Publications
220 results found
Irvine MA, Stolk WA, Smith ME, et al., 2016, Effectiveness of a triple-drug regimen for global elimination of lymphatic filariasis: a modelling study, Lancet Infectious Diseases, Vol: 17, Pages: 451-458, ISSN: 1473-3099
BackgroundLymphatic filariasis is targeted for elimination as a public health problem by 2020. The principal approach used by current programmes is annual mass drug administration with two pairs of drugs with a good safety profile. However, one dose of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) has been shown to clear the transmissible stage of the helminth completely in treated individuals. The aim of this study was to use modelling to assess the potential value of mass drug administration with the triple-drug regimen for accelerating elimination of lymphatic filariasis in different epidemiological settings.MethodsWe used three different transmission models to compare the number of rounds of mass drug administration needed to achieve a prevalence of microfilaraemia less than 1% with the triple-drug regimen and with current two-drug regimens.FindingsIn settings with a low baseline prevalence of lymphatic filariasis (5%), the triple-drug regimen reduced the number of rounds of mass drug administration needed to reach the target prevalence by one or two rounds, compared with the two-drug regimen. For areas with higher baseline prevalence (10–40%), the triple-drug regimen strikingly reduced the number of rounds of mass drug administration needed, by about four or five, but only at moderate-to-high levels of population coverage (>65%) and if systematic non-adherence to mass drug administration was low.InterpretationSimulation modelling suggests that the triple-drug regimen has potential to accelerate the elimination of lymphatic filariasis if high population coverage of mass drug administration can be achieved and if systematic non-adherence with mass drug administration is low. Future work will reassess these estimates in light of more clinical trial data and to understand the effect on an individual country's programme.
Deol AK, Webster JP, walker M, et al., 2016, Development and evaluation of a Markov model to predict changes in schistosomiasis prevalence in response to praziquantel treatment: a case study of Schistosoma mansoni in Uganda and Mali, Parasites & Vectors, Vol: 9, ISSN: 1756-3305
Background: Understanding whether schistosomiasis control programmes are on course to control morbidityand potentially switch towards elimination interventions would benefit from user-friendly quantitative tools thatfacilitate analysis of progress and highlight areas not responding to treatment. This study aimed to develop andevaluate such a tool using large datasets collected during Schistosomiasis Control Initiative-supported controlprogrammes.Methods: A discrete-time Markov model was developed using transition probability matrices parameterized withcontrol programme longitudinal data on Schistosoma mansoni obtained from Uganda and Mali. Four matrix variants(A-D) were used to compare different data types for parameterization: A-C from Uganda and D from Mali. Matrix Aused data at baseline and year 1 of the control programme; B used year 1 and year 2; C used baseline and year 1from selected districts, and D used baseline and year 1 Mali data. Model predictions were tested against 3 subsetsof the Uganda dataset: dataset 1, the full 4-year longitudinal cohort; dataset 2, from districts not used toparameterize matrix C; dataset 3, cross-sectional data, and dataset 4, from Mali as an independent dataset.Results: The model parameterized using matrices A, B and D predicted similar infection dynamics (overall andwhen stratified by infection intensity). Matrices A-D successfully predicted prevalence in each follow-up year for lowand high intensity categories in dataset 1 followed by dataset 2. Matrices A, B and D yielded similar and closematches to dataset 1 with marginal discrepancies when comparing model outputs against datasets 2 and 3. MatrixC produced more variable results, correctly estimating fewer data points.Conclusion: Model outputs closely matched observed values and were a useful predictor of the infection dynamicsof S. mansoni when using longitudinal and cross-sectional data from Uganda. This also held when the model wastested with data from Mali. This was most
Marshall JM, Touré M, Ouédraogo AL, et al., 2016, Key traveller groups of relevance to spatial malaria transmission: a survey of movement patterns in four sub-Saharan African countries, Malaria Journal, Vol: 15, ISSN: 1475-2875
Fowler AC, Hollingsworth TD, 2016, The Dynamics of Ascaris lumbricoides Infections, Bulletin of Mathematical Biology, Vol: 78, Pages: 815-833, ISSN: 1522-9602
The Anderson–May model of human parasite infections and specifically that for the intestinal worm Ascaris lumbricoides is reconsidered, with a view to deriving the observed characteristic negative binomial distribution which is frequently found in human communities. The means to obtaining this result lies in reformulating the continuous Anderson–May model as a stochastic process involving two essential populations, the density of mature worms in the gut, and the density of mature eggs in the environment. The resulting partial differential equation for the generating function of the joint probability distribution of eggs and worms can be partially solved in the appropriate limit where the worm lifetime is much greater than that of the mature eggs in the environment. Allowing for a mean field nonlinearity, and for egg immigration from neighbouring communities, a negative binomial worm distribution can be predicted, whose parameters are determined by those in the continuous Anderson–May model; this result assumes no variability in predisposition to the infection.
