512 results found
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 Negl Trop Dis, Vol: 13
INTRODUCTION: Few 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. METHODS: Using 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. FINDINGS: We 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. CONCLUSION: Findings support the importance of providing good sanitation facilities to support mass drug administration in reducing the burden of STH infection in children.
Hardwick RJ, Vegvari C, Truscott JE, et al., 2019, The 'breakpoint' of soil-transmitted helminths with infected human migration., J Theor Biol, Vol: 486
Building on past research, we here develop an analytic framework for describing the dynamics of the transmission of soil-transmitted helminth (STH) parasitic infections near the transmission breakpoint and equilibria of endemic infection and disease extinction, while allowing for perturbations in the infectious reservoir of the parasite within a defined location. This perturbation provides a model for the effect of infected human movement between villages with differing degrees of parasite control induced by mass drug administration (MDA). Analysing the dynamical behaviour around the unstable equilibrium, known as the transmission 'breakpoint', we illustrate how slowly-varying the dynamics are and develop an understanding of how discrete 'pulses' in the release of transmission stages (eggs or larvae, depending on the species of STH), due to infected human migration between villages, can lead to perturbations in the deterministic transmission dynamics. Such perturbations are found to have the potential to undermine targets for parasite elimination as a result of MDA and/or improvements in water and sanitation provision. We extend our analysis by developing a simple stochastic model and analytically investigate the uncertainty this induces in the dynamics. Where appropriate, all analytical results are supported by numerical analyses.
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
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.
McRae-McKee K, Chinedu T, Udeh-Momoh CT, et al., 2019, Perspective: Clinical relevance of the dichotomous classification of Alzheimer’s disease biomarkers: Should there be a “grey zone”?, Alzheimers & Dementia, Vol: 15, Pages: 1348-1356, ISSN: 1552-5260
The 2018 National Institute on Aging and the Alzheimer's Association (NIA-AA) research framework recently redefined Alzheimer's disease (AD) as a biological construct, based on in vivo biomarkers reflecting key neuropathologic features. Combinations of normal/abnormal levels of three biomarker categories, based on single thresholds, form the AD signature profile that defines the biological disease state as a continuum, independent of clinical symptomatology. While single thresholds may be useful in defining the biological signature profile, we provide evidence that their use in studies with cognitive outcomes merits further consideration. Using data from the Alzheimer's Disease Neuroimaging Initiative with a focus on cortical amyloid binding, we discuss the limitations of applying the biological definition of disease status as a tool to define the increased likelihood of the onset of the Alzheimer's clinical syndrome and the effects that this may have on trial study design. We also suggest potential research objectives going forward and what the related data requirements would be.
Clarke NE, Dinh N-N, Traub RJ, et al., 2019, A cluster-randomised controlled trial comparing school and community-based deworming for soil transmitted helminth control in school-age children: the CoDe-STH trial protocol, BMC Infectious Diseases, Vol: 19, Pages: 1-10, ISSN: 1471-2334
BackgroundCurrent guidelines and targets for soil-transmitted helminth (STH) control focus on school-based deworming for school-age children, given the high risk of associated morbidity in this age group. However, expanding deworming to all age groups may achieve improved STH control among both the community in general and school-age children, by reducing their risk of reinfection. This trial aims to compare school-based targeted deworming with community-wide mass deworming in terms of impact on STH infections among school-age children.MethodsThe CoDe-STH (Community Deworming against STH) trial is a cluster-randomised controlled trial (RCT) in 64 primary schools in Dak Lak province, Vietnam. The control arm will receive one round of school-based targeted deworming with albendazole, while in the intervention arm, community-wide mass deworming with albendazole will be implemented alongside school-based deworming. Prevalence of STH infections will be measured in school-age children at baseline and 12 months following deworming. The primary outcome is hookworm prevalence in school-age children at 12 months, by quantitative PCR. Analysis will be intention-to-treat, with outcomes compared between study arms using generalised linear and non-linear mixed models. Additionally, cost-effectiveness of mass and targeted deworming will be calculated and compared, and focus group discussions and interviews will be used to assess acceptability and feasibility of deworming approaches. Individual based stochastic models will be used to predict the impact of mass and targeted deworming strategies beyond the RCT timeframe to assess the likelihood of parasite population ‘bounce-back’ if deworming is ceased due to low STH prevalence.DiscussionThe first large-scale trial comparing mass and targeted deworming for STH control in South East Asia will provide key information for policy makers regarding the optimal design of STH control programs.
