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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
Imtiaz R, Campbell SJ, Vegvari C, et al., 2019, Insights from quantitative analysis and mathematical modelling on the proposed who 2030 goals for soil-transmitted helminths., Gates Open Research, Vol: 3
Soil-transmitted helminths (STHs) are a group of parasitic worms that infect humans, causing a wide spectrum of disease, notably anaemia, growth retardation, and delayed cognitive development. The three main STHs are Ascaris lumbricoides, Trichuris trichiura and hookworm (Necator americanus and Ancylostoma duodenale). Approximately 1.5 billion people are infected with STHs worldwide. The World Health Organization goal for 2030 is morbidity control, defined as reaching <2% prevalence of medium-to-high intensity infections in preschool-age children and school-age children (SAC). Treatment guidelines for achieving this goal have been recommended. The Neglected Tropical Diseases Modelling Consortium has developed mathematical and statistical models to quantify, predict, and evaluate the impact of control measures on STHs. These models show that the morbidity target can be achieved following current guidelines in moderate prevalence settings (20-50% in SAC). In high prevalence settings, semi-annual preventive chemotherapy (PC) ideally including adults, or at least women of reproductive age, is required. For T. trichiura, dual therapy with albendazole and ivermectin is required. In general, stopping PC is not possible without infection resurgence, unless effective measures for improved access to water, hygiene, and sanitation have been implemented, or elimination of transmission has been achieved. Current diagnostic methods are based on egg counts in stool samples, but these are known to have poor sensitivity at low prevalence levels. A target threshold for novel, more sensitive diagnostics should be defined relative to currently preferred diagnostics (Kato-Katz). Our analyses identify the extent of systematic non-access to treatment and the individual patterns of compliance over multiple rounds of treatment as the biggest unknowns and the main impediment to reaching the target. Moreover, the link between morbidity and infection intensity has not been fully elucidated.
Vegvari C, Hardwick R, Truscott J, et al., 2019, RELEVANT SPATIAL SCALE FOR EVALUATION UNITS FOR ELIMINATION PROGRAMS FOR SOIL-TRANSMITTED HELMINTHS GIVEN GEOGRAPHY OF SETTLEMENTS AND HUMAN MOVEMENT, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 618-618, ISSN: 0002-9637
Ower AK, Nigussu N, Seife F, et al., 2019, COMPLIANCE TO TREATMENT IN THE GESHIYARO PROJECT: TESTING THE FEASIBILITY OF INTERRUPTING TRANSMISSION, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 355-355, ISSN: 0002-9637
Toor J, Truscott JE, Werkman M, et al., 2019, POST-TREATMENT SURVEILLANCE CRITERIA FOR <i>SCHISTOSOMA MANSONI</i>: WILL ELIMINATION OR RESURGENCE OCCUR AFTER STOPPING MASS DRUG ADMINISTRATION?, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 371-371, ISSN: 0002-9637
Kura K, Truscott J, Toor J, et al., 2019, MODELLING THE IMPACT OF VACCINATION STRATEGIES ON THE TRANSMISSION OF SCHISTOSOMIASIS, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 373-373, ISSN: 0002-9637
Phillips AE, Mekete K, Ower A, et al., 2019, IMPACT OF WATER, SANITATION AND HYGIENE ON COMMUNITY-LEVEL INTESTINAL PARASITES IN ETHIOPIA: THE GESHIYARO PROJECT, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 579-579, ISSN: 0002-9637
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Dunn JC, Walker M, Bettis AA, et al., 2019, PREDISPOSITION AND HOUSEHOLD CLUSTERING OF SOIL-TRANSMITTED HELMINTH INFECTION EVIDENT IN MYANMAR COMMUNITIES THAT HAVE RECEIVED EXTENSIVE MASS DRUG ADMINISTRATION, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 616-617, ISSN: 0002-9637
Mekete K, Ower A, Dunn JC, et al., 2019, INTERRUPTING TRANSMISSION OF SOIL-TRANSMITTED HELMINTHS AND SCHISTOSOME PARASITES IN ETHIOPIA - THE GESHIYARO PROJECT PROTOCOL, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 167-167, ISSN: 0002-9637
Clarke N, Dinh N-N, Traub R, et al., 2019, A COMPARISON OF QUANTITATIVE PCR, KATO-KATZ TECHNIQUE, AND SODIUM NITRATE FLOTATION FOR THE DIAGNOSIS OF HOOKWORM INFECTIONS IN VIETNAM, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 390-390, ISSN: 0002-9637
Truscott J, Hardwick RJ, Werkman M, et al., 2019, FORECASTING THE IMPACT OF MASS DRUG ADMINISTRATION IN A HETEROGENEOUS ENVIRONMENT WITHIN THE DEWORM3 TRAIL IN BENIN, MALAWI AND INDIA, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 354-354, ISSN: 0002-9637
Clarke NE, Dinh N-N, Traub RJ, et al., 2019, A CLUSTER-RANDOMIZED CONTROLLED TRIAL COMPARING SCHOOL AND COMMUNITY-BASED DEWORMING FOR SOIL TRANSMITTED HELMINTH CONTROL IN SCHOOL-AGE CHILDREN: THE CODE-STH TRIAL PROTOCOL, 68th Annual Meeting of the American-Society-for-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 357-357, ISSN: 0002-9637
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.