Turner HC, Truscott JE, Bettis AA, et al., 2016, Analysis of the population-level impact of co-administering ivermectin with albendazole or mebendazole for the control and elimination of Trichuris trichiura, Parasite Epidemiology and Control, Vol: 1, Pages: 177-187, ISSN: 2405-6731
INTRODUCTION: Soil-transmitted helminth (STH) infections are predominately controlled by providing children with preventive chemotherapy with either albendazole or mebendazole. However, neither has a high efficacy against Trichuris trichiura. This low efficacy limits the overall effectiveness of the current STH control programmes against T. trichiura. It has been demonstrated that co-administering ivermectin with albendazole or mebendazole significantly increases the efficacy of current treatments, which may increase the overall effectiveness of control programmes. METHODS: Using a STH transmission mathematical model, we evaluated the potential impact of co-administering ivermectin with albendazole or mebendazole to treat T. trichiura within a preventive chemotherapy programme targeting children (2-15 year olds). We evaluated the impact in terms of reduction in prevalent infections, mean worm burden, and prevalence of heavy infections. RESULTS: Although the current treatment strategy reduced T. trichiura worm burden and prevalence of heavy infections, due to their poor efficacy the long term impact of preventive chemotherapy for children was smaller compared to the other STH. Co-administering ivermectin increased the projected impact of the preventive chemotherapy programme in terms of all three of the explored metrics, practically in high transmission settings. Furthermore, ivermectin co-administration greatly increased the feasibility of and timeframe for breaking transmission. CONCLUSIONS: Co-administering ivermectin notably increased the projected impact of preventive chemotherapy in high transmission settings and increased the feasibility for breaking transmission. This has important implications for control programmes, some of which may be shifting focus from morbidity control to interruption of transmission, and some of which may be logistically unable to provide preventive chemotherapy twice a year as recommended. However, the benefit of co-administerin
Turner HC, Truscott JE, Fleming FM, et al., 2016, Cost-effectiveness of scaling up mass drug administration for the control of soil-transmitted helminths: a comparison of cost function and constant costs analyses., Lancet: Infectious Diseases, Vol: 16, Pages: 838-846, ISSN: 1473-3099
BACKGROUND: The coverage of mass drug administration (MDA) for neglected tropical diseases, such as the soil-transmitted helminths (STHs), needs to rapidly expand to meet WHO's 2020 targets. We aimed to compare use of a cost function to take into account economies of scale to the standard method of assuming a constant cost per treatment when investigating the cost and cost-effectiveness of scaling up a STH MDA programme targeting Ascaris lumbricoides. METHODS: We fitted a cost function describing how the costs of MDA change with scale to empirical cost data and incorporated it into a STH transmission model. Using this cost function, we investigated the consequences of taking into account economies of scale on the projected cost-effectiveness of STH control, by comparison with the standard method of assuming a constant cost per treatment. The cost function was fitted to economic cost data collected as part of a school-based deworming programme in Uganda using maximum likelihood methods. We used the model to investigate the total reduction in the overall worm burden, the total number of prevalent infection case-years averted, and the total number of heavy infection case-years averted. For each year, we calculated the effectiveness as the difference between the worm burden or number of cases and the number in absence of treatment. FINDINGS: When using the cost function, the cost-effectiveness of STH control markedly increased as the programme was scaled up. By contrast, the standard method (constant cost per treatment) undervalued this and generated misleading conclusions. For example, when scaling up control in the projected district from 10% to 75% coverage of at-risk school-age children, the cost-effectiveness in terms of prevention of heavy burden infections was projected to increase by over 70% when using the cost function, but decrease by 18% when assuming a constant cost per treatment. INTERPRETATION: The current exclusion of economies of scale in most economic
