Evaluation of Interventions and Diagnostics of Neglected Tropical Diseases in sub-Saharan Africa

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

Abstract

Most of the Neglected Tropical Diseases (NTDs) have little name-recognition in industrialized nations, but together they cause severe disability in the world‘s poorest countries, decreasing productivity by billions of dollars. Both the World Health Organization (WHO) and the US Centers for Disease Control and Prevention (CDC) have recently identified these diseases as ‘targets of opportunity‘ to improve global health. By providing safe and effective drug treatments to individuals, mass drug administration (MDA) can control seven NTDs.
The proposed research aims to: i) evaluate the effect of different MDA-based interventions on the infection prevalence and intensity of two NTDs: schistosomiasis and trachoma, and on the likelihood of their elimination; and ii) evaluate the performance of the diagnostic tools currently used for Monitoring & Evaluation of interventions against these two NTDs. Robust statistical analysis of relevant data will help to optimize the design of future NTD control programmes, and evaluate the impact of current strategies so that a better quality of life for some of the world‘s poorest communities can be achieved. The results of this research will have implications for infections prevalent in the UK, such as genital Chlamydia, partly responsible for infertility in reproductive age women.

Technical Summary

The two infectious diseases discussed in this fellowship application (schistosomiasis, and trachoma) are among the most prevalent of the so-called Neglected Tropical Diseases (NTDs), an umbrella term encompassing a group of parasitic, bacterial, and viral infections collectively imposing a similar disease burden to that of malaria and HIV. Decisions on Mass Drug Administration (MDA), estimates of the burden of morbidity, infection prevalence and intensity of infection and evaluation of control measures, all depend on the results from diagnostic tests.

The proposed research aims to use advanced biostatistical analysis to further understanding of the effect upon the prevalence and intensity of schistosomiasis and of the ocular bacteria causing trachoma, and the likelihood of their elimination, of interventions based on MDA, as well as to evaluate the performance of the diagnostic tools currently used for the Monitoring & Evaluation (M&E) of these two infections.

The main data sources to be used are: (i) annual longitudinal surveys from the Monitoring & Evaluation (M&E) National Schistosomiasis Control Programmes in Niger and Tanzania (iii) monthly longitudinal trachoma studies conducted in The Gambia and Tanzania.

Latent Variable models (LVM) will be fitted in these datasets as measurement error is acknowledged and estimated, by making use of the information from multiple indicators while validation of scales is particularly important in resource-constrained settings.

Specific objectives are to: (i) classify people according to different intensities of Schistosoma haematobium infection who experience poor quality of life in Niger at baseline and follow-ups in order to address questions of schistosomiasis morbidity; (ii) estimate changes in sensitivities and specificities of one and two consecutive days of stool samples for the intensity classifications of S. mansoni infection following treatment; (iii) estimate the true intensity of S. mansoni infection pre- and post-treatment in the Tanzanian schistosomiasis control programme so that its impact can be evaluated; (iv) quantify changes in sensitivity and specificity of active trachoma disease for true infection status at follow-up particularly focused on the households and the dynamics of infection and disease; (v) estimate the true prevalence of Chlamydia trachomatis infection at baseline and follow-up in order to address questions of persistence in some infected households.

LVM applied to these detailed datasets, provides a unique opportunity to answer important questions related to human health issues in the tropics as well as a useful illustration to serve as a guide to the careful application of these modelling ideas to other conditions.

Publications

10 25 50
 
Title Could modern statistical methods be useful tools for NTDs control program M & E research 
Description During my visit in March to the Gates-funded project "Improved diagnosis and prevention of Female Genital Schistosomiasis (FGS)" in South Africa, I learnt about the associations of cervical schistosomiasis lesions with HIV and HPV and the potential prevention of these infections and other reproductive tract morbidity through MDA. I was fascinated to witness how clinicians from Oslo University Hospital as well as Kwazulu-Natal University lab researchers diagnose FGS. Their consortium identified my analyses as key to evaluate non-invasive and syndromic FGS diagnostics. Senior members of the Leiden University Diagnostics and Epidemiology Research Group became interested in my approaches to evaluate intestinal schistosomiasis diagnostics they have developed and used in longitudinal Ugandan studies-so that rapid cost-effective field diagnostics can be identified. Recently I gave a special seminar at the Task Force for Global Health, in Atlanta, US, illustrating how Latent Markov Models apart from evaluating diagnostics they can provide useful insights in answering key epidemiological questions about persistence of disease, clearance of infection, or probability of reinfection. These novel proposed analyses the evaluation and validation of NTDs diagnostics can become generic tools and bridge gaps in the evidence base on diagnostics' performance in the developing world. 
Type Of Material Data analysis technique 
Year Produced 2012 
Provided To Others? Yes  
Impact Several academic and research groups are interested in the afore mentioned statistical approaches and I am now working of developping further these potential collaborations. 
 
