Dr George Busby, Dr Isaac Ghinai and Jason Hendry Big Data Institute, Oxford University - Application to the Oxford University Expeditions Council ...
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Dr George Busby, Dr Isaac Ghinai and Jason Hendry Big Data Institute, Oxford University Application to the Oxford University Expeditions Council November 13, 2018
Mobile Malaria Project Expedition Proposal Executive Summary Malaria cases have halved in the last 20 years thanks mainly to better drugs and bednets. This success is, however, fragile. Drug resistance is beginning to spread and we are in danger of becoming complacent. If we are to stop malaria, we need new approaches to monitor the disease so that we can stop its transmission and contain the spread of resistance. We also need to maintain pressure on governments and funding agencies to continue to commit resources, lest the fight against malaria become a victim of its own success. The Mobile Malaria Project is a scientific expedition that aims to document and communicate the past success, current innovations and future challenges to malaria control. We will achieve this by driving coast to coast across Africa, from Namibia to Kenya, in an All New Land Rover Discovery interviewing researchers and recording and documenting our experiences as we travel. It will be a unique record of the state of malaria research in sub-Saharan Africa in 2019. We will also trial the potential for genetic data to be used as a tool to help control and eliminate malaria. We will take the very latest mobile genetic sequencing technology into remote malarial regions of Africa and perform realtime genetic analysis of parasite DNA in the field. For the first time, this will allow scientists on the ground to test new malarial infections for the presence of drug resistance and to understand where they have come from. The Mobile Malaria Project is a collaboration between British and African scientists and a major ambition for the expedition is to raise awareness for the need for scientific training and infrastructure investment in Africa so that future African scientists can perform similar analyses to those undertaken during the expedition. 2
Mobile Malaria Project Expedition Proposal CONTENTS Contents 1 Introduction 5 1.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1.2 Expedition Aims . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 1.3 Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 2 Project Methodology 7 2.1 Itinerary and Route . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2.2 Study timeline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2.3 Documenting and communicating malaria research . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2.4 Mobile genetic sequencing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 2.5 Zambia: sequencing malaria parasites from dried blood spots . . . . . . . . . . . . . . . . . . . . 11 2.5.1 Eligibility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 2.5.2 Recruitment and consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 2.5.3 Collection of samples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 2.5.4 Material transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 2.6 Kenya: sequencing mosquito DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 2.7 Engaging with local scientific communities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 2.8 Statistical methods and analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 2.9 Data management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 2.10 Compliance with guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 3 Expedition Communications 16 3.1 Communicating the science of malaria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 3.2 Our Land Rover Adventure in DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4 Personnel 18 5 Safety and Risk Assessment 20 5.1 Risks of a vehicle-dependent expedition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 5.2 Responding to a potential situation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 5.3 Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 5.3.1 Pre-expedition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 5.3.2 Malaria risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 5.3.3 First aid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 5.3.4 First aid kit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 5.4 Health and Safety in the Mobile Laboratory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 5.5 Insurance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 5.6 Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 5.7 Emergency measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 5.8 Safety Management Plan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 6 Budget and Finances 29 6.1 Projected expenses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 6.2 Sources of income . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 6.2.1 The Royal Geographical Society and Jaguar Land Rover . . . . . . . . . . . . . . . . . . 30 6.2.2 Oxford University . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 6.2.3 Oxford Nanopore Technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 3
Mobile Malaria Project Expedition Proposal LIST OF TABLES 6.2.4 DB Schenker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 6.2.5 what3words . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 6.2.6 Kathmandu clothing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 7 Logistics 31 7.1 Visas and permits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 A Letters of approval and support 36 List of Figures 1 Overview of The Mobile Malaria Project route . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2 The Mobile Malaria Project route with FCO travel advice and OpenStreetMap roads overlaid . . 10 3 Malaria prevalence, topographic and climatic profile of The Mobile Malaria Project route . . . . . 11 4 The onset and end month of the malaria transmission season . . . . . . . . . . . . . . . . . . . . 12 5 Taking a dried blood spot from a capillary blood sample . . . . . . . . . . . . . . . . . . . . . . . 13 6 A 2018 map of political and security risk in Africa . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 List of Tables 1 Proposed Mobile Malaria Project Itinerary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2 Mobile Malaria Project Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2 Mobile Malaria Project Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 2 Mobile Malaria Project Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 3 Proposed Mobile Malaria Project Budget . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 4 Summary of Permissions needed for driving through Mobile Malaria Project countries . . . . . . 32 4
