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

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.

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.