Irvine MA, Njenga SM, Gunawardena S, et al., 2016, Understanding the relationship between prevalence of microfilariae and antigenaemia using a model of lymphatic filariasis infection, Transactions of the Royal Society of Tropical Medicine and Hygiene, Vol: 110, Pages: 118-124, ISSN: 0035-9203
Cameron MM, Acosta-Serrano A, Bern C, et al., 2016, Understanding the transmission dynamics of Leishmania donovani to provide robust evidence for interventions to eliminate visceral leishmaniasis in Bihar, India, Parasites & Vectors, Vol: 9, ISSN: 1756-3305
Visceral Leishmaniasis (VL) is a neglected vector-borne disease. In India, it is transmitted to humans by Leishmania donovani-infected Phlebotomus argentipes sand flies. In 2005, VL was targeted for elimination by the governments of India, Nepal and Bangladesh by 2015. The elimination strategy consists of rapid case detection, treatment of VL cases and vector control using indoor residual spraying (IRS). However, to achieve sustained elimination of VL, an appropriate post elimination surveillance programme should be designed, and crucial knowledge gaps in vector bionomics, human infection and transmission need to be addressed. This review examines the outstanding knowledge gaps, specifically in the context of Bihar State, India.The knowledge gaps in vector bionomics that will be of immediate benefit to current control operations include better estimates of human biting rates and natural infection rates of P. argentipes, with L. donovani, and how these vary spatially, temporally and in response to IRS. The relative importance of indoor and outdoor transmission, and how P. argentipes disperse, are also unknown. With respect to human transmission it is important to use a range of diagnostic tools to distinguish individuals in endemic communities into those who: 1) are to going to progress to clinical VL, 2) are immune/refractory to infection and 3) have had past exposure to sand flies.It is crucial to keep in mind that close to elimination, and post-elimination, VL cases will become infrequent, so it is vital to define what the surveillance programme should target and how it should be designed to prevent resurgence. Therefore, a better understanding of the transmission dynamics of VL, in particular of how rates of infection in humans and sand flies vary as functions of each other, is required to guide VL elimination efforts and ensure sustained elimination in the Indian subcontinent. By collecting contemporary entomological and human data in the same geographical locat
Medley GF, Turner HC, Baggaley RF, et al., 2016, The Role of More Sensitive Helminth Diagnostics in Mass Drug Administration Campaigns: Elimination and Health Impacts, ADVANCES IN PARASITOLOGY, VOL 94: MATHEMATICAL MODELS FOR NEGLECTED TROPICAL DISEASES: ESSENTIAL TOOLS FOR CONTROL AND ELIMINATION, PT B, Editors: Basanez, Anderson, Publisher: ELSEVIER ACADEMIC PRESS INC, Pages: 343-392
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Macpherson EE, Adams ER, Bockarie MJ, et al., 2015, Mass Drug Administration and beyond: how can we strengthen health systems to deliver complex interventions to eliminate neglected tropical diseases?, BMC Proceedings, Vol: 9, ISSN: 1753-6561
Achieving the 2020 goals for Neglected Tropical Diseases (NTDs) requires scale-up of Mass Drug Administration (MDA) which will require long-term commitment of national and global financing partners, strengthening national capacity and, at the community level, systems to monitor and evaluate activities and impact.For some settings and diseases, MDA is not appropriate and alternative interventions are required. Operational research is necessary to identify how existing MDA networks can deliver this more complex range of interventions equitably.The final stages of the different global programmes to eliminate NTDs require eliminating foci of transmission which are likely to persist in complex and remote rural settings. Operational research is required to identify how current tools and practices might be adapted to locate and eliminate these hard-to-reach foci.Chronic disabilities caused by NTDs will persist after transmission of pathogens ceases. Development and delivery of sustainable services to reduce the NTD-related disability is an urgent public health priority.LSTM and its partners are world leaders in developing and delivering interventions to control vector-borne NTDs and malaria, particularly in hard-to-reach settings in Africa. Our experience, partnerships and research capacity allows us to serve as a hub for developing, supporting, monitoring and evaluating global programmes to eliminate NTDs.