Mobile Malaria Project Expedition Proposal 1 INTRODUCTION 1 Introduction 1.1 Overview Malaria is an infectious disease that is transmitted between humans by mosquitoes. There are four types of malaria that infect humans, but most human disease is caused by two species, Plasmodium vivax and P. falciparum. Together they account for over 400,000 deaths every year, ninety per cent of which occur in Africa [1]. Significant international effort over the last 20 years means that this number is now around half of what it was in the year 2000 [2]. Although malaria transmission is influenced by a number of factors, including climate and land use [3], it is likely that the main contributors to recent reductions in transmission have been human interventions: the widespread use of insecticide treated bednets, which stop infected mosquitoes from biting people and therefore infecting them, and the better use of drugs to treat disease. It is with renewed confidence then, that the global community has articulated a grand plan to eradicate malaria by 2040 [4]. However, there are at least two important sets of challenges to this ambitious proposal. Firstly, the fight against malaria is being prolonged by a lack of sustained financial and political commitment and regional collaboration at the highest levels [5]. Recent progress is fragile and dependent upon continued funding into the generation and application of interventions at scale. The last thing that the global fight against malaria needs now is complacency lest it become a victim of its own recent, yet historically modest [3], success. The second set of challenges relate to the biology of malaria. Just as we are starting to make real gains, the parasite is beginning to fight back, and progress is in danger of being reversed because the parasite is evolving resistance to our drugs and this resistance is spreading [6]. Therefore a crucial part of the global strategy for malaria control is to monitor the spread of antimalarial drug resistance, and identify and contain drug resistant strains when they’re found [7]. On top of this, the dynamics of malaria transmission are complex. For example, as parasite prevalence drops, fewer people are infected, which is clearly a good thing. However, this reduction in malaria endemicity (disease intensity) alters the rules of engagement between people and parasite. In the most endemic settings, many people will be infected by parasites, leading to high levels of asymptomatic infection due to the acquisition of functional immunity that comes from frequent exposure to the parasite. But as endemicity drops, by definition the number of people infected drops which leads to lower levels of natural immunity. Both the spread of drug-resistant infections in endemic regions, and the dynamics of infection in low endemicity settings, can therefore behave more like a disease outbreak. So, to control and eventually eliminate malaria we need to continue to push for financial and political action and develop innovative ways of monitoring parasite and mosquito populations. We need to be able to assess levels of antimalarial drug and insecticide resistance, to understand where resistance first occurs and how it spreads, and to identify how interventions are affecting populations. What we need, in other words, is some sort of surveillance system. A number of different types of data are currently used to understand malaria parasite and vector populations, but none has more potential for inferring key aspects of populations than genomic analysis. DNA sequencing can provide both up-to-date information about which drugs a parasite is resistant to and where a new infection comes from. This is because drug resistance is the result of mutations in the parasite genome, and by comparing an unknown parasite genome to a reference database, we can understand where it comes from. Traditionally, genome sequencing has been expensive and lab-based, and global parasite reference datasets have been unavailable. However, recent advances in mobile genetic sequencing and the development of cloud- based genome analytics with MalariaGEN1 , the largest repository of parasite and mosquito sequence data in the world, mean that we now have the tools to take genetic sequencing into the field and provide the necessary information to malaria control programs, in close to real time. 1 https://www.malariagen.net 5
Mobile Malaria Project Expedition Proposal 1 INTRODUCTION 1.2 Expedition Aims The Mobile Malaria Project will travel from the very edge of malaria transmission in sub-Saharan Africa, through a spectrum of diverse malaria-endemic environments. Along the way we will tell the story of malaria by understanding the challenges of those living with malaria today. We will show how interventions have worked to disrupt transmission and reduce the burden of malaria, but also highlight the need for continued investment in malaria interventions and research. As a team of geneticists, we will also utilise the very latest mobile genetic sequencing technology and test its ability to sequence and analyse parasite genomes in the field. Specifically, our aims are: 1. To convert an off road vehicle into a mobile genetic sequencing laboratory Technological advances mean that it is now possible, although rarely achieved, to perform DNA sequencing in remote regions with minimal equipment. We will convert an All New Land Rover Discovery into a mobile laboratory containing the most up-to-date mobile genetic sequencing technology. 2. To document and communicate the past success, current innovation and future challenges of malaria control in sub-Saharan Africa. We’ll meet and speak with malaria researchers in Namibia, Zambia, Tanzania and Kenya, documenting how malaria has previously been controlled and understand the challenges of future elimination. 3. To trial realtime analysis of malaria samples in the field to assess its potential to provide action- able information. Using our lab in a Land Rover, we will trial Oxford Nanopore Technologies mobile genetic sequencing technology, the MinION, aiming to assess its capabilities for sequencing DNA in remote field locations. 1.3 Objectives To achieve the expedition aims our objectives are: 1. To work with the Royal Geographical Society and Jaguar Land Roverto build a mobile genetic lab. The Mobile Malaria Project is the recipient of the 2018 RGS Land Rover Bursary. We will work with the RGS and Jaguar Land Rover Special Vehicle Operations to build a unique vehicle capable of driving across Africa with genetic sequencing capabilities. 2. To drive 6,300km across Africa. A major challenge of this expedition will be to drive from Namibia on the west coast of Africa to Kenya on the east coast. We will do this in a specially adapted vehicle that will act as transport and mobile laboratory. 3. To visit malaria research laboratories and organisations along the route and document our ex- periences. To ensure that we connect with important labs, our travel strategy is to move between main research hubs in four countries. We will use documentary film, live blogs and vlogs to promote the ex- pedition and raise awareness for the continued financial, political, and scientific commitment to the fight against malaria. We will use our expedition website (www.mobilemalaria.com) as the central content repository for the expedition. 4. To sequence parasite and mosquito DNA in remote regions field locations. Using our mobile se- quencing laboratory, we will set up DNA sequencing facilities at field sites and perform genome sequenc- ing in situ. Until very recently, this was only possible in a complex and large laboratory setting. New technology built by Oxford Nanopore Technologies changes this paradigm. We will use a cheap, portable sequencing machine, with minimal sample preparation requirements, to attempt to sequence parasites and mosquitoes in remote villages. 6