Toor J, Truscott JE, Werkman M, et al., 2019, Determining post-treatment surveillance criteria for predicting the elimination of Schistosoma mansoni transmission, Parasites and Vectors, Vol: 12, ISSN: 1756-3305
BACKGROUND: The World Health Organization (WHO) has set elimination (interruption of transmission) as an end goal for schistosomiasis. However, there is currently little guidance on the monitoring and evaluation strategy required once very low prevalence levels have been reached to determine whether elimination or resurgence of the disease will occur after stopping mass drug administration (MDA) treatment. METHODS: We employ a stochastic individual-based model of Schistosoma mansoni transmission and MDA impact to determine a prevalence threshold, i.e. prevalence of infection, which can be used to determine whether elimination or resurgence will occur after stopping treatment with a given probability. Simulations are run for treatment programmes with varying probabilities of achieving elimination and for settings where adults harbour low to high burdens of infection. Prevalence is measured based on using a single Kato-Katz on two samples per individual. We calculate positive predictive values (PPV) using PPV ≥ 0.9 as a reliable measure corresponding to ≥ 90% certainty of elimination. We analyse when post-treatment surveillance should be carried out to predict elimination. We also determine the number of individuals across a single community (of 500-1000 individuals) that should be sampled to predict elimination. RESULTS: We find that a prevalence threshold of 1% by single Kato-Katz on two samples per individual is optimal for predicting elimination at two years (or later) after the last round of MDA using a sample size of 200 individuals across the entire community (from all ages). This holds regardless of whether the adults have a low or high burden of infection relative to school-aged children. CONCLUSIONS: Using a prevalence threshold of 0.5% is sufficient for surveillance six months after the last round of MDA. However, as such a low prevalence can be difficult to measure in the field using Kato-Katz, we recommend using 1% two ye
Vegvari C, Truscott JE, Kura K, et al., 2019, Human population movement can impede the elimination of soil-transmitted helminth transmission in regions with heterogeneity in mass drug administration coverage and transmission potential between villages: a metapopulation analysis, Parasites and Vectors, Vol: 12, Pages: 1-12, ISSN: 1756-3305
BackgroundSoil-transmitted helminth (STH) infections affect predominantly socio-economically disadvantaged populations in sub-Saharan Africa, East Asia and the Americas. Previous mathematical modelling studies have evaluated optimal intervention strategies to break STH transmission in clusters of villages. These studies assumed that villages are closed independent units with no movement of people in or out of communities. Here we examine how human population movement, for example, of seasonal migrant labourers, affect the outcome of mass drug administration (MDA) programmes.ResultsWe used a stochastic individual-based metapopulation model to analyse the impact of human population movement at varying rates on STH elimination efforts. Specifically, we looked at seasonal clumped movement events of infected individuals into a village. We showed that even if on average 75% of the entire resident population within a village are treated, an annual rate of 2–3% of the population arriving from an untreated source village can reduce the probability of STH elimination to less than 50% in high-prevalence settings. If a village is infection-free, an annual movement rate of 2–3% from an infected source village imposes a risk of re-introduction of STH of 75% or higher, unless the prevalence in the source village is less than 20%. Even a single arrival of 2–3% of the population can impose a risk of re-introducing STH of 50% or greater depending on the prevalence in the source village. The risk of re-introduction also depends on both the age group of moving individuals and STH species, since the pattern of cross-sectional age-prevalence and age-intensity profiles of infection in the human host are species-specific.ConclusionsPlanning for STH elimination programmes should account for human mobility patterns in defined regions. We recommend that individuals arriving from areas with ongoing STH transmission should receive preventive chemotherapy for STHs. This can mos
Truscott JE, Ower AK, Werkman M, et al., 2019, Heterogeneity in transmission parameters of hookworm infection within the baseline data from the TUMIKIA study in Kenya, Parasites and Vectors, Vol: 12, ISSN: 1756-3305
BACKGROUND: As many countries with endemic soil-transmitted helminth (STH) burdens achieve high coverage levels of mass drug administration (MDA) to treat school-aged and pre-school-aged children, understanding the detailed effects of MDA on the epidemiology of STH infections is desirable in formulating future policies for morbidity and/or transmission control. Prevalence and mean intensity of infection are characterized by heterogeneity across a region, leading to uncertainty in the impact of MDA strategies. In this paper, we analyze this heterogeneity in terms of factors that govern the transmission dynamics of the parasite in the host population. RESULTS: Using data from the TUMIKIA study in Kenya (cluster STH prevalence range at baseline: 0-63%), we estimated these parameters and their variability across 120 population clusters in the study region, using a simple parasite transmission model and Gibbs-sampling Monte Carlo Markov chain techniques. We observed great heterogeneity in R0 values, with estimates ranging from 1.23 to 3.27, while k-values (which vary inversely with the degree of parasite aggregation within the human host population) range from 0.007 to 0.29 in a positive association with increasing prevalence. The main finding of this study is the increasing trend for greater parasite aggregation as prevalence declines to low levels, reflected in the low values of the negative binomial parameter k in clusters with low hookworm prevalence. Localized climatic and socioeconomic factors are investigated as potential drivers of these observed epidemiological patterns. CONCLUSIONS: Our results show that lower prevalence is associated with higher degrees of aggregation and hence prevalence alone is not a good indicator of transmission intensity. As a consequence, approaches to MDA and monitoring and evaluation of community infection status may need to be adapted as transmission elimination is aimed for by targeted treatment approaches.
