Transmission Dynamics and Control of Human Onchocerciasis

Lead Research Organisation: Imperial College London
Department Name: Infectious Disease Epidemiology

Abstract

Human infections caused by parasitic worms remain a major public health problem for most tropical and sub-tropical regions of the world, causing disability and chronic poor health in all age-groups. Examples are intestinal worms, river blindness (onchocerciasis), and diseases such as elephantiasis with grossly swollen legs (arising from lymphatic filariasis). A number of these infections (e.g. onchocerciasis, filariasis) are spread by specific biting insects, called vectors because they transmit the diseases. Parasitic worms may also have the effect of suppressing the immune system although the mechanisms for this are not yet well understood. Control programmes exist for a number of these infections. These operations include programmes that kill the vectors with insecticides, or treat people with medication that kills the parasites inside the body, alleviate the ill-health effects of the infection, and help protect other people from contracting the disease. However, individuals treated are nearly always reinfected and control programmes must be carried out for long periods of time. It is important to find out how long control programmes should last, because they are expensive, and may fail if interrupted too early. The interaction between the lifecycles of these worms and those of humans and insect vectors; the way in which the parasites are distributed through the human population in affected regions; the way in which these populations evolve through time in the presence or absence of control measures, and the way in which possible resistance to control measures may spread are all highly complex processes. It is possible, however, to describe these processes using statistics and mathematics. The proposed research involves the incorporation of such complex descriptions within computer-based models of the transmission of infection and its distribution through human populations. Inputs to the models will be provided by data to be collated and incorporated into a database. In addition to allowing greater understanding of the processes of transmission, persistence and disease, use of the models will aid in the design of cost-effective control programmes in the afflicted communities.

Technical Summary

Human helminth infections remain a public health problem worldwide. Control programmes aim to alleviate the chronic disability burdens imposed by these infections on individuals and communities. Interventions include long-term antivectorial measures and/or mass chemotherapy, yet, elimination of infection is not feasible with current tools. Onchocerciasis control programmes operate in countries with limited health resources, concerned with an optimal and cost-effective implementation and surveillance that will prevent infection and disease recrudescence after control cessation. All this requires a sound understanding of key biological processes regulating parasite populations. This project will use complex statistical and mathematical techniques for analysis of large epidemiological datasets across endemic areas in Africa and Latin America, aiming to furthering the understanding of Onchocerca volvulus population biology and developing quantitative models to inform control policies. A key question will be the significance of low levels of transmission for disease persistence/extinction. Methods include analyses of infection profiles in humans and vectors for detection and identification of regulatory processes; quantifying the relationship between parasitological and immunological data; estimating infection-induced excess host mortality; developing predictive models for infection and morbidity; incorporating the above into mathematical (stochastic) frameworks, and investigating rates of drug resistance under varying control pressures. Models will be linked to programme costing for cost-effectiveness analyses. Stochastic frameworks, based on partial differential equations will be initially solved using moment closure approximations. The full stochastic solution may be derived. Microsimulations will be implemented to check various stages of model development. Worm population genetics will be embedded into transmission dynamics frameworks. Itemised cost menus will be developed and implemented. Although focusing on onchocerciasis as a well documented case study, the expected outcomes will be relevant to the population biology and control of other macroparasitic infections. Results will be of interest to scientists and to those implementing and funding helminth control programmes.

Publications

10 25 50
 
Description Disease Reference Group on Helminths
Geographic Reach Multiple continents/international 
Policy Influence Type Membership of a guidance committee
Impact Report to be written in 2010 on Research and Control Priorities for Diseases of Poverty
 
Description Global Burden of Disease
Geographic Reach North America 
Policy Influence Type Membership of a guidance committee
Impact Global Burden of Disease Reassessment, Onchocerciasis
 
Description Program Coordinating Committee, OEPA
Geographic Reach North America 
Policy Influence Type Membership of a guidance committee
Impact Overall membership of the expert committee
 
Description Royal Society Leverhulme Trust Africa Award
Amount £150,000 (GBP)
Organisation The Royal Society 
Sector Academic/University
Country United Kingdom
Start 10/2010 
End 09/2013
 
Description TransMalariaBloc - Malaria transmission blocking by vaccines, drugs and immune mosquitoes: efficacy assessment and targets (3m euros across 7 participants)
Amount £1,676,440 (GBP)
Funding ID 223736 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 12/2008 
End 11/2012
 
Description Wellcome Trust Project Grant (Density-Dependent Host Choice by Onchocerciasis Vectors)
Amount £381,768 (GBP)
Funding ID 085133 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2009 
End 02/2012
 
Description Wellcome Trust Project Grant (The detection and management of ivermectin resistance in human onchocerciasis)
Amount £338,756 (GBP)
Funding ID 092677 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2011 
End 01/2014
 
Title Database of aggregate and individual responses to ivermectin treatment 
Description Databases of published and unedited data on repopulation of skin by microfilariae of Onchocerca volvulus following ivermectin treatment prior to the introduction of widespread mass drug administration for the purposes of analysing individual variation in responses against which to compare responses to treatment that are deemed suboptimal for the early detection of loss of ivermectin efficacy and ivermectin resistance 
Type Of Material Database/Collection of Data/Biological Samples 
Year Produced 2009 
Provided To Others? Yes  
Impact Publication in PNAS USA, 2009; Presentation in Anthelmintic resistance symposium at the 57th annual meeting of the Am Soc Trop Med Hyg, 2008; Preparation of joint research proposals 
 
