TAMA | MRC Unit, The Gambia Newsletter | Vol. 12 | Issue ...cdn.mrc.gm/downloads/Tama_Vol12-Issue02_2013_LowRes.pdf · chickenpox substantially reduces the risk of varicella zoster

Nutrition Group’s Scientific Director elected to Fellowship of the Academy of Medical Sciences

Forty four researchers from across the UK have been recognised for their contribution to the advancement of medical science by election to the Fellowship of the Academy of Medical Sciences.

Professor Andrew Prentice is among this year's newly-elected Fellows of the Academy. Andrew directs the MRC International Nutrition Group based at the London School of Hygiene & Tropical Medicine (LSHTM), and he is the Scientific Director of the Nutrition Programme in The Gambia.

TAMANEWSLETTERTAMA: Wolof. n. a talking drumVOL: 12 ISSUE: 02 / 2013

Medical Research Council Unit, The Gambia

Dr Alfred Ngwa: MRC career development fellow

Dr Alfred Amambua Ngwa was awarded a competitive MRC Career Development Fellowship recently, marking his return to full-time research, having spent the last two years as Manager of the Molecular Diagnostics Platform.

The focus of his project is research into drug resistant malaria. ‘Malaria remains a fatal infection for millions worldwide and 80% of cases and deaths occur in Africa.’ He says. ‘While most malaria infections can be cured with drugs, the deadly malaria pathogen Plasmodium falciparum has in every case found new ways of resisting the effect of drugs that are used for treatment. This is why the drugs we grew up with such as Chloroquine and Fansidar no longer cure malaria in all infected people.’

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TheGambiaUnit

CONTENTS

Exploring the ethics of biomedical research

Vaccinology

Child Survival

Disease Control & Elimination

News from Basse

News from Keneba

Recent Unit Publications

News from Clinical Services

Training

Quality Assurance

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About Alfred

Dr Alfred Amambua Ngwa, from Cameroon, defended his PHD in Biochemistry (University of Buea) in 2004. Following two years as a university lecturer, he decided on a research career and joined the MRC in 2006. ‘I joined the Malaria Programme led by Professor David Conway to work on the pathogenesis of severe malaria.’ He says. ‘My decision to join the MRC was guided purely by my interest in malaria vaccine research, after reading several publications by Professors Conway and Kevin Marsh.’

Following 4 years under the direct mentorship of Drs Natalia Gomez and Michael Walther, contributing to studies on the immunology, cell biology and genetics of Plasmodium falciparum resulting in several publications, Alfred’s malaria research focus took a ‘thematic’ turn to genomics ‘when I optimised protocols for depleting human cells and isolated malaria parasite DNA for NextGeneration genome Sequencing.’ he says. ‘From then I have contributed parasite populations for whole genome variation studies and enjoy a fruitful experience managing and analysing genetic data in collaboration with the Wellcome Trust Sanger Centre; The Broad Institute and Harvard School of Public Health.’

Population genetic analysis of malaria and other infectious pathogens have become Alfred’s passion. He says ‘I am happy the MRC bought into my dream to continue doing this. It is one of the most powerful approaches available for discovery of markers and candidates for vaccines and diagnostics against infectious pathogens that plague Africa.’

Alfred believes that this was the right time in his career to develop independence and lead a research team. He thanks Professor Corrah and his mentors ‘for the support and opportunities over the last 6 years to experience both research and management that were vital for success in this fellowship.’ He also thanks a large number of other people ‘Most importantly, I don’t have enough words to thank my wife Delphine and my children (Brandon, Jason and Kelma) whose love have been the fuel in my drive towards greater academic heights.’

Currently, treating malaria requires combinations of drugs (ACTS) containing a compound, Artemisinin. In The Gambia, the combination used is Artemisinin and Lumefantrine (CoARTEM). But, as Alfred says ‘Once more, the scientific and medical communities have been embarrassed by findings that malaria infections in South East Asia no longer respond to these new combination treatments. If this starts happening in Africa, it will have disastrous consequences for malaria control.’

Alfred’s research fellowship project aims at beginning a search to identify malaria infections that are resistant to ACTs and for markers in the genetic material of malaria parasites that make them resist drugs. ‘This will enable us to develop better ways of treating the disease in the future.’ He says. ‘The research will be based in The Gambia and has three phases that will analyse parasites before ACTs were introduced, those present in infected people in different regions across The Gambia and in-depth lab analysis of any parasites that show signs of resistance.’

The MRC career development fellowship is designed to provide the training needed to become a research leader. ‘I want to lead in the research I am doing right here in Africa: pathogen genomics.’ Says Alfred. ‘I therefore hope that within five years I will have developed in leadership through the acquisition of more research grants and be in charge of a research team that can accommodate and train other scientists and students with interest in using cutting-edge technologies to fight infectious diseases in Africa and the world.’

Dr Alfred Ngwa: MRC career development fellow

Commenting on Alfred Ngwa’s acquisition of this prestigious MRC Fellowship, Unit Director Professor Tumani Corrah said ‘I sincerely hope that this will be the first of many more; this will undoubtedly inspire the Unit’s young and talented African scientists. It could be the beginning of a dream come true: the development of a critical mass of African scientists who will contribute to sub-regional and international public health.’

04 MRC TAMA - VOL: 12 / ISSUE: 02 / 2013

Nutrition Group’s Scientific Director elected to Fellowship of the Academy of Medical Sciences

Andrew's research focuses on the connections between early-life nutrition and health problems in developing countries, with a major portion of the work centred around the groups clinical laboratories at MRC Keneba. He is a member of The Bill & Melinda Gates Foundation's Global Health Discovery Expert Group.

Academy Fellows are elected for excellence in medical research, for innovative application of scientific knowledge or for their conspicuous service to healthcare. The expertise of the new Fellows spans pharmacology, cell biology, biomedical engineering, childhood cancers, suicide prevention and international health.

Professor Sir John Tooke PMedSci, President of the Academy of Medical Sciences said, ‘The Academy of Medical Sciences exists to promote the best of medical science for the benefit of society. Our new Fellows are recognised for their exceptional contribution and collectively represent the array of talent present in the UK medical science community. They will further strengthen the Academy and I look forward to working with them over the coming years.’

The new Fellows were formally admitted to the Academy ata ceremony on Wednesday 26 June 2013. For further information visit: http://www.acmedsci.ac.uk/

Professor Andrew Hall knighted in the Queen's Birthday Honours list

Andy Hall is an alumnus of MRC Unit, The Gambia and until recently, he was a member of the Unit's Scientific Advisory Board. He retired this year from the London School of Hygiene & Tropical Medicine after 22 years.

Andy has an illustrious history in tropical infectious disease research. He led the Gambian trial of hepatitis B vaccine, the first and longest running trial of a vaccine against any cancer, and subsequently demonstrating that adult exposure to children with chickenpox substantially reduces the risk of varicella zoster.

He has also contributed to public health policy relating to infectious disease control, serving on the Board of Health Protection Agency during 2002-09 and on the Joint Committee on Vaccines and Immunisation, which had a significant role in the UK's national vaccination policy. He has served on the WHO committee reviewing the Global Polio Eradication Initiative and was on the independent review committee of the Global Alliance on Vaccines and Immunisation.

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Exploring the ethics of biomedical research

Talks at the WorkshopProfessor Koen Peeters (Institute of Tropical Medicine, Antwerp) presented on ëOral Consent in Human Behavioural Research in International Health.í Professor Peeters argued that there is a strong relationship between the quality of data collected and the way informed consent is obtained and/or documented. The use of standard informed consent procedures can bias and change the study results; this may necessitate the use of different consenting methods ñ including oral consent depending on the circumstances, he argued.

Dr Siga Fatima Jagne (a social scientist) has recently accepted to join the Gambia Government/MRC Ethics Committee. She gave a presentation on the UNESCO/MRC bioethics project, which specifically looks at research participation from a vulnerability perspective. The project aims at building awareness around bioethics and groups (including women and children) in The Gambia, and will seek to build capacity in terms of setting bioethical standards, recognising that concern for the interests of the research participant must prevail over the interests of science and society.

Sr Vivat Thomas-Njie (Senior Clinical Trials Monitor, MRC Unit, The Gambia) presented on ethical oversight of clinical trials, citing the International Conference on Harmonisation (ICH) Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines (1996): ‘[an institutional review board] should safeguard the rights, safety and well being of all trial subjects’. The Council for International Organizations of Medical Sciences (CIOMS) guidelines further state that review committees must be ‘independent’, with at least five members, including a minimum of one lay person, and

a member independent from project sponsor or site. Sr Thomas-Njie also stressed that Committees should reflect community representation, a fair gender balance, and should endeavour to visit study sites on a periodical basis.

Dr Kalifa Bojang (Head of Paediatrics, Edward Francis Small Teaching Hospital) gave an overview of the History of Medical Ethics. He cited some of the highest profile cases of unethical experimentation, including those under the Nazi government in Germany and elsewhere; the Willowbrook studies; the Jewish chronic disease hospital study; and the Tuskeegee syphilis experiment. In these and other instances, there was no informed consent process; coercion was used and available treatment withheld. The growth of regulation in the ethics of biomedical research was traced through the post World War II Nuremberg Code; the Declaration of Helsinki (1964) and the subsequent establishment of international structures aimed at protecting the rights of research participants.

Professor Ousman Nyan (Provost, School of Medicine & Allied Health Sciences and Vice Chancellor, The University of The Gambia) reflected on the challenges in biomedical research, citing Ezekiel Emmanuelís paper in the Journal of Infectious Diseases (2004) ëWhat makes clinical research in developing countries ethical?í Professor Nyan argued for the development of capacity among researchers, health policy makers and the community, stressing that the communities should benefit from the conduct of research. He also stated that the research should realise scientific objectives, while guaranteeing research participants the health care interventions to which they are entitled.

The Gambia Government/MRC Ethics Committee has existed for over 30 years and is one of the oldest in Africa. The current Committee has served for a number of years; and recently, a new set of people have been approached – and accepted – to join.

On Saturday 15th June, a workshop was convened at MRC Fajara, bringing together old and new members. In his welcome, Professor Tumani Corrah

stated that the Ethics Committee was there to protect the rights of humans involved in studies. ‘No study is carried out unless it is relevant and has a strong scientific basis with information that can be used here and in the developing world.’ He said.

There is one Ethics Committee (EC) in The Gambia. It is an independent body, chaired by a lay person; the current Chair, Mr Malcolm Clarke is a retired WHO administrator and has been an EC member for 15 years. The Committee looks at the ethical aspects of research projects after their scientific merit has been ascertained by the Scientific Coordinating Committee (SCC). Indeed, in many countries there is no distinction between an SCC and an EC.


VACCINOLOGY

Open Day in the Fonis

1.Alhaji Momodou Lamin Jarju, Head Chief of Foni Kansala District is a former employee of MRC Keneba and a keen advocate of the Unit’s work. In his address, he urged the community to support MRC studies ‘for the betterment of mankind.’ 2. Posters at the CCF’s Dingding Bantaba compound where the Open Day took place. 3. Dr Martin Antonio and a young member of the community. ‘Much pioneering work started in the Fonis – the children and grandchildren of today’s participants will benefit from the vaccine studies.’ Said Dr Antonio. 4. Dr Adama Demba, Director of Health Services.

1.Head of The Gambia’s Expanded Programme on Immunisation, Mrs Yamandow Lowe-Jallow said ‘Vaccines are one of the most effective public health interventions, saving 3 million lives globally each year.’ 2. Governor, West Coast Region, Hon Lamin Sanneh ‘Good health produces a focused citizenry and an improved economy.’ 3. Professor Tumani Corrah, MRC Unit Director. 4. Dr Thomas Sukwa, WR, WHO The Gambia said that partnership in The Gambia had contributed to the generation of data for the introduction of vaccines including PCV 7 - and the conjugate meningitis vaccine , scheduled for introduction into The Gambia’s EPI in November 2013 through GAVI.

MRC Unit The Gambia has worked in Sibanor and 20 surrounding villages in the Western Region of the country for over 20 years. Research amongst the population of 68,000 people in the area has focused on acute lower respiratory infections, which account for the majority of the deaths in children under five in most developing countries, including The Gambia.