Mobile Malaria Project Expedition Proposal 2 PROJECT METHODOLOGY 5. To explore the use case for genetic sequencing for malaria control. We will understand what in- formation malaria control and elimination programs need to make decisions in the field and learn the potential of our genetic analyses to help. 2 Project Methodology 2.1 Itinerary and Route Our proposed itinerary (Table 1) has been designed to allow us to travel through countries with varying levels of malaria prevalence at a time of year when there is a high incidence of malaria, increasing our chances of finding people with malaria to sample (Figure 1). However, this itinerary is that from our original RGS Land Rover bursary proposal. Whilst it is generally accurate in terms of direction, the timings along the route are subject to change and further refinement in consultation with our collaborators. An overview of the climatic variables that we are expecting along the route is shown in Figure 3. We have currently chosen one or two main stops in each country that split the itinerary into similar sized distance chunks. However, the main towns or villages where we will stop to attempt genetic sequencing are not finalised and will depend on where local collaborators are able to visit. We have begun to fill out intermediate stops between these main waypoints. The route overview was designed with the following objectives in mind: 1. A coast to coast crossing of south central Africa 2. Travel through four countries with different ambitions and strategies for malaria elimination (Table 1). 3. Visits to border posts in Namibia and Zambia, where malaria surveillance is currently undertaken by the Elimination8 initiative and which border additional Elimination8 countries: Angola, Botswana and Mozambique. 4. Avoidance of regions defined by FCO guidance as “Only Essential Travel” or “No Travel” (Figure 2). Visits to collaborators who are members of the MalariaGEN community in Tanzania and Kenya 5. 90% of the route includes roads defined as either ‘Trunk’ or ‘Primary’ by OpenStreetMap (data down- loaded 6 June 2018; Figure 3) 6. Route finishes at KEMRI-Wellcome research institute in Kilifi Kenya. 7. Two 10-14 days sequencing projects in Zambia and Kenya 8. The car shipped will be shipped in mid-February 2019 from the UK to Walvis Bay, Namibia and then shipped back from Mombasa at the beginning of April 2019. 7
Est. drive Leg Dist. Cum. Dist. Drive Field Leg Avg. dist. Leg Latitude Longitude Road Town Cty time (hr: Cum. Days Start Date Finish Date Notes (km) (km) days days total per day mn) C28: drive from 1 -22.959350 14.504119 Walvis Bay Swakopmund NAM 337 5:00:00 337 1 2 3 337 3 20/02/2019 25/02/2019 Swakopmund port to Windhoek B1 north: to Namutoni; 2 -22.566789 17.06668 MEI/E8 HQ Windhoek NAM 540 5:30 877 1 0 1 540 4 25/02/2019 26/02/2019 1 night camp B1: Oshikango border 3 -18.854112 16.925991 Etosha NP Namutoni NAM 209 3:00 1,086 1 2 3 209 7 26/02/2019 03/03/2019 post; 2 days - possible trip into Angola 4 -17.423829 15.926235 E8 border post Oshikango NAM 446 5:00 1,532 1 0 1 446 8 03/03/2019 04/03/2019 C45, B10: to Rundu TransCaprivi Highway: 5 -17.935422 19.734771 Roy's Camp Rundu NAM 403 5:00 1,935 1 1 2 403 10 04/03/2019 07/03/2019 visit to Cambuindi E8 border post 1 night camp in 6 -17.766840 25.187429 Kongola Kongola NAM 112 1:30 2,047 0.5 0 1 112 11 07/03/2019 07/03/2019 Caprivi Mobile Malaria Project Expedition Proposal Bridge to C49: Border crossing 7 -17.503011 24.277816 Katima Mulilo NAM 217 4:00 2,264 0.5 1 2 217 12 07/03/2019 10/03/2019 Zambia into Zambia M10: drive to 8 -17.928365 25.863371 E8 border post Victoria Falls ZMB 334 6:00 2,598 1 0 1 334 13 10/03/2019 11/03/2019 Livingstone M10: drive alongside 9 -16.688096 23.567552 Camp Sioma Falls ZMB 186 3:00 2,784 1 2 3 186 16 11/03/2019 16/03/2019 Zambezi river 8 M10: visit PATH PATH malaria 10 Mongu ZMB 328 5:00 3,112 1 0 1 328 17 16/03/2019 17/03/2019 malaria clinic in centre -15.275266 23.128077 Mongu M9: travel to Kafue 11 Mukambi Lodge Muketa ZMB 275 4:00 3,387 1 0 1 275 18 17/03/2019 18/03/2019 -14.980033 25.981066 NAtional Park M9: to lusaka, visit 12 Lusaka ZMB 300 4:30 3,687 1 2 3 300 21 18/03/2019 23/03/2019 -15.42531 28.33214 PATH HQ collaborators 13 -13.654294 29.391291 Malaria Clinic Mkushi ZMB 353 4:00 4,040 1 0 1 353 22 23/03/2019 24/03/2019 T2: north via Kabwe 14 -11.843462 31.467707 Malaria Clinic Mpika ZMB 383 5:00 4,423 1 1 2 383 24 24/03/2019 27/03/2019 T2: via Kanona 15 Mbala ZMB 299 5:00 4,722 1 0 1 299 25 27/03/2019 28/03/2019 M1: via Kasama Table 1: Proposed Mobile Malaria Project Itinerary. -8.88508 31.368238 Malaria Clinic 2 B345: north, border 16 Camp Mbeya TZA 297 6:00 5,019 1 1 2 297 27 28/03/2019 31/03/2019 -8.912069 33.475433 crossing into Tanzania B345: north to 17 Camp Rungwa TZA 359 6:00 5,378 1 0 1 359 28 31/03/2019 01/04/2019 -6.920835 33.48642 Dodoma, vist collabs A104: to Arusha, visit 18 Hostel Dodoma TZA 422 6:00 5,800 2 0 2 211 30 01/04/2019 03/04/2019 -6.174882 35.796651 clinic A23, A109 to Kilifi, 19 Camp Arusha TZA 426 7:30 6,226 2 2 4 213 34 03/04/2019 09/04/2019 -3.416290 36.653585 cross into Kenya 20 -3.525951 39.927511 KEMRI Kilifi KEN 0 0:00 6,226 1 0 1 0 35 09/04/2019 10/04/2019 finish PROJECT METHODOLOGY
Mobile Malaria Project Expedition Proposal 2 PROJECT METHODOLOGY Figure 1: Overview of The Mobile Malaria Project route. The map shows malaria parasite prevalence (PfPR) across Africa. Hotter colours mean more people infected with malaria. 2.2 Study timeline This study will take place between February and April 2019. Malaria transmission peaks when disease ecolo- gies favour breeding of the Anopheles vector, in Zambia this is the rainy season between November and April (Figure 4). Malaria transmission is highest at the end of this period. The Zambian phase will take place between February and March. In Kenya, the ‘long rains’, which also favour mosquito breeding, occur from April. The study of mosquitos in Kenya will take place in March and April. Sequencing will happen in country, within a week of sample collection. However, analysis of the results may take some time, and we expect full results to be available within one year, and written up for publication within two years (i.e. in 2021). 2.3 Documenting and communicating malaria research Throughout our journey we will collect notes, images and recordings of the researchers that we visit. We are in the process of developing a detailed list of topics to talk about with researchers, but these will centre around what interventions have worked in the past, what innovative techniques and methods people are trialling now, and what are the most important challenges in the future. We will record these experiences and disseminate them through our website, and will work with project partners to share our experiences more widely. We also interested in finding out the story behind the scientists that we meet and will promote their work sharing it with new audiences through our expedition website and other communication channels. 9
