final event programme - Workspace

Wellcome Centre for
Global Health Research
Annual Meeting
Thursday 13th and Friday 14th November 2014
Event Programme
Introduction
It gives me great pleasure to welcome you all to the 2014 Annual
Scientific Meeting of the Wellcome Trust - Imperial College for
Global Health Research Centre, held here at the Institute of
Mechanical Engineers.
We are thrilled to be celebrating the 19th year of our involvement
in international health. The Wellcome Centre has supported
research in international health since 1995 and its success
is evident by the many clinicians and scientists who received
training through the centre and now hold senior positions both
at Imperial College and at other institutions. The new Centre
for Global Health Research builds on the achievements of the
previous Wellcome Centre for Clinical Tropical Medicine but
also broadens the activities to include partnerships with institutes in Asia, Africa and South
America. These partnerships will encourage the training of fellows from partner countries
as well as a wider focus on both communicable and non-communicable diseases.
We are honoured by the presence from the Wellcome Trust of Dr Mike Turner (Head of
Infection and Immunobiology). None of our activities would be possible without the support
of the Wellcome Trust. We are grateful to them for providing an unrivalled opportunity for
global health research. I would also like to thank our delegates from our overseas partner
institutions for the continued collaborations and making the effort to attend this meeting.
I hope you will all enjoy this meeting and encourage you all to participate fully, stimulating
new ideas, collaborations and friendships in the field of Global Health.
Do remember to join the debate on Twitter using the hashtag #GHWTRC2014.
Professor Michael Levin
Director, Centre for Global Health Research, Imperial College London
Bringing together primary and secondary care data to improve patient care
3
EVENT PROGRAMME
Thursday 13 th November
Registration
08.30
Tea, coffee and networking
SESSION 1
09.00
Welcome: Mike Levin, Director of the Wellcome Trust-Imperial College Centre for Global Health Research
09.15
Mike Turner, Head of Infection and Immunobiology Wellcome Trust
9:30
Centre Manager Peter Norsworthy: Annual update on Global Health Research Centre Activities WT ISSF and other
funding schemes
9:45
Yolande Harley: Collaboration and capacity development between Imperial and the University of Cape Town via its
Clinical Infectious Diseases Research Initiative
10:00
Tara Lindstedt: DREAM Project
10.20 – 11:00
Coffee break
Welcome:
Introduction Wellcome
Trust-Imperial College
Centre for Global Health
research
Coffee break
Chair: Robert Wilkinson
SESSION 2
11:00
Robert Wilkinson: Innate receptor-activated and inflammasome-mediated immunopathogensis of HIV-tuberculosisassociated immune reconstitution inflammatory syndrome
Research into health
problems of the Southern
African Region
11.30
Hanif Esmail: Serum biomarkers for the early detection of tuberculosis in HIV-1 infected adults
11:45
Neesha Rockwood: Pharmacokinetic and bacteriological determinants of pulmonary TB treatment response in a
programmatic setting with a high prevalence of HIV co-infection
12:00
Ashley Jacobs: Generation of Human Monoclonal Antibodies to M. tuberculosis
12:15
Sarah Fidler: HPTN071-PopART trial: A population level implementation trial of the impact of Universal HIV test
and treat on HIV incidence in Sub-Saharan Africa
LUNCH
12:30
Graham Cooke: Advances in HCV treatment and their relevance for global health
12:45 to 14:00
LUNCH
Chair: Tom Williams / Kath Maitland
SESSION 3
East Africa Region
Coffee break
14.00
Kath Maitland: Future trials in severe life threatening illnesses in African Children
14:15
Sophie Uyoga: The Kilifi Genetic Birth Cohort Study
14:30
Peter Olupot-Olupot: The Prevalence, clinical features and outcomes of Dark Urine Syndrome (DUS) among Easte
African Children
14.45
Nchafasto Obonyo: Assessment of myocardial function in critical illness
15.00
Kelsey Jones: Inflammatory bowel disease in Africa: hiding in plain sight?
15;15
Philip Bergin: International AIDS Vaccine Initiative (IAVI)
15:30 to 16:00
Coffee break
Chair: Peter Burney
16:00
Majid Ezzati: A global epidemiological study with 20 million participants
16:15
Peter Burney: Global and Regional Trends in Chronic Obstructive Pulmonary Disease Mortality 1990-2010
16:30
Paiboon Thialand: Community-based screening of opisthorchiasis-associated morbidity and cholangiocarcinoma in
SESSION 4
Global Health Issues
northeast Thailand
Reception
16:45
Narong Khuntikeo: Cholangiocarcinoma Screening and Care Program (CASCAP): an update
17:00
Jutarop Phetchacuranin: The Characterisation of plasma metabolic profiles following bariatric surgery using nuclear
magnetic resonance spectroscopy in obese diabetic rat model
17:15
Richard Syms: High Resolution Internal Magnetic Resonance Imaging of the Biliary Ductal System
17:30 to 18:30
Drinks Reception
Friday 14th November
Registration
08.30
Tea, coffee and networking
Welcome
09.00
Mike Levin
Chair: Beate Kampmann
SESSION 1
West Africa
09.10
Natalie MacDermott: Frontline Ebola: Novel methods in disease containment and reducing transmission – is
community based care the answer?
09.30
Beate Kampmann: Ebola crisis in West Africa- what can science contribute?
09.45
Aubrey Cunnington: Interpretation of individual and population-level responses to malaria in the context of
pathogen load dynamics
10.00
Anna Battersby: The Ontogeny of Innate Immunity in Gambian Infants
10.15
Kirsty Le Doare Mehring: Group B Streptococcus in the Gambia – 20 years on
10.30
Gibril Ndow: Assessment of the burden of liver disease in adults with Hepatitis B and HIV co-infection in The
Gambia
Coffee break
10.45
Serge Yerbanga: A field platform for developing malaria transmission-blocking interventions: Multi-target product
with Drugs, Antibiotics and vaccines
11:00 to 11:30
Coffee break
Chair: Carlton Evans
SESSION 2
11:30
Sumona Datta: Microscopy-based TB treatment response and drug-susceptibility testing
South America
11.45
Tom Wingfield: Combatting poverty-related risk factors for TB disease in Peruvian shanty towns
12:15
Carlton Evans: Addressing social determinants to strengthen TB control
12:45 to 14:00
LUNCH
LUNCH
Chair: Mike Levin
SESSION 3
14.00 to 14:30
Tumani Corrah: Building a better vision for AFRICA together
Capacity Building in
Global Health
Educational
Opportunities
14:30 to 15;00
Debra Humphris: Education links with Imperial College London: A global community of talent
15:00 to 15:20
Paul Seldon: UCT / Imperial Summer School
15:20 to 15:40
Paladd Asavarut: Social foundations of inequality in the developing world
Coffee break
15:40 to 16:10
Coffee break
16:10 to 17:10
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SESSION 4
Global Health
Opportunities
Session
Individual Table
Discussions
Mike Levin or Overseas Partner
Beate Kampmann over Overseas Partner
Robert Wilkinson or Overseas Partner
Majid Ezzati
George Christophides
Maria Gloria Basanez or representative
Carlton Evans
Simon Taylor Robinson
Close meeting
17:10 to 17:20
Mike Levin – vote of thanks
Networking Reception
17:20 – 18:20
Networking Reception
Thursday 13th November
Session 1: Introduction from the Wellcome Trust-Imperial College
Centre for Global Health Research
Mike Turner
Head of Infection and Immunobiology, Wellcome Trust
Dr Turner has been Head of Infection and Immunobiology at The Wellcome Trust since January 2014. The
remit of the department includes all infectious disease and immunology of biomedical and veterinary
relevance. Before that he was at the University of Glasgow, UK where he held Beit and Royal Society
Fellowships before becoming a member of staff; latterly as Professor of Parasitology. He was also at
various times head of division, assistant director of faculty and deputy dean of graduate school. His
research interests focussed on the cell biology, immunology, genetics, genomics and population biology
of trypanosome parasites that cause African sleeping sickness in humans and Nagana in livestock. He
has also worked on the genomics of malaria parasites and the immunoepidemiology of schistosomes.
Peter Norsworthy
Centre Manager, Wellcome Trust – Global Health Research Centre
Annual update on Global Health Research Centre Activities WT ISSF and other funding schemes
The Wellcome Global Health Research Centre at Imperial College was opened 1 year ago as a successor
to the Centre of Clinical Tropical Medicine. Since opening we have continued to support Imperial's
overseas activities and provide guidance and assistance to our fellows. In addition to this we have
forged new links with Khon Kaen University in Thailand and following a successful cholangiocarcinoma
workshop in March 2014, Prof Richard Syms and Dr Chris Wadsworth have secured a Wellcome Trust
Network of Excellence grant to investigate the high resolution internal magnetic resonance imaging of
biliary carcinoma.