MRC scientists have visited Sibanor periodically over the years to thank the community and give feedback on the studies. This year, the Open Day Programme titled ‘Fonis and the MRC: United to Improve Health and Save Lives’ took place on 12th June.

Addressing the invited guests, MRC Unit Director Professor Tumani Corrah said ‘We selected to work [in the Fonis] on a disease neglected by many

other researchers – pneumonia - focusing on something relevant to our community, and rampant in our country.’ He reaffirmed the Unit’s commitment to working in the Western Region of The Gambia. ‘Through Kim Mulholland, Richard Adegbola and now under the leadership of Beate Kampmann, we have never left this part of the country.’ He said.

Reiterating The Gambia’s mass vaccination success story Mrs Yamandow Lowe-Jallow (Head of the country’s EPI) said that The Gambia’s record on immunisation was outstanding; in 2009 Gambia won the World Global Alliance for Vaccines and Immunization (GAVI) Award in recognition of its EPI and the high immunization coverage over the previous five years. Mrs Lowe-Jallow reported that since the introduction of the pneumococcal conjugate vaccine in 2009 coverage had increased to a peak of 92% in 2012. She also stated that in addition to ten diseases targeted by the EPI schedule, a rotavirus vaccine would be introduced soon.

On behalf of the Minister of Health and Social Welfare, Dr Adama Demba acknowledged the MRC’s support of Gambia Government health facilities and the Medical School. She also thanked the communities for their continued participation in these important studies.


Foni Elders visit MRC Fajara

Ahead of Sibanor Open Day on Wednesday 12th June, a group of elders from the Fonis visited MRC Fajara on Monday 10th June.

Following a meeting with Leadership team members, the community leaders were given a tour of the Clinical Services Department, where they were received by Dr Suzanne Anderson and Matron Pamela Collier N'Jai.

They also visited the immunology/parasitology and microbiology labs, where they saw demonstrations of blood and NPS processing, and had the opportunity to ask questions about how blood is treated and

stored at the MRC.

VACCINOLOGY

1.Dr Karen Forester, Head of the WEC Mission Clinic, Sibanor and Mr Kebba Badjie, CEO of Bwiam Hospital. 2. Professor Beate Kampmann, Theme Leader, Vaccinology, MRC Unit, The Gambia. Professor Kampmann gave a back-to-basics talk on vaccines: their rationale and the continued necessity for testing new vaccines. 3. Students of St Martin’s Lower Basic School sensitising the community about ‘blood’ in research.

1.Dr Uzochukwu Egere gave feedback on the pneumococcal carriage studies that provided background information for the trial to determine the impact of immunisation of a whole community with PCV on nasopharyngeal carriage of pneumococci. 2. Mothers and babies of Sibanor and the surrounding villages. 3. Dr Claire Oluwalana stressed the importance of on-going disease surveillance, reporting that 20 cases of invasive Hib disease were detected in 2012, probably due to cross border/urban-rural migration.


The Government of The Gambia, The MRC and senior members of Fajikunda and surrounding communities came together on 10th April to thank the many parents and children who have taken part in MRC studies at Fajikunda Health Centre over recent years. These studies aim to improve children’s health and save lives, not only in The Gambia but also across the developing world, and would not have been possible without the cooperation of the Ministry of Health, the children and their families.

TB vaccine trial (presented by Dr Muyiwa Owolabi): The BCG vaccine helps to protect small babies from TB but it does not protect older children and adults effectively. This study demonstrated that the new trial vaccine was safe when given to children. It also showed that the vaccine stimulated the body to fight TB infection. Given the promising results, it is hoped that the trial in Fajikunda will eventually lead to a new TB vaccine which will prevent people of all ages from falling sick due to TB.

Pneumococcal protein vaccine trial (presented by Dr Aderonke Odutola): A study of a new vaccine to protect against meningitis and pneumonia is coming to an end at Fajikunda. Again, although there are existing vaccines, better vaccines are needed to afford children improved protection. This vaccine was shown to be safe in small babies and the investigators will soon know how well it worked in other ways.

Looking forward: polio vaccine (IPV) (presented by Dr Ed Clarke): Although there are only a few hundred cases of polio in the world each year, this disease remains a high priority for eradication.

The vaccine in the trial will be given as an injection, and will be used with the existing polio drops in the future. It is hoped that this combination will give children better protection against polio. The injected polio vaccine is already used in some parts of the world such as South Africa, and is known to be quite safe.

Looking forward: pneumonia vaccine studies (presented by Dr Olubokola Idoko): Later in the year, the Vaccinology team is planning to start a trial of a new preparation of the pneumococcal conjugate vaccine (PCV13) that is already in use. This new preparation will contain several doses in a vial, reducing storage costs and making the vaccine more affordable for more African countries. Children aged 2-3 months will be recruited for this trial at Fajikunda.

VACCINOLOGY

MRC researchers engage the community

Two open day programmes took place at local health facilities in April, aimed at giving feedback on recently concluded and on-going work. These events also gave the opportunity to sensitise the community about the upcoming Bill & Melinda Gates-funded Inactivated Polio Vaccine Trial (IPV), scheduled to start in June 2013. The IPV trial will take place in three locations in The Gambia: Fajikunda Health Centre, Sukuta Health Centre and the Jammeh Foundation for Peace Hospital. An open day programme is scheduled to take place at the Jammeh Foundation hospital in the near future.

Fajikunda Open Day

Commenting on Fajikunda’s key role in studies for better health in The Gambia and the developing world, Professor Beate Kampmann (Theme Leader – Vaccinology, MRC) said ‘Over the last few years, Fajikunda has become a very important partner to underpin our research for better vaccines in The Gambia and the wider global communities. We have built a very strong relationship with the community and our trials have achieved the highest retention rates we could wish for. This is very important for the completeness of our data but also for our funders, who trust when we tell them that Fajikunda is a site that always delivers. We look forward to the next study on polio starting soon and to build on this excellent track record.’


MRC & Sukuta: Celebrating 10 years of Working Together for Better Health

MRC, the Ministry of Health and the Sukuta community came together on 17th April to celebrate ten years of successful collaboration at the Sukuta Health Centre. The Open Day event was attended by the Speaker of the National Assembly, Hon Abdoulie Bojang, who spoke eloquently (in Mandinka) about the partnership between MRC and the Ministry of Health. Dr Adama Demba (Director of Health Services) delivered an address on behalf of the Minister of Health & Social Welfare. Homage was paid to Ms Sally Savage who recently retired after many years as the Principal Nursing Officer at Sukuta Health Centre. ‘Aunty Sally’ was acknowledged by all for the dedicated support she has given to the MRC's work over the years.

Recent and ongoing work: Studies at Sukuta over the years have included work on the measles vaccine schedule (Hilton Whittle); the trial of a new TB vaccine (MVA 85A - Martin Ota) and studies on how BCG vaccination influences the immune system (Sarah Burl).

Current work includes a trial of Vitamin A (presented by Dr Suzanna McDonald). The World Health Organization is sponsoring this study, investigating the role of Vitamin A in enhancing the protection of the newborn against early infections. Preliminary findings show that Vitamin A is well tolerated in newborns, with the full results expected in the coming year.

Beyond infants: The European Vaccine Initiative, in conjunction with MRC researchers, has successfully conducted malaria vaccine studies in adults, children and infants at Sukuta; the findings are paving ways for similar studies in other parts of Africa in the search for an effective vaccine to combat the disease (presented by Dr Muhammed Afolabi).

Looking forward: The Bill and Melinda Gates funded IPV trial investigating a new strategy of giving polio vaccines to children of 9 months is due to start in June (presented by Dr Ed Clarke).

VACCINOLOGY

Why Sukuta? Vaccines have been a success story in the developing world for a number of decades. However, as the number of vaccines administered increases, there is a growing need to understand how they affect the child’s health; how vaccines interact with each other and the best approach to administering them. Sukuta Health Centre has been a focal point for this research for over ten years, and from humble beginnings it has become an internationally respected site for clinical studies.

‘Studies involving newborns and infants are best carried out where the children are born and where they are being immunised.’ said MRC Unit Director Professor Tumani Corrah. ‘Distance is an important consideration: you look for a very productive health centre in terms of the number of deliveries and service to the community that is as close to the MRC’s laboratories as possible – and Sukuta clearly fits the bill.’

A ten year partnership: The Infant Immunology work at Sukuta was set up by Dr Arnaud Marchant (now based at the Universite libre de Bruxelles) in 2002, guided by Professor Hilton Whittle and others (although the MRC's collaboration with Sukuta dates back more than half a century). The first infant immunology study at Sukuta was focused on cytomegalovirus infection (CMV). Many of the studies that came subsequently were built on some of the principals established by this early work. Commenting on the choice of Sukuta as a field site, Dr Marchant said ‘Sukuta was chosen because it was a stable community; this stability is critical for the follow-up of the children. The Sukuta Health Centre also provided a strong basis because it was well organized by a highly motivated and dynamic team: we were made to feel very welcome by the staff.’

Pioneers of Sukuta include Marianne van der Sande (now based at RIVM, The Netherlands); Marianne was key to setting up the cohort and the site. David Miles played an important part in continuing the CMV work. And, as Dr Arnaud Marchant remarked ‘None of this would have been possible without the contribution of a highly dedicated, skilled field work team.’

Partnership: Studies conducted at Sukuta Health Centre have contributed to global policy changes, such as the addition of a measles booster dose to the childhood vaccine schedule. Such achievements could not have been realised without the partnership of the Ministry of Health and the cooperation of the people of Sukuta over many years.


Dr Ngozi Moneke did her first degree in Biochemistry at the University of Nigeria, Nsukka before proceeding to read Medicine, graduating in 2008. ‘I had a job offer in a bank which I abandoned to study Medicine in 2002’ she says.

Before coming to The Gambia, Dr Moneke worked in hospitals in Abuja and is now ‘working towards a life-long career in paediatrics and public Health.’ she says.

Her interest in paediatrics and public health is ‘based on the poor health systems in Africa that result in high rates of morbidity and mortality. I hope we will get to a time when the practice of medicine becomes more preventive than curative – and I am here to get equipped and to add my part to making the MDGs a reality in Africa.’ She says

Commenting on the IPV trials, she remarked ‘I am passionate about this project because it pains me to hear Nigeria listed among only 3 countries in the whole world with polio endemicity.’

And her expectations of her time in The Gambia? ‘To leave here a better person than I came; to leave my footprints in the MRC’s sands of time.’

Dr Ikechukwu Adigweme is a graduate of the University of Ibadan (Nigeria). A specialist in paediatrics, he arrived here from Lagos in June. Commenting on his new role with the IPV trials, he says ‘It promises to be a challenging (gulp) yet fulfilling experience, and I hope to contribute meaningfully both to the successful conduct of the project, as well as (hopefully) the broader issue of addressing child health in Africa.’

The Gambia is clearly a big change from the hustle and bustle of Nigeria. Dr Ikechukwu says ‘I'm immediately struck by the serenity and simplicity of life here...I think that I will enjoy the relaxed beauty of the social and physical environment with the focused intensity of the work environment!’

Dr Ama Onyebuchi Umesi graduated in Medicine and Surgery from the University of Port Harcourt in 2007. After graduation she did her National Youth Service with the Nigerian National Petroleum Corporation (NNPC) Medical Services and was employed by NNPC on completion of her Youth Service.

She proceeded to do a Masters in Public Health with emphasis on Health Service Research (HSR) at the University of Sheffield (UK), graduating in 2011 with Merit and receiving the Sheffield graduate award.

Dr Umesi says that she was motivated to do research as a result of her experience as an intern in the Naval Hospital in Lagos. ‘I realised that we practiced more curative than preventive medicine. My experience at Sheffield further

developed my skills and interest in research, and now I am here – I think that the MRC is a good place to realise my goals.’

Dr Umesi is married with two children.

VACCINOLOGY

IPV Trials Team welcomes new members

Kalilu Dibba

Recently, the Vaccinology Theme secured funding from the Bill and Melinda Gates Foundation to conduct a phase 4 clinical trial which is expected to determine the future role of the inactivated polio vaccine (IPV) within the expanded programme of immunisation (EPI) schedule. Just over 1400 infants are being recruited over a six month period, with results expected in the middle of 2014. The study is taking place at three sites: Sukuta, Fajikunda and at the Jammeh Foundation for Peace Hospital (Bundung). Meet the three IPV study clinicians who have joined the Unit to take up their busy, challenging new roles.


