immunity effect, a replacement effect was observed whereby disease was increasingly caused by serotypes not included in the vaccine. Dynamic transmission models can account for these effects to describe post-vaccination scenarios, whereas economic evaluations can enable decision-makers to compare vaccines of increasing valency for implementation.AimThe aim of this review was to examine epidemiological and economic models and their assumptions for their potential contributions to future research and immunisation policy.SourcesPubmed, Scopus, Ovid, ISI Web of Knowledge, Centre of Reviews and Dissemination (CRD) databases were searched.ContentTwenty-three dynamic transmission models and 21 economic models were retrieved and reviewed. Published models employed various templates, revealing several key uncertainties regarding the biology and epidemiology of pneumococcal infection. While models suggested that PCVs will reduce the burden of disease, the extent to which they are predicted to do so depended on various assumptions regarding features of pneumococcal infection and epidemiology that governed PCV cost-effectiveness as well. Such features include the duration of protection and competitive interactions between serotypes, which are unclear at present, but which directly relate to herd immunity and serotype replacement.ImplicationsEconomic evaluations are not typically based on transmission dynamic models and hence omit indirect herd immunity effects. The two tools could be used in conjunction to inform decision-makers on vaccine implementation, but so far there have been few attempts to build economic evaluations on transmission dynamic models, and none in this field. Future directions for research could include studies to evaluate key parameters for the models involv
Coffeng L, Malizia V, Vegvari C, et al., 2019, Impact of different sampling schemes for decision making in soil-transmitted helminthiasis control programs, Journal of Infectious Diseases, Vol: 221, Pages: S531-S538, ISSN: 0022-1899
Starting and stopping preventive chemotherapy (PC) for soil-transmitted helminthiasis is typically based on the prevalence of infection as measured by Kato-Katz (KK) fecal smears. Kato-Katz-based egg counts can vary highly over repeated stool samples and smears. Consequentially, the sensitivity of KK-based surveys depends on the number of stool samples per person and the number of smears per sample. Given finite resources, collecting multiple samples and/or smears means screening fewer individuals, thereby lowering the statistical precision of prevalence estimates. Using population-level data from various epidemiological settings, we assessed the performance of different sampling schemes executed within the confines of the same budget. We recommend the use of single-slide KK for determining prevalence of moderate-to-heavy intensity infection and policy decisions for starting and continuing PC; more sensitive sampling schemes may be required for policy decisions involving stopping PC. Our findings highlight that guidelines should include specific guidance on sampling schemes.
NTD Modelling Consortium Schistosomiasis Group, 2019, Insights from quantitative and mathematical modelling on the proposed WHO 2030 goal for schistosomiasis [version 2; peer review: 3 approved], Gates Open Research, Vol: 3, Pages: 1-25, ISSN: 2572-4754
Schistosomiasis remains one of the neglected tropical diseases (NTDs) impacting millions of people around the world. The World Health Organization (WHO) recently proposed a goal of elimination as a public health problem (EPHP) for schistosomiasis to be reached by 2030. Current WHO treatment guidelines for achieving EPHP focus on targeting school-aged children. The NTD Modelling Consortium has developed mathematical models to study schistosomiasis transmission dynamics and the impact of control measures. Our modelling insights on Schistosoma mansoni have shown that EPHP is likely to be attainable in low to moderate prevalence settings using the current guidelines. However, as prevalence rises within high prevalence settings, EPHP is less likely to be achieved unless both school-aged children and adults are treated (with coverage levels increasing with the adult burden of infection). We highlight the challenges that are faced by treatment programmes, such as non-adherence to treatment and resurgence, which can hinder progress towards achieving and maintaining EPHP. Additionally, even though EPHP may be reached, prevalence can still be high due to persisting infections. Therefore, without interruption of transmission, treatment will likely have to continue to maintain EPHP. Further modelling work is being carried out, including extending our results to S. haematobium . By providing these modelling insights, we aim to inform discussions on the goals and treatment guidelines for schistosomiasis.
Oswald WE, Halliday KE, Mcharo C, et al., 2019, Domains of transmission and association of community, school, and household sanitation with soil-transmitted helminth infections among children in coastal Kenya, PLoS Neglected Tropical Diseases, Vol: 13, Pages: 1-17, ISSN: 1935-2727
IntroductionFew studies have simultaneously examined the role of sanitation conditions at the home, school, and community on soil-transmitted helminth (STH) infection. We examined the contribution of each domain that children inhabit (home, village, and school) to STH infection and estimated the association of STH infection with sanitation in each domain.MethodsUsing data from 4,104 children from Kwale County, Kenya, who reported attending school, we used logistic regression models with cross-classified random effects to calculate measures of general contextual effects and estimate associations of village sanitation coverage (percentage of households with reported access to sanitation), school sanitation coverage (number of usable toilets per enrolled pupil), and sanitation access at home with STH infection.FindingsWe found reported use of a sanitation facility by households was associated with reduced prevalence of hookworm infection but not with reduced prevalence of T. trichiura infection. School sanitation coverage > 3 toilets per 100 pupils was associated with lower prevalence of hookworm infection. School sanitation was not associated with T. trichiura infection. Village sanitation coverage > 81% was associated with reduced prevalence of T. trichiura infection, but no protective association was detected for hookworm infection. General contextual effects represented by residual heterogeneity between village and school domains had comparable impact upon likelihood of hookworm and T. trichiura infection as sanitation coverage in either of these domains.ConclusionFindings support the importance of providing good sanitation facilities to support mass drug administration in reducing the burden of STH infection in children.