Mobile Malaria Project Expedition Proposal 2 PROJECT METHODOLOGY Figure 2: The Mobile Malaria Project route with FCO travel advice and OpenStreetMap roads overlaid. The route avoids areas of south central Africa that the FCO advises against travel to. The map shows the quality of the roads In Angola, Namibia, Zambia, Malawi, Mozambique, Tanzania and Kenya. With the exception of a short stretch of “Secondary” road in Tanzania, all roads in the expedition are classified at “Trunk” (main road with a motorway-like layout which is restricted to motorised vehicles; other than motorways, trunk roads might have crossings or traffic lights) or “Primary” (Major transportation routes between and into major cities within a country. Passable by vehicles with 4 or more wheels, engineered alignment. Motorcycles, bicycles, or foot traffic may be restricted. Indicative info only - can vary. Width: 5 to 20 meter; often paved.) 2.4 Mobile genetic sequencing We will work on two main genetics project during the expedition. In Zambia, we will work with the Ministry of Health and PATH (an NGO) to trial mobile genetic sequencing technology on parasite DNA extracted from dried blood spots. In Kenya, we will work with Dr Eric Ochumu of KEMRI out of Kisumu field research sta- tion. Spending between 10 and 14 days on each project, we will work with our local collaborators to test the equipment’s ability to generate informative data. At all other times and when travelling between these research institutes, we will concentrate on visiting malaria researchers and documenting their work. Our final itinerary is in constant preparation and dependent 10
Mobile Malaria Project Expedition Proposal 2 PROJECT METHODOLOGY Figure 3: Malaria prevalence, topographic and climatic profile of The Mobile Malaria Project route. The top panel shows the change in malaria prevalence along the proposed route. The second panel shows the altitude profile of the route. The third panel shows the average temperature during the first three months of the year (January to March) in black, with the average diurnal range (maximum to minimum temperature) shown in grey. The last panel shows the average rainfall along the route separately for January, February and March. Data for the bottom three panels comes from the worldclim project (www.worldclim.org). upon our leave date, which is TBD based on continued conversations with Jaguar Land Rover. 2.5 Zambia: sequencing malaria parasites from dried blood spots Zambia has a population of around 17 million, about 60% of whom live in rural areas. Almost all live in areas at risk of malaria, though the risk is greatest in rural areas. Despite significant progress in malaria control since the year 2000, there are still over 2 million cases and almost 2,000 deaths due to malaria each year in Zambia. Almost all cases of malaria in Zambia are caused by Plasmodium falciparum. Zambia is aiming to eliminate malaria infection and disease by the end of 2021 [8]. We will sequence P.falciparum DNA from anonymised dried blood spots that are taken routinely for surveil- lance purposes. In Zambia, national guidelines require all patients aged over 12 months with suspected malaria to have 11
Mobile Malaria Project Expedition Proposal 2 PROJECT METHODOLOGY Figure 4: The onset (a) and end (b) month of the malaria transmission season. In regions with two rainy seasons each year, these maps refer the the first season of the year, adapted from http://www.mara- database.org/docs/ENG_MARA_Tech_Rep.pdf. a capillary blood sample taken, by pricking the fingertip (fingerprick; Figure 5), for confirmatory testing by microscopy or rapid diagnostic test. In some parts of the country, an additional dried blood spot is taken from the same fingerprick for routine surveillance (e.g. confirmatory speciation for quality control, genetic analysis etc). We are partnering with PATH, based in Lusaka, who coordinate surveillance using these dried blood spots. For a convenience sample of patients, chosen irrespective of age, gender, clinical features or any other char- acteristic, at the time the fingerprick is taken for diagnosis four additional blood spots will be blotted onto filter paper for DNA analysis. Dried blood spots will be passed to us delinked from any patient identifiable data. 2.5.1 Eligibility All patients over 12 months old presenting to healthcare facilities at partner sites with clinical malaria will be eligible for inclusion in this study. Participants must: • Be over 12 months old • Present to healthcare facilities run by in-country collaborators • Have malaria confirmed by rapid diagnostic test or microscopy • Have a blood spot taken anyway as part of the patient’s routine clinical care/diagnostic process • Have given valid consent for analysis of their samples for surveillance purposes. Participants must not: • Be under 12 months old • unable to consent (e.g. due to language, drowsiness etc) 12
Mobile Malaria Project Expedition Proposal 2 PROJECT METHODOLOGY Figure 5: Taking a dried blood spot from a capillary blood sample, clockwise from top left: (1) A single-use lancet is used to break the skin, (2) a drop of blood forms (at this point, blood would be taken for diagnostic testing, e.g. microscopy or rapid diagnostic test), (3) blood is spotted onto filter paper, (4) three completed dried blood spots. 2.5.2 Recruitment and consent As outlined above, dried blood spots from a convenience sample of patients with clinical malaria will be anal- ysed in this study. Participants will be chosen from amongst patients presenting to healthcare facilities run by engaged collaborators. Informed, oral consent to take a capillary blood sample will be sought by in-country partners in accordance with the usual clinical guidelines in Zambia. This consent is for clinical diagnosis. Additional, oral consent is routinely sought for dried blood spots that are taken (from the same capillary blood sample) for genetic analysis for surveillance purposes conducted by the National Malaria Control Programme. We will be analysing discarded/excess dried blood spots after they have served their primary surveillance purpose. Oral consent follows a discussion with the clinician about the risks and benefits of taking these samples. No written or recorded informational material is used in these discussions beyond that which the clinician deems necessary to achieve informed consent. Consent is documented in the medical notes, but not on specific consent forms. For this study of parasite genetics, no specific consent will be sought as the blood samples are discarded after serving their routine purpose, data will be anonymised and not linkable to humans and no human DNA will be analysed. 13