The Centre and Imperial's Graduate School are collaborating with the University of Cape Town to
organise a joint summer school in Jan 2015 for 16 Imperial Students and 16 global health fellows.
Taking advantage of Imperial's unique position of having a world class alumni, engineering excellence
and healthcare experts with international reach, we are working with EP Global Energy (MD: Imperial
alumni Tara Linstedt) who have created DREAM (Developing Renewable Energy for Africa and the Middle
East) to install cheap reliable power supplies at various locations where Imperial has research activities.
Tara Lindstedt
DREAM Project Managing Director EP Global Energy
EP Global Energy launched its DREAM (Developing Renewable Energy for Africa and the Middle East)
Initiative to expand its developments further into Africa and Middle East. The premise of DREAM is to
deploy latest “distributed off-grid” hybrid technologies to provide affordable and dependable power at
local community level in collaboration with Healthcare and Education. DREAM Fund 1 will focus on high
investment grade utility scale developments similar to the Tafila Wind Farm in Jordan. DREAM Fund 2
will focus on socially motivated developments that yield lower returns on investment but meet the nonfinancial targets of investors.
The projects proposed in this document will be part of the DREAM 2 Fund, focussing on socially
responsible investments to bring electricity to remote and disadvantaged communities that are in
desperate need of cheap reliable power supply.
Professor Simon Taylor-Robinson and Dr Peter Norsworthy through Imperial’s Wellcome Trust Global
Health Research Centre have identified pilot projects for DREAM 2 around Kilifi in Kenya and also at
Mbale in Uganda, which if successful it is hoped that other projects could be rolled out could be rolled
to other sites e.g. south Sudan where Imperial academics have links.
Yolande Harley
CIDRI, University of Cape Town
Collaboration and capacity development between Imperial and the University of Cape Town via its
Clinical Infectious Diseases Research Initiative
Health Sciences contribute greatly to the University of Cape Town’s (UCT’s) impact as an internationally
recognised, locally relevant, African institution. UCT ranked 48 of ‘clinical, pre-clinical and health’
universities globally in the 2014/2015 Times Higher Education Rankings. Research collaboration with
Imperial contributes to UCT’s impact in tackling health problems of low- and middle- income countries
(aligned with Aim 1 of the Wellcome Trust- Imperial College Centre for Global Health Research (WTImperial CGHR)) and developing African research capacity (Aim 2).
Between 2009-2013, UCT co-published with 2090 institutions (SciVal; export 24/10/2014). Imperial is
UCT’s 12th most common collaborator by number of co-authored publications (213). Of the 12, Imperial
co-authored publications generated the highest citations per publication (44.3; range 8.6-44.3) and
highest field-weighted citation impact (8.34; 1.33-8.34). The latter metric for UCT/Imperial co-authored
publications is higher than for the institutions individually (1.74 and 2.06, respectively). The majority of
collaboration is in health research. The foremost links are through researchers affiliated with UCT’s
Clinical Infectious Diseases Research Initiative (CIDRI).
Established in 2008 via a WT Strategic Award, CIDRI develops research capacity and promotes scientific
collaboration in Southern Africa. CIDRI has provided and administered 38 research entry awards,
invested in laboratory facilities, strengthened clinical research facilities in Khayelitsha (where >150
publications have arisen from collaborative work), and encouraged regional collaboration and training
via 14 scientific meetings and workshops. Contributions towards policy and practice include a trial of
isoniazid preventive therapy in HIV-infected persons on ART, transcriptomic profiling to develop a TB
disease biosignature, research into association between vitamin D deficiency and HIV-TB, definitive
studies on HIV-TB immune reconstitution inflammatory syndrome, and an influential TB diagnostic study
of Gene Xpert.
Session 2: Research into health problems of the Southern African
Region
Robert Wilkinson
Professor in Infectious Diseases (Imperial College London)
Principal Investigator: Honorary Prof R. J. Wilkinson UCT
Wellcome Trust Senior Fellow in Clinical Tropical Medicine
MRC Programme Leader, National Institute for Medical Research, London
Innate receptor-activated and inflammasome-mediated immunopathogensis of HIV-tuberculosisassociated immune reconstitution inflammatory syndrome
Rachel PJ Lai 1,8, Graeme Meintjes 2,3,8, Katalin A Wilkinson1,2, Christine M Graham4, Suzaan Marais2, Helen
Van der Plas2, Armin Deffur2, Charlotte Schutz2, Chloe Bloom4, Indira Munagala5, Esperanza Anguiano5,
Rene Goliath2, Gary Maartens2, Jacques Banchereau5, Damien Chaussabel6, Anne O’Garra4,7 and Robert J
Wilkinson 3,1,2
Patients with HIV-associated tuberculosis (TB) can undergo hyperinflammation, clinically known as
immune reconstitution inflammatory syndrome (IRIS), following the commencement of antiretroviral
therapy (ART). No reliable prognostic markers or predictive biomarkers for TB-IRIS have been identified
and little is known about the mechanism mediating hyperinflammation. We prospectively recruited a
cohort of 63 patients with HIV-associated TB commencing ART, 33 of whom developed TB-IRIS.
Transcriptomic profiling was performed longitudinally using whole blood RNA samples from 15 non-IRIS
and 17 TB-IRIS patients.
Blood transcriptomic signatures characterizing patients who eventually developed IRIS were identified
as early as 2-5 days post-ART initiation and predicted downstream activation of proinflammatory
cytokines. At the characteristic time of onset of TB-IRIS (week 2), the signature was characterized by
overrepresentation of innate immune mediators including Toll-like receptor signaling and TREM-1
activation of the inflammasome.
Inhibition of the MyD88 adaptor decreased cytokine production in the peripheral blood mononuclear
cells (PBMC) of TB-IRIS patients, but had no effect in the non-IRIS controls. Concentrations of Caspase-1
and Caspase-5 were significantly higher in the PBMC of TB-IRIS patients and inhibition of group 1
caspases reduced proinflammatory cytokine secretion from PBMC, particularly in patients with TB-IRIS.
Together, these data provide insight into the pathogenesis of TB-IRIS, and give pointer for the
development of specific therapies.
1
Division of Mycobacterial Research, MRC National Institute for Medical Research, London, NW7 1AA, UK
Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine and Department of
Medicine, University of Cape Town, Observatory 7925, South Africa
3
Department of Medicine, Imperial College London, W2 1PG, UK
4
Division of Immunoregulation, MRC National Institute for Medical Research, London, NW7 1AA, UK
5
Baylor Institute for Immunology Research, Dallas, Texas, United States of America
6
Systems Immunology, Benaroya Research Institute, Seattle, Washington, United States of America
7
Department of Medicine, National Heart and Lung Institute, Imperial College, London, W2 1PG, UK
8
These authors contributed equally to this work
2
Hanif Esmail
Wellcome Trust Clinical Research Training Fellow completed (2014) at Imperial College London and
University of Cape Town
Serum biomarkers for the early detection of tuberculosis in HIV-1 infected adults
Esmail H1,2, Wilkinson KA1,2,3, Lesosky M4, Lai RP3, Graham CM3, Oni T1, Warwick JM5, Walzl G6, Young
DB2,3, Barry CE 3rd7, O’Garra A3, Wilkinson RJ1,2,3
Affiliations
1. Clinical Infectious Disease Research Initiative, IDM, University of Cape Town, South Africa
2. Division of Medicine, Imperial College London, Norfolk Place W2 1PG, United Kingdom
3. Medical Research Council National Institute for Medical Research, London NW7 1AA, United Kingdom
4. Department of Medicine, University of Cape Town, South Africa
5. Division of Nuclear Medicine, Stellenbosch University, South Africa
6. Division of Molecular Biology and Human Genetics, Stellenbosch University, South Africa
7. Tuberculosis Research Section, NIAID, NIH, Bethesda, USA
Background
The early detection of active tuberculosis (TB) could improve outcome and reduce transmission.
However, the available screening tools have considerable limitations, especially in HIV infected
persons.
We aimed to identify serum biomarkers for subclinical TB, based on early evidence of active disease
detected by [18F]-fluoro-2-deoxy-D-glucose combined positron emission and computed tomography
(FDG-PET/CT), in asymptomatic HIV-1 infected adults.
Methods
35 asymptomatic, anti-retroviral therapy (ART) naïve, HIV-1 infected adults living in Khayelitsha, South
Africa, with a positive QuanitiFERON Gold-in-tube and no history of TB underwent FDG-PET/CT.
Structured reporting identified FDG-PET/CT abnormalities consistent with subclinical TB. Blood was
drawn for RNA and serum from the 35 participants and 13 age, sex and CD4 count matched active TB
controls. Transcriptional signatures were determined by microarray and then used to select 45 serum
analytes, measured by multiplex assay and ELISA. Classification and Regression Tree (CRT) analysis was
used to identify cut-offs for combinations of analytes that distinguished those with active or subclinical
TB from those with no evidence of disease activity.