Vegvari C, Truscott J, Kura K, et al., 2019, IMPACT OF POPULATION MOVEMENT BETWEEN VILLAGES ON THE LIKELIHOOD OF BREAKING TRANSMISSION OF SOIL-TRANSMITTED HELMINTHS, Publisher: OXFORD UNIV PRESS, Pages: S53-S54, ISSN: 0035-9203
Toor J, Truscott JE, Werkman M, et al., 2019, BREAKING TRANSMISSION FOR SCHISTOSOMA MANSONI: DETERMINING POST-TREATMENT SURVEILLANCE CRITERIA FOR DETECTING ELIMINATION, Publisher: OXFORD UNIV PRESS, Pages: S53-S53, ISSN: 0035-9203
Halliday KE, Oswald WE, Mcharo C, et al., 2019, Community-level epidemiology of soil-transmitted helminths in the context of school-based deworming: Baseline results of a cluster randomised trial on the coast of Kenya, PLoS Neglected Tropical Diseases, Vol: 13, Pages: 1-22, ISSN: 1935-2727
Most epidemiological studies of soil-transmitted helminth (STH) infections focus on school-going children. The majority of large-scale cross-sectional and longitudinal community-based studies have been conducted prior to the implementation of wide-scale mass drug administration (MDA). This study investigates age-related patterns in prevalence and intensity of STH infection, and associated risk factors, in a region of south coastal Kenya that had previously received three consecutive years of school-based deworming (2012–14) and four rounds of community-based MDA for lymphatic filariasis between 2003 and 2014. Between March and May 2015, a cross-sectional survey was conducted in 120 community clusters as a baseline for a cluster randomised trial. Individuals aged two years and above were randomly selected during household surveys and requested to provide stool samples, which were assessed for presence and intensity of STH using the duplicate Kato-Katz thick smear method. Species-specific predictors of presence and intensity were investigated through multilevel logistic regression and zero-inflated negative binomial regression models. Of the 19,684 individuals who provided a stool sample, 21.5% were infected with at least one STH. Hookworm was the predominant species, with an overall prevalence of 19.1%; Trichuris trichiura prevalence was 3.6% and Ascaris lumbricoides was negligible (0.4% prevalence). The vast majority were light intensity infections. Prevalence and intensity of hookworm infection were significantly higher in adults and males, and were associated with environmental conditions, low socio-economic status, household flooring, individual and household water, sanitation and hygiene (WASH) characteristics and behaviours, previous treatment, lack of shoe-wearing and not attending school. In contrast, T. trichiura was more commonly found in school-aged boys and those living in communities close to the coast, with reduced infection in the least poor indi
Kura K, Truscott JE, Toor J, et al., 2019, Modelling the impact of a Schistosoma mansoni vaccine and mass drug administration to achieve morbidity control and transmission elimination, PLoS Neglected Tropical Diseases, Vol: 13, Pages: 1-21, ISSN: 1935-2727
Mass drug administration (MDA) is, and has been, the principal method for the control of the schistosome helminths. Using MDA only is unlikely to eliminate the infection in areas of high transmission and the implementation of other measures such as reduced water contact improved hygiene and sanitation are required. Ideally a vaccine is needed to ensure long term benefits and eliminate the need for repeated drug treatment since infection does not seem to induce lasting protective immunity. Currently, a candidate vaccine is under trial in a baboon animal model, and very encouraging results have been reported. In this paper, we develop an individual-based stochastic model to evaluate the effect of a vaccine with similar properties in humans to those recorded in baboons in achieving the World Health Organization (WHO) goals of morbidity control and elimination as a public health problem in populations living in a variety of transmission settings. MDA and vaccination assuming different durations of protection and coverage levels, alone or in combination, are examined as treatment strategies to reach the WHO goals of the elimination of morbidity and mortality in the coming decade. We find that the efficacy of a vaccine as an adjunct or main control tool will depend critically on a number of factors including the average duration of protection it provides, vaccine efficacy and the baseline prevalence prior to immunization. In low prevalence settings, simulations suggest that the WHO goals can be achieved for all treatment strategies. In moderate prevalence settings, a vaccine that provides 5 years of protection, can achieve both goals within 15 years of treatment. In high prevalence settings, by vaccinating at age 1, 6 and 11 we can achieve the morbidity control with a probability of nearly 0.89 but we cannot achieve elimination as a public health problem goal. A combined vaccination and MDA treatment plan has the greatest chance of achieving the WHO goals in the shorter t
Giardina F, Coffeng LE, Farrell SH, et al., 2019, Sampling strategies for monitoring and evaluation of morbidity targets for soil-transmitted helminths, PLoS Neglected Tropical Diseases, Vol: 13, ISSN: 1935-2727