Reimer LJ, Adams ER, Paine MJI, et al., 2015, Fit for purpose: do we have the right tools to sustain NTD elimination?, BMC Proceedings, Vol: 9, ISSN: 1753-6561
Priorities for NTD control programmes will shift over the next 10-20 years as the elimination phase reaches the ‘end game’ for some NTDs, and the recognition that the control of other NTDs is much more problematic. The current goal of scaling up programmes based on preventive chemotherapy (PCT) will alter to sustaining NTD prevention, through sensitive surveillance and rapid response to resurgence. A new suite of tools and approaches will be required for both PCT and Intensive Disease Management (IDM) diseases in this timeframe to enable disease endemic countries to:1. Sensitively and sustainably survey NTD transmission and prevalence in order to identify and respond quickly to resurgence.2. Set relevant control targets based not only on epidemiological indicators but also entomological and ecological metrics and use decision support technology to help meet those targets.3. Implement verified and cost-effective tools to prevent transmission throughout the elimination phase.Liverpool School of Tropical Medicine (LSTM) and partners propose to evaluate and implement existing tools from other disease systems as well as new tools in the pipeline in order to support endemic country ownership in NTD decision-making during the elimination phase and beyond.
Hollingsworth T, Langley I, Nokes D, et al., 2015, Infectious disease and health systems modelling for local decision making to control neglected tropical diseases, BMC Proceedings, Vol: 9, ISSN: 1753-6561
Most neglected tropical diseases (NTDs) have complex life cycles and are challenging to control. The “2020 goals” of control and elimination as a public health programme for a number of NTDs are the subject of significant international efforts and investments. Beyond 2020 there will be a drive to maintain these gains and to push for true local elimination of transmission. However, these diseases are affected by variations in vectors, human demography, access to water and sanitation, access to interventions and local health systems. We therefore argue that there will be a need to develop local quantitative expertise to support elimination efforts. If available now, quantitative analyses would provide updated estimates of the burden of disease, assist in the design of locally appropriate control programmes, estimate the effectiveness of current interventions and support ‘real-time’ updates to local operations. Such quantitative tools are increasingly available at an international scale for NTDs, but are rarely tailored to local scenarios. Localised expertise not only provides an opportunity for more relevant analyses, but also has a greater chance of developing positive feedback between data collection and analysis by demonstrating the value of data. This is essential as rational program design relies on good quality data collection. It is also likely that if such infrastructure is provided for NTDs there will be an additional impact on the health system more broadly. Locally tailored quantitative analyses can help achieve sustainable and effective control of NTDs, but also underpin the development of local health care systems.
Hollingsworth TD, Adams ER, Anderson RM, et al., 2015, Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases, Parasites & Vectors, Vol: 8, ISSN: 1756-3305
Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminatedisease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals forneglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyseswhich aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease,visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphaticfilariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: theimportance of epidemiological setting on the success of interventions; targeting groups who are at highest risk ofinfection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoirfor infection,. The results also highlight the challenge of maintaining elimination ‘as a public health problem’ whentrue elimination is not reached. The models elucidate the factors that may be contributing most to persistence ofdisease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall thiscollection presents new analyses to inform current control initiatives. These papers form a base from which furtherdevelopment of the models and more rigorous validation against a variety of datasets can help to give moredetailed advice. At the moment, the models’ predictions are being considered as the world prepares for a finalpush towards control or elimination of neglected tropical diseases by 2020.