Results
Of the 35 asymptomatic participants (median CD4 count of 517/mm3, viral load (VL) 10800 copies/mL,
age 31 years, 91% female), 10 had evidence of subclinical TB on FDG-PET/CT and 25 had no evidence of
disease activity. The 13 active TB controls had no significant differences in clinical characteristics other
than elevated VL. CRT analysis determined a combination of cut-off values for IP-10, IL-5, IFN-γ, TNF-α,
IL-1α and CCL-23 that correctly identified the 23 participants with active and subclinical TB,
misclassifying only a single person with no evidence of disease activity.
Conclusions
A combination of 6 serum analytes may successfully distinguish HIV infected persons with early
evidence of active TB. These biomarkers may have the potential to translate to a low cost screening tool.
Neesha Rockwood
Imperial College Global Health Fellow and Trainee in HIV/Genitourinary Medicine
Pharmacokinetic and bacteriological determinants of pulmonary TB treatment response in a
programmatic setting with a high prevalence of HIV co-infection
Tuberculosis (TB) remains the foremost cause of death in HIV-infected individuals in Africa. In a
programmatic setting, it is proposed that a proportion of individuals with baseline rifampicin sensitive
M. tuberculosis (MTB), will fail to culture convert and some may develop drug resistance. The literature
contains data from hollow fibre models showing that variability in antitubercular drug concentrations is
responsible for acquired drug resistance, even in the context of optimal adherence. There is
inconclusive evidence from clinical cohorts assessing the role of low serum drug concentrations and
varying MTB susceptibility on treatment outcomes. In this talk, I will describe a prospectively recruited
cohort of 308 (62% HIV co-infected) patients from Khayelitsha township, and their treatment outcomes
at 2 and 5 months. Intensive sampling pharmacokinetic (PK) studies, with corresponding minimum
inhibitory concentration (MIC) determination, were carried out on a sub-cohort of 100 patients. Nonlinear mixed effects modelling was carried out to determine area under the concentration-time profile
(AUC) and peak concentration (Cmax) for drugs rifampicin, isoniazid and pyrazinamide, the preliminary
results of which will be presented.
Dr. Neesha Rockwood: Clinical Research Fellow and PhD candidate, Imperial College, London and the
Clinical Infectious Diseases Research Institute, University of Cape Town, South Africa.
Ashley Jacobs
Imperial College Wellcome Trust ISSF Fellow
Generation of Human Monoclonal Antibodies to M. tuberculosis
A growing body of evidence has highlighted the potential role of antibodies in the development of novel
vaccination, treatment and rapid diagnostic strategies in tuberculosis. Newly described mechanisms of
how antibodies synergize with cellular immunity through intracellular effects mediated by Fc-receptors
have been shown in animal models to be relevant to tuberculosis. Transcription signatures of TB
patients have consistently found the human high-affinity antibody receptor FCGR1A gene to be actively
transcribed independent of HIV infection status. Monoclonal antibodies have already shown promise in
rapidly identifying M. tuberculosis in clinical specimens. Previous methods of producing antibodies to
M. tuberculosis have relied on lower-yield techniques developed in the past three decades. Here we
propose the utilization of a new molecular cloning technique to develop a panel of fully human
monoclonal antibodies from South African TB patient samples. The potential of these antibodies will
then be explored by mapping of their epitopes and functions.
Sarah Fidler
Senior lecturer Imperial College London and Honorary Consultant NHS consultant Imperial College NHS
Trust
HPTN071-PopART trial: A population level implementation trial of the impact of Universal HIV test
and treat on HIV incidence in Sub-Saharan Africa
HPTN052 study demonstrated the dramatic efficacy (96%) of ART to prevent HIV transmission between
HIV serodiscordant couples. Based on this observation mathematical models estimate that a strategy of
universal HIV testing and treatment (UTT) could significantly impact population level HIV incidence.
However, in order to convey a significant impact at a population level, extremely high coverage of the
UTT approach is required. How this can be achieved and at what possible risks and costs remain
unknown. The HPTN071 community randomised trial aims to address this question.
HPTN071-PopART; a community randomised trial in 21 urban and rural communities in Zambia and S
Africa commenced in January 2014. The total community population is estimated at 1.2million
individuals across both countries. Communities have been randomised into one of three arms; Current
standard of care, a universal testing strategy through household interventions delivered by a novel
cadre of “Community health care provider (CHiPs) with ART initiation according to current National
guidelines, and a full intervention package with CHiPs with universal offer of ART irrespective of CD4
count threshold.
The community based combination intervention includes; Household based sex and HIV prevention and
treatment education, HIV testing, TB and STI symptom screen and treatment where appropriate, referral
to male circumcision and PMTCT services, antenatal and post natal care, with support for linkage to
care, ART adherence. The study outcome will be measured through a separately enrolled randomly
selected population cohort of 50,000 individuals over 3 years.
There have been multiple challenges to starting the study, all of which are relevant to future “roll out”.
Infrastructure was built, capacity increased, ART drug procurement was undertaken to prevent stock
outs, staff were recruited and trained and community engagement and mobilisation was critical. The
intervention is delivered in close partnership with DoH funded through in country PEPFAR programs.
Mathematical modelling using trial data will inform the projected impact of the intervention. Cost
effectiveness will be an important secondary study outcome.
Graham Cooke
Clinical Senior Lecturer in Infectious Diseases, Imperial College London
Advances in HCV treatment and their relevance for global health
There are dramatic changes taking place in relation to Hepatitis C treatment which are beginning to
transform treatment in the NHS. Newer treatments have the potential to overcome many of the
traditional barriers to care in less well resourced settings. The impact of vrial hepatitis globally will be
discussed as well as the particular importance of HIV/HCV in sub-Saharan Africa.
Session 3 - East Africa Region
Kathryn Maitland
Professor of Tropical Paediatric Infectious Diseases, Imperial College London
Future trials in severe life threatening illnesses in African Children
Over the past 15 years her research group has highlighted the unique importance of emergency-care
research as a highly-targeted and cost-effective means of tackling childhood mortality in resourcelimited sub-Saharan Africa, previously neglected as an area for specific funder or policy investment. In
the next 5 years her group will investigate transfusion and other treatment strategies in 3900 African
children with severe life-threatening anaemia (TRACT trial) and oxygenation strategies in 4800 severely
ill African children (COAST) with pneumonia. An overview of these trials will be presented at the meeting.
Sophie Uyoga
Post Doctoral Researcher KEMRI; Wellcome Trust
Part-time lecturer at the School of Pure and Applied Sciences, Pwani University College, Kilifi, Kenya
The Kilifi Genetic Birth Cohort Study
The Kilifi Genetic Birth Cohort Study was established in 2006 with the objective of investigating the
natural history of red cell genetic polymorphisms in the population of Kilifi, Kenya.
Sixteen thousand children who were born within the area served by the Kilifi Health and Demographic
Surveillance System between 2005-2008 were recruited at 3-12 months of age. Heel prick samples were
collected at recruitment and used to phenotype or genotype for a range of haemoglobinopathies, blood
group typing and for quantification of red cell surface complement receptor 1 expression.
The impact of these different genetic polymorphisms on survival and disease-specific admission to
hospital has been explored by linkage to data from the Kilifi Health and Demographic Surveillance and
hospital surveillance systems. Through this presentation I will present data regarding the health impact
of a range of polymorphisms among members of this cohort. Peter Olupot Olupot
Clinical Epidemiologist, Paediatric Infectious Diseases (PID) Department of Paediatrics / Research Unit,
Mbale Regional Referral Hospital
The prevalence, clinical features and outcomes of Dark Urine Syndrome (DUS) among East African
children
Peter Olupot-Olupot1,2, Charles E. Engoru3, Sarah Kiguli4, Rita Muhindo1, Julius Nteziyaremye1, Martin
Chebet1, Sophie Uyoga5, Alex Macharia5 Elizabeth Russell George6, Thomas N. Williams5,7 and Kathryn
Maitland5,7
Affiliation
1 Mbale Regional Referral Hospital Clinical Research Unit, 2 Busitema University Faculty of Health
Sciences, Mbale Campus, 3 Soroti Regional Referral Hospital, 4 Makerere College of Health Sciences,
Department of Paediatrics, 5 Kenya Medical Research Institute/ Wellcome Trust Research programme, 6
Medical Research Council, Clinical Trials Unit, UK, 7 Imperial College, UK.
Abstract Background
In a recent clinical trial (Fluid Expansion as a Supportive Treatment; FEAST), an unexpectedly high
proportion of participants presented with blackwater fever (BWF), a condition rarely reported in African
children. Local investigators report that childhood BWF was rare until recently but that cases have been
rising during the last 5 years.