Mobile Malaria Project Expedition Proposal 2 PROJECT METHODOLOGY 2.5.3 Collection of samples No blood samples will be collected by the Mobile Malaria Project team. Instead, they will be collected by our in-country collaborators, who routinely take capillary blood samples for diagnostic purposes. Dried blood spots will be collected from the same fingerprick as the blood spots for diagnostic purposes. The procedure for taking a dried blood spot from a capillary blood sample is shown below and uses an aseptic, non-touch technique. For this study, we hope to receive four dried blood spots per participant to allow for poor quality samples, damage before reaching the Mobile Malaria Project team, insufficient parasite DNA on extraction and to allow us to run multiple/duplicate analyses if required, however, we acknowledge there may be fewer as these ‘extra’ blood spots will only be taken after collecting all other required clinical samples. We will be driving to clinical facilities where blood spots are collected to perform the genomic analysis from our mobile laboratory on site. 2.5.4 Material transfer The purpose of building the portable laboratory into a vehicle is that the laboratory can reach where it is needed. Therefore, there is no material transfer planned for this study. We envisage driving to remote facilities where the blood spots are collected and running analysis on site. Of note, no blood samples will leave the country of collection. 2.6 Kenya: sequencing mosquito DNA In Kenya, we will sequence DNA from wild-caught mosquitoes. Working with entomological collaborators, we will collect mosquitoes opportunistically using light traps. Subsequently the ethical paradigm for our work there is more relaxed. The expedition leader will travel to Kenya in January 2019 to finalise permissions and ethical approvals and to discuss specific sequencing protocols and sampling locations. 2.7 Engaging with local scientific communities We will meet many researchers and malaria organisations along the expedition route and will engage these communities by listening to documenting their research, thereby fulfilling our communications aim. Within Zam- bia and Kenya we will work with collaborators to ensure this study explores how mobile sequencing capacity can be built, and to begin to understand how our expertise can be shared with collaborators within malaria endemic countries in Africa and to understand the current barriers to the analysis and interpretation of genetic data. Indeed, capacity building for mobile genetic sequencing has been central to the design of the expedition, for example: • We will work on two mobile genetic sequencing projects for 10-14 days to fully trial the technology. • These projects will be co-led with local collaborators who have their own research programs and ques- tions on which the technology can be trialled. • We will conduct both formal and informal teaching sessions workshops describing the technology the potential application of genomics in malaria control and the specific laboratory protocols we have devel- oped. • We will actively to work to identify the social, technological, cultural and political barriers to developing mobile genetic surveillance systems. 14
Mobile Malaria Project Expedition Proposal 2 PROJECT METHODOLOGY 2.8 Statistical methods and analysis This study does not primarily aim to estimate parameters about the population of malaria parasites or mosquitoes in Zambia or Kenya, rather it aims to provide proof of concept that Nanopore sequencing may be a realistic option for more widespread application of Nanopore sequencing in Africa in the future. As such, no formal sample size calculation has been conducted. We are aiming to sequence between 10 and 100 P. falciparum samples in Zambia and a similar number of mosquitoes in Kenya. 2.9 Data management Genomic data will be generated from a MinION, and analysed on a MinIT. The sequencing method used will selectively amplify parasite DNA only, therefore we expect relatively little human DNA to be sequenced. However, despite the selective whole-genome amplification of parasite DNA, early experiments have shown a majority of the sequences generated were human rather than parasites. We will therefore develop a bioinformatics pipeline that automatically aligns all sequenced DNA with an appropriate human reference genome. Any DNA that aligns (i.e. appears to be human) will be automatically sorted (without human oversight or interaction) into a designated folder which will then be immediately deleted. Thus, no human DNA will be visible to the research team to be included in the analysis phase, only parasite DNA will remain. Genome sequence data will be stored on hard drives during the field research and transported back to the UK with the research team. 2.10 Compliance with guidelines All data will be collected and handled in accordance with the appropriate UK, Zambian and Kenyan guidelines and policy, including: 1. All members of the Mobile Malaria Project team will be trained in accordance with the Human Tissue Act (2004), 2. All data will be handled in accordance with the UK’s Data Protection Act and the EU’s General Data Protection Regulations, 3. The Human Rights Act, 4. The Helsinki Declaration, including: • Ethical approval from the University of Oxford Tropical Research Ethics Committee (OxTREC), granted October 22nd 2018, OxTREC reference number 554-18. • Ethical approval from the Ministry of Health, Zambia (letter sent October 2018). • An amendment of existing Kenyan ethical approval (held by our Kenyan collaborator) covering this extended analysis. 15
Mobile Malaria Project Expedition Proposal 3 EXPEDITION COMMUNICATIONS 3 Expedition Communications 3.1 Communicating the science of malaria Crossing the continent will allow us to experience the diverse habitats and environments of south central Africa, all of which are linked by the presence of malaria. The route has been designed to take the team from Namibia, which is close to elimination and aiming to be malaria-free by 2020, through Zambia, which recently cut its deadline for elimination from 2030 to an ambitious 2021, to Tanzania and Kenya, both of which are aiming for elimination in 2030 and where most of the population remains at risk. Such a transect will also allow us to experience and document the successes and challenges of different past elimination strategies, such as the distribution of insecticide treated bednets, the use of artemisinin-based drug treatment regimes and indoor residual spraying to kill mosquitoes. We will also introduce the novel ways that control programs are attempting to tackle these lofty ambitions. These include active case detection, where researchers aim to contain any new malaria case by focusing on halting transmission, so-called “mass drug administration”, where antimalarial drugs are given to everyone in a locale, infected or not, as well as genomic sequencing for drug resistance surveillance, which is our modus operandi. We will document and communicate our experience in the following ways: 1. www.mobilemalaria.com: we will build an expedition website to house all written material: • Blog we will describe the process of expedition planning, aiming to present our experiences in a lighthearted and approachable way. Our expected audience are scientists, interested adults and key stage 3 and 4 schoolchildren. We will interview malaria scientists both in the UK and whilst in the field. • Podcasts we will develop a series of episodes containing interviews with relevant people before and during the trip and will concentrate on using sound as a way of describing our journey. We will borrow the relevant equipment for university communications colleagues. • vlogs we will share a weekly video update from the field with our followers. • Images @mobilemalaria: we will use Instagram to share images and comments from the field. • Twitter @mobilemalaria: we will use Twitter to share images and comments from the field. 