Title Database of publications and grey literature on onchocercal disease 
Description A database has been created of all publications in peer review journals (various languages) and grey literature for preparation of systematic review of onchocercal disease for Global Burden of Disease reassessment 
Type Of Material Database/Collection of Data/Biological Samples 
Year Produced 2009 
Provided To Others? Yes  
Impact In Progress: Book chapter on Onchocerciasis Burden of Disease comparing 1990 and 2005 
 
Title Host age- and sex-stuctured onchocerciasis mathematical model 
Description A deterministic model based on partial differential equations to describe the distribution of onchocerciasis infection with host age, sex, and geographical location (West Africa, Central and South America) that can be used to investigate the impact of control interventions 
Type Of Material Data analysis technique 
Provided To Others? No  
Impact Publication in PNAS, 2005; Extension of the model to incorporate parasite genetic structure regarding ivermectin susceptibility for the investigation of drug resistance 
 
Title Parasite genetically-structured onchocerciasis mathematical model 
Description Genetic structure of Onchocerca volvulus with regard to ivermectin resistance (assumed to be conferred by 2-allele 1 locus autosomal system) has been incorporated in models ignoring and assuming explicit host age-structure 
Type Of Material Data analysis technique 
Provided To Others? No  
Impact Publications in Trends Parasitol, 2009; Evolution, 2008 and the preparation of joint research proposals 
 
Description Detection and Management of Ivermectin Resistance 
Organisation McGill University
Department Institute of Parasitology
Country Canada 
Sector Academic/University 
PI Contribution Mahematical modelling; preparation of papers; successful preparation of grant proposals
Collaborator Contribution Data on genetic analysis of filarial parasites (lymphatic filariasis, onchocerciasis) for mathematical modelling of the evolution and spread of anthelmintic resistance
Impact Outputs in the form of publications: PubMed ID numbers: 19805362; 19154624; 18382607; 17320006; 16834821. Outcomes in the form of invitations to speak at scientific meetings (Am Soc Trop Med Hyg, December 2008; Royal Society UK-Ghana collaboration, April 2008), and Expert Groups (WHO/World Bank, January 2008). Impacts in the form of invitation to belong to the Disease Reference Group on Helminths, World Health Organization.
 
Description Epidemiology and Control of Schistosomiasis and Soil-Transmitted Helminthiasis 
Organisation Natural History Museum
Country United Kingdom 
Sector Public 
PI Contribution Supervision of MSc (in Modern Epidemiology) students at ICSM, UK, for the analysis of data and preparation of joint publications
Collaborator Contribution Sharing of parasitological and epidemiological data pre- and post-implementation of control interventions based on anthelmintic chemotherapy in East Africa for joint analysis through shared MSc (in Modern Epidemiology) students at ICSTM, UK
Impact Publications, PubMed ID numbers: 19806223; 19409588; 19000385; 18947774; 17996207
 
Description Epidemiology and Transmission of Zoonotic Schistosomiasis 
Organisation Imperial College London
Department Department of Infectious Disease & Epidemiology
Country United Kingdom 
Sector Academic/University 
PI Contribution Data analysis and modelling through shared MRC-funded PhD student
Collaborator Contribution Sharing of data (parasitological, epidemiological, molecular genetics) for joint analysis through shared PhD students and mathematical modelling of schistosomiasis japonica in China and the Philippines
Impact Outputs in the form of joint papers, PubMed ID numbers: 19389178; 19030225. Outcomes in the form of invitations to talk at Divisional Symposium, Imperial College and Scientific meetings (Am Soc Trop Med Hyg, 2008, 2009). Impacts in the form of invitation to participate in Networking meeting for ESEI Catalyst grants; collaborative grant submitted (December 2009).
 
Description Epidemiology of Onchocerciasis and Loiasis in Central Africa 
Organisation University of Lyon
Department Institute for Research and Development
Country France 
Sector Academic/University 
PI Contribution Preparation of joint publications and research proposals
Collaborator Contribution Sharing of data for joint analysis of parasitological and epidemiological features of infections caused by Onchocerca volvulus and Loa loa
Impact Publications, PubMed ID numbers: 19805362; 18471776; 17002504; 16764737; 16469200
 
Description Population Dynamics of Human Ascariasis 
Organisation University of Westminster
Country United Kingdom 
Sector Academic/University 
PI Contribution Data analysis, statistical and mathematical modelling through MRc-funded PhD student
Collaborator Contribution Sharing of data on chemo-expulsion studies of Ascaris lumbricoides in Bangladesh for the analysis and modelling of the population dynamics of ascariasis in human populations
Impact Publications, PubMed ID Number: 19208229; 20385140; 20620142
Start Year 2006
 
Description Transmission Studies of Human Onchocerciasis in the Amazonian Focus 
Organisation Central University of Venezuela
Country Venezuela, Bolivarian Republic of 
Sector Academic/University 
PI Contribution Data analysis and preparation of joint publications
Collaborator Contribution Sharing of epidemiological, parasitological, and entomological data for the analysis of transmission and control studies of onchocerciasis in the Amazonian focus between Venezuela and Brazil
Impact Publications, PubMed ID numbers: 19289198; 18538741; Vivas-Martínez et al. (2007)
 
Description World Bank Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact Talk to a meeting organised by the WB / WHO on anthelmintic resistance

Book Chapter: Churcher TS, Kaplan RM, Ardelli BF, Schwenkenbecher JM, Basáñez M-G & Lammie PJ (2009). Mass treatment of parasitic disease: implications for the spread of anthelmintic resistance. In Antimicrobial Drug Resistance (Weber Todd J, ed.). Issues in Infectious Diseases Series, S. Karger AG, Basel, Switzerland (in press).
Year(s) Of Engagement Activity 2008