Defining the biomedical, environmental and social risk factors for human infection with Plasmodium knowlesi; opportuniti

Lead Research Organisation: London Sch of Hygiene and Trop Medicine
Department Name: Infectious and Tropical Diseases

Abstract

The disease malaria is caused by a single celled parasite that lives predominantly in the blood of its host, and is transmitted between hosts by the bite of a female mosquito. Humans were thought, until recently, to be the natural hosts for 4 different species of malaria parasite; greater than 100 species exist and infect many different animals. In Malaysian Borneo, 2004, an outbreak of malaria in humans resulted from a parasite species that had previously been found only in certain types of macaque in Southeast Asia. This species is Plasmodium knowlesi and, although benign in its natural monkey host, it caused severe and even fatal disease in a small proportion of human sufferers.
Currently, it is difficult to assess the potential threat to public health that might result from the apparent host switch. We know little about the proportion of humans carrying Plasmodium knowlesi and less about the prevalence of the parasite in its natural monkey host. Similarly, we need to investigate the reasons why the particular mosquito responsible for transmitting Plasmodium knowlesi bites both monkeys and humans. Environmental and social factors may lead to certain groups of people, such as forest workers, being at greater risk of Plasmodium knowlesi infection. These factors are also undefined, making prevention and control measures impossible to put into practice.
We propose to fill the gaps in our knowledge of human Plasmodium knowlesi infections by building a network of researchers from biomedical, environmental, and social science disciplines, both from the UK and regions of Southeast Asia affected by Plasmodium knowlesi.
Our objectives are:
To collect and analyse preliminary data from fieldwork in the Philippines with which to inform a broader research strategy. Samples will be collected from humans and mosquitoes for the detection of Plasmodium knowlesi DNA, and land-use mapping and questionnaires will help us to pinpoint risk factors for infection. Areas of the Philippines will be the initial focus due to existing links between the London School of Hygiene and Tropical Medicine and Philippine institutes.
To hold a workshop for all collaborators and potential end-users of the study in which a research strategy, management structure and full network is formalised.
Helped by preliminary results from the field sites, key research questions will be developed during the grant period, the aim of which is to produce a larger grant application for the regional wide study of Plasmodium knowlesi in humans.

Technical Summary

Until recently, medical science has attributed malaria infections in humans to only four parasite species. However, molecular investigations during a malaria epidemic in Malaysian Borneo in 2004 confirmed the causative agent as Plasmodium knowlesi, a parasite formerly thought to only infect primates. Molecular studies have since detected P. knowlesi in human populations in several other south Asian countries.

The primary hosts of P. knowlesi are thought to be macaques, which are widely distributed across Southeast Asia and in which infection is benign. P. knowlesi infections in humans however can cause severe and fatal disease. To date, very limited surveillance has been carried out and there is poor understanding of the timescale over which P. knowlesi infections in humans have been occurring. Molecular diagnosis is essential as the parasite closely resembles Plasmodium malariae on microscopy and may be misdiagnosed. The social and economic contexts in which humans interact with forest environments are likely to be influencing P. knowlesi emergence in Asia, and must be explicitly considered.

We propose therefore to develop a multidisciplinary network of investigators in order to identify the public health threat posed by P. knowlesi, through characterisation of the biological, environmental and social factors responsible for triggering its emergence within human populations. Only when the drivers of infection are identified can the risk of infection be assessed in each country and strategies formulated for prevention and control. A further benefit may be that in understanding the conditions that permit the host switch from monkey to human, predictions as to the risk of further species crossover events may be possible.

Objectives:
To build a network of researchers from biomedical, environmental, and social science disciplines, both from the UK and regions affected by P. knowlesi.
To hold a workshop for all collaborators in which a research strategy, management structure and network is formalised.
To identify and communicate with primary users and stakeholders who will benefit from the proposed research strategy.
To collect and analyse preliminary data from fieldwork in the Philippines with which to inform a broader research strategy.

Areas of the Philippines will be the focus for a pilot study using existing links between LSHTM and Philippine institutes. Broader research questions will be developed during the grant period, the overall aim of which will be to produce a larger consortia application for regional wide study of the epidemiology and control of P. knowlesi in humans.