2. We will work with Oxford-based nationally available children’s weekly comic, The Phoenix, to develop a series of comic strips about the expedition - “Notes from the field” - and will time these to occur during the expedition. We will use this as an additional way of extending our reach and getting feedback and questions for our podcasts. Expedition leader George Busby has been working with The Phoenix for the last couple of years on a series of features about genetics and evolution, which are due to be published in early 2019, so “Notes from the field” will add an exciting extra dimension to this existing project and provide a direct and innovative way for the expedition to access a young audience. The Phoenix’s mission is to use story to improve literacy, and this project fall clearly within this overarching goal. Contingent on additional funding, there is also a possibility that the pieces about the trip might contribute to a separate book about the expedition which could be published by associated publisher David Fickling Books. 3. We will look for a television production company to commit to making a documentary about the expedition and will aim to train at least one team member to use a film camera. Contingent on successful training in camera use, we will document the trip visually, but will concentrate on podcasts during the trip given our lack of experience editing film. We will consult with Land Rover at all times during this process 4. We will disseminate the results of our experiences across the malaria and genetics research communities at conferences. 16
Mobile Malaria Project Expedition Proposal 3 EXPEDITION COMMUNICATIONS 5. Research and experience during the expedition will contribute to a book about the success and chal- lenges of malaria elimination in the 21st century (currently in preparation by Expedition leader George Busby). As a first step, George will approach national newspapers/magazines to write a series of articles about the project. In addition, our final media plan will be developed in full collaboration and consultation with Land Rover and RGS-IBG. We are fortunate to have support from several sponsors already, each of whom will help promote our trip. We are actively working with the RGS, Jaguar Land Rover, DB Schenke (shipping) and Oxford University Department of Medicine communications teams to develop and integrated dissemination and communications strategy. 3.2 Our Land Rover Adventure in DNA Our expedition represents a twist of Land Rover’s pitch “Adventure. It’s in our DNA”: 1. We will modify the Land Rover Discovery to house a small DNA extraction and sequencing laboratory in the rear, the first such system of its kind. This will be reasonably lightweight, requiring a single pull out work bench, space for a small centrifuge, storage cupboards for genomic analysis consumables and a small fridge freezer to keep a small number of reagents cold. This equipment must be securely installed, taking up the space of the two seats in the third row at the rear of the vehicle. 2. We will use onboard computers to control equipment and, if specifications allow, analyse genomic data generated in this lab. The All New Land Rover’s infotainment system will be used to upload data into the cloud in close to real time. The two main experimental machines can be controlled with a tablet/mobile phone by bluetooth, so we will work to install the relevant apps so that this can be done within the infotainment system. 3. We will install Tracks4Africa, the premier GPS navigation system onto the onboard computer to aid navigation. This is the most up to date source of information about roads and even has locations of petrol stations. 4. We will need novel and innovative ways to generate power to run the analysis equipment and keep a small on-board fridge-freezer cold. Depending on power needs, we will explore installing solar panels on the roof to help power equipment, storing additional batteries that can recharge as we drive or through the solar panels, or potentially carry a small generator. 5. We will use the All New Discovery’s connectivity and ability to install a sim card to speak with our sup- porters and keep connected to followers in the UK and further afield during the expedition. Over 35 days, we will drive 6,300 kilometres across roads of varying quality necessitating the need for a rugged yet comfortable vehicle to access remote regions. 6. We will live in and around the Land Rover, camping in the bush whenever possible. 7. We will be travelling through southern Africa during the wet season. This is necessary as the rain brings water, pools of which are required for mosquitoes to breed and thus transmit malaria. So it will be wet and muddy; the perfect environment to test Land Rover’s All Terrain Progress Control, Wade Sensing and Terrain Response 2 systems. The Mobile Malaria Project will be a challenge to the expedition members, allowing us to forge new col- laborations with African scientists working on the front line of malaria eradication, share their stories, and demonstrate how new technology is helping us move towards a malaria-free future. 17
Mobile Malaria Project Expedition Proposal 4 PERSONNEL 4 Personnel Dr George Busby FRGS Expedition Leader George is a geneticist currently working at one of the world’s best malaria genetics research groups at the Big Data Institute at Oxford University. He has a first class honours degree in Zoology from the University of Edinburgh, an MRes in Ecology, Evolution and Conservation from Imperial College London, and DPhil from Oxford University. In his final year at Edinburgh he led The Lone Wolf Project, an RGS-supported expedition to the Simien Mountains in Ethiopia. As a result, he was elected as a postgraduate Fellow of the Royal Society in 2008 which was upgraded to full fellowship in 2013. George has travelled widely in Africa and Asia, completing three further expeditions to southern Africa, to Malawi on a conservation expedition and to Lesotho and Namibia collecting saliva samples from Khoesan individuals for genetic analysis into human origins. He has published over 20 scientific papers on the genetics of everything from paper wasps to ancient humans. George has a growing portfolio of public engagement projects. He designed a card game to describe the genetics of malaria susceptibility to schoolchildren that is currently being used as teaching aid on Wellcome supported public engagement workshops in Africa. He is currently working with The Phoenix, childrens’ comic in Oxford on a series of animated stories about genetics, and is currently leading the development and produc- tion of an innovative play about the use of genetics and data in our medical future. He has written many articles for popular audiences, including a prize winning entry for Natureblogs and for The Conversation, where he is the 16th most read author from Oxford University, out of over 500 academics. He presented a documentary about ancient DNA for the History Channel in America and has been involved with several television develop- ment projects, including research for Origins of Us for the BBC. His current work in malaria involves developing an innovative web application that aims to visualise and communicate the status of drug resistance in malaria parasite and mosquito populations. This application is built on large reference datasets that have been collected over the last 15 years. However, the full potential of the infrastructure that he is helping to build will only