Evans S, McRae-McKee K, Wong MM, et al., 2018, The importance of endpoint selection: how effective does a drug need to be for success in a clinical trial of a possible Alzheimer's disease treatment?, European Journal of Epidemiology, Vol: 33, Pages: 635-644, ISSN: 0393-2990
To date, Alzheimer's disease (AD) clinical trials have been largely unsuccessful. Failures have been attributed to a number of factors including ineffective drugs, inadequate targets, and poor trial design, of which the choice of endpoint is crucial. Using data from the Alzheimer's Disease Neuroimaging Initiative, we have calculated the minimum detectable effect size (MDES) in change from baseline of a range of measures over time, and in different diagnostic groups along the AD development trajectory. The Functional Activities Questionnaire score had the smallest MDES for a single endpoint where an effect of 27% could be detected within 3 years in participants with Late Mild Cognitive Impairment (LMCI) at baseline, closely followed by the Clinical Dementia Rating Sum of Boxes (CDRSB) score at 28% after 2 years in the same group. Composite measures were even more successful than single endpoints with an MDES of 21% in 3 years. Using alternative cognitive, imaging, functional, or composite endpoints, and recruiting patients that have LMCI could improve the success rate of AD clinical trials.
Wright JE, Werkman M, Dunn J, et al., 2018, Current epidemiological evidence for predisposition to high or low intensity human helminth infection: a systematic review, Parasites & Vectors, Vol: 11, ISSN: 1756-3305
Background: The human helminth infections include ascariasis, trichuriasis, hookworm infections, schistosomiasis,lymphatic filariasis (LF) and onchocerciasis. It is estimated that almost 2 billion people worldwide are infected withhelminths. Whilst the WHO treatment guidelines for helminth infections are mostly aimed at controlling morbidity,there has been a recent shift with some countries moving towards goals of disease elimination through mass drugadministration, especially for LF and onchocerciasis. However, as prevalence is driven lower, treating entire populationsmay no longer be the most efficient or cost-effective strategy. Instead, it may be beneficial to identify individuals ordemographic groups who are persistently infected, often termed as being “predisposed” to infection, and targettreatment at them.Methods: The authors searched Embase, MEDLINE, Global Health, and Web of Science for all English language, humanbasedpapers investigating predisposition to helminth infections published up to October 31st, 2017. Thevarying definitions used to describe predisposition, and the statistical tests used to determine its presence, are summarised.Evidence for predisposition is presented, stratified by helminth species, and risk factors for predisposition to infection areidentified and discussed.Results: In total, 43 papers were identified, summarising results from 34 different studies in 23 countries. Consistentevidence of predisposition to infection with certain species of human helminth was identified. Children were regularlyfound to experience greater predisposition to Ascaris lumbricoides, Schistosoma mansoni and S. haematobium than adults.Females were found to be more predisposed to A. lumbricoides infection than were males. Household clustering ofinfection was identified for A. lumbricoides, T. trichiura and S. japonicum. Ascaris lumbricoides and T. trichiura also showedevidence of familial predisposition. Whilst strong evidence for predisposition
Farrell SH, Anderson RM, 2018, Helminth lifespan interacts with noncompliance in reducing the effectiveness of anthelmintic treatment, PARASITES & VECTORS, Vol: 11, ISSN: 1756-3305
BackgroundThe success of mass drug administration programmes targeting the soil-transmitted helminths and schistosome parasites is in part dependent on compliance to treatment at sequential rounds of mass drug administration (MDA). The impact of MDA is vulnerable to systematic non-compliance, defined as a portion of the eligible population remaining untreated over successive treatment rounds. The impact of systematic non-compliance on helminth transmission dynamics - and thereby on the number of treatment rounds required to interrupt transmission - is dependent on the parasitic helminth being targeted by MDA.ResultsHere, we investigate the impact of adult parasite lifespan in the human host and other factors that determine the magnitude of the basic reproductive number R 0 , on the number of additional treatment rounds required in a target population, using mathematical models of Ascaris lumbricoides and Schistosoma mansoni transmission incorporating systematic non-compliance. Our analysis indicates a strong interaction between helminth lifespan and the impact of systematic non-compliance on parasite elimination, and confirms differences in its impact between Ascaris and the schistosome parasites in a streamlined model structure.ConclusionsOur analysis suggests that achieving reductions in the level of systematic non-compliance may be of particular benefit in mass drug administration programmes treating the longer-lived helminth parasites, and highlights the need for improved data collection in understanding the impact of compliance.