Methods and findings
We describe the prevalence, clinical characteristics, and outcome of BWF among FEAST trial
participants. Clinical and laboratory data were compared among participants presenting with (cases)
and without a clinical history of dark urine (controls) to the two hospitals (Mbale and Soroti), in Eastern
Uganda where prevalence was highest. Additionally, we compared the prevalence of a number of
malaria-associated red blood cell genetic polymorphisms among cases and a group of population
controls with a view to investigating the possible role of malaria in the aetiology of BWF in the study
population. Of 394/3,170 (12.4%) of FEAST trial participants with clinical history of haemoglobinuria,
318(81.0%) presenting to Mbale and Soroti hospitals in Eastern Uganda, were subjected to more
detailed analysis. 256/318 cases (80.5%) were clinically jaundiced and 238/310 (77%) had severe
anaemia (Hb<5g/dl). Compared to FEAST controls, cases were older [median age 36 months (IQR 26,56)
versus 22 months (IQR 13, 36); p<0.001], had lower admission haemoglobin concentrations [3.7g/dl (IQR
2.9, 4.8) versus 7.1 g/dl, (IQR 4.3, 9.7); p<0.001], and a higher prevalence of acute renal injury (blood
urea nitrogen >20mmol/L) (65.8% versus 38.6%; P<0.001). Plasmodium falciparum parasitaemia was
lower in cases (49%) than controls (63%; p<0.001), but a higher proportion of cases (192/246; 78.0%)
than controls (811/1154; 70.3%; p=0.014) were positive for P. falciparum Histidine Rich Protein-2
(PfHRP2), suggesting parasite clearance secondary to recent anti-malarial treatment. In keeping with
other studies showing malaria protection of inherited red cell disorders we found the prevalence of both
+thalassaemia was significantly lower among cases than population controls. G6PD
HbAS and of 
deficiency was not significantly different between cases 15/224 (15.6%) compared to controls 53/489
(10.8%).
Conclusions
We report an unexpectedly high prevalence of BWF associated with recent treatment for malaria among
children recruited to the FEAST study at two hospitals in Eastern Uganda. Further studies investigating
the possibility of the link between artemesinin based combination and BWF are urgently needed.
Nchafatso Obonyo
Research Fellow 2013/2014, Centre for Global Health Research, Imperial College, London, UK
Kenya Medical Research Institute/Wellcome Trust Research Programme, Kilifi, Kenya
Assessment of myocardial function in critical illness
MAPS Study (Management of Paediatric Shock)
WHO guidelines recommend large and rapid fluid boluses for the management of shock in children.
Whilst a common practice in the rest of the world, this management strategy is not based on any clinical
trial data and the evidence for its effectiveness is weak (Dellinger 2C). The FEAST (Fluid Expansion as
Supportive Therapy) trial, the only randomised controlled trial of fluid resuscitation demonstrated that
fluid boluses lead to excess mortality in children in the bolus arms, with further analysis indicating that
the adverse effects of fluid boluses resulted from excess myocardial and haemodynamic (shock) events.
These data raise questions on effectiveness of this intervention in children with shock in other
populations but also in other conditions where boluses are recommended. The MAPS study is a
prospective, observational study examining cardiac physiology and haemodynamic changes in children
with gastroenteritis (excluded from FEAST) receiving aggressive fluid replacement recommended by
WHO and children with septic shock, now receiving maintenance-only fluids following FEAST.
Kelsey Jones:
KEMRI-Wellcome Trust Research Programme, Kenya
Imperial-Wellcome Centre for Global Health Research and Section of Paediatrics, Imperial College,
London, UK
Inflammatory bowel disease in Africa: hiding in plain sight?
Kelsey DJ Jones,1,2* Barbara Hünten-Kirsch,3 Ahmed MR Laving,4 Caroline W Munyi,3 Moses Ngari,1 Jenifer
Mikusa,1 Musa M Mulongo,1 Dennis Odera,1 H Samira Nassir,3 Molline Timbwa,1 Moses Owino,5 Greg
Fegan,1,6 Simon H Murch,7 Peter B Sullivan,8 John O Warner,2 James A Berkley.1,6
1. KEMRI-Wellcome Trust Research Programme, Kenya
2. Imperial-Wellcome Centre for Global Health Research and Section of Paediatrics, Imperial College,
London, UK
3. Baraka Health Centre, German Doctors Nairobi, Kenya
4. Department of Paediatrics and Child Health, University of Nairobi, Kenya
5. Ministry of Health, Government of Kenya
6. Centre for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine,
University of Oxford, UK
7. Warwick Medical School, University of Warwick, UK
8. Department of Paediatrics, University of Oxford, UK
Background
A syndrome of growth failure, developmental delay and persistent diarrhoea with chronic intestinal and
systemic inflammation is almost ubiquitous amongst African children living in poverty. Intestinal
inflammation has been conceptualised as an adaptive response to high levels of pathogen exposure
inevitably encountered by children living without access to basic sanitation facilities, and growth failure
tends to be considered the result of ‘malnutrition’, although the syndrome is refractory to nutritional or
hygiene-based interventions. Has an excessive focus on such putative environmental determinants
blinded us to how much this syndrome looks like inflammatory bowel disease (IBD)? Could an aberrant
or over-exuberant host inflammatory response be a potential target for therapy in these children?
Methods
Double-blind randomised placebo-controlled trial of the use of mesalazine (a gut-specific antiinflammatory/immunomodulatory agent commonly used in IBD) alongside nutritional rehabilitation in
severely malnourished children living in an urban slum in Kenya. Primary outcomes were safety and
acceptability of the intervention.
Results
Treatment with mesalazine was safe: There was no excess of adverse events, evidence of deterioration
in intestinal barrier integrity, or impact on nutritional recovery. There were modest reductions in several
inflammatory markers with mesalazine compared to placebo.
Conclusions
Intestinal inflammation in malnourished African children is non-essential for mucosal homeostasis and
is at least partly maladaptive. It should be considered an inflammatory bowel disease. Host response is
a rational target for therapy and understanding the immunopathology of living in poverty is a key
research priority.
Philip Bergin
International Aids Vaccine Initiative, Human Immunology Laboratories, Imperial College London
Session 4: Global Health Problems
Majid Ezzati
Chair in Global Environmental Health, Imperial College London
A global epidemiological study with 20 million participants
Peter Burney
Chair in Respiratory Epidemiology & Public Health, Imperial College London
Global and Regional Trends in Chronic Obstructive Pulmonary Disease Mortality 1990-2010.
Background
Chronic Obstructive Pulmonary Disease (COPD) moved from fourth to third commonest cause of death in
the world between 1990 and 2010.
Methods
Using data from the Global Burden of Disease programme we quantified regional changes in number of
COPD deaths and COPD mortality rates between 1990 and 2010. We estimated the proportion of the
change attributable to gross national income/capita and an index of cumulative smoking exposure, and
quantified the difference in mortality rates attributable to demographic changes.
Findings
Despite a substantial decrease in COPD mortality rates COPD deaths fell only slightly, from 2,995,058 in
1990 to 2,837,877 in 2010 because the mean age of the population increased. The number of COPD
deaths in 2010 would have risen to 5,231,916 if the age-sex specific mortality rates had remained
constant. Changes in smoking led to a small increase in age-sex specific mortality rates, which were
strongly associated with changes in gross national income.
Interpretation
The increased global burden of COPD mortality was mainly driven by changes in age distribution, while
age-sex specific COPD mortality rates fell in proportion to rising incomes. Changes in smoking have been
limited, with falls in some areas offset by increases in others. The immediate response to changes in
national wealth suggests that the link between COPD mortality and poverty is not simply reflecting
conditions in early childhood.
Paiboon Sithithaworn
Liver fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University
Community-based screening of opisthorchiasis-associated morbidity and cholangiocarcinoma in
northeast Thailand
Paiboon Sithithaworn, Watcharin Loilome, Puangrat Yongvanit, Nitaya Chamadol, Narong Khuntikeo
Morbidities in asymptomatic opisthorchiasis cover of a range of hepatobiliary diseases (HBD) as well
ascholangiocarcinoma (CCA). In the past, the frequency of these abnormalities was determined by
abdominal ultrasonography correlated with intensity of Opisthorchis viverrini infection and the patient’s
age and sex. Based on tumor registry data, northeast Thailand has the world highest incidence of CCA,
with incidences of up to 150/100,000. However, whether these data reflect the current community-based
incidence of CCA is not known. Several strategies have been employed for the recruitment of the sample
population in order to estimate the community-based data by ultrasonography examination but the
results have been inconsistent. Based on the existing risk factors of HBD and CCA, a set of inclusion
criterion was established and applied for the morbidity screening of villagers in an endemic community
in Khon Kaen, northeast Thailand. The inclusion criterion included: age 40 years onward, history of
opisthorchiasis, member in the family with liver cancer and history of praziquantel treatment. Using this
recruitment approach we have discovered considerable morbidities, including 18% of HBD, and
approximately 1% of CCA or (1000/100,000). Further study based on a larger population in a wider
endemic area is required to validate this screening strategy.