Title Latent Variable Models for the evaluation of NTDs diagnostics 
Description I have provided estimates of sensitivity and specificity for different diagnostic tests by latent class analysis (LCA) for schistosomiasis data acquired from the John Hopkins University (this is in addition to the data I am analysing for my fellowship work). LCA is a statistical modeling technique which examines associations between observed variables that imperfectly measure a non-observable (latent) variable. I am in the process of developing similar models for evaluating diagnostics of soil transmitted heminths (STHs) in India for The Partnership for Child Development (PCD) within Imperial College (this is again in addition to the data I am analysing for my fellowship work). At the end of this month I am presenting for the 1st time since the fellowship started at 2 scientific conferences in the US complete results (sensitivity and specificity for diagnostic tests of trachoma-this work comes from 2 out of the 4 datasets I am analysing during this fellowship) as estimated through Latent Markov models (LMMs). LMMs are mixture models and can either be seen as either an extension of the Latent Class (LC) models for the analysis of longitudinal data or an extension of the discrete-time Markov chain model for dealing with measurement error in the observed variable of interest. I am hoping that experts of the field will find again these results and methods useful. 
Type Of Material Data analysis technique 
Year Produced 2010 
Provided To Others? Yes  
Impact With the research conducted in collaboration with John Hopkins University and LSE, we propose a definite diagnostic test for schistosomiasis in adults. With the research conducted in collaboration with PCD, Indian government will decide based on the results provided, which diagnostic test they should use for their Monitoring & Evaluation activities for STHs in the near future. 
 
Description Co-author on a poster presented at a conference and a scientific paper (recently published in PloS NTDs) resulting from a a consensus meeting held at the LSHTM 
Organisation Centers for Disease Control and Prevention (CDC)
Department Division of Parasitic Diseases
Country United States 
Sector Public 
PI Contribution I described current diagnostic tools that are used in the Monitoring and Evaluation of Schistosomiasis Control Programmes for population-based assessment. I had also the chance to give a brief update of the statistical methods I would use for evaluation of diagnostics during my fellowship work in the next 3 years and this initiated fruitful discussions.
Collaborator Contribution This was a consensus meeting of disease experts, program managers, mathematical modellers and health economists, and all together we discussed transmission dynamics, current diagnostic algorithms, and possible unified approaches for neglected tropical diseases (NTDs). It was highly beneficial to my research to interact during this meeting particularly with disease experts and programme managers and getting expert insight about the biology and control of the 2 NTDs I am working with. I believe that it is highly beneficial to my research to interact as much as possible with policy makers and programme implementers so that effective translation of research findings can be put eventually into practical action. As mentioned above it is highly beneficial to my research to be able to interact with Senior Staff Scientists and policy makers
Impact A poster presented at the American Society of Tropical Medicine and Hygiene in Atlanta in November 2010 and a scientific paper which is currently under review with PloS NTDs were a summary of that consultation's outcomes, suggesting target product profiles and a list of immediate research priorities, as well as drafting a road map for future efforts. As mentioned before, disease experts, program managers, mathematical modellers and health economists are involved in this collaboration.
Start Year 2010
 