Medley GF, Hollingsworth TD, Olliaro PL, et al., 2015, Health-seeking behaviour, diagnostics and transmission dynamics in the control of visceral leishmaniasis in the Indian subcontinent, Nature, Vol: 528, Pages: S102-S108, ISSN: 0028-0836
Countries in the Indian subcontinent have committed to reducing the incidence of kala-azar, a clinical manifestation of visceral leishmaniasis, to below 1 in 10,000 by 2020. We address the role of timing of use and accuracy of diagnostics in kala-azar control and elimination. We use empirical data on health-seeking behaviour and health-system performance from the Indian state of Bihar, Bangladesh and Nepal to parameterize a mathematical model. Diagnosis of cases is key to case management, control and surveillance. Treatment of cases prevents onward transmission, and we show that the differences in time to diagnosis in these three settings explain the observed differences in incidence. Shortening the time from health-care seeking to diagnosis is likely to lead to dramatic reductions in incidence in Bihar, bringing the incidence down to the levels seen in Bangladesh and Nepal. The results emphasize the importance of maintaining population and health-system awareness, particularly as transmission and disease incidence decline. We explore the possibility of diagnosing patients before the onset of clinical kala-azar (before 14 days fever), and show that this could have a marked impact on incidence, even for a moderately sensitive test. However, limited specificity (that results in false positives) is a major barrier to such a strategy. Diagnostic tests of high specificity used at an early stage of active infection, even if sensitivity is only moderate, could have a key role in the control of kala-azar, and prevent its resurgence when paired with the passive health-care system and tests of high sensitivity, such as the test for rK39 antibody response.
Drake LJ, Singh S, Mishra CK, et al., 2015, Bihar's Pioneering School-Based Deworming Programme: Lessons Learned in Deworming over 17 Million Indian School-Age Children in One Sustainable Campaign., PLOS Neglected Tropical Diseases, Vol: 9, ISSN: 1935-2735
Turner HC, Truscott JE, Bettis AA, et al., 2015, An economic evaluation of expanding hookworm control strategies to target the whole community., Parasites & Vectors, Vol: 8, ISSN: 1756-3305
BACKGROUND: The WHO treatment guidelines for the soil-transmitted helminths (STH) focus on targeting children for the control of morbidity induced by heavy infections. However, unlike the other STHs, the majority of hookworm infections are harboured by adults. This untreated burden may have important implications for controlling both hookworm's morbidity and transmission. This is particularly significant in the context of the increased interest in investigating STH elimination strategies. METHODS: We used a deterministic STH transmission model and parameter estimates derived from field epidemiological studies to evaluate the impact of child-targeted (2-14 year olds) versus community-wide treatment against hookworm in terms of preventing morbidity and the timeframe for breaking transmission. Furthermore, we investigated how mass treatment may influence the long-term programmatic costs of preventive chemotherapy for hookworm. RESULTS: The model projected that a large proportion of the overall morbidity due to hookworm was unaffected by the current child-targeted strategy. Furthermore, driving worm burdens to levels low enough to potentially break transmission was only possible when using community-wide treatment. Due to these projected reductions in programme duration, it was possible for community-wide treatment to generate cost savings - even if it notably increases the annual distribution costs. CONCLUSIONS: Community-wide treatment is notably more cost-effective for controlling hookworm's morbidity and transmission than the current child-targeted strategies and could even be cost-saving in many settings in the longer term. These calculations suggest that it is not optimum to treat using the same treatment strategies as other STH. Hookworm morbidity and transmission control require community-wide treatment.
Moraga P, Cano J, Baggaley RF, et al., 2015, Modelling the distribution and transmission intensity of lymphatic filariasis in sub-Saharan Africa prior to scaling up interventions: Integrated use of geostatistical and mathematical modelling, Parasites & Vectors, Vol: 8, ISSN: 1756-3305
Background: Lymphatic filariasis (LF) is one of the neglected tropical diseases targeted for global elimination. The ability to interrupt transmission is, partly, influenced by the underlying intensity of transmission and its geographical variation. This information can also help guide the design of targeted surveillance activities. The present study uses a combination of geostatistical and mathematical modelling to predict the prevalence and transmission intensity of LF prior to the implementation of large-scale control in sub-Saharan Africa. Methods: A systematic search of the literature was undertaken to identify surveys on the prevalence of Wuchereria bancrofti microfilaraemia (mf), based on blood smears, and on the prevalence of antigenaemia, based on the use of an immuno-chromatographic card test (ICT). Using a suite of environmental and demographic data, spatiotemporal multivariate models were fitted separately for mf prevalence and ICT-based