Narong Khuntikeo
Liver Fluke and Cholangiocarcinoma Research Center, Faculty of medicine, Khon Kaen University, Khon
Kaen, Thailand
Cholangiocarcinoma Screening and Care Program (CASCAP): an update
Narong Khuntikeo, Watcharin Loilome, Puangrat Yongvanit, Nitaya Chamadol and Bandit Thinkhamrop
Cholangiocarcinoma (CCA) is a bile duct cancer caused by liver fluke (Opisthorchis viverrini) infection
with a very high fatality rate. There are an estimated 14,000cases annually in the northeast Thailand
with a late stage five year survival of less than 10%.The Cholangiocarcinoma Screening and Care
Program (CASCAP) aims at screening 150,000 individuals using ultrasonography in order to provide a
high quality database on CCA in the endemic region, to determine the optimal screening program for
early diagnosis and to maximize the success of surgical treatment, thus increasing both the patient’s
quality of life and chances of long-term survival. Online consultation is part of the larger scheme called
CASCAP Tools, whichis accessible free of charge to public and private hospitals. The surveillance system
stores both information regarding risk factors of CCA and ultrasonography imaging data. For the patient
group, CASCAP Tools follows the treatment and success of the medical intervention. Both types of
information are regularly updated over 6- and 12-month intervals for individuals whose ultrasonographic
findings were positive and negative, respectively. Six months after the launch of CASCAP Tools, there
were more than 75,000 individuals enrolled into the risk group for further screening. More than 45,000
have received an ultrasonography examination and more than 500 cases of CCA have been detected for
confirmation and treatment.
Jutarop Phetchacuranin
Currently a PhD student Imperial College London from Khon Kaen University Thialand
The Characterisation of plasma metabolic profiles following bariatric surgery using nuclear
magnetic resonance spectroscopy in obese diabetic rat model
Obesity is an epidemic medical health condition in which fat accumulation increases to the extent that
health is adversely affected through the development of comorbidities. Approximately 1.5 billion adults
over the age of 20 and 43 million children under the age of five are over-weight (Body Mass Index [BMI]
>25 kg/m2) and 500 million are clinically obese (BMI>30 kg/m2). High energy is derived from dense foodenergy intake, in combination with markedly low physical activity, leading to excess energy storage and
ultimately obesity. Although lifestyle modification is simply and commonly used to reduce weight
among obese individuals, it has not yet to be reported for substantial long-term outcomes – insufficient
weight reduction and inadequate reduction in obesity-associated complications. Instead, bariatric
surgery provides dramatic and sustained weight reduction in morbid obese patients and resolution of
type 2 diabetes mellitus. In this study, Roux-en-Y gastric bypass (RYGB) was performed in a rat model
compared with sham-operated and calorie-restricted controls. Plasma samples were collected and
analysed using nuclear magnetic resonance (NMR) spectroscopy. Results showed that RYGB alters
plasma metabolic profiles and indicates the reduction of insulin resistance-associated metabolite
levels. In addition, RYGB operation and caloric restriction exhibited different metabolic profiles.
However, further correlation analysis involving body weight and insulin resistance should be conducted
in order to obtain better understanding of mechanism underlying RYGB operation.
Richard Syms
EEE Dept, Optical and Semiconductor Devices Group Imperial College London
High Resolution Internal Magnetic Resonance Imaging Of The Biliary Ductal System
Richard Syms a, Ian Younga, Evi Kardoulakia, Simon Taylor-Robinsonb, Chris Wadsworthc, Marc Read,
Nittaya Chamadole and Wuttisuk Boonpongsathaine
EEE Dept., Imperial College London, Exhibition Road, London SW7 2AZ, UK
St. Mary’s Hospital, South Wharf Road, London, W2 1PG, UK.
cHammersmith Hospital, Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 OHS
dDepartment of Radiology, Imperial College Healthcare NHS Trust, Paddington, London, W2 1NY
eDepartment of Radiology, Khon Kaen University, Khon Kaen, Thailand
a
b
Magnetic resonance imaging (MRI) is a powerful imaging modality with excellent soft-tissue contrast.
However, its resolution is limited by the low signal-to-noise-ratio (SNR) for regions deep inside the body
such as the liver and biliary ductal system. The fundamental cause is the high sensitivity of external
detectors to electrical noise from the body itself. Unfortunately, because of patient motion, SNR cannot
be significantly improved by averaging. We have shown that SNR may be improved locally by using
internal detectors with a much smaller field of view, which (provided they may still detect signals from
the tissue of interest) are then much less sensitive to body noise. We have developed two internal RF
receivers and the hardware to introduce them into the body: a MR-imaging duodenoscope and a MRimaging biliary catheter. In each case, thin-film technology was used to construct the detection coil, and
systems were developed for use in standard clinical scanners. Both systems show a useful increase in
local SNR, and consequently a reduction in image acquisition times or an increase in image resolution to
the sub-mm regime. The systems have been designed for improved diagnosis and staging of biliary
carcinoma, and a Wellcome ISSF program for early-stage trials at Khon Kaen University Hospital in
Thailand is now in place.
Friday 14th November
Session 1: Research into health problems of the West African Region
Natalie Macdermott
Wellcome Trust Imperial College ISSF Global Health Fellow 2012-2013
Now at Cardiff University
Frontline Ebola: Novel methods in disease containment and reducing transmission – is community
based care the answer?
The Ebola virus epidemic in West Africa is unprecedented in both the number of cases and the size of
the geographical area it covers. Up to 22nd October 2014 there were 9911 reported cases and 4868
deaths. The Centres for Disease Control (CDC) estimates up to 1.4 million people could be infected with
Ebola Virus Disease (EVD) before the epidemic comes to an end and the World Health Organisation
predicts there may be 10,000 new cases per week in the coming months. Previously Ebola epidemics
have been brought under control through containment of patients in Ebola treatment units (ETU’s),
contact tracing and public awareness campaigns. So far these efforts have failed in West Africa and so
novel approaches are being sought. Addressing the epidemic at a community level is one of these
approaches. Through public awareness campaigns, home based care initiatives and smaller Ebola
community care centres (CCC), attempts are being made at reducing transmission of the virus within
households and communities. Placing smaller treatment facilities within communities also proposes to
reduce community mistrust of ETU’s and denial of the existence of EVD, encouraging communities to
bring potentially infected members to CCC’s during the early stages of disease. An unprecedented
epidemic requires unique approaches when tried and tested methods fail, but is community based care
the answer?
Beate Kampmann
Professor of Paediatric Infection & Immunity, Imperial College London
Theme Leader Vaccinology MRC Gambia
Ebola crisis in West Africa- what can science contribute?
I will provide a brief overview of challenges in the field to diagnostics, therapeutics and vaccine
development and testing.
My presentation will include the virological and immunological data available from the centres of the
highest disease burden. I will reflect on the most recent situation from the perspective of a country
bordering on the hotspots of the epidemic and the quest to develop, test and roll out a useful vaccine in
record time.
Aubrey Cunnington
Clinical Senior Lecturer, Imperial College London
Interpretation of individual and population-level responses to malaria in the context of pathogen
load dynamics
Interpretation of the host immune response during acute infection requires knowledge of the
contemporaneous dynamic changes in pathogen load. This is rarely considered in assessment of human
responses to severe infection, because assessment of pathogen load is extremely difficult. An exception
is Plasmodium falciparum malaria, where pathogen load can be readily estimated and the dynamics of
infection have been well described. Here we show that a simple mathematical model can overcome
these limitations, by integrating real host responses with dynamic changes in parasite load and duration
of illness, allowing us to explain many paradoxical observations about the interactions between host
response, disease severity, age, and intensity of malaria transmission. Not only are these findings
important for the interpretation of studies of malaria, but they also demonstrate the feasibility of an
approach which could be much more widely applied to distinguish association from causation in the
pathogenesis of severe infectious diseases.
Dr Anna Battersby
Wellcome Trust Clinical Research Fellow, Imperial College London
The Ontogeny of Innate Immunity in Gambian Infants
Dr Anna Battersby will describe the longitudinal study that she is currently conducting in Sukuta, The
Gambia. The study explores the ontogeny of innate immunity in a cohort of healthy Gambian infants
from birth through till 12 months of age. The research focuses on the functional development of the
innate immune system during infancy in a resource-limited setting with a high microbial burden. The
presentation will discuss some of the challenges and successes in setting up and running an
immunology study in a developing world setting. It will specifically cover the methods used to assess
the function of a group of innate immune receptors: the pattern recognition receptors (PRRs), which
include nucleotide oligomerization domain (NOD)-like receptors (NLRs) and toll like receptors (TLRs).