Hadjichrysanthou C, Ower AK, de Wolf F, et al., 2018, The development of a stochastic mathematical model of Alzheimer's disease to help improve the design of clinical trials of potential treatments, PLOS ONE, Vol: 13, ISSN: 1932-6203
Alzheimer’sdisease(AD)is a neurodegenerative disordercharacterisedbya slowprogres-sivedeteriorationof cognitivecapacity.Drugsareurgentlyneededforthetreatmentof ADandunfortunatelyalmostallclinicaltrialsof ADdrugcandidateshavefailedor beendiscon-tinuedto date.Mathematical,computationalandstatisticaltoolscanbeemployedin theconstructionof clinicaltrialsimulatorsto assistin theimprovementof trialdesignandenhancethechancesof successof potentialnewtherapies.Basedontheanalysisof a setof clinicaldataprovidedbytheAlzheimer’sDiseaseNeuroimagingInitiative(ADNI)wedevelopeda simplestochasticmathematicalmodelto simulatethedevelopmentandpro-gressionof Alzheimer’sin a longitudinalcohortstudy.Weshowhowthismodellingframe-workcouldbeusedto assesstheeffectandthechancesof successof hypotheticaltreatmentsthatareadministeredat differentstagesanddelaydiseasedevelopment.Wedemonstratethatthedetectionof thetrueefficacyof anADtreatmentcanbeverychalleng-ing,evenif thetreatmentis highlyeffective.Animportantreasonbehindtheinabilitytodetectsignalsof efficacyin a clinicaltrialin thistherapyareacouldbethehighbetween-andwithin-individualvariabilityin themeasurement of diagnosticmarkersandendpoints,whichconsequentlyresultsin themisdiagnosisof anindividual’sdiseasestate.
Asbjornsdottir KH, Rao Ajjampur SS, Anderson R, et al., 2018, Assessing the feasibility of interrupting the transmission of soil-transmitted helminths through mass drug administration: The DeWorm3 cluster randomized trial protoco, PLoS Neglected Tropical Diseases, Vol: 12, ISSN: 1935-2727
Current control strategies for soil-transmitted helminths (STH) emphasize morbidity control through mass drug administration (MDA) targeting preschool- and school-age children, women of childbearing age and adults in certain high-risk occupations such as agricultural laborers or miners. This strategy is effective at reducing morbidity in those treated but, without massive economic development, it is unlikely it will interrupt transmission. MDA will therefore need to continue indefinitely to maintain benefit. Mathematical models suggest that transmission interruption may be achievable through MDA alone, provided that all age groups are targeted with high coverage. The DeWorm3 Project will test the feasibility of interrupting STH transmission using biannual MDA targeting all age groups. Study sites (population ≥80,000) have been identified in Benin, Malawi and India. Each site will be divided into 40 clusters, to be randomized 1:1 to three years of twice-annual community-wide MDA or standard-of-care MDA, typically annual school-based deworming. Community-wide MDA will be delivered door-to-door, while standard-of-care MDA will be delivered according to national guidelines. The primary outcome is transmission interruption of the STH species present at each site, defined as weighted cluster-level prevalence ≤2% by quantitative polymerase chain reaction (qPCR), 24 months after the final round of MDA. Secondary outcomes include the endline prevalence of STH, overall and by species, and the endline prevalence of STH among children under five as an indicator of incident infections. Secondary analyses will identify cluster-level factors associated with transmission interruption. Prevalence will be assessed using qPCR of stool samples collected from a random sample of cluster residents at baseline, six months after the final round of MDA and 24 months post-MDA. A smaller number of individuals in each cluster will be followed with annual sampling to monitor trends in prev
Davis EL, Danon L, Prada JM, et al., 2018, Seasonally timed treatment programs for Ascaris lumbricoides to increase impact-An investigation using mathematical models, PLOS NEGLECTED TROPICAL DISEASES, Vol: 12, ISSN: 1935-2735