prevalence within a Bayesian framework and used to make predictions for non-sampled areas. Maps of the dominant vector species of LF were also developed. The maps of predicted prevalence and vector distribution were linked to mathematical models of the transmission dynamics of LF to infer the intensity of transmission, quantified by the basic reproductive number (R0). Results: The literature search identified 1267 surveys that provide suitable data on the prevalence of mf and 2817 surveys that report the prevalence of antigenaemia. Distinct spatial predictions arose from the models for mf prevalence and ICT-based prevalence, with a wider geographical distribution when using ICT-based data. The vector distribution maps demonstrated the spatial variation of LF vector species. Mathematical modelling showed that the reproduction number (R0) estimates vary from 2.7 to 30, with large variations between and within regions. Conclusions: LF transmission is highly heterogeneous, and the developed maps can help guide intervention
Irvine MA, Reimer LJ, Njenga SM, et al., 2015, Modelling strategies to break transmission of lymphatic filariasis - aggregation, adherence and vector competence greatly alter elimination, Parasites & Vectors, Vol: 8, ISSN: 1756-3305
BackgroundWith ambitious targets to eliminate lymphatic filariasis over the coming years, there is a need to identify optimal strategies to achieve them in areas with different baseline prevalence and stages of control. Modelling can assist in identifying what data should be collected and what strategies are best for which scenarios.MethodsWe develop a new individual-based, stochastic mathematical model of the transmission of lymphatic filariasis. We validate the model by fitting to a first time point and predicting future timepoints from surveillance data in Kenya and Sri Lanka, which have different vectors and different stages of the control programme. We then simulate different treatment scenarios in low, medium and high transmission settings, comparing once yearly mass drug administration (MDA) with more frequent MDA and higher coverage. We investigate the potential impact that vector control, systematic non-compliance and different levels of aggregation have on the dynamics of transmission and control.ResultsIn all settings, increasing coverage from 65 to 80 % has a similar impact on control to treating twice a year at 65 % coverage, for fewer drug treatments being distributed. Vector control has a large impact, even at moderate levels. The extent of aggregation of parasite loads amongst a small portion of the population, which has been estimated to be highly variable in different settings, can undermine the success of a programme, particularly if high risk sub-communities are not accessing interventions.ConclusionEven moderate levels of vector control have a large impact both on the reduction in prevalence and the maintenance of gains made during MDA, even when parasite loads are highly aggregated, and use of vector control is at moderate levels. For the same prevalence, differences in aggregation and adherence can result in very different dynamics. The novel analysis of a small amount of surveillance data and resulting simulations highlight the need for more
Chapman LAC, Dyson L, Courtenay O, et al., 2015, Quantification of the natural history of visceral leishmaniasis and consequences for control, PARASITES & VECTORS, Vol: 8, ISSN: 1756-3305
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Brooker SJ, Mwandawiro CS, Halliday KE, et al., 2015, Interrupting transmission of soil-transmitted helminths: a study protocol for cluster randomised trials evaluating alternative treatment strategies and delivery systems in Kenya, BMJ Open, Vol: 5, ISSN: 2044-6055
Introduction In recent years, an unprecedented emphasis has been given to the control of neglected tropical diseases, including soil-transmitted helminths (STHs). The mainstay of STH control is school-based deworming (SBD), but mathematical modelling has shown that in all but very low transmission settings, SBD is unlikely to interrupt transmission, and that new treatment strategies are required. This study seeks to answer the question: is it possible to interrupt the transmission of STH, and, if so, what is the most cost-effective treatment strategy and delivery system to achieve this goal?Methods and analysis Two cluster randomised trials are being implemented in contrasting settings in Kenya. The interventions are annual mass anthelmintic treatment delivered to preschool- and school-aged children, as part of a national SBD programme, or to entire communities, delivered by community health workers. Allocation to study group is by cluster, using predefined units used in public health provision—termed community units (CUs). CUs are randomised to one of three groups: receiving either (1) annual SBD; (2) annual community-based deworming (CBD); or (3) biannual CBD. The primary outcome measure is the prevalence of hookworm infection, assessed by four cross-sectional surveys. Secondary outcomes are prevalence of Ascaris lumbricoides and Trichuris trichiura, intensity of species infections and treatment coverage. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, worm burden and proportion of unfertilised eggs will be assessed longitudinally. A nested process evaluation, using semistructured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system.