Publications

10 25 50
 
Description 2012 - 2016 Manual of Operations
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
Impact The Malaria Program called attention to the fact that the four human malaria species and zoonotic malaria are endemic in the Philippines. Included in the 2012 - 2016 manual of operations is the instruction for the collection of blood spots from P malariae malaria cases and shipment to RITM. The specimens will undergo molecular assay for P knowlesi infection.
 
Description WHO Informal Consultation on Public Health Importance of Plasmodium knowlesi
Geographic Reach Asia 
Policy Influence Type Membership of a guidance committee
 
Description Diploma in Applied Parasitology and Entomology - Ms. Majhalia Torno
Amount RM100,000 (MYR)
Organisation Malaysian Technical Cooperation Program 
Sector Public
Country Malaysia
Start 06/2016 
End 12/2017
 
Description Environmental and Social Ecology of Human Infectious Diseases (ESEI) Phase II Research Consortia Grant (MRC, ESRC, BBSRC, NERC)
Amount £2,896,956 (GBP)
Funding ID G1100796 
Organisation Research Councils UK (RCUK) 
Sector Public
Country United Kingdom
Start 03/2012 
End 02/2017
 
Description Establish platform to investigate human genetics and plasmodium knowlesi with the Department of Biotechnology.
Amount RM50,000 (MYR)
Organisation Malaysian University of Sabah 
Sector Academic/University
Country Malaysia
Start 04/2016 
End 12/2017
 
Description PhD in Medical Entomology - Wilfredo Aure
Amount RM100,000 (MYR)
Organisation Malaysian University of Sabah 
Sector Academic/University
Country Malaysia
Start 06/2014 
End 12/2017
 
Description WHO Fellowship
Amount Php0 (PHP)
Organisation World Health Organization (WHO) 
Sector Public
Country Global
Start 06/2015 
End 12/2015
 
Description WHO Fellowship - Ms. Paulene Joy Lorenzo
Amount Php600,000 (PHP)
Organisation World Health Organization (WHO) 
Sector Public
Country Global
Start 06/2015 
End 12/2015
 
Description ESEI Phase II Research Consortium - Plasmodium knowlesi 
Organisation Government of the Republic of the Philippines
Department Research Institute for Tropical Medicine (RITM) Phillippines
Country Philippines 
Sector Public 
PI Contribution PI and coordinator of a network of multidisciplinary researchers who, building on the Catalyst Grant, applied for an ESEI Phase II Research Consortium Grant. The research team at LSHTM contributed particular expertise in parasitology, epidemiology, entomology, land use and GIS mapping and molecular biology.
Collaborator Contribution Partners at the University of Glasgow made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in entomology and ecological modelling.Partner at the University of Greenwich made a large contribution to preparing the ESEI grant application, with particular expertise in entomology.Partners at the Research Institute for Tropical Medicine made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in social science, entomology, and malaria control in the Philippines.Partners at the University of the Philippines, Los Banos made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in primatology.Partners at the Menzies School of Health Research made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in clinical sciences and managing human P. knowlesi malaria infections.Partners at the Queen Elizabeth Hospital Clinical Research Centre made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in clinical sciences and diagnosing and managing human P. knowlesi malaria infections.
Impact The major output has been the successful application for funding to the joint Research Councils ESEI initiative for a Phase II Research Consortia Grant (Award letter pending). The collaboration is multidisciplinary, with the following disciplines represented: Clinical sciences, parasitology, entomology, primatology, social science, land use/mapping, epidemiology, ecological modelling and molecular biology.
Start Year 2010
 