Description Co-author on a poster presented at a conference and a scientific paper (recently published in PloS NTDs) resulting from a a consensus meeting held at the LSHTM 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Faculty of Infectious and Tropical Diseases
Country United Kingdom 
Sector Academic/University 
PI Contribution I described current diagnostic tools that are used in the Monitoring and Evaluation of Schistosomiasis Control Programmes for population-based assessment. I had also the chance to give a brief update of the statistical methods I would use for evaluation of diagnostics during my fellowship work in the next 3 years and this initiated fruitful discussions.
Collaborator Contribution This was a consensus meeting of disease experts, program managers, mathematical modellers and health economists, and all together we discussed transmission dynamics, current diagnostic algorithms, and possible unified approaches for neglected tropical diseases (NTDs). It was highly beneficial to my research to interact during this meeting particularly with disease experts and programme managers and getting expert insight about the biology and control of the 2 NTDs I am working with. I believe that it is highly beneficial to my research to interact as much as possible with policy makers and programme implementers so that effective translation of research findings can be put eventually into practical action. As mentioned above it is highly beneficial to my research to be able to interact with Senior Staff Scientists and policy makers
Impact A poster presented at the American Society of Tropical Medicine and Hygiene in Atlanta in November 2010 and a scientific paper which is currently under review with PloS NTDs were a summary of that consultation's outcomes, suggesting target product profiles and a list of immediate research priorities, as well as drafting a road map for future efforts. As mentioned before, disease experts, program managers, mathematical modellers and health economists are involved in this collaboration.
Start Year 2010
 
Description Co-author on a poster presented at a conference and a scientific paper (recently published in PloS NTDs) resulting from a a consensus meeting held at the LSHTM 
Organisation National Institute for Parasitic Diseases
Country China 
Sector Public 
PI Contribution I described current diagnostic tools that are used in the Monitoring and Evaluation of Schistosomiasis Control Programmes for population-based assessment. I had also the chance to give a brief update of the statistical methods I would use for evaluation of diagnostics during my fellowship work in the next 3 years and this initiated fruitful discussions.
Collaborator Contribution This was a consensus meeting of disease experts, program managers, mathematical modellers and health economists, and all together we discussed transmission dynamics, current diagnostic algorithms, and possible unified approaches for neglected tropical diseases (NTDs). It was highly beneficial to my research to interact during this meeting particularly with disease experts and programme managers and getting expert insight about the biology and control of the 2 NTDs I am working with. I believe that it is highly beneficial to my research to interact as much as possible with policy makers and programme implementers so that effective translation of research findings can be put eventually into practical action. As mentioned above it is highly beneficial to my research to be able to interact with Senior Staff Scientists and policy makers
Impact A poster presented at the American Society of Tropical Medicine and Hygiene in Atlanta in November 2010 and a scientific paper which is currently under review with PloS NTDs were a summary of that consultation's outcomes, suggesting target product profiles and a list of immediate research priorities, as well as drafting a road map for future efforts. As mentioned before, disease experts, program managers, mathematical modellers and health economists are involved in this collaboration.
Start Year 2010
 
Description Co-author on a poster presented at a conference and a scientific paper (recently published in PloS NTDs) resulting from a a consensus meeting held at the LSHTM 
Organisation National Institute of Hygiene
Country Morocco 
Sector Academic/University 
PI Contribution I described current diagnostic tools that are used in the Monitoring and Evaluation of Schistosomiasis Control Programmes for population-based assessment. I had also the chance to give a brief update of the statistical methods I would use for evaluation of diagnostics during my fellowship work in the next 3 years and this initiated fruitful discussions.
Collaborator Contribution This was a consensus meeting of disease experts, program managers, mathematical modellers and health economists, and all together we discussed transmission dynamics, current diagnostic algorithms, and possible unified approaches for neglected tropical diseases (NTDs). It was highly beneficial to my research to interact during this meeting particularly with disease experts and programme managers and getting expert insight about the biology and control of the 2 NTDs I am working with. I believe that it is highly beneficial to my research to interact as much as possible with policy makers and programme implementers so that effective translation of research findings can be put eventually into practical action. As mentioned above it is highly beneficial to my research to be able to interact with Senior Staff Scientists and policy makers
Impact A poster presented at the American Society of Tropical Medicine and Hygiene in Atlanta in November 2010 and a scientific paper which is currently under review with PloS NTDs were a summary of that consultation's outcomes, suggesting target product profiles and a list of immediate research priorities, as well as drafting a road map for future efforts. As mentioned before, disease experts, program managers, mathematical modellers and health economists are involved in this collaboration.
Start Year 2010
 