BackgroundThe current World Health Organization (WHO) target for the three major soil-transmitted helminth (STH) infections is to reduce prevalence of moderate-to-heavy infections to below 1% by 2020. In terms of monitoring and evaluation (M&E), the current WHO guidelines for control of STHs recommend evaluation of infection levels in school-age children (SAC) after five to six years of preventive chemotherapy (PC), using the standard Kato-Katz faecal smear. Here, we assess the predictive performance of various sampling designs for the evaluation of the morbidity target.Methodology/Principal findingsUsing two mathematical models for STH transmission and control, we simulate how the number of villages and SAC sampled affect the ability of survey results in sentinel villages to predict the achievement of the morbidity target in PC implementation units (e.g. districts). As PC is stopped when the prevalence of infection in SAC in sentinel villages is less than 1%, we estimate the positive predictive value (PPV) of this indicator for meeting the morbidity target in the whole district. The PPV varies by species and PC strategy, and it is generally higher in areas with lower pre-control prevalence. Sampling a fixed number of SAC spread out over 10 instead of 5 sentinel villages may increase the PPV by up to 20 percentage points. If every SAC in a village is tested, a higher number of villages may increase the PPV by up to 80 percentage points. Increasing the proportion of SAC tested per village does not result in a relevant increase of PPV.Conclusions/SignificanceAlthough the WHO guidelines provide a combined strategy to control the three STH species, the efficacy of PC strategies clearly differs by species. There is added value in considering more villages within implementation units for M&E of morbidity targets, the extent varying by STH species. A better understanding of pre- and post-control local STH prevalence levels is essential for an adequate M&E strat
Pullan RL, Halliday KE, Oswald WE, et al., 2019, Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted helminths in Kenya: a cluster-randomised controlled trial, The Lancet, Vol: 393, Pages: 2039-2050, ISSN: 0140-6736
Background School-based deworming programmes can reduce morbidity attributable to soil-transmitted helminthsin children but do not interrupt transmission in the wider community. We assessed the effects of alternative masstreatment strategies on community soil-transmitted helminth infection.Methods In this cluster-randomised controlled trial, 120 community units (clusters) serving 150 000 households inKenya were randomly assigned (1:1:1) to receive albendazole through annual school-based treatment targeting2–14 year olds or annual or biannual community-wide treatment targeting all ages. The primary outcome wascommunity hookworm prevalence, assessed at 12 and 24 months through repeat cross-sectional surveys. Secondaryoutcomes were Ascaris lumbricoides and Trichuris trichiura prevalence, infection intensity of each soil-transmittedhelminth species, and treatment coverage and costs. Analysis was by intention to treat. This trial is registered withClinicalTrials.gov, number NCT02397772.Findings After 24 months, prevalence of hookworm changed from 18·6% (95% CI 13·9–23·2) to 13·8% (10·5–17·0)in the annual school-based treatment group, 17·9% (13·7–22·1) to 8·0% (6·0–10·1) in the annual community-widetreatment group, and 20·6% (15·8–25·5) to 6·2% (4·9–7·5) in the biannual community-wide treatment group.Relative to annual school-based treatment, the risk ratio for annual community-wide treatment was 0·59 (95% CI0·42–0·83; p<0·001) and for biannual community-wide treatment was 0·46 (0·33–0·63; p<0·001). More modestreductions in risk were observed after 12 months. Risk ratios were similar across demographic and socioeconomicsubgroups after 24 months. No adverse events related to albendazole were reported.Interpretation Community-wide treat
McRae-McKee K, Evans S, Hadjichrysanthou C, et al., 2019, Combining hippocampal volume metrics to better understand Alzheimer's disease progression in at-risk individuals, Scientific Reports, Vol: 9, ISSN: 2045-2322
To date nearly all clinical trials of Alzheimer’s disease (AD) therapies have failed. These failures are, at least in part, attributable to poor endpoint choice and to inadequate recruitment criteria. Recently, focus has shifted to targeting at-risk populations in the preclinical stages of AD thus improved predictive markers for identifying individuals likely to progress to AD are crucial to help inform the sample of individuals to be recruited into clinical trials. We focus on hippocampal volume (HV) and assess the added benefit of combining HV and rate of hippocampal atrophy over time in relation to disease progression. Following the cross-validation of previously published estimates of the predictive value of HV, we consider a series of combinations of HV metrics and show that a combination of HV and rate of hippocampal atrophy characterises disease progression better than either measure individually. Furthermore, we demonstrate that the risk of disease progression associated with HV metrics does not differ significantly between clinical states. HV and rate of hippocampal atrophy should therefore be used in tandem when describing AD progression in at-risk individuals. Analyses also suggest that the effects of HV metrics are constant across the continuum of the early stages of the disease.