Mekete K, Ower A, Dunn J, et al., 2019, The Geshiyaro Project: a study protocol for developing a scalable model of interventions for moving towards the interruption of the transmission of soil-transmitted helminths and schistosome infections in the Wolaita zone of Ethiopia, Parasites and Vectors, Vol: 12, ISSN: 1756-3305
BACKGROUND: National deworming programmes rely almost exclusively on mass drug administration (MDA) to children to control morbidity caused by these parasitic infections. The provision of other interventions, consisting of preventive chemotherapy at high population level coverage together with water, sanitation and hygiene (WaSH) and changes in risk behaviour, should enable sustainable control of soil-transmitted helminths (STH) and schistosomiasis and ultimately interrupt transmission. METHODS/DESIGN: Two interventions will be implemented by the project: (i) community-wide biannual albendazole and annual praziquantel treatment with a target of 80-90% treatment coverage ("expanded MDA"); and (ii) provision of WaSH with behaviour change communication (BCC), within the Wolaita zone, Ethiopia. The project has three study arms: (i) expanded community-wide MDA, WaSH and BCC; (ii) expanded community-wide MDA only; and (iii) annual school-based MDA (the current National STH/schistosomiasis Control Programme). The impact of these interventions will be evaluated through prevalence mapping at baseline and endline (after four rounds of MDA), combined with annual longitudinal parasitological surveillance in defined cohorts of people to monitor trends in prevalence and reinfection throughout the project. Treatment coverage and individual compliance to treatment will be monitored by employing fingerprint biometric technology and barcoded identification cards at treatment. WaSH utilisation will be evaluated through school and household level observations and annual WaSH assessment survey. Complementary qualitative surveys will explore practices, cultural and social drivers of risk behaviours, uptake of WaSH and treatment, and assessing the impact of the BCC. DISCUSSION: The study has the potential to define an 'End Game' for STH and schistosomiasis programmes through provision of multiple interventions. Interrupting transmission of these infections would eliminate the ne
Collyer BS, Turner HC, Hollingsworth TD, et al., 2019, Vaccination or mass drug administration against schistosomiasis: a hypothetical cost-effectiveness modelling comparison, Parasites and Vectors, Vol: 12, Pages: 1-14, ISSN: 1756-3305
BackgroundSchistosomiasis is a neglected tropical disease, targeted by the World Health Organization for reduction in morbidity by 2020. It is caused by parasitic flukes that spread through contamination of local water sources. Traditional control focuses on mass drug administration, which kills the majority of adult worms, targeted at school-aged children. However, these drugs do not confer long-term protection and there are concerns over the emergence of drug resistance. The development of a vaccine against schistosomiasis opens the potential for control methods that could generate long-lasting population-level immunity if they are cost-effective.MethodsUsing an individual-based transmission model, matched to epidemiological data, we compared the cost-effectiveness of a range of vaccination programmes against mass drug administration, across three transmission settings. Health benefit was measured by calculating the heavy-intensity infection years averted by each intervention, while vaccine costs were assessed against robust estimates for the costs of mass drug administration obtained from data. We also calculated a critical vaccination cost, a cost beyond which vaccination might not be economically favorable, by benchmarking the cost-effectiveness of potential vaccines against the cost-effectiveness of mass drug administration, and examined the effect of different vaccine protection durations.ResultsWe found that sufficiently low-priced vaccines can be more cost-effective than traditional drugs in high prevalence settings, and can lead to a greater reduction in morbidity over shorter time-scales. MDA or vaccination programmes that target the whole community generate the most health benefits, but are generally less cost-effective than those targeting children, due to lower prevalence of schistosomiasis in adults.ConclusionsThe ultimate cost-effectiveness of vaccination will be highly dependent on multiple vaccine characteristics, such as the efficacy, cost, safety
Evans S, McRae-McKee K, Hadjichrysanthou C, et al., 2019, Alzheimer's disease progression and risk factors: A standardized comparison between six large data sets., Alzheimers & Dementia, Vol: 5, Pages: 515-523, ISSN: 1552-5260
There exist a large number of cohort studies that have been used to identify genetic and biological risk factors for developing Alzheimer's disease (AD). However, there is a disagreement between studies as to how strongly these risk factors affect the rate of progression through diagnostic groups toward AD. We have calculated the probability of transitioning through diagnostic groups in six studies and considered how uncertainty around the strength of the effect of these risk factors affects estimates of the distribution of individuals in each diagnostic group in an AD clinical trial simulator. In this work, we identify the optimal choice of widely collected variables for comparing data sets and calculating probabilities of progression toward AD. We use the estimated transition probabilities to inform stochastic simulations of AD progression that are based on a Markov model and compare predicted incidence rates to those in a community-based study, the Cardiovascular Health Study.
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