The role of these receptors in immune responses are analysed through measurement of cytokine and
antimicrobial peptide levels by enzyme-linked immunosorbent assay (ELISA) and a Bio-Plex multiplex
system which enables the detection and quantification of multiple analytes in a single small sample
volume. Intracellular signaling pathways are also explored using real-time quantitative polymerase
chain reaction (RT-qPCR). The presentation will consider how the study results may contribute to the
design of novel interventions against susceptibility to infection in infants.
Kirsty Le Doare Mehring
Wellcome Trust Clinical Research Fellow, Imperial College London
Group B Streptococcus in the Gambia – 20 years on
Background
Twenty-year old reports suggest that Gambian mothers were predominantly colonized with serotype-V
GBS whilst the trivalent capsular polysaccharide conjugate vaccine currently in phase III trial includes
serotypes Ia, Ib, III. Knowledge of the current serotype prevalence in regions such as the Gambia is vital
to ensure vaccine development matches regional requirements.
Methods
Rectovaginal swabs from Gambian mothers and nasopharyngeal and rectal swabs from their infants
were collected in a prospective cohort study of mother-infant pairs. Swabs were precultured in Todd
Hewitt Broth (THB), followed by culture on selective agar. Negative samples were analysed for the
presence of DNA via real-time PCR. Positive isolates were serotyped using multiplex PCR and gel-agarose
electrophoresis.
Results
450 women and their infants were recruited to the study. 162 women (36%) were found to be colonized
with GBS (152 culture alone, 10 culture and PCR). 112 infants were found to be colonized (25%) at birth
and all but one remained colonized at six days. By three months, only 27 infants remained colonized
(6%) and 9 infants were newly colonized (2%). The predominant serotypes amongst mothers and infants
was Serotype V (40%), serotype II (28%), Serotype Ib (20%), serotype Ia (10%) and serotype III (2%). 7
colonised infants were treated for presumed neonatal sepsis and 2 for presumed meningitis. Blood
cultures were positive for GBS in one case, equivalent to 1.4/1000 live-births.
Conclusions
Serotype distribution in the Gambia remains unchanged versus twenty years ago with serotype V
predominating. It is vital that the second stage development of the maternal GBS vaccine includes
serotype V if it is to be effective in this setting.
Gibril Ndow
Imperial College Wellcome Trust ISSF Fellow
Assessment of the burden of liver disease in adults with Hepatitis B and HIV co-infection in The
Gambia
Gibril Ndow, M. Thursz, R. Njie
Liver disease has emerged as a leading cause of morbidity and mortality among HIV infected adults in
Western populations, mostly among patients co-infected with viral hepatitis. Despite international
guidelines, Hepatitis B (HBV) screening is not routinely done in most HIV treatment centres in subSaharan Africa (sSA). Consequently, the actual burden of liver disease in HBV/HIV co-infected adults in
this region of high endemicity for both infections remains unknown.
We hypothesize that there is a huge burden of undiagnosed liver disease in patients co-infected with
HBV and HIV, and the risk factors differ based on the severity of immune failure, HIV RNA viral load, and
HBV genetic resistance.
Under the PROLIFICA (Prevention of Liver Fibrosis and Liver Cancer in Africa) platform, we are conducting
a multi-group cross-sectional study to determine the burden and risk factors of severe liver disease in
HIV patients co-infected with viral hepatitis in The Gambia.
The study aims to describe the differential severity of liver disease in HIV, HBV and HIV/HBV co-infected
adults. Specifically, we aim to:
1.
2.
3.
4.
5.
6.
7.
8.
Assess the efficacy and applicability of the public health strategy of incorporating HBV care into
the existing HIV clinics as a means of providing mass treatment for HBV in sSA
Test and validate the sensitivity and cost effectiveness of a rapid Hepatitis B surface antigen
(HBsAg) point-of-care kit for HIV patients in sSA.
To test the applicability of using dried blood spot (DBS) for HBsAg screening and HBV DNA viral
load measurement among HIV infected adults in sSA.
To demonstrate that comprehensive liver assessment can be incorporated within the already
established HIV clinics.
Determine the burden of HBV resistance in a cohort of unscreened HIV patients exposed to
Lamivudine as part of their first-line ART regimen.
The impact of HBV infection on HIV replication, as well as HIV infection on HBV replication.
The correlation between HIV immunological and virological markers and severity of liver disease
in co-infected adults.
Demonstrate that a relatively cheap PCR technique can be used to assess and monitor HBV DNA
in HIV patients.
The primary outcome of this study will be the impact of either virus on the differential severity of liver
disease between patients infected with both HBV and HIV as compared to those infected with either
virus, and the associated risk factors on liver fibrosis in the respective groups.
To achieve these objectives, all HIV infected individuals at the Hands on Care (HoC) clinic are being
screened for HBsAg using the Determine® kits. Eight drops of blood from the same finger prick are put
on DBS filter paper for HBsAg serology testing.
All HBsAg positive subjects, along with age-, sex- and immune status matched HBsAg negative controls
will be invited for a comprehensive clinical assessment. This includes a detailed medical, family and
social history, fasting transient elastography (Fibroscan®) and bedside abdominal ultrasonography.
Reference will be made to the patients’ HoC clinical case notes to ascertain initial and most recent CD4
count, anti-retroviral treatment, and documented past medical history.
Twenty four millilitres of whole blood, collected in three serum-separator tubes (SST) and three
ethylenediaminetetraacetate (EDTA) tubes will be will be withdrawn from each patient. Real time full
blood count and liver function tests (LFTs) are done, along with ELISA test for HBsAg serology. The rest of
the samples are processed and stored in -80˚C for further tests which will include HBsAg quantification,
HBeAg, HBeAb, HBV DNA viral load, HBV genome sequencing and HIV RNA viral load.
The expected results of this project will impact individual patient care and patient outcomes by
providing screening and diagnostic facilities which are otherwise not available. It will guide treatment
initiation or regimen change as per the WHO recommendations. The final results will influence public
health policy and development/strengthening of relevant guidelines and recommendations in The
Gambia, as well as fill a knowledge and evidence gap in this sub-region and beyond. It will provide
research experience and high quality pilot data for a competitive PhD application.
Serge Yerbanga
Research Institute of Health Sciences Burkina Faso
A field platform for developing malaria transmission-blocking interventions: Multi-target product
with Drugs, Antibiotics and vaccines.
Rakiswendé S Yerbanga1,*, Dari Da1, Mathilde Gendrin2, Jean Bosco Ouédraogo1 and George K
Christophides2
Institut de Recherche en Sciences de la Santé, 01 BP545 Bobo Dioulasso 01, Burkina Faso. 2Department
of Life Sciences, Imperial College London, London, United Kingdom.
1
The fight against malaria progress achieved remains under threat from the development of artemisinins
resistant. This scenario calls for the acceleration of the discovery of novel antiplasmodial molecules
and the design and development of new combination drugs tailored to the pharmacological needs of
malaria control (i.e. to cure and prevent the disease in individuals and control/eliminate transmission).
To date, transmission of the sexual stages of Plasmodium to the vector have been neglected. To develop
malaria transmission-blocking measures that inactivate or eliminate parasites in both the human host
and the mosquito vector, with for example drugs, vaccines or antibiotics, a field platform for developing
malaria transmission-blocking interventions (TBI) needs to be set up.
TBIs candidates have a key role to play both as a resistance containment strategy and to equip countries
entering the malaria elimination phase with the required tools.
To optimise that strategy, a characterization of the area with different malaria endemicity are required,
immunology, biochemistry and hematology parameters of the study population are needed as well as
diversity of the vector complex, social and environmental factors of the study site.
The field platform for developing malaria transmission-blocking intervention will help to properly
evaluate the effectiveness of this strategy from laboratory experiment on field-like conditions before the
widespread implementation.
Session 2: South America
Sumona Datta
ISSF Fellow, Imperial College London based at Universad Peruana Cayetano Heredia, Peru
Microscopy-based TB treatment response and drug-susceptibility testing
Tuberculosis and multidrug-resistant tuberculosis (MDR-TB) control are confounded by inadequate
appropriate-technology diagnostic tools. Sputum smear microscopy is the most widely used technique
but provides limited information.
Objectives
1. Assess the diagnostic sensitivity of TB auramine-stained fluorescent microscopy (AFM).
2. In smear-positive samples, assess TB quantitative viability microscopy (QVM) using fluorescein
diacetate for predicting:
(a) quantitative culture results.
