33 results found
Gambhir M, Grassly NC, Burton MJ, et al., 2015, Estimating the Future Impact of a Multi-Pronged Intervention Strategy on Ocular Disease Sequelae Caused by Trachoma: A Modeling Study, Ophthalmic Epidemiology, Vol: 22, Pages: 394-402, ISSN: 1744-5086
Purpose: Trachoma control programs are underway in endemic regions worldwide. They are based on the SAFE strategy (Surgery for trichiasis, Antibiotic distribution, Facial cleanliness, and Environmental improvement). Although much is known about the effect of community-wide treatment with antibiotics on the prevalence of Chlamydia trachomatis, the impact of the SAFE strategy on severe ocular disease sequelae (the main focus of the Global Elimination of blinding Trachoma by 2020 program) remains largely unknown.Methods: We use a mathematical model to explore the impact of each of the components of the SAFE strategy, individually and together, on disease sequelae, arising from repeat infection and subsequent conjunctival scarring. We ask whether two elimination goals, to reduce the prevalence of trachomatous trichiasis to 1 per 1000 persons, and the incidence of corneal opacity to 1 per 10,000 persons per annum, are achievable, and which combinations of interventions have the greatest impact on these indicators.Results: In high prevalence communities (here, >20% infection of children aged 1–9 years), a combination of efforts is needed to bring down sustainably the prevalence and incidence of ocular disease sequelae.Conclusion: The mass delivery of antibiotics is highly beneficial for the clearance of infection, inflammation and prevention of subsequent scarring, but needs to be supplemented with sustained reductions in transmission and surgery to consider realistically the elimination of blindness by the year 2020.
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.
Gambhir M, Clark TA, Cauchemez S, et al., 2015, A Change in Vaccine Efficacy and Duration of Protection Explains Recent Rises in Pertussis Incidence in the United States, PLOS Computational Biology, Vol: 11, ISSN: 1553-734X
Over the past ten years the incidence of pertussis in the United States (U.S.) has risen steadily, with 2012 seeing the highest case number since 1955. There has also been a shift over the same time period in the age group reporting the largest number of cases (aside from infants), from adolescents to 7–11 year olds. We use epidemiological modelling and a large case incidence dataset to explain the upsurge. We investigate several hypotheses for the upsurge in pertussis cases by fitting a suite of dynamic epidemiological models to incidence data from the National Notifiable Disease Surveillance System (NNDSS) between 1990–2009, as well as incidence data from a variety of sources from 1950–1989. We find that: the best-fitting model is one in which vaccine efficacy and duration of protection of the acellular pertussis (aP) vaccine is lower than that of the whole-cell (wP) vaccine, (efficacy of the first three doses 80% [95% CI: 78%, 82%] versus 90% [95% CI: 87%, 94%]), increasing the rate at which disease is reported to NNDSS is not sufficient to explain the upsurge and 3) 2010–2012 disease incidence is predicted well. In this study, we use all available U.S. surveillance data to: 1) fit a set of mathematical models and determine which best explains these data and 2) determine the epidemiological and vaccine-related parameter values of this model. We find evidence of a difference in efficacy and duration of protection between the two vaccine types, wP and aP (aP efficacy and duration lower than wP). Future refinement of the model presented here will allow for an exploration of alternative vaccination strategies such as different age-spacings, further booster doses, and cocooning.