Medley GF, Hollingsworth TD, 2015, MDA helminth control: More questions than answers, The Lancet Global Health, Vol: 3, Pages: e583-e584, ISSN: 2214-109X
Soil-transmitted helminths (STH) and schistosomiasis have been recognised as important diseases. Diagnostics, treatments, and understanding of these were accrued throughout the 20th century, and reached the point that control and elimination seemed to be mostly a matter of implementation of mass drug administration (MDA) programmes.1 However, in 2015, both STH and schistosomiasis are global health problems, so perhaps we do not have the right methods or they are not being effectively applied. To our knowledge, MDA for STH and schistosomiasis has never been reported to eliminate infection without concomitant economic development. What are we missing?Most understanding about infection and disease is from longitudinal intervention studies completed in the 1980s and 1990s,2, 3, 4 and 5 which are now ageing and rarely benefited from modern techniques, such as next-generation sequencing. Very surprising is how much is not fully understood about these infections—eg, the biological or ecological basis of predisposition to high worm burdens, the importance of household-based transmission, the causes and resulting effects of co-infection with many parasites, and how to measure the burden of disease.Measurement of the burden of disease is particularly vexing. Cochrane reviews, published in 20126 and 20157, have emphasised the paucity of information (only 42 and 45 papers were included, respectively) and reported that little evidence was available for any beneficial effect of deworming, even though people in the field were convinced that these result in a great effect on physical and mental health.8 By contrast, evidence of the effects in livestock and wildlife is accruing.9 More than 1 billion children worldwide live at risk of helminth infection,10 and yet the effect on their health and development still cannot be quantified.In The Lancet Global Health, Nathan Lo and colleagues 11 introduce two advances that should be highlighted. First is the inclusion of five differen
Deol AK, Webster JP, Harrison W, et al., 2015, Development of a Markov transition probability model to predict changes in schistosomiasis infection following treatment, TROPICAL MEDICINE & INTERNATIONAL HEALTH, Vol: 20, Pages: 237-237, ISSN: 1360-2276
Anderson RM, Turner HC, Truscott JE, et al., 2015, Should the Goal for the Treatment of Soil Transmitted Helminth (STH) Infections Be Changed from Morbidity Control in Children to Community-Wide Transmission Elimination?, PLOS Neglected Tropical Diseases, Vol: 9, Pages: e0003897-e0003897, ISSN: 1935-2735
Fowler AC, Hollingsworth TD, 2015, Simple Approximations for Epidemics with Exponential and Fixed Infectious Periods, BULLETIN OF MATHEMATICAL BIOLOGY, Vol: 77, Pages: 1539-1555, ISSN: 0092-8240
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Turner HC, Truscott JE, Hollingsworth TD, et al., 2015, Cost and cost-effectiveness of soil-transmitted helminth treatment programmes: systematic review and research needs., Parasites & Vectors, Vol: 8, ISSN: 1756-3305
BACKGROUND: In this time of rapidly expanding mass drug administration (MDA) coverage and the new commitments for soil-transmitted helminth (STH) control, it is essential that resources are allocated in an efficient manner to have the greatest impact. However, many questions remain regarding how best to deliver STH treatment programmes; these include which age-groups should be targeted and how often. To perform further analyses to investigate what the most cost-effective control strategies are in different settings, accurate cost data for targeting different age groups at different treatment frequencies (in a range of settings) are essential. METHODS: Using the electronic databases PubMed, MEDLINE, and ISI Web of Knowledge, we perform a systematic review of costing studies and cost-effectiveness evaluations for potential STH treatment strategies. We use this review to highlight research gaps and outline the key future research needs. RESULTS: We identified 29 studies reporting costs of STH treatment and 17 studies that investigated its cost-effectiveness. The majority of these pertained to programmes only targeting school-aged children (SAC), with relatively few studies investigating alternative preventive chemotherapy (PCT) treatment strategies. The methods of cost data collection, analysis and reporting were highly variable among the different studies. Only four of the costing studies were found to have high applicability for use in forthcoming economic evaluations. There are also very few studies quantifying the costs of increasing the treatment frequency. CONCLUSIONS: The absence of cost data and inconsistencies in the collection and analysis methods constitutes a major research gap for STH control. Detailed and accurate costs of targeting different age groups or increasing treatment frequency will be essential to formulate cost-effective public health policy. Defining the most cost-effective control strategies in different settings is of high significance durin
Hollingsworth TD, Pilcher CD, Hecht FM, et al., 2015, High Transmissibility During Early HIV Infection Among Men Who Have Sex With Men-San Francisco, California., Journal of Infectious Diseases, Vol: 211, Pages: 1757-1760, ISSN: 1537-6613
We estimate the relative transmission rate in early versus later infection among men who have sex with men (MSM) in San Francisco, California, by studying the characteristics of a sample of transmitters, recruited through newly diagnosed, recently infected MSM between 1996 and 2009. Of 36 transmitters identified, 9 were determined on the basis of testing history and serologic testing to have been recently infected. The unadjusted odds ratio of transmitting during early infection was 15.2 (95% confidence interval [CI], 6.3-33.4; P < .001); the odds ratio was 8.9 (95% CI, 4.1-19.4) after adjustment for self-reported antiretroviral treatment. This high transmissibility could be due to both high infectiousness and high rates of sex partner change or concurrent partnerships.