Description Co-author on a poster presented at a conference and a scientific paper (recently published in PloS NTDs) resulting from a a consensus meeting held at the LSHTM 
Organisation Natural History Museum
Country United Kingdom 
Sector Public 
PI Contribution I described current diagnostic tools that are used in the Monitoring and Evaluation of Schistosomiasis Control Programmes for population-based assessment. I had also the chance to give a brief update of the statistical methods I would use for evaluation of diagnostics during my fellowship work in the next 3 years and this initiated fruitful discussions.
Collaborator Contribution This was a consensus meeting of disease experts, program managers, mathematical modellers and health economists, and all together we discussed transmission dynamics, current diagnostic algorithms, and possible unified approaches for neglected tropical diseases (NTDs). It was highly beneficial to my research to interact during this meeting particularly with disease experts and programme managers and getting expert insight about the biology and control of the 2 NTDs I am working with. I believe that it is highly beneficial to my research to interact as much as possible with policy makers and programme implementers so that effective translation of research findings can be put eventually into practical action. As mentioned above it is highly beneficial to my research to be able to interact with Senior Staff Scientists and policy makers
Impact A poster presented at the American Society of Tropical Medicine and Hygiene in Atlanta in November 2010 and a scientific paper which is currently under review with PloS NTDs were a summary of that consultation's outcomes, suggesting target product profiles and a list of immediate research priorities, as well as drafting a road map for future efforts. As mentioned before, disease experts, program managers, mathematical modellers and health economists are involved in this collaboration.
Start Year 2010
 
Description Co-author on a poster presented at a conference and a scientific paper (recently published in PloS NTDs) resulting from a a consensus meeting held at the LSHTM 
Organisation World Health Organization (WHO)
Department Department of Control of Neglected Tropical Diseases
Country Global 
Sector Public 
PI Contribution I described current diagnostic tools that are used in the Monitoring and Evaluation of Schistosomiasis Control Programmes for population-based assessment. I had also the chance to give a brief update of the statistical methods I would use for evaluation of diagnostics during my fellowship work in the next 3 years and this initiated fruitful discussions.
Collaborator Contribution This was a consensus meeting of disease experts, program managers, mathematical modellers and health economists, and all together we discussed transmission dynamics, current diagnostic algorithms, and possible unified approaches for neglected tropical diseases (NTDs). It was highly beneficial to my research to interact during this meeting particularly with disease experts and programme managers and getting expert insight about the biology and control of the 2 NTDs I am working with. I believe that it is highly beneficial to my research to interact as much as possible with policy makers and programme implementers so that effective translation of research findings can be put eventually into practical action. As mentioned above it is highly beneficial to my research to be able to interact with Senior Staff Scientists and policy makers
Impact A poster presented at the American Society of Tropical Medicine and Hygiene in Atlanta in November 2010 and a scientific paper which is currently under review with PloS NTDs were a summary of that consultation's outcomes, suggesting target product profiles and a list of immediate research priorities, as well as drafting a road map for future efforts. As mentioned before, disease experts, program managers, mathematical modellers and health economists are involved in this collaboration.
Start Year 2010
 
Description Collaborator in successful Bill & Melinda Gates Foundation submission grant with LSHTM and Imperial College London 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Faculty of Infectious and Tropical Diseases
Country United Kingdom 
Sector Academic/University 
PI Contribution I have agreed to be one of the collaborators and acting as the lead statistical collaborator on reinfection studies, including sample size estimation, study design and statistical modelling on a $3.4 million grant over 4 years- submitted by the London School of Hygiene & Tropical Medicine and Imperial College London to the Bill & Melinda Gates Foundation. I have already contributed knowledge on existing data that could be included in mathematical models plus in preliminary sample size calculations. Once new data are collected, I will be able to apply the methodological techniques developed during my MRC fellowship to Soil Transmitted Helinths (STH) (-another group of Neglected Tropical Diseases) over multiple time points, since the grant involves a detailed reinfection that will use different diagnostic tests in a range of transmission settings.
Collaborator Contribution All collaborators are experts in the field of neglected tropical diseases, epidemiology and mathematical modeling. Interacting with them will only benefit my fellowship research and my future career in the long run. In general, several aspects of this Gates' grant will be synergistic with my MRC fellowship.
Impact This proposal was submitted in July 2011 and it has been approved by the Gates foundation in October 2011. The title was 'Developing tools for optimizing school-based deworming in the context of integrated neglected tropical disease control' while GIS, mathematical and statistical modeling would be used to develop these. During 2012, I have participated in several meetings to discuss availlable dataset for parametirization of mathematical models and exchanged ideas for study design of new studies. This research will eventually contribute to better STH control efforts and better health.
Start Year 2011
 