Lanzieri TM, Bialek SR, Ortega-Sanchez IR, et al., 2014, Modeling the potential impact of vaccination on the epidemiology of congenital cytomegalovirus infection, VACCINE, Vol: 32, Pages: 3780-3786, ISSN: 0264-410X
Lopman B, Simmons K, Gambhir M, et al., 2014, Epidemiologic Implications of Asymptomatic Reinfection: A Mathematical Modeling Study of Norovirus, AMERICAN JOURNAL OF EPIDEMIOLOGY, Vol: 179, Pages: 507-512, ISSN: 0002-9262
Wu J, Dhingra R, Gambhir M, et al., 2013, Sensitivity analysis of infectious disease models: methods, advances and their application, JOURNAL OF THE ROYAL SOCIETY INTERFACE, Vol: 10, ISSN: 1742-5689
Dhingra R, Jimenez V, Chang HH, et al., 2013, Spatially-Explicit Simulation Modeling of Ecological Response to Climate Change: Methodological Considerations in Predicting Shifting Population Dynamics of Infectious Disease Vectors, ISPRS INTERNATIONAL JOURNAL OF GEO-INFORMATION, Vol: 2, Pages: 645-664
Wong KK, Gambhir M, Finelli L, et al., 2013, Transmissibility of Variant Influenza From Swine to Humans: A Modeling Approach, CLINICAL INFECTIOUS DISEASES, Vol: 57, Pages: S16-S22, ISSN: 1058-4838
Gambhir M, Swerdlow DL, Finelli L, et al., 2013, Multiple Contributory Factors to the Age Distribution of Disease Cases: A Modeling Study in the Context of Influenza A(H3N2v), CLINICAL INFECTIOUS DISEASES, Vol: 57, Pages: S23-S27, ISSN: 1058-4838
Singh BK, Bockarie MJ, Gambhir M, et al., 2013, Sequential Modelling of the Effects of Mass Drug Treatments on Anopheline-Mediated Lymphatic Filariasis Infection in Papua New Guinea, PLOS ONE, Vol: 8, ISSN: 1932-6203
Slater HC, Gambhir M, Parham PE, et al., 2013, Modelling Co-Infection with Malaria and Lymphatic Filariasis, PLoS Comput Biol, Vol: 9
<title>Author Summary</title><p>Malaria and lymphatic filariasis (LF) are thought to be co-endemic in many regions of Africa. Currently, most interventions targeted at these infections do not consider the impacts of co-infection. However, there have been increasing calls to adopt integrated control programmes that can achieve synergistic effects. Malaria and LF are both vector-borne diseases transmitted by <italic>Anopheles</italic> spp. mosquitoes, suggesting that well-designed vector control strategies have the potential to affect the transmission of both infections. In this study, we develop a modelling framework incorporating the specifics of malaria-LF co-infection to investigate how the transmission of each infection is altered for a range of possible interaction scenarios. We find that a control strategy that reduces LF transmission (via mass drug administration, for example) could potentially increase malaria prevalence. This work illustrates the potential perverse effects of targeting just one infection and emphasises the need to take into account co-endemic diseases when designing control programmes. The developed modelling framework can provide the basis for exploring the mix of options for joint control of these infections. We also highlight the need for better data on how co-infection impacts hosts and vectors in order for future predictions on both co-transmission dynamics and control to become more reliable.</p>
Koukounari A, Moustaki I, Grassly NC, et al., 2013, Using a Nonparametric Multilevel Latent Markov Model to Evaluate Diagnostics for Trachoma, American Journal of Epidemiology, Vol: 177, Pages: 913-922, ISSN: 0002-9262
In disease control or elimination programs, diagnostics are essential for assessing the impact of interventions, refining treatment strategies, and minimizing the waste of scarce resources. Although high-performance tests are desirable, increased accuracy is frequently accompanied by a requirement for more elaborate infrastructure, which is often not feasible in the developing world. These challenges are pertinent to mapping, impact monitoring, and surveillance in trachoma elimination programs. To help inform rational design of diagnostics for trachoma elimination, we outline a nonparametric multilevel latent Markov modeling approach and apply it to 2 longitudinal cohort studies of trachoma-endemic communities in Tanzania (2000–2002) and The Gambia (2001–2002) to provide simultaneous inferences about the true population prevalence of Chlamydia trachomatis infection and disease and the sensitivity, specificity, and predictive values of 3 diagnostic tests for C. trachomatis infection. Estimates were obtained by using data collected before and after mass azithromycin administration. Such estimates are particularly important for trachoma because of the absence of a true “gold standard” diagnostic test for C. trachomatis. Estimated transition probabilities provide useful insights into key epidemiologic questions about the persistence of disease and the clearance of infection as well as the required frequency of surveillance in the postelimination setting.
