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 ...
Dr George Busby, Dr Isaac Ghinai and Jason Hendry
        Big Data Institute, Oxford University

    Application to the Oxford University Expeditions Council
                      November 13, 2018
Dr George Busby, Dr Isaac Ghinai and Jason Hendry Big Data Institute, Oxford University - Application to the Oxford University Expeditions Council ...
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.

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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 ...
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

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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 ...
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

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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 ...
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

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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 ...
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.

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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 ...
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.

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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 ...
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
Dr George Busby, Dr Isaac Ghinai and Jason Hendry Big Data Institute, Oxford University - Application to the Oxford University Expeditions Council ...
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
Dr George Busby, Dr Isaac Ghinai and Jason Hendry Big Data Institute, Oxford University - Application to the Oxford University Expeditions Council ...
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.

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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.

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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.

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