(b) infectiousness
(c) treatment response
Methods and Results
1. Sputum samples (n=1009) from patients with culture-proven Mycobacterium tuberculosis disease
underwent duplicate smears for: Ziehl-Neelsen stained light microscopy and auramine-stained
fluorescent microscopy (AFM). AFM results were unaffected by variations in the staining protocol1. In
samples from patients with drug-susceptible TB, relative to culture results, AFM had 77% sensitivity,
greater than 62% for Ziehl-Neelsen (p<0.001). In contrast, in samples from patients with MDR-TB, ZiehlNeelsen and AFM had similar sensitivities. Thus, MDR-TB was associated with more false-negative
microscopy results than drug-susceptible TB for AFM (OR=1.9, p=0.001), but not for ZN (p=0.3)2.
2. 35 patients had sputum (N=124) tested on days 0, 3, 6 and 9 of empiric first-line therapy.
(a) QVM predicted quantitative culture results3 (rS=0.85, p<0.001) within 1-hour.
(b) Patients’ household contacts were followed-up for 6 years. 6.4% (13/209) contacts developed TB
disease, which was paradoxically more likely to occur in contacts of patients with lower than median
QVM results in crude (HR=3.8, p=0.03) and adjusted analysis (HR=3.7, p=0.03)4,5.
(c) Patients with drug-susceptible TB and available data (n=31) had more than a 10-fold reduction in
QVM by treatment day 9, whereas QVM for patients with MDR-TB (n=4) did not change (p=0.4, Figure).
Change in QVM and quantitative culture results differed significantly for patients with drug-susceptible
versus MDR-TB (both p<0.001). AFM results changed little and were similar for patients with drugsusceptible versus MDR-TB (p=0.6)3.
Conclusion
Sputum smear microscopy was adapted to better inform TB patient care and control.
References
1. S Datta, M Ching, T Valencia, E Ramos, M Tovar, D Coleman, C A Evans
Auramine staining & fluorescent microscopy for TB diagnosis: a controlled comparison of sputum smear
microscopy protocols
Published abstract - Proceedings of the International Union Against TB and Lung Disease, World
Conference, October 2014, Barcelona, Spain
2, S Datta, W Quino, T Valencia, E Ramos, C Osorio, M Llacza, S Glover, R Montaya, CA Evans
Reduced sensitivity of auramine stained sputum smears in MDR-tuberculosis
Published abstract – Proceedings of the North America Region Union Against TB and Lung Disease
Conference, February 2013, Vancouver, Canada
3. S Datta, JM Sherman, MA Bravard, T Valencia, RH Gilman, CA Evans
Clinical evaluation of sputum viability staining for assessing TB treatment response
Revisions undergoing peer-review by the journal Clinical Infectious Diseases; manuscript number
75618
4. S Datta, JM Sherman, LJ Martin, L Grandjean, MA Bravard, MA Tovar, T Valencia, R Montoya, W Quino,
N D’Arcy, ES Ramos, RH Gilman, CA Evans
Assessment of sputum viability microscopy for predicting TB infectiousness
Revisions undergoing peer-review by the Journal of Clinical Microbiology; manuscript number
JCM02014-14
5. S Datta, J Sherman, T Valencia, W Quino, MA Tovar, R Montoya, RH Gilman, C A Evans
Predicting patient infectiousness with quantitative sputum viability microscopy.
Published abstract – Proceedings of the American society of tropical medicine and hygiene conference,
November 2014, New Orleans, USA
Figure. Mean treatment response for 31 patients with non-MDR-TB (top) and 4 patients with MDR-TB
(bottom) on days 0, 3, 6 and 9 of TB treatment. The horizontal-axis shows days of treatment. Dashed
lines indicate cut-offs for positivity.
Tom Wingfield
PhD Student Imperial College London based at Universad Peruana Cayetano Heredia, Peru
Combatting poverty-related risk factors for TB disease in Peruvian shantytowns
Introduction
Tuberculosis (TB) kills 1.3 million people per year and remains a major global health problem.1 Poverty
causes TB disease2 by mediation of determinants in the TB causal pathway including: infectious
diseases (such as intestinal helminth co-infection);3 non-communicable diseases (such as diabetes);4
household crowding;5 poor nutrition with vitamin D deficiency;5,6 and marginalization,7 lack of access to
healthcare,8 and associated delayed health-seeking behaviour.9 There is minimal impact evidence
concerning social protection interventions to reduce poverty-related TB risk factors and control TB
disease.10,11,12
Objectives
Measure poverty and clinical impact of catastrophic costs of “free” TB treatment in TB-affected families;
and inform the design and implementation of a complex social protection intervention to reduce
poverty-related TB risk factors in TB-affected families.
Methods
TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n=487) were
recruited to a cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2–
4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related
costs. Poverty was measured using a composite household index incorporating 13 variables, including
education, housing, services, and assets.5,10 Costs were expressed as a proportion of the household’s
annual income. Catastrophic costs were defined as the threshold above which total household
expenses as a proportion of annual income were most strongly associated with adverse TB outcome; the
strength of the association was assessed by the highest sensitivity, specificity, and population
attributable fraction for adverse outcome. Adverse TB outcome was defined as death, treatment
abandonment or treatment failure during therapy, or recurrence within 2 years.
Results
Healthy controls were poorer, had greater income, and were less likely to be unemployed, than TB
patients (all p<0.02). In poorer TB-affected households, costs were lower but constituted a higher
proportion of the household’s annual income: 27% (95%CI=20%–43%) in the least-poor houses versus
48% (95%CI =36%–50%) in the poorest. 23% (166/725) of patients with a defined treatment outcome
had an adverse outcome. Total costs $20% of household annual income was defined as catastrophic
because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were
incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring
catastrophic costs (54% [95%CI=43%–61%] versus 38% [95%CI=34%–41%], p=0.003). Adverse
outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95%CI=4.7–15], p,0.001),
previous TB (OR=2.1 [95%CI=1.3–3.5], p = 0.005), days too unwell to work pre-treatment (OR=1.01
[95%CI=1.00–1.01], p=0.02), and catastrophic costs (OR=1.7 [95%CI=1.1–2.6], p = 0.01, Figure). The
adjusted population attributable fraction of adverse outcomes explained by catastrophic costs was 18%
(95%CI=6.9%–28%), similar to that of MDR TB (20% [95%CI=14%–25%]).
Discussion
Despite free TB care, having TB disease was expensive for impoverished TB patients in Peru. Incurring
higher relative costs was associated with adverse TB outcome. The population attributable fraction
indicated that catastrophic costs and MDR TB were associated with similar proportions of adverse
outcomes. These findings13 have informed the World Health Organisation’s post-2015 global TB strategy
which, for the first time in the modern era of TB control, explicitly identifies poverty reduction strategies,
including social protection and mitigation of catastrophic costs, as key pillars of the future global
response to TB.12,14,15 In order to evaluate such strategies, our group has designed a novel TB-specific
social protection intervention incorporating conditional cash transfers that is currently being
implemented and refined for subsequent impact assessment during the Community Randomized
Evaluation of a Socioeconomic Intervention to Prevent TB (CRESIPT).16,17
Conclusion
TB is a socioeconomic as well as infectious problem, and TB control interventions should aim to address
both the economic and clinical aspects of this disease.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
World Health Organization (2013) Global TB report 2013. Accessed 31/10/ 2013. Available:
http://apps.who.int/iris/bitstream/10665/75938/1/9789241564502_eng.pdf.
Tovar M, Wingfield T, Montoya R, et al. Undiagnosed TB cases among previously TB-affected
families: results of a prevalence survey in Peru. Published abstract from oral presentation OAP234-30 International Journal of TB and Lung Disease 2014; 18(11): S1.
Zevallos K, Sandhu G, Sacksteder K, Yori P, Kosek M, Pan W, Banda C, Herrera B, Valencia T,
Gilman RH, Vidal C, Meza G, Vergara K, Garcia H, Wingfield T, Evans CA. Human immunity
against MTB antigens is augmented by treating intestinal helminths. Published abstract #1083
American J Tropical Medicine & Hygiene 2006; 75 supplement: 312.
Wingfield T, Zevallos K, Gavino A, Tovar M, Montoya R, Alva J, Franco J, Evans C. Risk of ever
having had tuberculosis disease is associated with self-reported diabetes and lower body mass
index in a transitional community in Peru. Published abstract PC-390-17 International Journal of
Tuberculosis and Lung Disease 2012; 16(12): supplement 1.
Wingfield T, Schumacher SG, Sandhu G, et al. The seasonality of tuberculosis, sunlight, vitamin
D, and household crowding. J Infect Dis. 2014 Sep 1;210(5):774-83. doi: 10.1093/infdis/jiu121.
Epub 2014 Mar 4.