VACCINOLOGY

In conversation with ‘TB’s technical man-in-charge’

Patrick Owiafe from Ghana has worked with the Unit since 2000. Here he tells Ifunanya Egere his story.

Patrick, what is your background?After my secondary education, I enrolled in the school of medical laboratory technology at the Korle-Bu Teaching Hospital in Accra, graduating as a medical lab technician in 1983. After a year’s internship within the hospital, I finally settled in the Department of Microbiology of the University of Ghana Medical School where I worked until I joined the Unit.

In 1998, I was awarded a 4-month NIH/FOGARTY Fellowship for International Training in Emerging Diseases. I spent this period at the University of Virginia Charlottesville, USA. It was lab based training with emphasis on the practical application of technology, methodologies and practice related to emerging infectious diseases.

I started work at MRC Unit, The Gambia in October 2000. I was recruited as a lab technician initially, before we were re-designated as Scientific Officers.

What’s your current job? I oversee the routine running of the TB

Immunology lab; we have several studies that are running concurrently under TB immunology.

At what stage in your life did you become interested in science?I’ve always been interested in the medical science field. Initially I wanted to become a doctor, but due to financial constraints I ended up in the medical lab sciences field, and my interest grew when we began to study anatomy and physiology.

What are the least and the most satisfying aspects of your work?The most satisfying aspect is looking back from where I began in Ghana...

...Now, when I receive a sample or a patient comes to me and I take a sample, when it’s processed and examined and I see something confirming the cause of the illness, I get excited because that person’s problem has a potential solution.

The least satisfying aspect of my work is not getting meaningful results after long periods of assays and analysis, such as the disappointing TB vaccine MVA85A. I was deeply involved in this trial for 10 years.

What is your motivation?In 1982 whilst still a student, and applying a little of what I’d learned, I helped a friend with a diagnosis of infertility. This nearly ruined his marriage, but today he has 3 children and grandchildren, following 5 years of childlessness. This really motivated me to continue - and I can attest that I have helped a lot of people in solving their health problems through my work.

How has working with the MRC impacted your life?I’ve broadened my knowledge and my understanding of people’s health problems. I’ve had several training opportunities - both local and abroad - including a Masters degree, and I’ve been privileged to be part of four vaccine trials in this Unit.

At the MRC, I have had cross-cultural interactions with workers from all over the world. And I’ve been motivated by the well equipped laboratories and good facilities; in fact I’m still gaining more experience every day.

What are some of the highlights so far?I have gained skills in immunological research and clinical trials, giving me a better understanding of protective immune responses by our body cells. I have had a series of line managers and it gives me great joy to say that they have all attested to my performance and dedication - I’ve been the pillar of the TB Immunology Lab ever since I took up the role of ‘technical man in charge’! I really appreciate my role and the acknowledgement I get from my line managers, the people I’ve trained, the junior and senior staff and students who come for attachments - I’ve handled every one of them with lots of respect and support.

I see myself as being very open, friendly, always accommodating, so every now and then, even in busy times I still find time to attend to others’ needs including members of other programmes. For me this is exciting and fulfilling.

What are the challenges you face in your day to day work?Being in charge of the lab entails ensuring that the work is completed on time, especially when we receive samples late and have to process and set up assays etc, so I always go home late. This almost affected my marriage but thank God my wife was understanding.

What are your future plans?My long term goal is to be part of a team of highly successful professionals whose target is to identify and develop tools for the diagnosis, prevention, treatment and control of all forms of diseases of public health concern. I’ll continue to offer my expertise to achieve this wherever I’m favourably accepted to work.

VACCINOLOGY


The Stop-TB partnership/TB Reach scheme awarded a grant to MRC Unit, The Gambia and the National Leprosy & TB Control Programme of The Gambia at the end of 2011 to improve the diagnosis and management of children affected by TB in the Greater Banjul Area. In June, members of the MRCís TB Reach 4 Kids team visited the National Leprosy & TB Control Programme office to donate computer equipment to help boost capacity.

Centre: Mr Adama Jallow (Director NLTBP) with Professor Beate Kampmann.

About Stop TB

The Stop TB Partnership is leading the way to a world without tuberculosis (TB), a disease that is curable but still kills three people every minute. Founded in 2001, the Partnership's mission is to serve every person who is vulnerable to TB and ensure that high-quality treatment is available to all who need it.

Together our nearly 1000 partners are a collective force that is transforming the fight against TB in more than 100 countries. They include international and technical organizations, government programmes, research and funding agencies, foundations, NGOs, civil society and community groups and the private sector.

We operate through a secretariat hosted by the World Health Organization (WHO) in Geneva, Switzerland and seven working groups whose role is to accelerate progress on access to TB diagnosis and treatment; research and development for new TB diagnostics, drugs and vaccines; and tackling drug resistant- and HIV-associated TB. The secretariat is governed by a coordinating board that sets strategic direction for the global fight against TB.

CHILD SURVIVAL


Translational research is scientific research that helps to make findings from basic science useful for practical applications that enhance human health and well-being. Valorisation of research is the use, for socio-economic purposes, of the results of research financed by public authorities. It represents society’s direct and indirect return on the public sector’s investment in research and development.

Translational research, when conducted by Public Institutions, becomes Valorisation of Research.

Dr Stephen Howie (Theme Leader – Child Survival, MRC Unit, The Gambia) in collaboration with the London School of Hygiene and Tropical Medicine has recently been involved in a Biomarkers UK patent application with high potential to become an example of Valorisation of Research. The invention relates to one or more novel biomarkers for determining pneumococcal infection in a subject; it may also be used to assess the type of treatment that is appropriate for such an individual.

The invention also provides a kit for use in determining the diagnosis of severe malaria or severe pneumococcal infection. The kit may provide an indication useful in determining whether the subject should be referred to hospital due to the severity of the pneumococcal or malarial infection.

Dr Stephen Howie has also recently received a grant from the MRC Developmental Pathway Funding Scheme to develop and test a low-maintenance oxygen supply system for children with pneumonia and other diseases. The objective is to develop an oxygen (O2) delivery system for use in resource-limited settings that will operate 24/7 with little or no maintenance and limited or absent mains power - no such solution currently exists - with the aim to patent it. We propose to develop and field test a 24/7 oxygen system incorporating oxygen concentrator technology

and power storage, and independently power it using solar power where no power is available. With such a product, lifesaving treatment could reach those for whom it is currently beyond reach, and do so at a much lower cost than traditional oxygen cylinders. Roy Porter in his History of Medicine talks about the biomedical research paradox, “the unresolved disequilibrium between the remarkable capacities of an increasingly powerful science-based biomedical tradition and, on the other hand, the wider and unfulfilled health requirements of economically impoverished and politically mismanaged societies”.

Research valorisation may help to attract investment in research focused on solving the health problems of those who cannot pay for the development of those solutions, becoming the “magic bullet” that we are looking for to boost translational research to meet the health requirements of resource poor societies.

Translational Research: Child Survival Theme leading the way

Joan Vives Tomas

The Medical Research Council supports research across the whole spectrum of medical sciences, with the aim of improving human health. The MRC’s translational research strategy, developed in partnership with the Office for Strategic Coordination of Health Research (OSCHR) and partner organisations, aims to increase the scale and speed of progress from scientific discovery to clinical benefit.

A prototype oxygen system to deliver oxygen to up to five children where mains power is not reliable. Pictured in the foreground from left to right: Ebrima Nyassi (a biomedical engineering technologist at the unit), Bev Bradley, Stephen Howie and David Peel (standing).


CHILD SURVIVAL

About JessicaI grew up in Nova Scotia on the east coast of Canada and am the oldest of three children (I have a younger brother and sister). My bachelor’s degree in Biochemistry was completed in Montreal, Quebec and my PhD in Medical Genetics in Vancouver, British Columbia. I am here with my husband Don, who is also a Canadian. My free time at home was largely taken up by various sports- mainly skiing and mountain biking.

Work ExperienceAfter my PhD work in cancer genetics I transitioned to molecular microbiology. Most recently I have worked in two Canadian hospitals on influenza diagnostics and surveillance. I have been involved with test development and validation and have worked with a Canadian wide influenza serious outcomes surveillance project.

New RoleI am working as a Senior Scientific Officer with the PERCH project with Drs Howie, Antonio and Ebruke. I oversee all laboratory aspects of this project, which occur in both Basse and Fajara. I work closely with a team of Scientific Officers and Laboratory Technicians to undertake a wide range of traditional and molecular microbiology assays with the goal of understanding the etiology of severe pneumonia in young children.

Early Impressions of The GambiaMy husband and I have had an incredible adventure so far in The Gambia. For both of us this is our first time living in Africa and learning about life and the culture here has been an eye opening and enriching experience. We are definitely curious to see what the rainy season brings!

Future PlansI am just starting to feel settled in my new role and in The Gambia, and I am looking forward to enjoying the next year here. I am very interested in the clinical side of the research done by this Unit and hope to learn more about that aspect in the future.

New face for PERCH project

Tisbeh Faye-Joof

Meet Jessica McClellan who joined the Unit recently as a Senior Scientific Officer with The Bill & Melinda Gates-funded Pneumonia Etiology Research for Child Health (PERCH) project.


DISEASE CONTROL & ELIMINATION

PregnAnZI – Control of neonatal infections study takes off A double blind randomized control trial

Drs Claire Oluwalana, Bully Camara and Anna Roca

Why PregnAnZI?In sub-Saharan African countries, The Gambia inclusive, under-five mortality has seen a marked reduction. However, mortality in newborns (first 28 days of life) has remained high and currently represents about 40% of all under five deaths. Many of these deaths are caused by bacterial infections in the neonatal period that can be transmitted by the mother if she carries the bacteria. An intervention which will be cost effective is therefore needed to address this problem.

The focus of this study is to prevent bacterial infections in neonates by blocking maternal bacterial transmission using a low-cost intervention, the antibiotic Azithromycin (AZI) which will be administered to mothers in labour. The primary endpoint of the study is to assess prevalence of bacterial carriage of Streptococcus pneumonaie, Staphylococcus aureus, and group B Streptococcus (GBS) in the baby one week after birth. Other bacterial determinations in the mother and the baby will also be done within the first 4 weeks after delivery.

The journey so far….. On April 3 2013, the first participant was enrolled into this novel Medical Research Council sponsored trial. The study is being conducted by the MRC at the Jammeh Foundation for Peace Hospital which has comprehensive antenatal facilities. Post–natal care ensures mothers are observed for a period of 6-12 hours before discharge home to avoid complications resulting from post partum haemorrhage and sepsis. The health facility records approximately 4000 deliveries annually and 850 participants are required for enrolment within one year. At present, this initial target has been met; 61 participants have been enrolled and more than 200 women have signed consent to participate in the study.

The challenges…One of the main challenges so far has been the higher than expected use of antibiotics by mothers before coming into hospital in labour; an additional issue is that mothers often come to the health facility too late to be given the intervention before they deliver.

Recruitment has been slower than planned as maternal consent is given during pregnancy and we have to wait until these mothers are due. Deliveries are seasonal in The Gambia and we are still (at the time of writing) in the lower season. However, the number of sensitized and consented women is steadily increasing, thanks to good sensitization activities conducted by our field team, and we still believe we will get our targeted numbers within the timeframe.

Despite these and other challenges involved in running a clinical trial, the committed study staff and drivers are working diligently day and night to ensure timely delivery of study targets.

The outcome of this study is very important because this low cost intervention targets the most vulnerable population in Africa, where deaths are concentrated. If the results are positive, the intervention will be scaled up to a lower level of care.



Control & Elimination of Malaria: the PRINOGAM Trial

Joan Vives Tomas

Primaquine, an 8-aminoquinoline is effective against the sexual stage of the malaria parasite which is needed for continuing transmission in the mosquito. The current WHO treatment guideline recommends adding a single dose of primaquine to an artemisinin-based combination treatment (ACT) in the context of (pre-) elimination programmes. Such a recommendation could be extended to either mass-drug administration or systematic screening and treatment programmes targeting asymptomatic parasite carriers. However, concerns on its safety and dosage especially in malaria endemic areas which also have high prevalence of glucose-6-phosphate dehydrogenase deficiency limit its use.