Description ESEI Phase II Research Consortium - Plasmodium knowlesi 
Organisation Menzies School of Health Research
Country Australia 
Sector Academic/University 
PI Contribution PI and coordinator of a network of multidisciplinary researchers who, building on the Catalyst Grant, applied for an ESEI Phase II Research Consortium Grant. The research team at LSHTM contributed particular expertise in parasitology, epidemiology, entomology, land use and GIS mapping and molecular biology.
Collaborator Contribution Partners at the University of Glasgow made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in entomology and ecological modelling.Partner at the University of Greenwich made a large contribution to preparing the ESEI grant application, with particular expertise in entomology.Partners at the Research Institute for Tropical Medicine made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in social science, entomology, and malaria control in the Philippines.Partners at the University of the Philippines, Los Banos made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in primatology.Partners at the Menzies School of Health Research made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in clinical sciences and managing human P. knowlesi malaria infections.Partners at the Queen Elizabeth Hospital Clinical Research Centre made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in clinical sciences and diagnosing and managing human P. knowlesi malaria infections.
Impact The major output has been the successful application for funding to the joint Research Councils ESEI initiative for a Phase II Research Consortia Grant (Award letter pending). The collaboration is multidisciplinary, with the following disciplines represented: Clinical sciences, parasitology, entomology, primatology, social science, land use/mapping, epidemiology, ecological modelling and molecular biology.
Start Year 2010
 
Description ESEI Phase II Research Consortium - Plasmodium knowlesi 
Organisation Queen Elizabeth Hospital Birmingham
Department Queen Elizabeth Hospital Clinical Research Centre
Country United Kingdom 
Sector Hospitals 
PI Contribution PI and coordinator of a network of multidisciplinary researchers who, building on the Catalyst Grant, applied for an ESEI Phase II Research Consortium Grant. The research team at LSHTM contributed particular expertise in parasitology, epidemiology, entomology, land use and GIS mapping and molecular biology.
Collaborator Contribution Partners at the University of Glasgow made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in entomology and ecological modelling.Partner at the University of Greenwich made a large contribution to preparing the ESEI grant application, with particular expertise in entomology.Partners at the Research Institute for Tropical Medicine made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in social science, entomology, and malaria control in the Philippines.Partners at the University of the Philippines, Los Banos made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in primatology.Partners at the Menzies School of Health Research made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in clinical sciences and managing human P. knowlesi malaria infections.Partners at the Queen Elizabeth Hospital Clinical Research Centre made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in clinical sciences and diagnosing and managing human P. knowlesi malaria infections.
Impact The major output has been the successful application for funding to the joint Research Councils ESEI initiative for a Phase II Research Consortia Grant (Award letter pending). The collaboration is multidisciplinary, with the following disciplines represented: Clinical sciences, parasitology, entomology, primatology, social science, land use/mapping, epidemiology, ecological modelling and molecular biology.
Start Year 2010
 
Description ESEI Phase II Research Consortium - Plasmodium knowlesi 
Organisation University of Glasgow
Department Institute of Biomedical and Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution PI and coordinator of a network of multidisciplinary researchers who, building on the Catalyst Grant, applied for an ESEI Phase II Research Consortium Grant. The research team at LSHTM contributed particular expertise in parasitology, epidemiology, entomology, land use and GIS mapping and molecular biology.
Collaborator Contribution Partners at the University of Glasgow made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in entomology and ecological modelling.Partner at the University of Greenwich made a large contribution to preparing the ESEI grant application, with particular expertise in entomology.Partners at the Research Institute for Tropical Medicine made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in social science, entomology, and malaria control in the Philippines.Partners at the University of the Philippines, Los Banos made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in primatology.Partners at the Menzies School of Health Research made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in clinical sciences and managing human P. knowlesi malaria infections.Partners at the Queen Elizabeth Hospital Clinical Research Centre made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in clinical sciences and diagnosing and managing human P. knowlesi malaria infections.
Impact The major output has been the successful application for funding to the joint Research Councils ESEI initiative for a Phase II Research Consortia Grant (Award letter pending). The collaboration is multidisciplinary, with the following disciplines represented: Clinical sciences, parasitology, entomology, primatology, social science, land use/mapping, epidemiology, ecological modelling and molecular biology.
Start Year 2010
 