be realised when parasites and mosquitoes are sequenced in the field and this data uploaded into the cloud for realtime analysis. This ambition has the potential to be realised during the Costa Pwani expedition. George will have overall responsibility for the expedition. He will lead the navigation, logistics, stakeholder management, and will oversee the genetic analysis. Dr Eric Ochumu Field Project Co-lead Eric is a mosquito researcher at the Kenya Medical Research Institute. He will co-lead one of the field projects whilst the team is in Kenya. He has published multiple scientific papers on the surveillance of insecticide resistance in Kenyan mosquitoes and will work with the team to trial our new mobile sequencing technology in the field. The team will work with Eric to trial nanopore sequencing technology in Kisumu near Lake Victoria. Dr Isaac Ghinai Expedition Medic Isaac is a doctor and global health researcher. He is currently an Academic Clinical Fellow in public health at Oxford University. He studied International Health at UCL graduating with first class honours, a Deans List 18
Mobile Malaria Project Expedition Proposal 4 PERSONNEL commendation for outstanding academic performance, and the Sessional Prize for highest mark. He qualified with merit from UCL Medical School, winning the Holdstock-Piachaud Prize for Medicine, Conflict and Survival whilst a student. He completed his academic foundation training in London, simultaneously leading a large malaria study in Southeast Asia. He has held honorary and visiting research positions at UCL, the London School of Hygiene and Tropical Medicine and Imperial College Institute for Global Health. His research has spanned HIV, TB, malaria, Ebola, polio and other vaccine-preventable diseases and been published in leading medical journals including Nature, Lancet Infectious Diseases, Global Public Health, Malaria Journal and Philosophical Transactions of the Royal Society. In policy roles, has worked for the World Health Organisation, Chatham House Centre on Global Health Security and the UK All-Party Parliamentary Group on Global Health. He has worked in Kenya, Uganda, Myanmar and the refugee camps in Greece and in 2017, held an NHS ‘Improving Global Health’ fellowship in Cambodia. He has travelled widely across Africa, Europe, South America and Asia, including a 5,000 mile expedition crossing Asia from coast to coast following the ancient Silk Road trading route. As a qualified doctor, Isaac will be the expedition medic and will be expedition health and safety officer. He will run the genetic sequencing technology. He will also maintain the expedition website and lead the team’s communications whilst in the field. Jason Hendry Expedition Scientist Jason is reading for his DPhil at the University of Oxford, the focus of his thesis being to understand the ways in which malaria genetic data can be used to inform the policy decisions guiding malaria control and elimination. He is enrolled as part of the four-year Genomic Medicine and Statistics Programme funded by the Wellcome Trust. Prior to Oxford, he studied biochemistry and the University of Toronto, graduating with an Honours Bachelor of Science with high distinction and a Masters of Science. Cumulatively, Jason has more than five years of experience processing DNA samples and has further expertise in computational and statistical analysis of genetic data. He has spent 3 months backpacking in South America, is an avid rock climber, cyclist, and martial artist. 19
Mobile Malaria Project Expedition Proposal 5 SAFETY AND RISK ASSESSMENT 5 Safety and Risk Assessment We are aware that a driving trip through Africa is not without risk. The map below (Figure 6) shows an up to date assessment of the political and security risk in Africa. We have endeavoured to find a route across the continent that avoids areas of high geopolitical risk but where malaria still occurs. It is no coincidence that the main burden of malaria falls in the more unsafe African countries. Nevertheless, our route accesses some of the safest parts of the continent. A tabular risk assessment is shown in Table 2 Africa Port Sudan Mauritania Nouakchott Mali Cabo Verde Niger Eritrea Khartoum Asmara Dakar Senegal Chad Niamey Sudan Gambia Banjul Bamako Ouagadougou Bissau Kano Ndjamena Burkina Faso Djibouti Djibouti city Guinea-Bissau Guinea Hargeisa Benin Nigeria Conakry Ghana Abuja Addis Ababa Somaliland Freetown Côte Togo Sierra Leone D'Ivoire Ethiopia Yamoussoukro Cotonou Monrovia Lomé Lagos Central African South Liberia Abidjan Accra Republic Sudan Port Harcourt Cameroon Juba Douala Bangui Malabo Yaoundé Somalia Equatorial Guinea Mogadishu São Tomé and Príncipe Uganda Libreville Kampala Congo Congo (Democratic Republic of) Kenya Kismayo Gabon Nairobi Rwanda Kigali Bujumbura Brazzaville Burundi Mombasa Kinshasa Cabinda Tanzania Seychelles (Angola) Zanzibar Mbuji-Mayi Dodoma Dar es Salaam Luanda Comoros Lubumbashi Mayotte Angola Malawi Lilongwe Zambia Lusaka Blantyre Harare Mozambique Antananarivo Zimbabwe Bulawayo Beira Port Louis Madagascar Mauritius Namibia Réunion (France) Windhoek Botswana Gaborone Pretoria Copyright © Control Risks 2017. All rights reserved. Reproduction in whole or in part prohibited without the prior consent of the Company. Johannesburg Mbabane Maputo The Risk Ratings are compiled from sources that Control Risks considers to be reliable or are expressions of opinion. Control Risks has made reasonable commercial efforts to ensure the accuracy of the information on which the Swaziland Risk Ratings are based, however, the Risks Ratings are provided ‘as is’ and include reasonable judgments in the circumstances prevailing at the time. The Risk Ratings provided should not be construed as definitive or binding advice. Boundaries and names shown on this map do not imply endorsement or acceptance by Control Risks. Maseru Lesotho Security risk forecast Political risk forecast Durban South Africa HIGH security in deprived urban areas Very Low Medium High Extreme Low controlrisks.com Very Low Low Medium High Extreme Cape Town Figure 6: A 2018 map of political and security risk in Africa www.controlrisks.com. 5.1 Risks of a vehicle-dependent expedition All expedition members have full clean driving licenses, held for at least three years. We recognise that the group has only modest experience in mechanics or expedition driving. We will be arranging specialist driver training with Jaguar Land Rover in January 2019, in the expedition vehicle, which will include hands-on training in vehicle maintenance and off-road driving. In the field we will use Tracks4Africa GPS, which includes information on roads and petrol stations to plan the safest route. There are recognised risks with a vehicle-dependent expedition including: • Theft from parked cars (we will always lock the car, sleep near it and stay in camps with good perimeter security). • Poor quality roads outside of major cities, particularly in rainy season (need to drive at an appropriate speed aware of the shortcomings of the surface). 20