The Disease Control & Elimination Theme led by Professor Umberto D’Alessandro recently secured funds to conduct a trial to determine the lowest possible dose of primaquine needed for eliminating gametocytes in asymptomatic malaria carriers. The primary end point is the gametocyte prevalence in individuals treated with dihydroartemisin-piperaquine either alone or in association with primaquine. Also known by the acronym PRINOGAM, it is being conducted in collaboration with the partners in the Gambia Government and external collaborators. The study will run over two transmission seasons in 2013 and 2014 around the Basse and Walikunda field stations.

Results of the trial will be generalisable to settings where P. falciparum transmission has declined significantly with the possibility of reducing it to extremely low levels or even interrupting it. Results will provide the necessary assurance to policy makers and national malaria control programs that primaquine can be used on a large scale with little or no risk for a targeted population.

P. faciparum


TB prevalence survey: Gambia in the lead

Joan Vives Tomas

The Tuberculosis (TB) epidemic declared in 1993 by the World Health Organization (WHO) persists today, as TB remains one of the leading causes of death from an infectious disease, with an estimated incidence of 8.7 million cases in 2011 causing 1.4 million deaths. All countries are affected, but 85% of cases occur in Africa (30%) and Asia (55%), while India and China alone represent 35%.

TB prevalence surveys are useful for obtaining a direct measurement of the absolute burden of disease caused by TB especially in many countries with a high burden of TB where there is considerable uncertainty about the number of TB cases and deaths, due to incomplete coverage or absence of surveillance systems.

The prevalence of TB is the only TB-related MDG indicator that can be directly measured in most high-burden countries. However, they are considered an interim solution for assessing the burden of TB disease with a long-term goal of direct measurement using routine surveillance data i.e. case notification data for TB and vital registration data for TB-related mortality.

MRC Unit, The Gambia has successfully completed the first prevalence survey to be done in West Africa for the last 50 years (although Nigeria has now joined in).

The Gambia Survey of Tuberculosis Prevalence (GAMSTEP) screened 43,100 people in 80 clusters over a 14-month period. GAMSTEP was the first survey in Africa to deploy a mobile, direct digital radiology solution for chest X-ray screening and other countries including Rwanda, Ghana and Senegal have benefitted from the Gambian experience.

The use of portable X ray machines, the presence of a dedicated principal investigator (Dr Ifedayo Adetifa), project manager and finance officer were essential to the success of the survey. These, together with the robust project and finance management system at the MRC Unit, The Gambia provided strong monitoring and evaluation (M&E) capabilities to support this survey. Organizing shifts to ensure the laboratory was able to cope with a significantly increased sample flow, a committed field team that flexibly dealt with unexpected changes to the survey schedule, the support of a strong institution, together with the collaboration of civic and government institutions are examples of good practices that should be shared.

There were a number of challenges during the life of the survey including budget shortfalls; unforeseen increases in fuel costs, challenges in the use of mobile direct digital X-ray in difficult operating conditions; and other costs pressures. These experiences would no doubt help others planning TB prevalence surveys in the future.

There is limited, albeit slowly increasing, experience in the sub-continent of designing and conducting TB prevalence surveys. Countries in sub-Saharan Africa vary substantially in terms of socioeconomic standing, infrastructure, climate etc, and such factors make it difficult to generalise. However, MRC Unit, The Gambia’s experience should, in addition to providing quality TB epidemiology data for the country, provide evidence and data that will help the WHO, National TB Programmes and other local, regional and international partners in planning and monitoring the implementation of TB prevalence surveys.


Global Fund TB project (GAMSTEP) community sensitisation in Bakau


Update from the Head of Operations

The Field Station has strengthened its capacity to host more projects and meet the operational needs of our scientists and collaborators. Here are a few developments:

Ms Gyasiwaa AmofaHead of Operations – Basse

NEWS FROM BASSE Amulai Touray

� A new site was acquired last year and construction of 8 x 2 bedroom flats has commenced. This will alleviate current accommodation problems and could serve as a flood response site.

� An on-site general store has been constructed to help ensure proximity of consumables and supplies on demand for projects and the Platform.

� The famous Basse heat surge with its attendant power disruption problems was alleviated this year by the commissioning of a new 250 kva generator.

� There has been a major refurbishment of the Walikunda entomology field site. The

site will be hosting the Prinogam and the MRC malaria programme grant projects for the next 3 years.

� In addition to Prinogam and the MRC Malaria Programme Grant project, Basse Field Station welcomes the following new studies:

� Malaria in Pregnancy

� The Oxygen project.

We are delighted with the overall progress we are making at the MRC’s field flag ship.

Health and Safety Week and Centenary Celebrations in URR

In recognition of Basse Field Station’s growing strategic importance to the MRC, this year’s Health & Safety celebrations were hosted at the field site. The programme was combined with commemorative activities to mark the Medical Research Council’s 100th birthday.

Governor URR (centre) visiting the Field Station during Health & Safety Week activities; Health and Safety Inspection teams led by Professor Tumani Corrah and Ms Sarah Sarpong touring Basse site to identify safety concerns


A number of senior staff travelled from the coast to the Field Station for the programme. The opening ceremony was also attended by the Governor of URR, Alhaji Omar Khan; The Director of the Regional Health Team, Alhaji Sankareh and other local luminaries.

The theme of this year’s ILO World Day for Safety and Health at Work was the prevention of occupational diseases. Reflecting on this theme, Professor Tumani Corrah emphasized the importance of pre-employment medical examinations, proper job placement according to physical and mental capabilities, First Aid provision and immunization, particularly relevant to our setting where teams may work in remote, rural locations. He highlighted the importance of Personal Protective Equipment (PPE), urging staff to use these where appropriate. Staff were also reminded to report accidents without fear of reprimand from management to ensure the implementation of remedial action where necessary.

In her address, Health and Safety Manager Sarah Sarpong lamented the general lack of attention to health and safety at work in Africa and stated that organizations, including the International Labour Organisation and the Health & Safety Executive work to raise the level of consciousness amongst various countries - including those in Africa. These organisations are vital because they advocate the incorporation of health and safety into national policy and encourage tripartite consultation between the government, employers and workers.

After the opening ceremony, Dr Shahito Shah gave a talk on stress management. Other activities on day one of the programme included a Health and Safety Quiz and a football match between Basse Town and the MRC Basse team, with Professor Corrah taking the kick off.

On the second day of the programme, a set-settal (clean up) exercise was conducted on the Basse main road, starting from the entrance to Basse Major Health Centre.

Later that day, Professor Tumani Corrah, Drs Jahangir Hossain, Bernard Ebruke and Mr Musa Jawara visited Nassir Senior Secondary School in Basse where they addressed the students on diarrhoea, pneumonia and malaria. Ms Sarpong spoke on health & safety.

Following the talks, Ms Rosemond Gyasiwaa presented commemorative centenary books and other items to the school.

As part of the Health & Safety Week celebrations, First Aid training was conducted by Musa Colley, attracting participation from all sections of the workforce.

Basse also ran a special '100 Ideas' competition to mark the Medical Research Councilís centenary, with prizes awarded by the Head of Operations, Basse Field Station.

NEWS FROM BASSE

Set Settal in Basse Town; Scientific Laboratory Supplies donated a Hull City football kit, which was given to Basse Town Football Club

Students of Nassir Amadiyya Senior Secondary School


Science students visit Basse labs

Pupils of St George’s Senior Upper Basic School visited the Field Station recently, accompanied by Father Fredrick Agame, the resident priest of the Catholic Church in Basse (also a member of the school’s management board); Mr Ebenezer K Osei, head of the science department; and Mr SA Gardrie, chemistry teacher. They were given a tour of the various labs, the Insectary and received a lecture from Mr Rasheed Salaudeen (Scientific Officer) on the work, the importance of science and career prospects for science students.

Lamin S Jaiteh and Sainey Kanteh also gave the visitors a tour of the Insectary where they were shown how mosquitoes are bred and how a colony of parasite free mosquitoes is kept for research purposes.

Following the tour, Father Agame expressed his gratitude to the MRC, expressing the hope that MRC staff would talk to ñ and encourage - more students in the future.

NEWS FROM BASSE

Basse and the community

MRC supports Basse Major Health Centre

Following the signing of a Memorandum of Understanding between the Ministry of Health and the MRC, a cleaning support programme was launched on 23rd April 2013 at Basse Major Health Centre.

MRC Unit, The Gambia has undertaken to pay the salaries of six orderlies based at the Health Centre. Cleaning materials were also donated.

The Officer in Charge of the Health Centre, Mr Burama Badjie, thanked the Unit and gave assurances that this support would boost the level of cleanliness at the facility.

Donating cleaning materials at Basse Major Health Centre with Professor Corrah, Gyasiwaa and Pa Cheboh Saine

Rasheed Salaudeen and the pupils of St George’s School


NEWS FROM BASSE

New Global Study Pinpoints Main Causes of Childhood Diarrheal Diseases, Suggests Effective Solutions

Findings published in The Lancet can guide prevention, treatment and research on diarrheal diseases, which claim the lives of 800,000 children annually

An international study published in The Lancet provides the clearest picture yet of the impact and most common causes of diarrheal diseases, the second leading killer of young children globally, after pneumonia.

The Global Enteric Multicenter Study (GEMS) is the largest study ever conducted on diarrheal diseases in developing countries, enrolling more than 20,000 children from seven sites across Asia and Africa. The multisite study was co-ordinated by the University Of Maryland School Of Medicine’s Center for Vaccine Development.

“Our ability to reduce the burden of diarrheal diseases has always been limited by a lack of understanding of exactly which pathogens cause the most disease,” said Dr Jahangir Hossain, GEMS GEMS Principal Investigator at The Gambia trial site. “GEMS data serves as a guide on how to reach our goals for reducing this burden and improving child health.”

Despite many causes, GEMS found that targeting just four pathogens could prevent the majority of MSD cases. Expanding access to vaccines for rotavirus, the leading cause of MSD among infants at every site, could save hundreds of thousands of lives. Likewise, GEMS data suggests that accelerating research on vaccines, treatments and diagnostics for the three other leading pathogens – Shigella, Cryptosporidium and ST-ETEC, a type of E. coli – could have a similar impact. Prior to GEMS, Cryptosporidium was not considered a major cause of diarrheal disease and as a result there is currently little research on this pathogen underway.

The GEMS findings also suggest that longer-term monitoring and care of children with diarrheal diseases could reduce mortality and

developmental delays. Children with MSD grew significantly less in height in the two months following the diarrheal episode when compared with control children without diarrhea, and were 8.5 times more likely to die over the course of the two-month follow-up period. Notably, 61 percent of deaths occurred more than a week after the initial diarrheal episode, with 56 percent of deaths happening after families had returned home from a healthcare facility.

At Basse, similar to other sites, rotavirus was found to be the leading cause of MSD in infants – reinforcing the importance of rotavirus vaccines – and Shigella, Cryptosporidium and ST-ETEC were all major contributors. Unlike at other sites, Norovirus GII was the third leading cause of MSD and the overall burden of MSD was greater among toddlers than infants. Linear growth delays were significant among children ages 1-5 years old in the two months following their MSD episode, and a single episode of MSD increased children’s risk of death sevenfold over the same period. In The Gambia, just a small proportion of children with MSD in the community are routinely receiving oral rehydration solution and zinc, which are known to be effective treatments.

According to Dr Jahangir, expanding access to existing interventions that protect against or treat all diarrheal diseases, including oral rehydration solutions, zinc supplements, clean water and sanitation, can save lives and improve the health of children immediately. He continued by lamenting that only 16% of care-givers in The Gambia use ORS when their child is suffering from diarrhea. It is important to promote ORS, Zinc and rotavirus vaccine in The Gambia and globally for diarrhea management to reduce childhood death due to diarrheal illness. As Dr Jahangir concluded ‘the success achieved is great, not only from the GEMS team but for the Basse Field Station family as whole and the Unit in general.’