Løchen A, Anderson RM, 2019, Dynamic transmission models and economic evaluations of pneumococcal conjugate vaccines: a quality appraisal and limitations., Clin Microbiol Infect
BACKGROUND: Of 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. AIM: The aim of this review was to examine epidemiological and economic models and their assumptions for their potential contributions to future research and immunisation policy. SOURCES: Pubmed, Scopus, Ovid, ISI Web of Knowledge, Centre of Reviews and Dissemination (CRD) databases were searched. CONTENT: Twenty-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. IMPLICATIONS: Economic 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
Easton AV, Quiñones M, Vujkovic-Cvijin I, et al., 2019, The impact of anthelmintic treatment on human gut microbiota based on cross-sectional and pre- and postdeworming comparisons in Western Kenya, mBio, Vol: 10, ISSN: 2150-7511
Murine studies suggest that the presence of some species of intestinal helminths is associated with changes in host microbiota composition and diversity. However, studies in humans have produced varied conclusions, and the impact appears to vary widely depending on the helminth species present. To demonstrate how molecular approaches to the human gut microbiome can provide insights into the complex interplay among disparate organisms, DNA was extracted from cryopreserved stools collected from residents of 5 rural Kenyan villages prior to and 3 weeks and 3 months following albendazole (ALB) therapy. Samples were analyzed by quantitative PCR (qPCR) for the presence of 8 species of intestinal parasites and by MiSeq 16S rRNA gene sequencing. Based on pretreatment results, the presence of neither Ascaris lumbricoides nor Necator americanus infection significantly altered the overall diversity of the microbiota in comparison with age-matched controls. Following ALB therapy and clearance of soil-transmitted helminths (STH), there were significant increases in the proportion of the microbiota made up by Clostridiales (P = 0.0002; average fold change, 0.57) and reductions in the proportion made up by Enterobacteriales (P = 0.0004; average fold change, -0.58). There was a significant posttreatment decrease in Chao1 richness, even among individuals who were uninfected pretreatment, suggesting that antimicrobial effects must be considered in any posttreatment setting. Nevertheless, the helminth-associated changes in Clostridiales and Enterobacteriales suggest that clearance of STH, and of N. americanus in particular, alters the gut microbiota.IMPORTANCE The gut microbiome is an important factor in human health. It is affected by what we eat, what medicines we take, and what infections we acquire. In turn, it affects the way we absorb nutrients and whether we have excessive intestinal inflammation. Intestinal worms may have an important
Truscott JE, Dunn JC, Papaiakovou M, et al., 2019, Calculating the prevalence of soil-transmitted helminth infection through pooling of stool samples: Choosing and optimizing the pooling strategy, PLoS Neglected Tropical Diseases, Vol: 13, ISSN: 1935-2727
Prevalence is a common epidemiological measure for assessing soil-transmitted helminthburden and forms the basis for much public-health decision-making. Standard diagnostictechniques are based on egg detection in stool samples through microscopy and these techniques are known to have poor sensitivity for individuals with low infection intensity, leadingto poor sensitivity in low prevalence populations. PCR diagnostic techniques offer very highsensitivities even at low prevalence, but at a greater cost for each diagnostic test in terms ofequipment needed and technician time and training. Pooling of samples can allow prevalence to be estimated while minimizing the number of tests performed. We develop a modelof the relative cost of pooling to estimate prevalence, compared to the direct approach oftesting all samples individually. Analysis shows how expected relative cost depends on boththe underlying prevalence in the population and the size of the pools constructed. A criticalprevalence level (approx. 31%) above which pooling is never cost effective, independent ofpool size. When no prevalence information is available, there is no basis on which to choosebetween pooling and testing all samples individually. We recast our model of relative cost ina Bayesian framework in order to investigate how prior information about prevalence in agiven population can be used to inform the decision to choose either pooling or full testing.Results suggest that if prevalence is below 10%, a relatively small exploratory prevalencesurvey (10–15 samples) can be sufficient to give a high degree of certainty that pooling maybe relatively cost effective.
