Defining the biomedical, environmental and social risk factors for human infection with Plasmodium knowlesi; opportuniti
Lead Research Organisation:
London School of Hygiene & Tropical Medicine
Department Name: Infectious and Tropical Diseases
Abstract
Malaria is caused by a single celled parasite found predominantly in the blood of its host, and is transmitted between hosts by the bite of a mosquito. Greater than 100 species of malaria exist, infecting many different animals. Until recently, humans were thought to be the natural hosts for 4 malaria species. However, since 2004 reports appeared of malaria infections in humans that are caused by a parasite species found previously in certain types of macaque in Southeast Asia. This species is Plasmodium knowlesi and, although benign in its natural monkey host, it has caused severe and even fatal disease in a proportion of human sufferers.
Currently, we know little about the true burden of disease caused by this macaque parasite, or why it has emerged as a human pathogen. Initial descriptions of humans with Plasmodium knowlesi malaria suggested that they had been bitten and infected while working in forested areas, common in many countries of Southeast Asia. However, a more recent study in Malaysian Borneo shows that communities there are also being infected, even though there is little forest in existence. There may be a number of factors related to the environment, the types of mosquito in the area, people?s behaviour or movement and their proximity to troops of macaques that will have an effect on how at risk they are to being infected with Plasmodium knowlesi.
We have built a network of researchers with different skills and expertise from the UK, the Philippines, Malaysia and Australia to tackle the various knowledge gaps by working together in a concerted approach. We plan to conduct studies in both the Philippines (on Palawan island) and in Sabah, a region of Malaysian Borneo. A larger number of cases of human Plasmodium knowlesi infection have been found in Sabah, compared to Palawan, and we will attempt to find out why communities here seem at higher risk. In treating their infections we can produce guidelines to help other clinicians faced with this disease. We also want to study the macaques, the mosquitoes that transmit the parasite, and the environment in which the infections occur to give us the whole picture and to produce maps that describe the risk factors existing in the different areas. We hope this will provide important information to ministries of health trying to control malaria disease in the affected regions and prevent further outbreaks of malaria originating from primates.
Currently, we know little about the true burden of disease caused by this macaque parasite, or why it has emerged as a human pathogen. Initial descriptions of humans with Plasmodium knowlesi malaria suggested that they had been bitten and infected while working in forested areas, common in many countries of Southeast Asia. However, a more recent study in Malaysian Borneo shows that communities there are also being infected, even though there is little forest in existence. There may be a number of factors related to the environment, the types of mosquito in the area, people?s behaviour or movement and their proximity to troops of macaques that will have an effect on how at risk they are to being infected with Plasmodium knowlesi.
We have built a network of researchers with different skills and expertise from the UK, the Philippines, Malaysia and Australia to tackle the various knowledge gaps by working together in a concerted approach. We plan to conduct studies in both the Philippines (on Palawan island) and in Sabah, a region of Malaysian Borneo. A larger number of cases of human Plasmodium knowlesi infection have been found in Sabah, compared to Palawan, and we will attempt to find out why communities here seem at higher risk. In treating their infections we can produce guidelines to help other clinicians faced with this disease. We also want to study the macaques, the mosquitoes that transmit the parasite, and the environment in which the infections occur to give us the whole picture and to produce maps that describe the risk factors existing in the different areas. We hope this will provide important information to ministries of health trying to control malaria disease in the affected regions and prevent further outbreaks of malaria originating from primates.
Technical Summary
Background:
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. Studies have since detected P. knowlesi in human populations in several other Southeast Asian countries.
The primary hosts of P. knowlesi are macaque species that are widely distributed across Southeast Asia and in which infection is benign. P. knowlesi infections in humans however can cause severe and fatal disease. Moreover recent studies in Sabah, Malaysia, have suggested that transmission is not confined to adults or the forest fringe as previously described. We hypothesize that the change in land use patterns has lead to this apparent increase in cases and changing epidemiology. The appearance of other primate-associated pathogens within human populations has been linked with activities such as deforestation (eg Yellow fever) and hunting (eg Ebola). A common feature of these zoonoses is that community perceptions of disease risk strongly impact on the economic activities that drive exposure, and demonstrate the value of an integrated approach to prevention and control.
Methods:
We propose an interdisciplinary approach to examine the extent of infection with P.knowlesi at 2 study sites and to identify risk factors for infection that ultimately contribute to its control. A case control study, the first of its kind for P.knowlesi, will allow analysis of broad scale spatial and socio-behavioural factors associated with symptomatic infections. Alongside this we will conduct detailed entomological trapping experiments and primatology studies within habitats of potential epidemiological importance (closed canopy primary forest, secondary forest, etc.). These data together with mosquito and macaque infection rates will be incorporated into spatial and mathematical models to generate risk maps for P.knowlesi infection. We will use these maps to define areas in which to conduct cross sectional surveys to identify asymptomatic infections and exposure patterns with P.knowlesi.
Outputs:
We aim to identify the scale of public health threat posed by P. knowlesi, through characterisation of the biological, environmental and social factors responsible for triggering its emergence within human populations. By understanding these factors we will generate risk maps to define and focus appropriate control strategies. This will allow an understanding of the conditions that permit the parasite host switch from macaque to human, and predictions of the risk of further species crossover events may be possible.
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. Studies have since detected P. knowlesi in human populations in several other Southeast Asian countries.
The primary hosts of P. knowlesi are macaque species that are widely distributed across Southeast Asia and in which infection is benign. P. knowlesi infections in humans however can cause severe and fatal disease. Moreover recent studies in Sabah, Malaysia, have suggested that transmission is not confined to adults or the forest fringe as previously described. We hypothesize that the change in land use patterns has lead to this apparent increase in cases and changing epidemiology. The appearance of other primate-associated pathogens within human populations has been linked with activities such as deforestation (eg Yellow fever) and hunting (eg Ebola). A common feature of these zoonoses is that community perceptions of disease risk strongly impact on the economic activities that drive exposure, and demonstrate the value of an integrated approach to prevention and control.
Methods:
We propose an interdisciplinary approach to examine the extent of infection with P.knowlesi at 2 study sites and to identify risk factors for infection that ultimately contribute to its control. A case control study, the first of its kind for P.knowlesi, will allow analysis of broad scale spatial and socio-behavioural factors associated with symptomatic infections. Alongside this we will conduct detailed entomological trapping experiments and primatology studies within habitats of potential epidemiological importance (closed canopy primary forest, secondary forest, etc.). These data together with mosquito and macaque infection rates will be incorporated into spatial and mathematical models to generate risk maps for P.knowlesi infection. We will use these maps to define areas in which to conduct cross sectional surveys to identify asymptomatic infections and exposure patterns with P.knowlesi.
Outputs:
We aim to identify the scale of public health threat posed by P. knowlesi, through characterisation of the biological, environmental and social factors responsible for triggering its emergence within human populations. By understanding these factors we will generate risk maps to define and focus appropriate control strategies. This will allow an understanding of the conditions that permit the parasite host switch from macaque to human, and predictions of the risk of further species crossover events may be possible.