NEWS FROM BASSE

Basse & Farafenni Health & Demographic Surveillance Systems

Verbal autopsies training for field assistants

In resource-poor settings, characterized by incomplete or absent registration systems, most deaths occur at home and are not registered with certified causes of death by qualified physicians. There is a consequent dearth of information on causes of death in such areas, presenting significant challenges in terms of effective planning, monitoring and evaluation of national and district health care delivery systems.

The Verbal Autopsy (VA) is used to ascertain the cause of death using interviews with the next of kin or other caregivers of the deceased person. A standardized questionnaire elicits information on signs, symptoms, medical history and circumstances preceding the death; in many areas, this has become the only viable option for generating cause-of-death information, including areas of rural Gambia.

Since the cause of death, or the sequence of events leading to death, are assigned based on the data collected by the questionnaire and any other available information, it is essential that field assistants are familiar with the questionnaires and maintain a high degree of consistency in the way they ask questions across the different languages. To address these issues, Dr Momodou Jasseh (Unit Demographer) recommended a two-week training session for 13 field assistants and data entry clerks. The training included the adoption of a standard way of asking questions during interviews in Mandinka, Fula, Sarahule and Wolof.

In the absence of formal death registration systems, VA is an essential public health tool for obtaining reasonable information on cause of death at the community or population level, providing an evidence base for health policy, planning, monitoring and evaluation.

Pierre Gomez and Mamadi Sidibe, Field Coordinators for Farafenni HDSS and Basse HDSS respectively (front row) with the VA Team. There are plans to conduct over 6,000 VA interviews in the Basse and Farafenni HDSS sites between June and August 2013.


NEWS FROM BASSE

Encounter with Dr Ebirim Ahamefula

Meet the new Research Clinician with the Pneumococcal Surveillance Project in Basse, Dr Ebirim Ahamefula. He came to The Gambia as a doctor with the Nigerian Technical Assistance Corps originally. After his tour ended he joined Dr Kalifa Bojang’s malaria control study 2004, and has worked with the Unit ever since. Here he continues his story.

Trekking...Whilst I was working on the malaria control study, especially at the field survey stage, I had the opportunity to visit various locations all over the country. When I was based in Fajara, I also worked full time in the Clinical Services Department, including a short stint as the Staff Medical Doctor.

From there I moved on to Keneba, where I remained until December 2012. Within this 7 year period, I was privileged to be involved in all the studies that went on in Keneba, as a Study/Research Clinician; these gave me a wealth of experience in clinical, supplementation and interventional studies - I enjoyed my stay in Keneba.

...To BasseBasse’s like Keneba, only better in the sense that it is more cosmopolitan with a mix of different ethnic groups and nationalities, yet retaining the sense of isolation of a provincial settlement. You do not stand out as much as a foreigner here; in Keneba I was often referred to by the kids as “Toubabi”, during my keep fit strolls through the village. On the coast, there are more distractions and getting around is more problematic. Also I enjoy working with the indigenous population and I believe my clinical skills and experience will be more needed here than at the coast where there are more doctors and facilities. In fact I can sense it already that people – colleagues and clients alike – are happy to have me around and for that I am grateful to all of them for their warmth and hospitality.

PSP is not entirely novel to me (having done epidemiology in medical school), but in terms of what I have done in MRC in the past, it represents a new challenge. Here the emphasis is not so much on treatment as is the case in interventional/supplementation studies, but on surveillance – unearthing and quantifying/ categorizing the disease burden in order to empower government and other stake holders to take appropriate action. It’s a bit different, but no less important. It is quite interesting and I am happy to be here. As you attend the routine Data cleaning meetings, the QA (Quality Assurance) and QC (Quality Control) sessions, you begin to see yourself not just as a clinician, but also as a researcher. It broadens your resource base and helps you to appreciate the bigger picture.

What are your future plans?Let me state ab initio that at this stage of my evolution, I am happy to take life one day at a time... But I do have plans for the future, one of which is to see how best to utilise this occasion of my second missionary journey in the MRC to improve my career through on-line learning. A MPH would do quite nicely, God willing!

I’d also like the opportunity to supervise a project sooner rather than later. A career in research no longer seems the distant prospect as it once was to me...

I want to thank everyone that has impacted positively on my stay here in the MRC. From the Unit leadership, to the Keneba management team and now my colleagues in Basse who have given me such a warm welcome - especially to Dr Grant Mackenzie (my line manager) for giving me the opportunity to be involved in the project.


Georgia’s Cambridge/Keneba experience

Georgia Billing is a PhD student with the MRC Human Nutrition Research (HNR) unit, Cambridge. Her supervisor is Dr Gail Goldberg, a senior research scientist at HNR. Georgia came to Keneba a year ago to conduct a feasibility assessment for her PhD research work and she is now here to do her project.

NEWS FROM KENEBA Yankuba Sawo

Georgia, what’s the background to your arrival in Keneba?I had completed my MSc in Skeletal Bioarchaeology and was volunteering in Argentina as an osteoarchaeologist when I applied for a PhD with The Nutrition and Bone Health Group at HNR. The research area interested me because of similarities to my previous work, where I had looked at nutritional deficiencies and bone growth, particularly rickets, and comparing different social contexts. The chance to study in Cambridge and travel to The Gambia were also very attractive!

What is your study about?The Breast Milk Vitamin D in Gambian Women study looks at quantifying vitamin D compounds in human breast milk samples and vitamin D that circulates in maternal blood (vitamin D status). Vitamin D is made in skin when exposed to UVB-wavelengths in sunlight, which we measure by placing electronic UVB-dosimeter badges with individual mothers and infants. We also record maternal vitamin D and calcium intakes using a food questionnaire.

How does that relate to Gambian children?Newborns have two natural sources of vitamin D: their mother’s milk, and skin-synthesis if exposed to a little UVB-sunlight. The sun shines intensely throughout the year in The Gambia, and although mothers usually protect their young children from direct sunlight, some UVB

exposure is inevitable. We are looking at relationships between mother and infant pairs, and we are interested in how breastfeeding and each infant’s own UVB-exposure may contribute to infant vitamin D status.

What is it that you are trying to prove, or seeking to add to scientific knowledge? Previous studies have shown that vitamin D in breast milk is low, placing some exclusively breastfed infants at risk of vitamin D deficiency and rickets. However, these studies have only been done in populations where vitamin D status is poor or marginal. My study is novel because it measures breast milk vitamin D from rural Gambian women, who have good vitamin D status due to year-round UVB-sunlight availability. The results will represent natural biological relationships between vitamin

D metabolism and lactation, which will help policy-makers understand if supplements should be recommended for mothers and/or infants in different settings.

Describe the method(s) you are using for these investigationsWe are assessing total breast milk intakes of infants using water labelled with a stable isotope. The mother drinks a dose of deuterium (2H2O), which then enriches her body water, including her saliva and breast milk. When she nurses her infant, the deuterium appears in his/her body water and is excreted through urine. Small samples of maternal saliva and infant urine are collected daily over two weeks, and the enrichment and gradual disappearance of deuterium in these samples is measured to estimate how much breast milk the infant consumed. The technique is non-invasive, does not interrupt feeding patterns, and will be teamed with nutrient analysis in breast milk samples to calculate vitamin D intakes from breastfeeding.

What comparative studies are you doing at HNR?I am waiting for ethical approval to recruit mothers and infants from Cambridge to take part in a parallel study to obtain directly comparable information from both countries. The Cambridge protocol is designed almost identically to that in The Gambia, with a few logistical differences. In Cambridge, mothers collect breast milk samples themselves and


NEWS FROM KENEBA

Keneba women express their solidary with the MRC

In the last issue of Tama, readers will recall that the Keneba community pledged to support MRC research and participate in cleaning the MRC premises periodically, and on Sunday 26th May, the women’s Kaffoos (community groups) came to fulfil their promise by staging a clean-up operation.

freeze them at home, whereas here in The Gambia, dedicated fieldworkers ride motorbikes along dusty roads, visiting mothers each day to collect their samples for storage back at the Keneba laboratory.

I am now in my final year of my PhD - juggling between running studies and drafting my thesis! Completing the final chapters will be quite tight because I have lots of samples to analyse, but valuable support from both my supervisor and group is helping enormously to keep my outlook positive.

How do you find working in MRC Keneba?Fieldwork in Keneba is certainly a change from the archaeological excavations and dry-bone specimens I am used to! Working with live human volunteers has been an enjoyable but challenging transition, and I feel lucky to learn from motivated and experienced staff so willing to patiently share their expertise.

Any lasting memories of The Gambia?The tasty food of course - I’ll miss peanut durango, fresh mangoes straight from the tree, and baobab juice! Trying to learn some African dances was also unforgettable, as well as taking part in the Keneba sports events. It’s a real privilege to be involved within such a close sense of team spirit- everyone has been so welcoming and I’ll always be grateful.

After their work, the women met Dr Rita Wegmuller, Head of Station and Mr Buba Jabang (Field Station Administrator) and once again pledged their support for the MRC. The older women narrated the histories of the research activities they had participated in at a time when things were very difficult. They spoke of the positive changes they had witnessed over the years and advised young women of child bearing age to unite and support the MRC.

Dr Wegmuller thanked the women’s groups for embarking on the cleaning exercise and their continued support for the MRC’s research activities.

She assured them of the MRC’s commitment to serving the community and people of The Gambia. Mr Buba Jabang also thanked the women’s groups for helping him to maintain the estate. He pledged to work with the women to promote general cleanliness as a foundation of good health.

Keneba Field Station management provided breakfast for the women, with Fatou Colley and Kanimang (administration) helping to coordinate the catering.


RECENT UNIT PUBLICATIONS

Malaria Phase Ib Clinical Trial ‘promising’

Dr Muhammed Afolabi

The paper “Safety and Immunogenicity of Heterologous Prime-Boost Immunisation with Plasmodium falciparum Malaria Candidate Vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in Healthy Gambian and Kenyan Adults” describes the results of the heterologous prime boost immunisation with chimpanzee adenovirus 63 (ChAd63) and Modified vaccinia Virus Ankara (MVA) vectored vaccines, carrying the P. falciparum pre-erythrocytic antigen ME-TRAP (multiple epitope string with thrombospondin-related adhesion protein). This strategy has already been shown to be capable of inducing strong cell mediated responses against several other antigens from the malaria parasite. For the MVVC study, a phase Ib dose escalation clinical trial was assessing the safety and immunogenicity of the vaccine in 46 healthy malaria exposed adults in Kenya and The Gambia. The team reports that the vaccine was shown to be safe and immunogenic, inducing high-level T cell responses. The paper therefore concludes that the tested vectored vaccine is safe and highly immunogenic in adults with prior exposure to malaria.

Ogwang C, Afolabi M, Kimani D, Jagne YJ, Sheehy SH, Bliss CM, Duncan CJ, Collins KA, Garcia Knight MA, Kimani E, Anagnostou NA, Berrie E, Moyle S, Gilbert SC, Spencer AJ, Soipei P, Mueller J, Okebe J, Colloca S, Cortese R, Viebig NK, Roberts R, Gantlett K, Lawrie AM, Nicosia A, Imoukhuede EB, Bejon P, Urban BC, Flanagan KL, Ewer KJ, Chilengi R, Hill AV, Bojang K. PLoS One. 2013;8(3):e57726. doi: 10.1371/journal.pone.0057726. Epub 2013 Mar 19.

Microbes and the malnourished child More than 20 million children worldwide suffer from severe malnutrition including a form called marasmus. Two new studies of malnourished children in Malawi, discussed in a Focus in this issue by Prentice et al., provide vital new insights into the causes of and potential treatments for severe malnutrition. One study demonstrates that combining antibiotics with a special feeding regimen for severely malnourished children provided greater reductions in mortality than treatment with therapeutic foods alone. The second study, which analyzed the gut microbiomes of malnourished twin pairs fed a Malawian diet versus ready-to-use therapeutic foods, clearly demonstrates the part played by a dysfunctional gut microbiome and altered microbial metabolism in severe malnutrition

Prentice AM, Nabwera H, Kwambana B, Antonio M, Moore SE. M Sci Transl Med. 2013 Apr 10;5(180):180fs11. doi: 10.1126/scitranslmed.3006212.