Dunn JC, Bettis AA, Wyine NY, et al., 2019, Soil-transmitted helminth reinfection four and six months after mass drug administration: Results from the delta region of Myanmar, PLoS Neglected Tropical Diseases, Vol: 13, ISSN: 1935-2727
BackgroundMass drug administration (MDA), targeted at school-aged children (SAC) is the method recommended by the World Health Organization for the control of morbidity induced by soil-transmitted helminth (STH) infection in endemic countries. However, MDA does not prevent reinfection between treatment rounds and research suggests that only treating SAC will not be sufficient to bring prevalence to low levels and possibly interrupt transmission of STH. In countries with endemic infection, such as Myanmar, the coverage, who is targeted, and rates of reinfection will determine how effective MDA is in suppressing transmission in the long-term.Methods/principal findingsIn this paper, data from an epidemiological study on STH, comprising three surveys conducted between June 2015 and June 2016 in the delta region of Myanmar, are analysed to determine how STH prevalence and intensity in the study community changes over the course of a year, including reinfection after two MDA rounds in which the whole study sample (all age groups, n = 523) were treated with albendazole. Prevalence in the first survey (August 2015) was 27.92% for any STH, 5.54% for Ascaris lumbricoides, 17.02% for Trichuris trichiura and 9.75% for hookworm. Over the year (survey one to survey three), prevalence of any STH decreased by 8.99% (P < 0.001) and mean EPG significantly decreased for T. trichiura (P < 0.01) and hookworm (P < 0.001). Risk ratios (RRs) for a four-month reinfection period (August to December) were statistically significant and were below one, indicating that STH prevalence had not bounced back to the prevalence levels recorded immediately prior to the last round of treatment (any STH RR = 0.67, 95% CI 0.56–0.81; A. lumbricoides RR = 0.31, 95% CI 0.16–0.59; T. trichiura RR = 0.70, 95% CI 0.55–0.88; hookworm RR = 0.69, 95% CI 0.50–0.95). The only statistically significant RR for the six-month reinfection period (December to June) was for A. lumbricoides
Anderson RM, Hadjichrysanthou C, Evans S, et al., 2019, Unsuccessful trials of therapies for Alzheimer's disease Reply, LANCET, Vol: 393, Pages: 29-30, ISSN: 0140-6736
Anderson RM, Hadjichrysanthou C, Evans S, et al., 2019, Unsuccessful trials of therapies for Alzheimer's disease - Authors' reply, Lancet, Vol: 393, Pages: 29-30, ISSN: 0140-6736
Hadjichrysanthou C, McRae-McKee K, Evans S, et al., 2018, Potential factors associated with cognitive improvement of individuals diagnosed with mild cognitive impairment or dementia in longitudinal studies, Journal of Alzheimer's Disease, Vol: 66, Pages: 587-600, ISSN: 1387-2877
Despite the progressive nature of Alzheimer’s disease and other dementias, it is observed that many individuals that are diagnosed with mild cognitive impairment (MCI) in one clinical assessment, may return back to normal cognition (CN) in a subsequent assessment. Less frequently, such ‘back-transitions’ are also observed in people that had already been diagnosed with later stages of dementia. In this study, an analysis was performed on two longitudinal cohort datasets provided by 1) the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and 2) the National Alzheimer’s Coordinating Centre (NACC). The focus is on the observed improvement of individuals’ clinical condition recorded in these datasets to explore potential associations with different factors. It is shown that, in both datasets, transitions from MCI to CN are significantly associated with younger age, better cognitive function, and the absence of ApoE ɛ4 alleles. Better cognitive function and in some cases the absence of ApoE ɛ4 alleles are also significantly associated with transitions from types of dementia to less severe clinical states. The effect of gender and education is not clear-cut in these datasets, although highly educated people who reach MCI tend to be more likely to show an improvement in their clinical state. The potential effect of other factors such as changes in symptoms of depression is also discussed. Although improved clinical outcomes can be associated with many factors, better diagnostic tools are required to provide insight into whether such improvements are a result of misdiagnosis, and if they are not, whether they are linked to improvements in the underlying neuropathological condition.