Lopman BA, Pitzer VE, Sarkar R, et al., 2012, Understanding Reduced Rotavirus Vaccine Efficacy in Low Socio-Economic Settings, PLOS ONE, Vol: 7, ISSN: 1932-6203
Fung IC-H, Gambhir M, van Sighem A, et al., 2012, The Clinical Interpretation of Viral Blips in HIV Patients Receiving Antiviral Treatment: Are We Ready to Infer Poor Adherence?, JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, Vol: 60, Pages: 5-11, ISSN: 1525-4135
Basanez M-G, McCarthy JS, French MD, et al., 2012, A Research Agenda for Helminth Diseases of Humans: Modelling for Control and Elimination, PLOS Neglected Tropical Diseases, Vol: 6, ISSN: 1935-2735
Human helminthiases are of considerable publichealth importance in sub-Saharan Africa, Asia, and LatinAmerica. The acknowledgement of the disease burden dueto helminth infections, the availability of donated oraffordable drugs that are mostly safe and moderatelyefficacious, and the implementation of viable mass drugadministration (MDA) interventions have prompted theestablishment of various large-scale control and eliminationprogrammes. These programmes have benefited fromimproved epidemiological mapping of the infections, betterunderstanding of the scope and limitations of currentlyavailable diagnostics and of the relationship betweeninfection and morbidity, feasibility of community-directedor school-based interventions, and advances in the design ofmonitoring and evaluation (M&E) protocols. Considerablesuccess has been achieved in reducing morbidity orsuppressing transmission in a number of settings, whilstchallenges remain in many others. Some of the obstaclesinclude the lack of diagnostic tools appropriate to thechanging requirements of ongoing interventions andelimination settings; the reliance on a handful of drugsabout which not enough is known regarding modes ofaction, modes of resistance, and optimal dosage singly or incombination; the difficulties in sustaining adequate coverageand compliance in prolonged and/or integrated programmes;an incomplete understanding of the social,behavioural, and environmental determinants of infection;and last, but not least, very little investment in research anddevelopment (R&D). The Disease Reference Group onHelminth Infections (DRG4), established in 2009 by theSpecial Programme for Research and Training in TropicalDiseases (TDR), was given the mandate to undertake acomprehensive review of recent advances in helminthiasesresearch, identify research gaps, and rank priorities for anR&D agenda for the control and elimination of theseinfections. This review presents the processes undertakento identify and rank ten t
Methods of diagrammatic modelling have been greatly developed in the past two decades. Outside the context of infectious diseases, systematic use of diagrams in epidemiology has been mainly confined to the analysis of a single link: that between a disease outcome and its proximal determinant(s). Transmitted causes ("causes of causes") tend not to be systematically analysed.The infectious disease epidemiology modelling tradition models the human population in its environment, typically with the exposure-health relationship and the determinants of exposure being considered at individual and group/ecological levels, respectively. Some properties of the resulting systems are quite general, and are seen in unrelated contexts such as biochemical pathways. Confining analysis to a single link misses the opportunity to discover such properties.The structure of a causal diagram is derived from knowledge about how the world works, as well as from statistical evidence. A single diagram can be used to characterise a whole research area, not just a single analysis - although this depends on the degree of consistency of the causal relationships between different populations - and can therefore be used to integrate multiple datasets.Additional advantages of system-wide models include: the use of instrumental variables - now emerging as an important technique in epidemiology in the context of mendelian randomisation, but under-used in the exploitation of "natural experiments"; the explicit use of change models, which have advantages with respect to inferring causation; and in the detection and elucidation of feedback.