Deciphering the Growth Behaviour of Mycobacterium africanumHuman tuberculosis (TB) in West Africa is not only caused by M. tuberculosis but also by bacteria of the two lineages of M. africanum. For instance, in The Gambia, 40% of TB is due to infections with M. africanum West African 2. This bacterial lineage is associated with HIV infection, reduced ESAT-6 immunogenicity and slower progression to active disease. Although these characteristics suggest an attenuated phenotype of M. africanum, no underlying mechanism has been described. From the first descriptions of M. africanum in the literature in 1969, the time to a positive culture of M. africanum on solid medium was known to be longer than the time to a positive culture of M. tuberculosis. However, the delayed growth of M. africanum, which may correlate with the less virulent phenotype in the human host, has not previously been studied in detail.

The investigators compared the growth rates of M. tuberculosis and M. africanum isolates from The Gambia in two liquid culture systems. M. africanum grows significantly slower than M. tuberculosis, not only when grown directly from sputa, but also in growth experiments under defined laboratory conditions. They also sequenced four M. africanum isolates and compared their whole genomes with the published M. tuberculosis H37Rv genome. M. africanum strains have several non-synonymous SNPs or frameshift mutations in genes that were previously associated with growth-attenuation. M. africanum strains also have a higher mutation frequency in genes crucial for transport of sulphur, ions and lipids/fatty acids across the cell membrane into the bacterial cell. Surprisingly, 5 of 7 operons, recently described as

Muhammed Afolabi

Brenda Kwambana

Martin Antonio



essential for intracellular survival of H37Rv in the host macrophage, showed at least one non-synonymously mutated gene in M. africanum.

Conclusion: The altered growth behaviour of M. africanum might indicate a different survival strategy within host cells.

Gehre F, Otu J, Deriemer K, de Sessions PF, Hibberd ML, Mulders W, Corrah T, de Jong BC, Antonio M. PLoS Negl Trop Dis. 2013 May 16;7(5):e2220.

Viral hepatitis in resource-limited countries and access to antiviral therapies: current and future challenges

Chronic viral hepatitis is a major public health issue worldwide and mostly affects resource-limited countries. These regions combine a considerable set of barriers to containing the epidemic, including shortage of healthcare workers, poor medical infrastructures, insufficient screening and poor access to care and treatment. At a time when morbidity and mortality of chronic liver disease has been widely improved in wealthy countries by new innovative strategies and potent antiviral drugs, it is now urgent to face the challenges of better management of chronic hepatitis in resource-poor countries from the perspectives of global health and social justice.

Lemoine M, Nayagam S, Thursz M. Future Virol. 2013 Apr;8(4):371-380.

Skewing of the CD4+ T-Cell Pool Toward Monofunctional Antigen-Specific Responses in Patients With Immune Reconstitution Inflammatory Syndrome in The Gambia

A common complication of starting antiretroviral therapy (ART) for human immunodeficiency virus (HIV) is the development of immune reconstitution inflammatory syndrome (IRIS) in approximately 25% of patients. Despite similarities with paradoxical reactions to tuberculosis and reversal reactions in leprosy, the exact mechanisms, and therefore potential determinants, of IRIS are still unknown.

In this longitudinal cohort study, investigators analyzed 20 patients who developed IRIS following initiation of ART and 16 patients who did not, matched for ART time point. Peripheral blood mononuclear cells were stimulated overnight with a positive control antigen and 2 tuberculosis-specific antigens (purified protein derivative [PPD] and ESAT-6/CFP10), followed by polychromatic flow cytometry for analysis of cytokine production from CD4+ and CD8+ T cells.

Results: Responses to PPD were significantly higher in IRIS patients compared to controls during the IRIS time point, but CD4+ and CD8+ T-cell responses to the positive control stimulation were significantly lower in IRIS patients at all time points. Furthermore, whereas control patients had rejuvenated polyfunctional T-cell responses by 3 months after ART, IRIS patients were strikingly monofunctional (generally interferon γ alone), even up to 6 months of ART in response to all stimulations.

Conclusions: The investigators’ findings suggest that the peripheral T-cell responses to the underlying pathogen are exaggerated in IRIS patients but that the overall quality of the peripheral T-cell pool is significantly reduced compared

to non-IRIS patients. Furthermore, these effects are apparent at least up to 3 months after cessation of IRIS.

Wilson H, de Jong BC, Peterson K, Jaye A, Kampmann B, Ota MO, Sutherland JS. Am J Trop Med Hyg. 2013 Apr 29. [Epub ahead of print]

Maud Lemoine

Jayne Sutherland



Healthcare-Seeking for Childhood Diarrhea in Developing Countries: Evidence from Seven Sites in Africa and Asia.

The investigators performed serial healthcare use surveys among caretakers of children ages 0-59 months randomly selected from demographically defined populations participating in the Global Enteric Multicenter Study (GEMS), a case control study of moderate-to-severe diarrhea (MSD) in seven developing countries. The surveys aimed to estimate the proportion of children with MSD who would present to sentinel health centers (SHCs) where GEMS case recruitment would occur and provide a basis for adjusting disease incidence rates to include cases not seen at the SHCs.

The proportion of children at each site reported to have had an incident episode of MSD during the 7 days preceding the survey ranged from 0.7% to 4.4% for infants (0-11 months of age), from 0.4% to 4.7% for toddlers (12-23 months of age), and from 0.3% to 2.4% for preschoolers (24-59 months of age). The proportion of MSD episodes at each site taken to an SHC within 7 days of diarrhea onset was 15-56%, 17-64%, and 7-33% in the three age strata, respectively.

High cost of care and insufficient knowledge about danger signs were associated with lack of any care-seeking behavior outside the home. Most children were not offered recommended fluids and continuing feeds at home.

The investigators have shown the utility of serial healthcare use surveys as an invaluable tool for optimizing operational and methodological issues related to the performance of a large case control study and deriving population-based incidence rates of MSD. Moreover, the surveys suggest key targets for educational interventions that might improve the outcome of diarrheal diseases in low-resource settings.

Nasrin D, Wu Y, Blackwelder WC, Farag TH, Saha D, Sow SO, Alonso PL, Breiman RF, Sur D, Faruque AS, Zaidi AK, Biswas K, Van Eijk AM, Levine MM, Kotloff KL. Am J Trop Med Hyg. 2013 Apr 29. [Epub ahead of print]

Comparison of parasite sequestration in uncomplicated and severe childhood Plasmodium falciparum malaria

The objectives of the study were to determine whether sequestration of parasitized red blood cells differs between children with uncomplicated and severe Plasmodium falciparum malaria. The investigators quantified circulating-, total- and sequestered-parasite biomass, using a mathematical model based on plasma concentration of P. falciparum histidine rich protein 2, in Gambian children with severe (n = 127) and uncomplicated (n = 169) malaria.

Results: Circulating- and total-, but not sequestered-, parasite biomass estimates were significantly greater in children with severe malaria than in those with uncomplicated malaria. Sequestered biomass estimates in children with hyperlactataemia or prostration were similar to those in uncomplicated malaria, whereas sequestered biomass was higher in patients with severe anaemia, and showed a trend to higher values in cerebral malaria and fatal cases. Blood lactate concentration correlated with circulating- and total-, but not sequestered parasite biomass. These findings were robust after controlling for age, prior antimalarial treatment and clonality of infection, and over a realistic range of variation in model parameters.

Conclusion: Extensive sequestration is not a uniform requirement for severe paediatric malaria. The pathophysiology of hyperlactataemia and prostration appears to be unrelated to sequestered parasite biomass. Different mechanisms may underlie different severe malaria syndromes, and different therapeutic strategies may be required to improve survival.

Cunnington AJ, Bretscher MT, Nogaro SI, Riley EM, Walther M. J Infect. 2013 Apr 23. pii: S0163-4453(13)00102-3. doi: 10.1016/j.jinf.2013.04.013.

Correlates of T-cell-mediated viral control and phenotype of CD8+ T cells in HIV-2, a naturally contained human retroviral infection

While a significant proportion of HIV-2-infected individuals are asymptomatic and maintain undetectable viral loads (controllers), 15% to 20% progress to AIDS and are predicted by detectable viremia. Identifying immune correlates that distinguish these 2 groups should provide insights into how a potentially pathogenic retrovirus can be naturally controlled.

The investigators performed a detailed study of HIV-2-specific cellular responses in a unique community cohort in Guinea-Bissau followed

Debasish Saha

Aubrey Cunnington



for over 2 decades. T-cell responses were compared between controllers (n = 33) and viremic subjects (n = 27) using overlapping peptides, major histocompatibility complex class I tetramers, and multiparameter flow cytometry. HIV-2 viral control was significantly associated with a high-magnitude, polyfunctional Gag-specific CD8(+) T-cell response but not with greater perforin upregulation. This potentially protective HIV-2-specific response is surprisingly narrow. HIV-2 Gag-specific CD8(+) T cells are at an earlier stage of differentiation than cytomegalovirus-specific CD8(+) T-cells, do not contain high levels of cytolytic markers, and exhibit low levels of activation and proliferation, representing distinct properties from CD8(+) T cells associated with HIV-1 control.

These data reveal the potential T-cell correlates of HIV-2 control and the detailed phenotype of virus-specific CD8(+) T cells in a naturally contained retroviral infection.

de Silva TI, Peng Y, Leligdowicz A, Zaidi I, Li L, Griffin H, Blais ME, Vincent T, Saraiva M, Yindom LM, van Tienen C, Easterbrook P, Jaye A, Whittle H, Dong T, Rowland-Jones SL. Blood. 2013 May 23;121(21):4330-9. doi: 10.1182/blood-2012-12-472787. Epub 2013 Apr 4.

Critical windows for nutritional interventions against stuntingAn analysis of early growth patterns in children from 54 resource-poor countries in Africa and Southeast Asia shows a rapid falloff in the height-for-age z score during the first 2 years of life and no recovery until ≥5 y of age. This finding has focused attention on the period -9 to 24 months as a window of opportunity for interventions against stunting and has garnered considerable political backing for investment targeted at the first 1000 days.

These important initiatives should not be undermined, but the objective of this study was to counteract the growing impression that interventions outside of this period cannot be effective. The researchers illustrate their arguments using longitudinal data from the Consortium of Health Oriented Research in Transitioning collaboration (Brazil, Guatemala, India, Philippines, and South Africa) and their own cross-sectional and longitudinal growth data from rural Gambia.

The investigators show that substantial height catch-up occurs between 24 months and mid-childhood and again between mid-childhood and adulthood, even in the absence of any interventions. Longitudinal growth data from rural Gambia also illustrate that an extended pubertal growth phase allows very considerable height recovery, especially in girls during adolescence.

In light of the critical importance of maternal stature to her children's health, these arguments are a reminder of the importance of the more comprehensive UNICEF/Sub-Committee on Nutrition Through the Life-Cycle approach. In

particular, the researchers argue that adolescence represents an additional window of opportunity during which substantial life cycle and intergenerational effects can be accrued. The regulation of such growth is complex and may be affected by nutritional interventions imposed

Prentice AM, Ward KA, Goldberg GR, Jarjou LM, Moore SE, Fulford AJ, Prentice A. Am J Clin Nutr. 2013 May;97(5):911-8. doi: 10.3945/ajcn.112.052332. Epub 2013 Apr 3.

Observational study of vaccine efficacy 24 years after the start of hepatitis B vaccination in two Gambian villages: no need for a booster dose.

The objectives of this study were to determine the duration of protection from hepatitis B vaccine given in infancy and early childhood and assess risk factors for HBV infection and chronic infection.

In 1984 infant HBV vaccination was started in two Gambian villages. Cross sectional serological surveys have been undertaken every 4 years to determine vaccine efficacy. In the current survey 84.6% of 1508 eligible participants aged 1-28 years were tested. A spouse study was conducted in females (aged 14 years and above) and their male partners.

Vaccine efficacy against chronic infection with hepatitis B virus was 95.1% (95% confidence interval 91.5% to 97.1%), which did not vary significantly between age groups or village. Efficacy against infection was 85.4% (82.7% to 87.7%), falling significantly with age. Concentrations of hepatitis B antibody fell exponentially with age varying according to peak response: 20 years after vaccination only 17.8% (95% CI 10.1-25.6) of persons with a low peak response (10-99 mIU/ml) had detectable HBs antibody compared to 27% (21.9% to 32.2%) of those with a high peak response (>999 mIU/ml). Time since vaccination and a low peak response were the strongest risk factors for HBV infections; males

Thushan de Silva

Ann Prentice

Maimuna Mendy



were more susceptible, marriage was not a significant risk for females. Hepatitis B DNA was not detected after infection, which tested soley core antibody positive. An undetectable peak antibody response of <10 mIU/ml and a mother who was hepatitis B e antigen positive were powerful risk factors for chronic infection.