Mobile Malaria Project Expedition Proposal 5 SAFETY AND RISK ASSESSMENT • Risk of car-jackings and armed robbery (see below). • Punctures common (we will carry 2 spare tyres and 20l of spare water). • No roadside rescue (we have emergency supplies and a satellite phone). Given the risk of carjacking, we have identified measures to reduce vulnerability: • Avoid trouble spots and times, e.g. avoid driving at night (not driving at night also reduces the risk of accidents). • Always travel together (90% happen to people alone). • Keep fuel high and vehicle well maintained to avoid breakdowns (we have ensured the fuel tank has a lock to avoid fuel theft). • Apply a protective, non-breakable coating to the vehicle windows. • Lock doors and windows when driving (and when parked). • Use mirrors to stay vigilant to people approaching or following. • Drive in middle lane (more difficult to target and more easy to escape). • Leave 1.5 car lengths between us and car in-front when stopping at junctions. • Hide valuables at all times. • Don’t buy things from hawkers. • Park in well-lit areas. • Look around the car and inside the car before getting in. 5.2 Responding to a potential situation • We will not stop immediately for minor accidents, people flagging us down, if bumped in the back of the car or if we hit the back of the car in-front after they stop abruptly (these are common tactics to get people to stop). • Instead, we will drive to a safe place (service station, police or fire station) and calling for assistance or deal with the problem there (initially by opening the window a small amount and conversing with the driver). • We will check ID of policemen and keeping engine running at road blocks, and carry spare ID ourselves (passport photocopy). • If attacked, we will not resist. 5.3 Health 5.3.1 Pre-expedition • All expedition members are previously healthy with no medical conditions, no regular medication and no known drug allergies. • All have confirmed their immunisation and past medical history with their GP. 21
Mobile Malaria Project Expedition Proposal 5 SAFETY AND RISK ASSESSMENT • All are also booking appointments with the University Travel Health Clinic two months before the ex- pedition. All expedition members will be vaccinated against yellow fever and hepatitis A (if not already immune) prior to travel, as well as receiving any necessary boosters. 5.3.2 Malaria risk • By definition, the countries that we are travelling through are malaria risk areas. The University travel clinic will dispense antimalarials as required. • Bite-prevention precautions will also be followed including using insecticide, covering arms and legs and avoiding key bite times. • A supply of antimalarials and a tympanic thermometer and rapid diagnostic tests will also be carried (see First Aid Kit) to enable prompt initiation of treatment before rapid transfer to a registered provider if malaria is suspected. 5.3.3 First aid • Isaac is a fully qualified doctor registered with the General Medical Council and a licence to practice in the UK. He is the designated first aider. He has completed 6 months of emergency medicine training, three months of acute medicine and various other hospital rotations as well as training on first aid in the community, basic life support and advanced life support. He has also worked extensively in resource- constrained environments abroad. • George and Jason will undertake training in first aid via the University safety department (Emergency First Aid for Fieldworkers, 4 December 2019). 5.3.4 First aid kit • Simple analgesia (paracetamol, ibuprofen etc) • Oral antihistamines and cream • Antiseptic creams • Oral rehydration solution • Sterile dressings, bandages, slings and safety pins, scissors, tweezers etc. • Sterile packs including sutures, clean needles, cannulae etc. • Tympanic thermometer • Rapid diagnostic tests for malaria and dengue fever. • Antibiotics (amoxicillin, coamoxiclav) • Antimalarial treatment (co-artemether/lumefantrine, “Riamet”) • Post-exposure prophylaxis for HIV We will maintain an up-to-date list of medical centres and hospitals in each country with contact details in case of a need for medical care. Isaac’s cousin (Yasser Darr) is a Kiswahili-speaking Kenyan doctor based at the Aga Khan University Hospital (Nairobi) who has agreed to offer telephone advice and coordinate with Kenyan and Tanzanian medical services if required. 22
Mobile Malaria Project Expedition Proposal 5 SAFETY AND RISK ASSESSMENT 5.4 Health and Safety in the Mobile Laboratory All members of the team will undergo laboratory training in University laboratories in the UK and in the mobile laboratory in the UK before working in the mobile laboratory in the field. All reagents used in the reactions are non-toxic, and safe to be mixed. Only relatively small volumes of liquid reagents will be taken, as we are not anticipating a large throughput of samples for this proof-of-concept study. Reagents will be stored and transported separately, labelled clearly in more than one place. Gloves and other appropriate personal protective equipment will be used when conducting experiments. Spills will be cleaned immediately with absorbent paper. Contact with exposed skin, eyes or mouth will be washed immediately with clean water. We do not anticipate generating a large volume of waste given the relatively small number of samples we intend to analyse in this proof-of-concept study. Liquid waste will be disposed of in the usual way at the clinical facilities we visit. If remote facilities do not have the facility to dispose of the very small amounts of liquid waste we generate, we will transport it in a plastic bottle to a central national facility where this is possible. Solid waste – for example discarded/used dried blood spots – will be disposed of in clinical waste bins in the facilities in which we are working – if there is no working incinerator on site, to avoid burdening our collaborators we will double-bag the clinical waste and transport it in the vehicle to a central national facility where incineration is possible. 5.5 Insurance This expedition will be insured by the University of Oxford. We are in discussions with Graham Waite (Risk and Insurance Manager, Medical Research Services, University of Oxford) to ensure all arrangements are in place for this and that this insurance will be sufficient for all aspects of the trip, including emergency evacuation from remote environments. 5.6 Training In addition to basic first aid training, Isaac and George will attend the University of Oxford Fieldwork Safety Overseas course (9th November 2018). 5.7 Emergency measures • Satellite phone – installed in the expedition vehicle. This will be maintained and tested weekly. We will also pick up local SIM cards and have a local contact in each country who we can contact in the event of an emergency. • Contingency routes – identified around potential natural hazards (e.g. flooding) and major cities (in case of civil unrest). • British Consulates/Embassies. We have already informed British Consulates/Embassies in each country about our trip. We will continue to update them and keep them up to date with progress. • UK liaison / home contact. We have a designated individual in the UK who will be contactable at any time and who can instigate and coordinate the emergency evacuation plan (Angel Busby, angel- busby@gmail.com). • Emergency contacts in Africa – We will arrange a professional contact in Kenya (KEMRI-Wellcome) who can be contacted in the event of an emergency. 23
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