Description ESEI Phase II Research Consortium - Plasmodium knowlesi 
Organisation University of Greenwich
Department Natural Resources Institute Greenwich
Country United Kingdom 
Sector Academic/University 
PI Contribution PI and coordinator of a network of multidisciplinary researchers who, building on the Catalyst Grant, applied for an ESEI Phase II Research Consortium Grant. The research team at LSHTM contributed particular expertise in parasitology, epidemiology, entomology, land use and GIS mapping and molecular biology.
Collaborator Contribution Partners at the University of Glasgow made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in entomology and ecological modelling.Partner at the University of Greenwich made a large contribution to preparing the ESEI grant application, with particular expertise in entomology.Partners at the Research Institute for Tropical Medicine made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in social science, entomology, and malaria control in the Philippines.Partners at the University of the Philippines, Los Banos made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in primatology.Partners at the Menzies School of Health Research made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in clinical sciences and managing human P. knowlesi malaria infections.Partners at the Queen Elizabeth Hospital Clinical Research Centre made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in clinical sciences and diagnosing and managing human P. knowlesi malaria infections.
Impact The major output has been the successful application for funding to the joint Research Councils ESEI initiative for a Phase II Research Consortia Grant (Award letter pending). The collaboration is multidisciplinary, with the following disciplines represented: Clinical sciences, parasitology, entomology, primatology, social science, land use/mapping, epidemiology, ecological modelling and molecular biology.
Start Year 2010
 
Description ESEI Phase II Research Consortium - Plasmodium knowlesi 
Organisation University of the Philippines Los Baños
Department Institute of Biological Sciences (encompassing former Dept of Zoology)
Country Philippines 
Sector Academic/University 
PI Contribution PI and coordinator of a network of multidisciplinary researchers who, building on the Catalyst Grant, applied for an ESEI Phase II Research Consortium Grant. The research team at LSHTM contributed particular expertise in parasitology, epidemiology, entomology, land use and GIS mapping and molecular biology.
Collaborator Contribution Partners at the University of Glasgow made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in entomology and ecological modelling.Partner at the University of Greenwich made a large contribution to preparing the ESEI grant application, with particular expertise in entomology.Partners at the Research Institute for Tropical Medicine made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in social science, entomology, and malaria control in the Philippines.Partners at the University of the Philippines, Los Banos made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in primatology.Partners at the Menzies School of Health Research made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in clinical sciences and managing human P. knowlesi malaria infections.Partners at the Queen Elizabeth Hospital Clinical Research Centre made large contributions to developing the research consortium and preparing the ESEI grant application, with particular expertise in clinical sciences and diagnosing and managing human P. knowlesi malaria infections.
Impact The major output has been the successful application for funding to the joint Research Councils ESEI initiative for a Phase II Research Consortia Grant (Award letter pending). The collaboration is multidisciplinary, with the following disciplines represented: Clinical sciences, parasitology, entomology, primatology, social science, land use/mapping, epidemiology, ecological modelling and molecular biology.
Start Year 2010
 
Description Molecular Biologist (CAS) 
Organisation University of the Philippines Los Baños
Country Philippines 
Sector Academic/University 
PI Contribution This is a new collaboration that involves LSHTM & RITM.
Collaborator Contribution Dr. Mary Grace Ducuma, a molecular biologist also of CAS, is a consultant for antimalaria drug resistance of a new collaboration between RITM and LSHTM (Newton Fund Collaboration)
Impact Pending.
Start Year 2012
 
Description Parasitology and ecotourism-related stress in hybrid macaques, PhD student (Lauren Gilhooly) 
Organisation Danau Girang Field Centre
Country Malaysia 
Sector Academic/University 
PI Contribution Provided logistical support to the student, advise on parasitology and genetics
Collaborator Contribution Proposed the project, provided funding, supervision of student on anthropology aspects
Impact Impact pending.
Start Year 2015
 
Description Parasitology and ecotourism-related stress in hybrid macaques, PhD student (Lauren Gilhooly) 
Organisation Western University
Department Department of Anthropology
Country Canada 
Sector Academic/University 
PI Contribution Provided logistical support to the student, advise on parasitology and genetics
Collaborator Contribution Proposed the project, provided funding, supervision of student on anthropology aspects
Impact Impact pending.
Start Year 2015
 
Description Primate census using Drones, MSc student (Amaziasisamoria Jumail) 
Organisation Danau Girang Field Centre
Country Malaysia 
Sector Academic/University 
PI Contribution DGFC Proposed the project in conjunction with the LSHTM, supervision of the student on primate ecology
Collaborator Contribution LSHTM - funding, supervision on remote sensing; ITBC - host the student, funding, supervision on remote sensing
Impact None yet.
Start Year 2016
 