Description Collaborator in successful Bill & Melinda Gates Foundation submission grant with LSHTM and Imperial College London 
Organisation Wellcome Trust
Department KEMRI-Wellcome Trust Research Programme
Country Kenya 
Sector Multiple 
PI Contribution I have agreed to be one of the collaborators and acting as the lead statistical collaborator on reinfection studies, including sample size estimation, study design and statistical modelling on a $3.4 million grant over 4 years- submitted by the London School of Hygiene & Tropical Medicine and Imperial College London to the Bill & Melinda Gates Foundation. I have already contributed knowledge on existing data that could be included in mathematical models plus in preliminary sample size calculations. Once new data are collected, I will be able to apply the methodological techniques developed during my MRC fellowship to Soil Transmitted Helinths (STH) (-another group of Neglected Tropical Diseases) over multiple time points, since the grant involves a detailed reinfection that will use different diagnostic tests in a range of transmission settings.
Collaborator Contribution All collaborators are experts in the field of neglected tropical diseases, epidemiology and mathematical modeling. Interacting with them will only benefit my fellowship research and my future career in the long run. In general, several aspects of this Gates' grant will be synergistic with my MRC fellowship.
Impact This proposal was submitted in July 2011 and it has been approved by the Gates foundation in October 2011. The title was 'Developing tools for optimizing school-based deworming in the context of integrated neglected tropical disease control' while GIS, mathematical and statistical modeling would be used to develop these. During 2012, I have participated in several meetings to discuss availlable dataset for parametirization of mathematical models and exchanged ideas for study design of new studies. This research will eventually contribute to better STH control efforts and better health.
Start Year 2011
 
Description Collaborator on NIH grant proposal entitled 'Validating a urine test for Schistosoma mansoni in Zambia' 
Organisation Johns Hopkins University
Department W. Harry Feinstone Department of Molecular Microbiology and Immunology
Country United States 
Sector Academic/University 
PI Contribution The PI of this grant Dr Clive Shiff, approached me to help writing this grant application for the statistical analysis and study design parts. If successful, I will perform Latent class analysis in collaboration with PI. The results will provide ample data to evaluate the sensitivity and specificity of amplification methods and extraction methods.
Collaborator Contribution Dr Shiff as the PI of this grant lead the writing of this proposal and proposed research. Dr Shiff's aim is to test the LAMP method in a field situation in Zambia where mass chemotherapy against schistosomiasis is under way. His experience with LAMP indicates that it will likely exceed the detection level achieved with PCR, but this needs to be demonstrated and compared with other diagnostic methods under current use. It is anticipated that LAMP will become a key component in the development of an improved control strategy for schistosomiasis in Africa.
Impact I have met with Dr Shiff in 2006 at a scientific conference and since then we co-authored two published articles which I list below: 1) Validation of a new test for Schistosoma haematobium based on detection of Dra1 DNA fragments in urine: evaluation through latent class analysis.Ibironke O, Koukounari A, Asaolu S, Moustaki I, Shiff C. PLoS Negl Trop Dis. 2012 Jan;6(1):e1464 2)Sensitivities and specificities of diagnostic tests and infection prevalence of Schistosoma haematobium estimated from data on adults in villages northwest of Accra, Ghana. Koukounari A, Webster JP, Donnelly CA, Bray BC, Naples J, Bosompem K, Shiff C. Am J Trop Med Hyg. 2009 Mar;80(3):435-41. Dr Shiff is an international expert on schistosomiasis and malaria research and collaborating with him has only benefits for my fellowship.
Start Year 2006
 