Toor J, Turner HC, Truscott JE, et al., 2018, The design of schistosomiasis monitoring and evaluation programmes: The importance of collecting adult data to inform treatment strategies for Schistosoma mansoni, PLoS Neglected Tropical Diseases, Vol: 12, ISSN: 1935-2727
Monitoring and evaluation (M&E) programmes are used to collect data which are required to assess the impact of current interventions on their progress towards achieving the World Health Organization (WHO) goals of morbidity control and elimination as a public health problem for schistosomiasis. Prevalence and intensity of infection data are typically collected from school-aged children (SAC) as they are relatively easy to sample and are thought to be most likely to be infected by schistosome parasites. However, adults are also likely to be infected. We use three different age-intensity profiles of infection for Schistosoma mansoni with low, moderate and high burdens of infection in adults to investigate how the age distribution of infection impacts the mathematical model generated recommendations of the preventive chemotherapy coverage levels required to achieve the WHO goals. We find that for moderate prevalence regions, regardless of the burden of infection in adults, treating SAC only may achieve the WHO goals. However, for high prevalence regions with a high burden of infection in adults, adult treatment is required to meet the WHO goals. Hence, we show that the optimal treatment strategy for a defined region requires consideration of the burden of infection in adults as it cannot be based solely on the prevalence of infection in SAC. Although past epidemiological data have informed mathematical models for the transmission and control of schistosome infections, more accurate and detailed data are required from M&E programmes to accurately determine the optimal treatment strategy for a defined region. We highlight the importance of collecting prevalence and intensity of infection data from a broader age-range, specifically the inclusion of adult data at baseline (prior to treatment) and throughout the treatment programme if possible, rather than SAC only, to accurately determine the treatment strategy for a defined region. Furthermore, we discuss addition
Werkman M, Toor J, Vegvari C, et al., 2018, Defining stopping criteria for ending randomized clinical trials that investigate the interruption of transmission of soil-transmitted helminths employing mass drug administration, PLoS Neglected Tropical Diseases, Vol: 12, ISSN: 1935-2727
The current World Health Organization strategy to address soil-transmitted helminth (STH) infections in children is based on morbidity control through routine deworming of school and pre-school aged children. However, given that transmission continues to occur as a result of persistent reservoirs of infection in untreated individuals (including adults) and in the environment, in many settings such a strategy will need to be continued for very extended periods of time, or until social, economic and environmental conditions result in interruption of transmission. As a result, there is currently much discussion surrounding the possibility of accelerating the interruption of transmission using alternative strategies of mass drug administration (MDA). However, the feasibility of achieving transmission interruption using MDA remains uncertain due to challenges in sustaining high MDA coverage levels across entire communities. The DeWorm3 trial, designed to test the feasibility of interrupting STH transmission, is currently ongoing. In DeWorm3, three years of high treatment coverage—indicated by mathematical models as necessary for breaking transmission—will be followed by two years of surveillance. Given the fast reinfection (bounce-back) rates of STH, a two year no treatment period is regarded as adequate to assess whether bounce-back or transmission interruption have occurred in a given location. In this study, we investigate if criteria to determine whether transmission interruption is unlikely can be defined at earlier timepoints. A stochastic, individual-based simulation model is employed to simulate core aspects of the DeWorm3 community-based cluster-randomized trial. This trial compares a control arm (annual treatment of children alone with MDA) with an intervention arm (community-wide biannual treatment with MDA). Simulations were run for each scenario for both Ascaris lumbricoides and hookworm (Necator americanus). A range of threshold prevalences meas
Ower AK, Hadjichrysanthou C, Gras L, et al., 2018, Temporal association patterns and dynamics of amyloid-β and tau in Alzheimer's disease, European Journal of Epidemiology, Vol: 33, Pages: 657-666, ISSN: 0393-2990
The elusive relationship between underlying pathology and clinical disease hampers diagnosis of Alzheimer's disease (AD) and preventative intervention development. We seek to understand the relationship between two classical AD biomarkers, amyloid-β1-42 (Aβ1-42) and total-tau (t-tau), and define their trajectories across disease development, as defined by disease onset at diagnosis of mild cognitive impairment (MCI). Using longitudinal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we performed a correlation analysis of biomarkers CSF Aβ1-42 and t-tau, and longitudinal quantile analysis. Using a mixed effects model, with MCI onset as an anchor, we develop linear trajectories to describe the rate of change across disease development. These trajectories were extended through the incorporation of data from cognitively normal, healthy adults (aged 20-62 years) from the literature, to fit sigmoid curves by means of non-linear least squares estimators, to create curves encompassing the 50 years prior to MCI onset. A strong right-angled relationship between the biomarkers Aβ1-42 and t-tau is detected, implying a highly non-linear relationship. The rate of change of Aβ1-42 is correlated with the baseline concentration per quantile, reflecting a reduction in the rate of loss across disease within subjects. Regression models reveal significant amyloid loss relative to MCI onset (- 2.35 pg/mL/year), compared to minimal loss relative to AD onset (- 0.97 pg/mL/year). Tau accumulates consistently relative to MCI and AD onset, (2.05 pg/mL/year) and (2.46 pg/mL/year), respectively. The fitted amyloid curve shows peak loss of amyloid 8.06 years prior to MCI diagnosis, while t-tau exhibits peak accumulation 14.17 years following MCI diagnosis, with the upper limit not yet reached 30 years post diagnosis. Biomarker trajectories aid unbiased, objective assessment of disease progression. Q