Conclusions: Adolescents and young adults vaccinated in infancy are at increased risk of hepatitis B infection, but not chronic infection. Married women were not at increased risk. There is no compelling evidence for the use of a booster dose of HBV vaccine in The Gambia.

Mendy M, Peterson I, Hossin S, Peto T, Jobarteh ML, Jeng-Barry A, Sidibeh M, Jatta A, Moore SE, Hall AJ, Whittle H. PLoS One. 2013;8(3):e58029. doi: 10.1371/journal.pone.0058029. Epub 2013 Mar 22.

Impact, challenges, and future projections of vaccine trials in AfricaImmunization remains the most cost effective method for the control of infectious diseases. Therefore, there is a global effort to deploy new vaccines for disease control and eradication. These new vaccines must be tested in the settings in which they will be used. This necessity has required the conduct of many vaccine trials in Africa, where several infectious diseases with significant public health impact are prevalent. However, these areas have peculiarities and are just beginning to gain expertise in the conduct of such trials. The vaccine developers and sponsors of these trials may also not be conversant with some issues unique to the trial site. The understanding gap from both partners can result in challenges if not addressed during the planning phase of the trial. This review seeks to highlight the issues surrounding the conduct of clinical trials in resource-constrained settings and suggests some ways of circumventing them.

Idoko OT, Kochhar S, Agbenyega TE, Ogutu B, Ota MOAm J Trop Med Hyg. 2013 Mar;88(3):414-9.

Comparing HIV-1 and HIV-2 infection: Lessons for viral immunopathogenesis.HIV-1 and HIV-2 share many similarities including their basic gene arrangement, modes of transmission, intracellular replication pathways and clinical consequences: both result in AIDS. However, HIV-2 is characterised by lower transmissibility and reduced likelihood of progression to AIDS. The underlying mechanistic differences between these two infections illuminate broader issues of retroviral pathogenesis, which remain incompletely understood. Comparisons between these two infections from epidemiological, clinical, virologic and immunologic viewpoints provide a basis for hypothesis generation and testing in this 'natural experiment' in viral pathogenesis.

In terms of epidemiology, HIV-2 remains largely confined to West Africa, whereas HIV-1 extends worldwide. Clinically, HIV-2 infected individuals seem to dichotomise, most remaining long-term non-progressors, whereas most HIV-1 infected individuals progress.

When clinical progression occurs, both diseases demonstrate very similar pathological processes, although progression in HIV-2 occurs at higher CD4 counts. Plasma viral loads are consistently lower in HIV-2, as are average levels of immune activation. Significant differences exist between the two infections in all components of the immune system. For example, cellular responses to HIV-2 tend to be more polyfunctional and produce more IL-2; humoral responses appear broader with lower magnitude intratype neutralisation responses; innate responses appear more robust, possibly through differential effects of tripartite motif protein isoform 5 alpha. Overall, the immune response to HIV-2

appears more protective against disease progression suggesting that pivotal immune factors limit viral pathology. If such immune responses could be replicated or induced in HIV-1 infected patients, they might extend survival and reduce requirements for antiretroviral therapy.

Nyamweya S, Hegedus A, Jaye A, Rowland-Jones S, Flanagan KL, Macallan DC. Rev Med Virol. 2013 Feb 26. doi: 10.1002/rmv.1739.

Olubukola Idoko

Samuel Nyamweya



Growth faltering in low-income countriesMeta-analysis of growth data from over 50 low and low-middle income countries shows a consistent pattern of stunting and poor weight gain from about 3 months of age and persisting until at least 5 years. Children tend not to be wasted because their short stature offsets their underweight, leading to a rather adequately proportioned appearance. This frequently conceals the true levels of malnutrition in communities. At the macro-environmental level such growth faltering is due to the combined effects of poverty, food insecurity, low-dietary diversity, a highly infectious environment, poor washing facilities and poor understanding of the principles of nutrition and hygiene. These tend to be ameliorated as communities pass through the demographic transition with improved incomes and education.

Because such changes will take generations to achieve, the global health community continues to search for effective interim solutions. Disappointingly, apart from intensive feeding programmes aimed at rehabilitating severely malnourished children, there are few examples of very successful nutrition interventions. This emphasizes the need for a better understanding of the etiology of growth failure. This paper uses anthropometric data collected over 6 decades in subsistence-farming communities from rural Gambia to illustrate the typical key features of growth faltering. Arising from this analysis, and from gaps in the published literature, the following issues are highlighted as still requiring a better resolution: (1) the pre-natal and inter-generational influences on growth failure; (2) the ontogeny of the infant immune system; (3) the exact nature of the precipitating insults that initiate gastroenteropathy; (4) the effects of both enteric and systemic infections on the hormonal regulation of growth; (5) interactions between macro- and micro-

nutrient deficiencies and infections in causing growth failure, and (6) the role of the microbiome in modulating dietary influences on health and growth.

Prentice AM, Moore SE, Fulford AJ. World Rev Nutr Diet. 2013;106:90-9. doi: 10.1159/000342563. Epub 2013 Feb 11.

The Decade of Vaccines

The Decade of Vaccines (DoV) Collaboration has been a catalyst to extend the full benefits of immunization to all people, regardless of where they live, contributing to and enhancing coordination across the international development, health, vaccine and immunization communities.

The DoV Collaboration brought together diverse stakeholders to develop a Global Vaccine Action Plan (GVAP) to stimulate the discovery, development and delivery of lifesaving vaccines. Immunization is one of the most cost-effective means to achieve this vision. Access to safe and effective vaccines is a human right that is currently not enjoyed by everyone, particularly in low and middle-income countries.

Tony Fulford

Anna Roca

As part of this effort, a supplement of case studies in the journal Vaccine (www.dovcollaboration.org) was published in April 2013. It includes 29 papers (delivery, strategy, implementation and development) and over 100 authors.

Dr Anna Roca from the MRC Unit, The Gambia, has participated in the case study of RSV. RSV is a major cause of lower respiratory tract infection in children worldwide, leading to an estimated 3 million annual hospitalizations and at least 66,000 deaths per year in children under 5 years of age. No licensed RSV vaccine is available. The purpose of this case study was to highlight challenges and opportunities for RSV vaccine development and identify priority activities that can facilitate vaccine development. Although RSV has been a high priority for vaccine development, efforts to develop a safe and effective vaccine have yet to lead to a licensed product. Clinical and epidemiologic features of RSV disease suggest there are at least 4

distinct target populations for vaccines, the RSV naïve young infant, the RSV naïve child ≥6 months of age, pregnant women (to provide passive protection to newborns), and the elderly. These target populations raise different safety and efficacy concerns and may require different vaccination strategies. The highest priority target population is the RSV naïve child.

The paper also highlights the need of better data on RSV-associated mortality in developing countries, better estimates of the risk of long term sequelae, better measures of protection in target populations,

and data on the costs and benefits of vaccines for target populations to support and justify funding this process. Addressing these challenges and needs should improve the efficiency and speed of achieving a safe and effective, licensed RSV vaccine.


RECENT UNIT SEMINARS

Compiled by Caroline Potin

Title:

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High diversity of Rotavirus and Shigella among Gambian children - What’s The Significance?

Demystifying Health Policy and Systems Research

Dr Brenda Kwambana

Dr Julie Balen, Imperial College London

Nearly a million children die from diarrheal diseases annually - a staggering statistic. The recently concluded Global Enterics Multi-Center Study (GEMS) showed that rotavirus and Shigella are among the most common diarrhoea pathogens in The Gambia as well as other parts of sub-Saharan Africa and South Asia.

To study the molecular epidemiology of these important pathogens, we genotyped the circulating strains found in healthy and sick Gambian children. The genotypic diversity of both rotavirus and Shigella strains in this setting was profound. At least 18 genotypes of rotavirus were found among 200 strains. To put this in perspective, just over 40 different rotavirus genotypes have been reported worldwide.

Another interesting finding was that a globally rare genotype of rotavirus, G2P[6] was the most common in The Gambia and appeared to be associated with more severe forms of disease. Another interesting finding was the association between rotavirus infections and having animals such as cats, cows and rodents which points towards zoonotic transmission. All four Shigella serogroups (S. flexneri, S. boydii, S. dysenteriae and S. sonnei) were found in The Gambia whereas in most places two or three serogroups are typically found.

Moreover, of the 160 Shigella strains typed, there were 50 unique sequence types. There are currently two licensed vaccines for rotavirus and several in the pipeline for Shigella.

The high genotypic diversity of rotavirus and Shigella strains found in this setting could have significant impact on vaccine efficacy and the generation of vaccine replacement genotypes. Molecular surveillance should be an integral part of pre- and post-vaccine implementation activities.

The presentation drew on theories of reality (ontology) and theories of knowledge (epistemology), as relevant to health policy and systems research (HPSR). Julie argued that all research is influenced by the researchers’ understanding of the terms ‘reality’ and ‘knowledge’ and that there is much value in relativism, as well as positivism. Julie’s research is situated along the epistemological continuum, within a critical realist paradigm, which includes both deductive and inductive research approaches.

Julie went on to discuss how HPSR contributes towards each of the three ‘themes’ of research at the MRC Unit, The Gambia, namely Vaccinology; Disease Control & Elimination; and Child Survival, adding to the Unit’s key strengths in biomedical research, clinical and behavioural research, and, population health research.

Pre-empting some tough questions from the audience related to the rigour of a more flexible design, Julie presented several ways of assessing research quality and compared and contrasted them to more traditional criteria available for assessing quantitative and experimental studies. Moreover, she presented some preliminary research results, though the project and data collection is ongoing.


RECENT UNIT SEMINARS

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Jesuits’ powder for Catholics and qinghaosu for communists: a brief history of antimalarial treatment

Professor Umberto D’Alessandro

Origins: It is still argued that Malaria originates from the Neolithic agrarian revolution, circa 8,000 BCE in the so-called ‘Fertile Crescent’ of southern Turkey and north eastern Iraq, reaching western and central Africa around 4,000-5,000 years ago and then spreading to the Mediterranean Basin around 400 BCE.

During the American Civil War (1861-1865) malaria accounted for 1,316,000 episodes and 10,000 deaths. Today, Sub-Saharan Africa bears the highest burden of malaria deaths.

Treatment: In 1632 in Peru a healing powder from a tree bark was introduced for the treatment of malaria and became known as ‘Jesuits’ powder’. The English Protestants considered this the “powder of the devil”, but in 1679, an English apothecary secretly used the “Jesuits’ Powder” and cured of malaria both King Charles II of England and the son of King Louis XIV of France.

Over the years, various attempts at finding the active ‘ingredient’ in curing malaria failed. However in 1820, Pelletier and Caventou, two French pharmacists isolated a gum highly effective against malaria, named quinquina. Soon after this discovery, from 1880 to 1899, the life cycle of the malaria parasite was described by various scientists.

In 1967, after a call for help from North Vietnam (then at war with South Vietnam), Chinese scientists set up ‘Project 523’ to look at traditional Chinese medicines to find a cure for malaria. From a list of 200 ‘candidates’, they found that a plant called Artemisia was effective against malaria. The active principle, artemisinin (qinghaosu), was isolated in 1971 and the first human trials were published in 1979. Today, Artemisinin (qinghaosu) is thought to be the most potent anti-malarial available. Artemisinin is given to malaria patients in combination with another drug; for example, Coartem is the combination of artemether and lumefantrine.

Resistance to various anti-malarial drugs has emerged over the last 50 years; Chloroquine resistance was detected in the 1950’s and Mefloquine in 1982. For artemisinins, a delay in clearance of infection was first detected in Pailin, on the Thai-Cambodian border in more recent times, and plans are in process to contain artemisinin resistance.