Description Collaborator on NIH grant proposal entitled 'Validating a urine test for Schistosoma mansoni in Zambia' 
Organisation University of Zambia
Country Zambia 
Sector Academic/University 
PI Contribution The PI of this grant Dr Clive Shiff, approached me to help writing this grant application for the statistical analysis and study design parts. If successful, I will perform Latent class analysis in collaboration with PI. The results will provide ample data to evaluate the sensitivity and specificity of amplification methods and extraction methods.
Collaborator Contribution Dr Shiff as the PI of this grant lead the writing of this proposal and proposed research. Dr Shiff's aim is to test the LAMP method in a field situation in Zambia where mass chemotherapy against schistosomiasis is under way. His experience with LAMP indicates that it will likely exceed the detection level achieved with PCR, but this needs to be demonstrated and compared with other diagnostic methods under current use. It is anticipated that LAMP will become a key component in the development of an improved control strategy for schistosomiasis in Africa.
Impact I have met with Dr Shiff in 2006 at a scientific conference and since then we co-authored two published articles which I list below: 1) Validation of a new test for Schistosoma haematobium based on detection of Dra1 DNA fragments in urine: evaluation through latent class analysis.Ibironke O, Koukounari A, Asaolu S, Moustaki I, Shiff C. PLoS Negl Trop Dis. 2012 Jan;6(1):e1464 2)Sensitivities and specificities of diagnostic tests and infection prevalence of Schistosoma haematobium estimated from data on adults in villages northwest of Accra, Ghana. Koukounari A, Webster JP, Donnelly CA, Bray BC, Naples J, Bosompem K, Shiff C. Am J Trop Med Hyg. 2009 Mar;80(3):435-41. Dr Shiff is an international expert on schistosomiasis and malaria research and collaborating with him has only benefits for my fellowship.
Start Year 2006
 
Description Collaborator on succesful MRC grant entitled 'Childhood Tuberculosis Integrating Tools for improved diagnosis and vaccines' 
Organisation Imperial College London
Department Department of Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Childhood tuberculosis (TB) in Africa faces similar diagnostic challenges to those of NTDs. The vaccinology theme leader at the MRC Unit, The Gambia and Professor of Pediatric Infection and Immunity at Imperial College Department of Medicine approached me to contribute to the writing of a 2 million pounds MRC grant where if succesful I would use statistical methods developped during my fellowship to combine expertise in key TB research areas (i.e. epidemiology and health economics); In early November we learnt that this application was succesful. In early 2013 meetings in order to plan work, will follow. In late 2013 and during 2014 I will fit latent variable models to uniquely detailed cohorts within households to evaluate the performance of several novel TB biomarkers by age group and time; results will guide cost-effectiveness analyses for the use of an integrated field toolset.
Collaborator Contribution Prof Beate Kampmann is the PI on this MRC programme grant and an international expert on Paediatric Tuberculosis, including HIV-co-infection as well as age-related immune responses to infections and vaccination.
Impact As mentioned above, in early November we heard that the programme grant application was succesful. Professor Kampmann's research has a strong translational element and in this grant she has engaged international experts in biomarker studies, development of molecular diagnostics and statistical modelling. Such collaborations can only create further synergies to her stream of work which eventually will enable future links with industry.
Start Year 2012
 
Description Collaborator on succesful MRC grant entitled 'Childhood Tuberculosis Integrating Tools for improved diagnosis and vaccines' 
Organisation Medical Research Council (MRC)
Department MRC Unit, The Gambia
Country Gambia 
Sector Public 
PI Contribution Childhood tuberculosis (TB) in Africa faces similar diagnostic challenges to those of NTDs. The vaccinology theme leader at the MRC Unit, The Gambia and Professor of Pediatric Infection and Immunity at Imperial College Department of Medicine approached me to contribute to the writing of a 2 million pounds MRC grant where if succesful I would use statistical methods developped during my fellowship to combine expertise in key TB research areas (i.e. epidemiology and health economics); In early November we learnt that this application was succesful. In early 2013 meetings in order to plan work, will follow. In late 2013 and during 2014 I will fit latent variable models to uniquely detailed cohorts within households to evaluate the performance of several novel TB biomarkers by age group and time; results will guide cost-effectiveness analyses for the use of an integrated field toolset.
Collaborator Contribution Prof Beate Kampmann is the PI on this MRC programme grant and an international expert on Paediatric Tuberculosis, including HIV-co-infection as well as age-related immune responses to infections and vaccination.
Impact As mentioned above, in early November we heard that the programme grant application was succesful. Professor Kampmann's research has a strong translational element and in this grant she has engaged international experts in biomarker studies, development of molecular diagnostics and statistical modelling. Such collaborations can only create further synergies to her stream of work which eventually will enable future links with industry.
Start Year 2012
 