Description Primate census using Drones, MSc student (Amaziasisamoria Jumail) 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Country United Kingdom 
Sector Academic/University 
PI Contribution DGFC Proposed the project in conjunction with the LSHTM, supervision of the student on primate ecology
Collaborator Contribution LSHTM - funding, supervision on remote sensing; ITBC - host the student, funding, supervision on remote sensing
Impact None yet.
Start Year 2016
 
Description Primate census using Drones, MSc student (Amaziasisamoria Jumail) 
Organisation Malaysian University of Sabah
Department Institute for Tropical Biology Conservation
Country Malaysia 
Sector Academic/University 
PI Contribution DGFC Proposed the project in conjunction with the LSHTM, supervision of the student on primate ecology
Collaborator Contribution LSHTM - funding, supervision on remote sensing; ITBC - host the student, funding, supervision on remote sensing
Impact None yet.
Start Year 2016
 
Description Rickettsiae in wildlife, MSc student (Cyrlen Jalius) 
Organisation Danau Girang Field Centre
Country Malaysia 
Sector Academic/University 
PI Contribution Proposed the project, collected all samples, funding the university fee and student stipend
Collaborator Contribution UMS - host the student and supervise on ectoparasite identification; MORU - supervise on immunology and molecular detectio of ricketssiae
Impact Pending.
Start Year 2017
 
Description University of the Philippines at Los Banos 
Organisation University of the Philippines Los Baños
Country Philippines 
Sector Academic/University 
PI Contribution 1. RITM is the designated WHO Regional Training Centre in the Western Pacific Region.
Collaborator Contribution 1. Dr. Gloria Nelson, Department of Sociology, CAS, is a point person for discussions to develop UP Los Banos as a sister institution of the WHO-TDR supported Regional Training Center for Good Health Research Practices (WHO RTC).
Impact 1. Dr. Gloria Nelson, Department of Sociology, CAS, is a point person for discussions to develop UP Los Banos as a sister institution of the WHO-TDR supported Regional Training Center for Good Health Research Practices (WHO RTC).
Start Year 2012
 
Title Thermal camera attached to drone 
Description Use of a thermal camera attached to a Drone to conduct a primate census. This is ongoing but to our knowledge this has never been attempted and there are no peer reviewed publications on this. 
Type Of Technology New/Improved Technique/Technology 
Year Produced 2015 
Impact None yet 
 
Description International Conference on Rainforest Ecology, Diversity and Conservation in Borneo. June 2015. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact International Conference on Rainforest Ecology, Diversity and Conservation in Borneo. June 2015. Sabah, Malaysia. [M. Salgado-Lynn, K.M. Fornace, N.M. Anstey, W.E. Aure, T.H. Chua, J. Dimalibot, F.E. Espino, H. Ferguson, B. Goossens, M.J. Grigg, R.R. Kao, J. Luchavez, K. Mariappan, S. Nathan, P. Porodong, D.J. Stark, A. McIntyre, L. Gilhooly,S.J. Torr, I. Vythilingam, T. Williams, T.W. Yeo, J. Cox, and C.J. Drakeley, "The MONKEYBAR project: Defining biomedical, environmental and social risk factors for human infection with Plasmodium knowlesi"]
Five postgraduate students approached the speaker, asking for advice about emerging infectious diseases career opportunities
Year(s) Of Engagement Activity 2015
 
Description Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Mosquito Borne Diseases Symposium. August 2015. Sabah, Malaysia. [Milena Salgado-Lynn, Danica Stark, Kimberly Fornace, Sergio Guerrero-Sánchez, Chris Drakeley, Benoit Goossens. "Vector borne diseases: A tale of two monkeys"]
Newspaper article about the talk.
Year(s) Of Engagement Activity 2015
 
Description WHO Expert consultation on Plasmodium Knowlesi malaria to guide malaria elimination strategies 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact MONKEYBAR had five delegates on the expert panel committee to update evidence and regional guidelines on plasmodium knowlesi. The MONKEYBAR team have contributed key evidence to optimal treatment and disease epidemiology.
Year(s) Of Engagement Activity 2017