MONKEYBAR: Defining the biomedical, environmental and social risk factors for human infection with Plasmodium knowlesi

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1 MONKEYBAR: Defining the biomedical, environmental and social risk factors for human infection with Plasmodium knowlesi; opportunities for prevention and control of an emerging zoonotic infection. Chris Drakeley London School of Hygiene and Tropical Medicine KM Fornace, NM Anstey, MJ Grigg, TH Chua, H Ferguson, P Brock, SJ Torr, M Salgado-Lynn, DJ Stark, I Vythilingam, T William, E Espino & J Cox

2 Plasmodium knowlesi Malaria parasite identified in 1930 s with contrasting virulence in different simian hosts Used in treatment of neurosyphilitics - infection of anopheles and to humans Little evidence of widespread infection in humans until 2004 when molecular assays revealed 80% of infections were P. knowlesi not P. malariae. Subsequently >1000 cases in Malaysian Borneo & is no the main cause of malaria Clinical infections associated with severe outcomes and a case fatality rate similar to P.falciparum Infections described in most SE Asian countries

3 MONKEYBAR Aims: Use innovative and interdisciplinary approaches to assess the basic epidemiology of an emerging infection to improve disease control What is the extent of the problem? Describe burden of P.knowlesi infection disease in humans: symptomatic and asymptomatic What are the risk factors for exposure? Are these the same as Pf & Pv? Is this classic forest malaria? What are the primary epidemiological components of transmission? What is the primary mosquito vector(s) and what are their binomics? What macaque factors influence transmission? Where are the principal sites of human/vector macaque interaction? How will the above affects the control & elimination strategies of regional countries? Are current vector control strategies sufficient/useful?

4 Study design CLINICAL COMPONENT CASE CONTROL STUDY All malaria cases reporting at Kudat and Kota Marudu hospitals in Sabah. Controls chosen based on residence of cases Areas with high number cases chosen as intensive study sites PASSIVE CASE MONITORING 3 facilities in Bacungan on Palawan island the Phillippines Retrospective analysis of all malaria Land use classification Entomology: vector species, abundance & infection - Trap evaluation - Longitudinal mosquito trapping - Trapping around case and controls Social science: human behaviour and disease perception sam - Focus group discussions - Time allocation studies & GPS tracking Primatology: macaque movement & infection - Transect observations - Phenology - GPS collars for movement and roosting patterns

5 Case control Oct 2012 to Jan P. knowlesi cases & 683 controls Cases predominantly adult males but >10% in those under 15 years and several household clusters Increased risk Activities near forest edge (e.g clearing), Male farmers & plantation workers, Travel to work/school in late afternoon, Villages where monkeys are more commonly seen, Sleeping outside when travelling Decreased risk Sparse secondary forest around house (no thick forest), Indoor residual spraying, G6PD deficiency Demonstrated for the first time asymptomatic (subpatent) carriage of knowlesi ~6% in household members of cases (women and children) Fornace et al JID 2015

6 Land use classification: broad scale Maps represent forest cover over time and village level microscopy records Significant correlations with proximity to forest and recent forest loss Fornace et al EID 2015

7 Land use classification: fine scale 1. Site selection and characterisation for detailed studies 2. Stratification of forest cover for village selection large cross section survey in phase 2 - Extended questionnaire - Biological assessment of infection and exposure to infection

8 Land use classification: fine scale Using drones to characterise land/land use Object oriented image processing using Ecognition Based on spectral signature and textures and relationship to other areas

9 Primatology: What is the range of a macaque troop? Where do they roost and in what numbers? Prevalence of infection? Any Seasonal changes in above?

10 Entomology: What is the distribution and abundance of vectors in different land use types? Longitudinal surveillance of 3 sites ~2000 anopheles, 10 different species An.balabacensis primary vector with ~6.5 bites per night (range 2-28) Bite as early as 6pm with ~40% of bites before 9pm Forest Farm Village 3% infected all with primate malarias High parity rate suggesting long survival and thus high transmission potential Abundance Biting time Wong et al 2015 PLoS NTD

11 Social science: Human movement & risk perception Individuals asked to wear GPS trackers for ~2 Different times of year and record when they see monkeys

12 Social science: Human movement & risk perception Participatory mapping using photovoice Focus group discussion identify areas where there is - They see mosquitoes - Perceive risk of malaria - See, hear macaques Potential to identify locally relevant and sustainable control approaches

13 Integrating data Land use classification Entomology: vector species, abundance & infection Infection in humans Cross sectional surveys Multiplex assays for exposure to infection sam Infection in macaques Duration of infection and prevalence from stool genotyping

14 Summary Integrated research & novel methodologies apply not just to malaria but other zoonotic and emerging diseases Accurate spatial data allowing us to pinpoint likely intersections of disease transmission Repeat assessments at frequent intervals to assess temporal effects of regular fluctuations (e.g seasonality of fruiting) or dramatic changes (e.g. land clearing) Infection rates in humans (symptomatic and asymptomatic), mosquitoes and macaques

15 FUNDERS Danau Girang Field Centre Benoit Goossens, Milena Salgado-Lynn, Danica Stark Sabah Wildlife Department Senthilvel Nathan Liverpool School of Tropical Medicine Steve Torr London School of Hygiene & Tropical Medicine Chris Drakeley, Jon Cox, Kim Fornace, Beth Downe Universiti Malaysia Sabah Chua Tock Hing, Kntayya Mariappan, Paul Porodong University of Glasgow Heather Ferguson, Rowland Kao, Paddy Brock Malaysian Ministry of Health, Queen Elizabeth Hospital Timothy William University of Malaya Indra Vythilingam Menzies School of Health Research Nick Anstey, Matt Grigg. Tsin Yeo Bridget Barber University of the Philippines Los Banos Judeline Dimalibot Research Institute for Tropical Medicine Fe Espino, Wilfredo Aure Royal Veterinary College Martha Betson, Julian Drewe University Putra Malaysia Reuben Sharma PARTNERS