Description Evaluating diagnostic tests and quantifying prevalence for Tropical Infectious Diseases: a Paradigm of Latent Class Modelling Approaches With and Without a Gold Standard for Schistosomiasis Diagnosis 
Organisation London School of Economics and Political Science (University of London)
Country United Kingdom 
Sector Academic/University 
PI Contribution In collaboration with three London School of Economics & University of Washington methodological researchers, we have been expanding upon this diagnostics stream of work, and via simulated data and relevant epidemiological scenaria, examining bias in estimating diagnostic error by considering specific latent variable modelling approaches, as well as partial gold standard information for the diagnosis of schistosomiasis. This work can be important in highlighting important statistical issues for design and evaluation of diagnostics' studies of major other tropical infectious diseases beyond schistosomiasis such as malaria, TB and other NTDs.
Collaborator Contribution I have the initial idea for this paper, found data from past collaborators to illustrate in real datasets the modeling approaches and drafted significant parts of the forthcoming paper for submission. I also came with the simulation scenaria after I have validated those with schistosomiasis experts colleagues of mine. Collaborators provided statistical expertise in the latent variable models used, performed simulations and analyses and contributed and reviewed the writing of the forthcoming paper.
Impact We are planning to submit this piece of work in the next weeks as a scientific paper and provide also R code for fitting relevant models to similar problems in a forthcoming publication in the Journal of American Statistical Association, Case Studies and Applications.
Start Year 2016
 
Description Evaluating diagnostic tests and quantifying prevalence for Tropical Infectious Diseases: a Paradigm of Latent Class Modelling Approaches With and Without a Gold Standard for Schistosomiasis Diagnosis 
Organisation University of Washington
Country United States 
Sector Academic/University 
PI Contribution In collaboration with three London School of Economics & University of Washington methodological researchers, we have been expanding upon this diagnostics stream of work, and via simulated data and relevant epidemiological scenaria, examining bias in estimating diagnostic error by considering specific latent variable modelling approaches, as well as partial gold standard information for the diagnosis of schistosomiasis. This work can be important in highlighting important statistical issues for design and evaluation of diagnostics' studies of major other tropical infectious diseases beyond schistosomiasis such as malaria, TB and other NTDs.
Collaborator Contribution I have the initial idea for this paper, found data from past collaborators to illustrate in real datasets the modeling approaches and drafted significant parts of the forthcoming paper for submission. I also came with the simulation scenaria after I have validated those with schistosomiasis experts colleagues of mine. Collaborators provided statistical expertise in the latent variable models used, performed simulations and analyses and contributed and reviewed the writing of the forthcoming paper.
Impact We are planning to submit this piece of work in the next weeks as a scientific paper and provide also R code for fitting relevant models to similar problems in a forthcoming publication in the Journal of American Statistical Association, Case Studies and Applications.
Start Year 2016
 
Description H1N1 pdm Serology working group 
Organisation World Health Organization (WHO)
Department Global Influenza Programme
Country Switzerland 
Sector Public 
PI Contribution In collaboration with staff from the Department of Infectious Disease Epidemiology (DIDE) at Imperial College where I am currently based, I have used metanalytic methods to provide pooled estimates from multicountry influenza studies.
Collaborator Contribution The working group and DIDE staff gathered the data and provided first drafts of relevant published and submitted scientific articles.
Impact One paper has been published (pls see below for further details): Risk factors for severe outcomes following 2009 influenza A (H1N1) infection: a global pooled analysis. PLoS Med. 2011 Jul;8(7):e1001053. Epub 2011 Jul 5. A second paper is now under revision (pls see below for further details): Van Kerkhove MD*, Siddhivinayak H*, Koukounari A, Mounts AW. for the H1N1pdm serology working group. Estimating Age-Specific Infection Rates for the 2009 Influenza Pandemic: a Meta-Analysis of A(H1N1)pdm09 Serological Studies from 19 countries. submitted to Influenza Other Respi Viruses. *Authors have contributed equally to the work
Start Year 2010
 