Zevallos K, Tovar M, Wingfield T, Montoya R, Ramos E, Gavino A, Rocha C, Evans CA. Financial
interventions and modulation of malnutrition/food security in the context of TB. Published
abstract S48 International Journal of TB and Lung Disease 2012; 16(12):S1.
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overlook the most vulnerable TB patients in low-resource countries. Published abstract S150 PC382-01 International Journal of TB and Lung Disease 2013; 17(12): S2.
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modern medicine in remote Peruvian Amazon communities: a descriptive study of knowledge,
attitudes and practices. Am J Trop Med Hyg, November 2014 (in press)
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and health seeking behaviour of household contacts in the Peruvian Amazon. Int J Tuberc Lung
Dis 2004;8(12):1484-1491.
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transfer and microfinance interventions for TB control: review of impact evidence and policy
implications. Int J TB Lung Dis. 2011; 15(S2): S37–S49. doi:10.5588/ijtld.10.0438.
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implementation challenges. Bull WHO, November 2014 (revisions invited).
13. Wingfield T, Boccia D, Tovar M, Gavino A, Zevallos K, et al. (2014) Defining Catastrophic Costs
and Comparing Their Importance for Adverse Tuberculosis Outcome with Multi-Drug Resistance:
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low- and middle-income countries: systematic review. Eur Resp J 2014;43:1763-75
16. Wingfield T, Tovar M, Huff D, et al. The CRESIPT project: community feedback and practical
challenges of conditional cash transfers for TB-affected families in Peru. Published abstract
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17. Wingfield T, Boccia D, Tovar M, et al. Designing and implementing a social protection
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Health Pol Plann, November 2014 (manuscript under review).
Figure: Percentage of patients experiencing an adverse TB outcome analysed by poverty, education
level, symptom duration, time too unwell to work, catastrophic costs, previous TB, and resistance
profile.
Error bars represent 95% confidence intervals. p-Values correspond to the association of each variable
with adverse TB outcome in univariable logistic regression, except for poverty and symptom duration,
which were analysed as continuous variables. In multivariable regression analysis, the following
variables remained independently associated with adverse TB outcome: days too unwell to work (OR
1.01, p=0.02), catastrophic costs (OR 1.7, p = 0.003), having had a previous episode of TB (OR 2.1,
p=0.004), and currently having MDR TB (OR 8.4, p=0.0001).
Carlton A Evans
Reader in Global Health, Imperial College London
Universad Peruana Cayetano Heredia, Peru
Addressing social determinants to strengthen TB control
Background
Poverty is associated with TB and with difficulty accessing even free TB care, but most TB control
resources are spent on biomedical care, not addressing poverty.
Objectives
In impoverished shantytowns in Peru to:
(a) characterise poverty-related factors adversely associated with TB;
and evaluate a socio-economic intervention to improve:
(b) access to TB care; and
(c) equity of access to TB care.
Methods and Findings
(a) Poverty: In a prospective cohort of TB patients (n=1029) and a nested case-control (n=478) study, TB
disease and adverse treatment outcomes were associated with incomplete schooling, depression, low
social capital, malnutrition and chronic poverty (all p<0.05).
(b) Socioeconomic intervention impact-access: In a randomized controlled evaluation, a
socioeconomic intervention was offered to 1888 members of TB-affected households. The intervention
constituted household visits, community workshops, microcredit loans, microenterprise, cash and food
transfers. Impact on access to TB care versus baseline included increased drug-susceptibility testing,
adherence with appropriate therapy and HIV testing (all p<0.01). Preventive therapy initiation and
completion both increased in children in 484 households in 8 communities offered the socio-economic
intervention compared with children living in 660 households in 8 control communities (both P<0.0001).
(c) Socioeconomic intervention impact-equity: In the 8 control communities, children living in
households that were crowded and/or had lower income were less likely to complete preventive therapy
(both p<0.05, Figure-left). In the 8 intervention communities, children living in more crowded and/or
lower income households had similar or higher preventive therapy completion rates than children living
in households that were less crowded and/or had higher income (both p>0.6, Figure-right).
Conclusions
TB disease and adverse TB treatment outcomes were associated with diverse poverty indicators. A
socioeconomic intervention that aimed to inform, incentivise and enable TB care and reduce povertyrelated TB risk factors increased uptake and equity of access to TB care including preventive therapy.
Session 3: Capacity Building in Global Health Educational
Opportunities
Tumani Corrah
MRC Director, Africa Research Development
Visiting Professor, University of Oxford
Building a better vision for AFRICA together
Professor Tumani Corrah is the founding Director of the newly created position of MRC Director, Africa
Research Development. Professor Corrah has over thirty years of progressively senior-level experience in
a leading research institution in Africa - MRC Unit in The Gambia - rising to the position of Unit Director, a
position he held successfully for over 10 years. As Director of the MRC Unit, The Gambia, he oversaw the
science portfolio of the Unit which is organised into three themes: Child Survival, Vaccinology and
Disease Control & Elimination. Professor Corrah retains active research interests in tropical and
infectious diseases, including tuberculosis, HIV and malaria. He is medically qualified and holds a PhD
from his studies on tuberculosis, which included the ground breaking science of the introduction of
immunotherapy as an adjunct for the treatment of tuberculosis in The Gambia. An expert on research
governance, he is a long-standing member of the Gambia Government/MRC Ethics Committee, including
four years as Chair. He has strong links with governmental and non-governmental organisations in Africa
and throughout the world. He is an expert in capacity building, having established a number of
productive, mutually beneficial ‘North-South’ collaborations. He has served on numerous scientific
review and advisory boards, including the EDCTP Partnership Board, and acts as Director of the
International Office of the West African College of Physicians, where he is responsible for establishing
partnerships.
Debra Humphris
Vice Provost (Education) Imperial College London
Education links with Imperial College London: A global community of talent
As Vice Provost (Education) Debra has overall responsibility for educational strategyand the quality of
the educational provision and across the College. Debra Humphris was appointed Pro Rector (Education)
in October 2012 and in August 2013 became Vice Provost (Education). Prior to her appointment at
Imperial College, Debra was the Pro Vice Chancellor (Education and Student Experience) at the
University of Southampton since 2008. Professor Humphris was responsible for the creation, leadership
and delivery of the University’s education strategic plan, which emphasised enhancing the student
experience and the importance of graduate employability.
Paul Seldon
Senior Teaching Fellow, Postgraduate Development Unit, Graduate School, Imperial College London
UCT and Imperial College London Summer School
The Graduate School provides an award winning professional development programme that not only
supports our students in their programmes of study or research, but also equips them for their future
careers.
ImperiaI College’s Graduate School and Wellcome Trust Global Research Centre in cooperation with the
University of Cape Town (UCT), Imperial is offering an opportunity to participate in the Global Health
Fellows Programme at UCT in Jan 14. Students from Imperial, the University of Cape Town and partner
institutions will participate in the Global Health Summer School to develop their research and
professional skills. This Programme lasts up to four-weeks and consists of a four-day professional skills
and Global Health course, followed by an opportunity to complete a three-week research placement in a
lab or group at UCT.
Paladd Asavarut
Phage Therapy Group, Department of Medicine, Faculty of Medicine, Imperial College London.
Academic and Welfare Officer (Faculty of Medicine), Graduate Students’ Union, Imperial College London.
Social foundations of inequality in the developing world
At Imperial College, we work in an accepting environment that encourages learning and innovation.
However, this is not the case in many parts of the world. As an international student from a developing
country who is consistently involved in student representation and welfare, I offer my reflections on
social inequality in the context of science and education.
My experience as a scientist with a keen interest in social sciences has strongly contributed to my
opinion that implementation of science requires extensive social engineering. After all, the worth of
innovation is dependent on the society’s ability to understand both social and natural sciences, and
willingness to accept policies, products, or ideas that contradict traditional beliefs. I believe it is often
the case that inequality is at the heart of problems in societies that our institutions are trying to resolve.
The presence of inequality perpetuates itself, especially in the developing world where resources that
counteract it are scarce.
The talk will discuss three key topics, which are “The social foundations of scientific problems”,
“Infrastructures that enable innovation” and “Authority of the collective community”. I hope to
encourage the audience to reflect upon the norms of societies that are ravaged by diseases.
Consequently, strategic implementation of open-mindedness in conjunction with scientific aid might be
key to addressing issues such as health in the developing world.
I will end the talk by providing a perspective on opportunities that exist for institutions like ours to
provide trained scientists and scholars with vision and a deeper understanding of society’s role in
encouraging learning and shaping behavior. An example of this is a pilot project I am trying to organise,
which aims to increase social and natural science literacy for the overseas community of Thai
government scholars.
Session 4: Global Health Opportunities Individual Table
Discussions
This 1 hour session will provide an opportunity to meet and greet the established academics and
overseas partners to explore career opportunities in global health.
Notes
Notes
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