There is clear empirical evidence that environmental conditions can influence Ascaris spp. free-living stage development and host reinfection, but the impact of these differences on human infections, and interventions to control them, is variable. A new model framework reflecting four key stages of the A. lumbricoides life cycle, incorporating the effects of rainfall and temperature, is used to describe the level of infection in the human population alongside the environmental egg dynamics. Using data from South Korea and Nigeria, we conclude that settings with extreme fluctuations in rainfall or temperature could exhibit strong seasonal transmission patterns that may be partially masked by the longevity of A. lumbricoides infections in hosts; we go on to demonstrate how seasonally timed mass drug administration (MDA) could impact the outcomes of control strategies. For the South Korean setting the results predict a comparative decrease of 74.5% in mean worm days (the number of days the average individual spend infected with worms across a 12 month period) between the best and worst MDA timings after four years of annual treatment. The model found no significant seasonal effect on MDA in the Nigerian setting due to a narrower annual temperature range and no rainfall dependence. Our results suggest that seasonal variation in egg survival and maturation could be exploited to maximise the impact of MDA in certain settings.
Werkman M, Wright JE, Truscott JE, et al., 2018, Testing for soil-transmitted helminth transmission elimination: Analysing the impact of the sensitivity of different diagnostic tools., PLoS Neglected Tropical Diseases, Vol: 12, ISSN: 1935-2727
In recent years, an increased focus has been placed upon the possibility of the elimination of soil-transmitted helminth (STH) transmission using various interventions including mass drug administration. The primary diagnostic tool recommended by the WHO is the detection of STH eggs in stool using the Kato-Katz (KK) method. However, detecting infected individuals using this method becomes increasingly difficult as the intensity of infection decreases. Newer techniques, such as qPCR, have been shown to have greater sensitivity than KK, especially at low prevalence. However, the impact of using qPCR on elimination thresholds is yet to be investigated. In this paper, we aim to quantify how the sensitivity of these two diagnostic tools affects the optimal prevalence threshold at which to declare the interruption of transmission with a defined level of confidence. A stochastic, individual-based STH transmission model was used in this study to simulate the transmission dynamics of Ascaris and hookworm. Data from a Kenyan deworming study were used to parameterize the diagnostic model which was based on egg detection probabilities. The positive and negative predictive values (PPV and NPV) were calculated to assess the quality of any given threshold, with the optimal threshold value taken to be that at which both were maximised. The threshold prevalence of infection values for declaring elimination of Ascaris transmission were 6% and 12% for KK and qPCR respectively. For hookworm, these threshold values are lower at 0.5% and 2% respectively. Diagnostic tests with greater sensitivity are becoming increasingly important as we approach the elimination of STH transmission in some regions of the world. For declaring the elimination of transmission, using qPCR to diagnose STH infection results in the definition of a higher prevalence, than when KK is used.
Easton A, Lawton S, Gao S, et al., 2018, A REFERENCE <it>ASCARIS LUMBRICOIDES</it> GENOME ALLOWS INSIGHTS INTO POPULATION-BASED GENOMIC CHANGES IN SPACE AND TIME, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 211-211, ISSN: 0002-9637
Dunn J, Bettis A, Wyine N, et al., 2018, LONGITUDINAL CHANGES IN RISK AND INTENSITY OF INFECTION WITH SOIL-TRANSMITTED HELMINTHS AFTER COMMUNITY-WIDE MASS DRUG ADMINISTRATION IN RURAL MYANMAR, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 238-239, ISSN: 0002-9637
Toor J, Turner H, Truscott J, et al., 2018, SCHISTOSOMIASIS MONITORING AND EVALUATION PROGRAMS: THE IMPORTANCE OF COLLECTING ADULT DATA TO INFORM TREATMENT STRATEGIES FOR <it>SCHISTOSOMA MANSONI</it>, 67th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTHM), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 20-20, ISSN: 0002-9637
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