Rock KS, Le Rutte EA, De Vlas SJ, et al., 2015, Uniting mathematics and biology for control of visceral leishmaniasis, Trends in Parasitology, Vol: 31, Pages: 251-259, ISSN: 1471-5007
The neglected tropical disease (NTD) visceral leishmaniasis (VL) has been targeted by the WHO for elimination as a public health problem on the Indian subcontinent by 2017 or earlier. To date there is a surprising scarcity of mathematical models capable of capturing VL disease dynamics, which are widely considered central to planning and assessing the efficacy of interventions. The few models that have been developed are examined, highlighting the necessity for better data to parameterise and fit these and future models. In particular, the characterisation and infectiousness of the different disease stages will be crucial to elimination. Modelling can then assist in establishing whether, when, and how the WHO VL elimination targets can be met.
Baggaley RF, Hollingsworth TD, 2015, HIV-1 transmissions during asymptomatic infection: exploring the impact of changes in HIV-1 viral load due to coinfections, Jaids-Journal of Acquired Immune Deficiency Syndromes, Vol: 68, Pages: 594-598, ISSN: 1944-7884
Abstract: High HIV-1 plasma viral loads (PVLs) in sub-Saharan Africa, partly because of high rates of coinfection, may have been one of the drivers of the “explosive” epidemics seen in that region. Using a previously published framework of infectiousness and survival, we estimate the excess onward HIV-1 transmission events (secondary infections) resulting from coinfection-induced changes in PVL during asymptomatic HIV-1 infection. For every 100 HIV-infected people, each suffering 1 episode of tuberculosis infection, there are 4.9 (2.7th–97.5th percentile: 0.2–21.5) excess onward HIV-1 transmission events attributable to this coinfection. Other estimates are malaria 0.4 (0.0–2.0), soil-transmitted helminths 3.1 (0.1–14.9), schistosomiasis 8.5 (0.2–38.6), filariasis 13.3 (0.3–89.2), syphilis 0.1 (0.0–1.6), herpes simplex virus 4.0 (0.0–24.2), and gonorrhea 2.1 (0.1–8.0) transmissions. If these higher PVLs confer a shorter life expectancy and higher infectiousness, then their impact on transmission is, in general, reduced. For most HIV-1 coinfections, the duration of a single infection is too short and/or the associated PVL elevation is too modest to contribute substantially to onward HIV-1 transmission.
Heesterbeek H, Anderson RM, Andreasen V, et al., 2015, Modeling infectious disease dynamics in the complex landscape of global health, SCIENCE, Vol: 347, Pages: 1216-U29, ISSN: 0036-8075
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Klepac P, Funk S, Hollingsworth TD, et al., 2015, Six challenges in the eradication of infectious diseases, Epidemics, Vol: 10, Pages: 97-101, ISSN: 1878-0067
Eradication and elimination are increasingly a part of the global health agenda. Once control measureshave driven infection to low levels, the ecology of disease may change posing challenges for eradicationefforts. These challenges vary from identifying pockets of susceptibles, improving monitoring during andafter the endgame, to quantifying the economics of disease eradication versus sustained control, all ofwhich are shaped and influenced by processes of loss of immunity, susceptible build-up, emergence ofresistance, population heterogeneities and non-compliance with control measures. Here we discuss howmodelling can be used to address these challenges.
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