Toor J, Alsallaq R, Truscott JE, et al., 2018, Are We on Our Way to Achieving the 2020 Goals for Schistosomiasis Morbidity Control Using Current World Health Organization Guidelines?, CLINICAL INFECTIOUS DISEASES, Vol: 66, Pages: S245-S252, ISSN: 1058-4838
BackgroundSchistosomiasis remains an endemic parasitic disease affecting millions of people around the world. The World Health Organization (WHO) has set goals of controlling morbidity to be reached by 2020, along with elimination as a public health problem in certain regions by 2025. Mathematical models of parasite transmission and treatment impact have been developed to assist in controlling the morbidity caused by schistosomiasis. These models can inform and guide implementation policy for mass drug administration programs, and help design monitoring and evaluation activities.MethodsWe use these models to predict whether the guidelines set by the WHO are on track for achieving their 2020 goal for the control of morbidity, specifically for Schistosoma mansoni. We examine whether programmatic adaptations; namely increases in treatment coverage and/or expansion to adult inclusion in treatment, will improve the likelihood of reaching the WHO goals.ResultsWe find that in low-prevalence settings, the goals are likely to be attainable under current WHO guidelines, but in moderate to high-prevalence settings, the goals are less likely to be achieved unless treatment coverage is increased and expanded to at least 85% for school-aged children and 40% for adults.ConclusionsTo improve the likelihood of reaching the WHO goals, programmatic adaptations are required, particularly for moderate- to high-prevalence settings. Furthermore, improvements in adherence to treatment, potential development of candidate vaccines, and enhanced snail control and WASH (water, sanitation, and hygiene) measures will all assist in achieving the goals.
Farrell SH, Coffeng LE, Truscott JE, et al., 2018, Investigating the Effectiveness of Current and Modified World Health Organization Guidelines for the Control of Soil-Transmitted Helminth Infections, CLINICAL INFECTIOUS DISEASES, Vol: 66, Pages: S253-S259, ISSN: 1058-4838
BackgroundConsiderable efforts have been made to better understand the effectiveness of large-scale preventive chemotherapy therapy for the control of morbidity caused by infection with soil-transmitted helminths (STHs): Ascaris lumbricoides, Trichuris trichiura, and the 2 hookworm species, Necator americanus and Ancylostoma duodenale. Current World Health Organization (WHO) guidelines for STH control include mass drug administration (MDA) programs based on prevalence measurements, aiming at reducing morbidity in pre–school-aged children (pre-SAC) and school-aged children (SAC) by lowering the prevalence of moderate- to heavy-intensity infections to <1%.MethodsWe project the likely impact of following the current WHO guidelines and assess whether the WHO morbidity goals will be achieved across a range of transmission settings. We also investigate modifications that could be made to the current WHO treatment guidelines, and project their potential impacts in achieving morbidity and transmission control.ResultsWhile the standard guidelines are sufficient at low transmission levels, community-wide treatment (ie, involving pre-SAC, SAC, and adults) is essential if WHO morbidity goals are to be met in moderate- to high-transmission settings. Moreover, removing the recommendation of decreasing the treatment frequency at midline (5–6 years after the start of MDA) further improves the likelihood of achieving morbidity control in SAC.ConclusionsWe meld analyses based on 2 mathematical models of parasite transmission and control by MDA for the dominant STH species, to generate a unified treatment approach applicable across all settings, regardless of which STH infection is most common. We recommend clearly defined changes to the current WHO guidelines.
Savioli L, Albonico M, Daumerie D, et al., 2018, Review of the 2017 WHO Guideline: Preventive chemotherapy to control soil-transmitted helminth infections in at-risk population groups. An opportunity lost in translation, PLOS NEGLECTED TROPICAL DISEASES, Vol: 12, ISSN: 1935-2735
Turner HC, Toor J, Hollingsworth TD, et al., 2018, Economic evaluations of mass drug administration: the importance of economies of scale and scope, Clinical Infectious Diseases, Vol: 66, Pages: 1298-1303, ISSN: 1058-4838
It is recognized that changing the current approaches for the control of the neglected tropical diseases will be needed to reach the World Health Organization’s (WHO) 2020 goals. Consequently, it is important that economic evaluations of the alternative approaches are conducted. A vital component of such evaluations is the issue of how the intervention’s costs should be incorporated. We discuss this issue—focusing on mass drug administration. We argue that the common approach of assuming an intervention’s cost per treatment is constant, regardless of the number of individuals treated, is a misleading way to consider the delivery costs of mass drug administration due to the occurrence of economies/diseconomies of scale and scope. Greater care and consideration are required when the costs are incorporated into such analyses. Without this, these economic evaluations could potentially lead to incorrect policy recommendations.
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