Description Member of the Africa at LSE blog/portal 
Organisation London School of Economics and Political Science (University of London)
Department Department of International Development
Country United Kingdom 
Sector Academic/University 
PI Contribution 'Africa at LSE' is a blog set up to promote African research at the London School of Economics and Political Science (LSE). I will give a presentation on my fellowship work in next year at the Africa Initiative Seminar Series (organized by the Department of Anthropology at LSE).
Collaborator Contribution Attending such talks enrich my general knowledge about the countries from which I am analysing health data and might lead to interesting future collaborations.
Impact 'Africa Initiative Seminar Series' includes talks on various disciplines (like for instance Anthropology and International Development) with LSE research from several regions of the African continent. Attending such talks enrich my general knowledge about the countries from which I am analysing health data and might lead to interesting future collaborations.
Start Year 2011
 
Description Statistical collaborator on a successful Wellcome Trust Senior Research Fellowship (SRF) application 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Faculty of Epidemiology and Population Health
Country United Kingdom 
Sector Academic/University 
PI Contribution This successfulSRF application will involve a programme of research investigating the changing spatial risks of soil-transmitted helminth (STH) infections and lymphatic filariasis (LF) in sub-Saharan Africa (SSA).It is important to acknowledge at the outset that the data available are of varying quality and availability and it is, therefore, necessary to consider the sensitivity and specificity of the diagnostic method used to detect infection. Latent class models will be used for the statistical analysis. I have agreed to co-supervise with the main SRF applicant a PhD student working on this topic.
Collaborator Contribution The Wellcome Trust SRF applicant is an expert on NTDs epidemiology and this application will be synergistic with my MRC fellowship. This collaboration can only be beneficial for my fellowship and my future career.
Impact In collaboration with the SRF applicant I have contributed intellectual input on specific parts of this application which was submitted to the Wellcome Trust recently. The outcome of this application will be known ealry 2012.
Start Year 2011
 
Description London Declaration for NTDs 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact In Jan 2012 I watched as global health leaders, senior government officials, academics, the CEOs of major pharmaceutical companies and the World Bank all backed the "London Declaration for Neglected Tropical Diseases (NTDs)" urging collaborations for the control and elimination of NTDs by 2020. A main discussion topic was accelerated research on diagnostics with demonstrated satisfactory performance in large-scale public health programmes for a) disease mapping to guide interventions; b) monitoring and evaluation (M&E) of impact of interventions particularly for the prompt detection of possible drug resistance; and c) assessment of elimination of infection.

This was an extraordinary gathering of international politicians, pharmaceutical chief executives and global health organisation heads threatened to take the 'neglect' out of 'neglected tropical diseases' (NTDs). Together they made a number of significant commitments to provide treatments, research and development funding and cooperation to control, eliminate or even eradicate ten NTDs by 2020.

All partners and attendees endorsed the "London Declaration on Neglected Tropical Diseases, " in which they pledged new levels of collaborative effort and tracking of progress in tackling 10 of the 17 neglected tropical diseases currently on WHO's list. I felt extremely privileged to be part of this event.
Year(s) Of Engagement Activity 2012
 
Description NTD 2020: Uniting to Combat NTDs: Translating the London Declaration into Action 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Over the weekend (Nov. 16-18, 2012) the Bill & Melinda Gates Foundation and the World Bank hosted "Uniting to Combat Neglected Tropical Diseases: Translating the London Declaration into Action."

The meetings brought together NTD partners from around the world to discuss progress since the January 30, 2012 London Declaration and build on the pledges made by various partners, including pharmaceutical companies, national governments and NGOs to control or eliminate the most common NTDs by 2020. Apart from the common meeting agenda, I attended a side meeting on schistosomiasis and STHs as well as brainstorming sessions related to academic research and e-tools and databases.




This meeting will no doubt contribute and enhance the momentum around NTDs while at the individual level in my case enabled me to verify that my research is on the right track, enhance my research trajectory and help me network with international NTDs experts.
Year(s) Of Engagement Activity 2012
 
Description NTD Data management meeting - WHO/HQ, Geneva 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Primary Audience Policymakers/politicians
Results and Impact Regional M&E focal points and regional NTD data managers and M&E officers/data maanagers from partner agencies supporting the implementation of preventive chemotherapy attended this meeting where I have presented mainly the research questions I am trying to anwer through my fellowship work. This sparked questions and discussion afterwards.

At the time of this presentation (03/11) there were not results included as this is a work in progress and so notable impact cannot be yet documented at this stage.
Year(s) Of Engagement Activity 2011