French MD, Churcher TS, Gambhir M, et al., 2010, Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study, PLOS NEGLECTED TROPICAL DISEASES, Vol: 4, ISSN: 1935-2735
Gambhir M, Michael E, Tisch D, et al., 2010, PREDICTING THE CHANCES OF ELIMINATION IN PARASITE INTERVENTION PROGRAMS, 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 20-20, ISSN: 0002-9637
Blake IM, Burton MJ, Solomon AW, et al., 2010, Targeting Antibiotics to Households for Trachoma Control, PLOS NEGLECTED TROPICAL DISEASES, Vol: 4, ISSN: 1935-2735
Gambhir M, Bockarie M, Tisch D, et al., 2010, Geographic and ecologic heterogeneity in elimination thresholds for the major vector-borne helminthic disease, lymphatic filariasis, BMC BIOLOGY, Vol: 8
Fung IC-H, Gambhir M, van Sighem A, et al., 2010, Superinfection with a heterologous HIV strain per se does not lead to faster progression, MATHEMATICAL BIOSCIENCES, Vol: 224, Pages: 1-9, ISSN: 0025-5564
Gambhir M, Basanez M-G, Blake IM, et al., 2010, Modelling Trachoma for Control Programmes, MODELLING PARASITE TRANSMISSION AND CONTROL, Vol: 673, Pages: 141-156, ISSN: 0065-2598
Michael E, Gambhir M, 2010, Transmission Models and Management of Lymphatic Filariasis Elimination, MODELLING PARASITE TRANSMISSION AND CONTROL, Vol: 673, Pages: 157-171, ISSN: 0065-2598
Michael E, Gambhir M, 2010, Vector Transmission Heterogeneity and the Population Dynamics and Control of Lymphatic Filariasis, MODELLING PARASITE TRANSMISSION AND CONTROL, Vol: 673, Pages: 13-31, ISSN: 0065-2598
Gambhir M, Basanez M-G, Burton MJ, et al., 2009, The Development of an Age-Structured Model for Trachoma Transmission Dynamics, Pathogenesis and Control, PLOS Neglected Tropical Diseases, Vol: 3, ISSN: 1935-2735
Background: Trachoma, the worldwide leading infectious cause of blindness, is due to repeated conjunctival infection with Chlamydia trachomatis. The effects of control interventions on population levels of infection and active disease can be promptly measured, but the effects on severe ocular sequelae require long-term monitoring. We present an age-structured mathematical model of trachoma transmission and disease to predict the impact of interventions on the prevalence of blinding trachoma.Methodology/Principal Findings: The model is based on the concept of multiple reinfections leading to progressive conjunctival scarring, trichiasis, corneal opacity and blindness. It also includes aspects of trachoma natural history, such as an increasing rate of recovery from infection and a decreasing chlamydial load with subsequent infections that depend upon a (presumed) acquired immunity that clears infection with age more rapidly. Parameters were estimated using maximum likelihood by fitting the model to pre-control infection prevalence data from hypo-, meso- and hyperendemic communities from The Gambia and Tanzania. The model reproduces key features of trachoma epidemiology: 1) the age-profile of infection prevalence, which increases to a peak at very young ages and declines at older ages; 2) a shift in this prevalence peak, toward younger ages in higher force of infection environments; 3) a raised overall profile of infection prevalence with higher force of infection; and 4) a rising profile, with age, of the prevalence of the ensuing severe sequelae (trachomatous scarring, trichiasis), as well as estimates of the number of infections that need to occur before these sequelae appear.Conclusions/Significance: We present a framework that is sufficiently comprehensive to examine the outcomes of the A (antibiotic) component of the SAFE strategy on disease. The suitability of the model for representing population-level patterns of infection and disease sequelae is discussed in
Blake IM, Burton MJ, Bailey RL, et al., 2009, Estimating Household and Community Transmission of Ocular Chlamydia trachomatis, PLOS NEGLECTED TROPICAL DISEASES, Vol: 3, ISSN: 1935-2735
Gambhir M, Michael E, 2008, COMPLEX DYNAMICS IN PARASITE ECOLOGY AND CONTROL, 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 41-41, ISSN: 0002-9637
Singh BK, Gambhir M, Hu C-K, 2008, Quasi-cycles and sensitive dependence on seed values in edge of chaos behaviour in a class of self-evolving maps, CHAOS SOLITONS & FRACTALS, Vol: 38, Pages: 641-649, ISSN: 0960-0779
Gambhir M, Michael E, 2008, Complex Ecological Dynamics and Eradicability of the Vector Borne Macroparasitic Disease, Lymphatic Filariasis, PLOS ONE, Vol: 3, ISSN: 1932-6203
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