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S TITLE DATE PRESENTER

Dissecting Malaria Transmission Hotspots in The Gambia: Roles of Mosquito Behaviour and Insecticide Resistance

Wednesday 3rd July Kevin Opondo (MRC PhD student, Disease Control & Elimination Theme)

The role of the natural killer cell in vaccination Wednesday 10th July Alansana Darboe (Scientific Officer, Nutrition Group)

Isoniazid prophylaxis for prevention of childhood TB in The Gambia

Wednesday 18th Sept Dr Uzochukwu Egere (Vaccinology Theme)

Trends in the Prevalence of Diarrhoegenic Escherichia coli among Diarrhoeal Children in The Gambia

Wednesday 25th Sept Usman Nurudeen Ikumapayi (Higher Scientific Officer, Child Survival Theme)


NEWS FROM CLINICAL SERVICES

Giving hope to children with heart disease

The UK based charity, Chain of Hope, provides the opportunity for children with life-threatening heart disease to have surgery and treatment to which they do not have access. This is either done by sending out medical teams to treat children in their own country and by setting up training programmes for local surgeons and medical staff, or bringing children to the UK for operations as an interim measure.

MRC Unit, The Gambia has worked with Chain of Hope for several years. About 30 patients have received surgery. This year, two have been sent and a further two were scheduled to go recently.

Dr Suzanne Anderson, MRC’s Head of Clinical Services said ‘We see the patients regularly in the clinic and do all the initial clinical evaluation required to determine the cause and severity of their problem and provide all of their drugs for free.’ Cases are referred to Chain of Hope

by way of a medical referral. Suzanne continued ‘If the patients are lucky enough to be selected for surgery we then have to complete all of their referral forms and do the visa application, which is no small task. Even just ensuring that the patients get to the airport on time and on the plane is something we inevitably end up doing. MRC also helps by often paying up front for the visa fee. For example, x2 visas for the UK, may be the equivalent of 4 months’ salary for many of our patients. This is then reimbursed by Chain of Hope.

Chain of Hope referrals with families visiting MRC Fajara’s Clinical Services Department

Tedani said ‘The most valuable part of my work is getting to meet the patients who would have had no or very little chance of their lives being saved, recovering after surgery and hearing that they are doing so well when they return to their homeland and now have a better chance of a brighter future.



Suzanne and the clinical services team are delighted to see sick children return well and playful. But she acknowledges that there are challenges. ‘We definitely need a new approach to how we send these kids overseas, with whom and also need to spend much more time counselling children and their families. It’s always a last minute surgical slot and as you know we all have other jobs to do so inevitably it’s a last minute rush!’

And here Dembo Drammeh and his mother Ndey Fatou Bah tell their story.Ndey Fatou: ‘My child Dembo Drammeh was having a heart problem. He came to the MRC four years back and we went to the UK, did the operation and now thank God everything is okay.

Now Dembo can play football, ride a bicycle, do many things. Before, he couldn’t do anything. When he walked he would get tired; he couldn’t eat properly; couldn’t sleep at night.

Dembo Drammeh: My life was terrible. But now my life has changed – I can do a lot of stuff. I can play basketball, football, run, do stuff I couldn’t do before, and I am back in school – in grade 10 at SOS school.

Ndey Fatou: We would like to thank the MRC and the people over there from the Chain of Hope like Lisa [Yacoub] and everybody.

Recently, Tedani El-Hassan (who works on Chain of Hope’s Child Referral Programme) visited the MRC to escort a patient and to get a first hand feel for the Unit. When patients are referred to the UK, Tedani liaises with the Programme Manager Lisa Yacoub, and the Child Placement Manager, Sue Nott. The child and accompanying adult are placed with a host family through Chain of Hope. There is also a team of Chain of Hope volunteers who visit the family in hospital and offer support. Here Tedani continues.

What are your impressions of the MRC and the hospital?The hospital is very well developed and organised. The clinical team are all very friendly, hardworking and dedicated. It’s a very pleasant environment to be in. The fact that the MRC provides a free clinical service and medicines to patients is an example of the amazing work that they do.

You are also visiting a patient in BrikamaYes. I am visiting the family of a young patient who is due to go to the Aswan Heart Centre in Egypt for treatment through the Chain of Hope. I am going to give the family their travel documents and explain what to expect on arrival in Aswan. This isn’t the first referral to Aswan: so far 7 Gambian children have been treated there and 25 in other centres Chain of Hope works with.

In the UK Chain of Hope refers patients to four centres in London: Great Ormond Street Hospital, The Harley Street Clinic, the Royal Brompton Hospital and Evelina Children’s Hospital. We also refer patients to Leipzig (Germany), Aarhus (Denmark), Italy, Doha (Qatar) and Bangalore (India).

I am very grateful that the MRC team organised for me to meet the patients treated through Chain of Hope at the MRC. It has been a heartfelt visit.



not waste eff ort and resources adapting their own guidelines for resource-limited settings. They should instead provide expertise and financial support to improve and implement WHO guidelines already of proven benefit.

The Emergency Triage Assessment and Treatment (ETAT) guidelines2 were developed by international consensus and specifically designed for resource limited settings; they address important causes of mortality, including malnutrition and malaria. ETAT was specifically designed to bridge the gap between the Integrated Management of Childhood Illness and Hospital Care for Children programmes, thus including the entire continuum of care. ETAT/ETAT+ promotes a systematic approach to triage and identification of emergency signs that has been internationally validated and shown to reduce mortality.

We agree that the evidence base for these guidelines should be improved. The excellent International Child Health Review Collaboration is already addressing this problem, but dangerous research gaps remain.

Ralston and colleagues include dopamine in fluid-refractory septic shock in their list of evidence-based guidelines.

But specific paediatric evidence for this within Paediatric Sepsis Initiative guidelines consists of two USA-based observational studies (total n=18). This point highlights that guidelines in developed countries are also largely empirical.

Guidelines are only effective if implemented: more research is required to address policy and practice gaps in paediatric emergency care. WHO has the international mandate required to influence governments, which must take local

ownership of guidelines, providing adequate resources and continuous training to support implementation.

We have supported the introduction of an adapted ETAT training programme in The Gambia, funded by MRC Unit: The Gambia as part of a linked training initiative with Imperial College London. LP is also an Advanced Paediatric Life Support instructor and has received travel expenses from the Scottish Government and UK Department for International Development grants to

implement ETAT in Malawi and Uganda.

We note your Review calling for the development of advanced paediatric life-support management in resource poor countries. Many additional lives can be saved by the immediate implementation of some inexpensive treatments, but the provision of a universal effective emergency care system (as developed countries have found) is difficult.

There are three important caveats about training in emergency care in low-resource countries. First, training is not enough! ECTH is part of a wider programme, Strengthening Emergency Care. Crucially, training has also been combined with strengthening of the emergency care system so that those trained have appropriate facilities, equipment, and

essential drugs to practise what they have been taught.

Second, one size does not fit all. Low-resource countries are not all the same. There needs to be local ownership and sustainability. Local trainers have been established by use of a modified generic instructor course originally developed and implemented for all its courses by the Advanced Life Support Group.

Finally, development of suitable training must involve clinicians who are knowledgeable and experienced in the clinical fields of emergency paediatrics and paediatric intensive care, in direct practice in low-resource countries, and in delivering high quality clinical education.

Paediatric emergency care in resource-limited settings

(Letter to The Lancet, Louisa Pollock (Imperial College London), Suzanne T B Anderson, Beate Kampmann, Vol 381 April 20, 2013)

Improvement of paediatric emergency care is crucial to reduce child mortality. However, we see no need for new international guidelines when existing WHO guidelines meet many of the requirements Mark Ralston and colleagues propose (Jan 19, p 256). International life-support organisations should

We have developed a course from the Advanced Paediatric Life Support course (Emergency Child and Trauma Health [ECTH]) which has been taught in The Gambia from 2007. The ECTH course has been modified jointly by us and local clinicians with the full support of the government, WHO, and UNFPA to make it fi t for the healthcare issues and resources in country.


NEWS FROM CLINICAL LABS

Looking forward to ISO 15189 recognition!

Tisbeh Faye-Joof

Meet MRC Unit, The Gambia’s (relatively) new Clinical Laboratories Manager, Ameh James

Who is Ameh James?I think I’m a simple and calm African (Nigerian) man – please be the judge! A husband and father to a lovely wife and daughter. I like reading, writing, watching TV and chatting with like-minded people – I draw my inspiration from such discussions.

What’s your professional background?I became an Associate of the Medical Laboratory Science Council of Nigeria in 2002, after 5 years of studies at the Federal School of Medical Laboratory Technology, Jos University Teaching Hospital. Thereafter, I got my first job with Poly Clinic and Maternity in Lokoja, Nigeria where I worked as a Medical Laboratory Scientist from July 2003 to September 2004. I then worked with Helping Hands Specialist Hospital in Lokoja as a Medical Laboratory Scientist for 7 months. From there, I worked with APIN/Jos University Teaching Hospital & Harvard School of Public Health, as a Medical Laboratory Scientist for 1 year 8 months. In 2007, I had Fellowship of Medical Laboratory Science Council of Nigeria from the Federal College of Veterinary and Medical Laboratory Technology, Vom. I attained Postgraduate Associate (Quality Management Systems) from University of Greenwich, UK in 2010 and was awarded Master of Science (Molecular Biology) from Staffordshire University, UK in 2011.

I was responsible for Quality Management Systems and Molecular Diagnostics portfolio of Family Health International 360 as Senior and Technical Officer(s) from March 2007 to January 2013. While with this Organization, I played the roles of a trainer, mentor and auditor per the portfolio. As a trainer and mentor, I played a key role in supporting four public health laboratories to attain 4-star and two laboratories 5-star, according to the WHO/AFRO accreditation (based on ISO 15189: 2007) rating per in-country assessment by Strengthening Laboratory Management towards Accreditation team supported by Centre for Diseases Control, USA. As an auditor, I was one of the African Auditors under the global Clinical Research Support Services funded by NIH/NIAIDS/DAIDS – audited several clinical research laboratories across African countries.

What inspired you to join MRC Unit, The Gambia?Actually, a colleague/friend forwarded the job advert to me because she believed I am the right person for the job. I was reluctant initially. When I came back from an audit in Malawi, my wife reminded me to apply. At that time, the deadline was a few hours away. My primary motivation to apply for the job was to help MRC, which is a renowned organisation to attain ISO 15189 accreditation. In addition to this, I have interest in research and I thought it was a good ground to build my research interest.

What are your plans for the Clinical laboratories?Primarily, I am looking forward to when the tests performed by the labs (Haematology, Biochemistry and Microbiology) will be ISO 15189 certified which will indicate International recognition of our quality and competence. Hopefully, we will utilize this recognition to engage manufacturers of rapid diagnostic kits for possible validation before its introduction into the market. These kits are usually introduced into the African Market (especially sub-Saharan countries) without evaluating it in the setting where it will be used. These POCT kits could be evaluated retrospectively, with the use of well characterized samples or prospectively. Fortunately, MRC The Gambia has the capacity to handle this kind of trials except for the International recognition of our quality and competence. So, we are looking forward to be engaged in such trials after the ISO 15189 recognition. This is like building on the existing GCLP accreditation by Qualogy Ltd.

What’s your experience in The Gambia so far?Gambia is more or less like home away from home because I am still in Africa. However, there are times I feel I should go back to the ‘actual home’ but overall, I think I’m fine for now. I have learnt to adapt.

Any final thoughts?Looking forward to ISO 15189 recognition!


TRAINING

Training researchers

MRC Unit, The Gambia’s record in developing people from diploma to PhD level is exemplary. However, by its own admission, nurturing careers beyond PhD is an area of weakness. Enter Dr Peter Dukes who has been seconded to the Unit from MRC Head Office for one year. Peter is tasked with making MRC Unit, The Gambia a preferred partner internationally in researcher training and development. Here he explains how he plans on going about this.

About PeterI’ve worked at MRC Head Office for over 22 years. Before that I was a researcher; I worked on African Sleeping Sickness which I enjoyed very much (visiting the Unit briefly). My most recent role at Head Office was Head of Research Career Awards, being responsible for the large budgets that the Council spends on research studentships and fellowships; the Unit has been successful recently in Alfred Ngwa who broke new ground in winning a prestigious personal fellowship from one of the schemes that I was managing.

I am absolutely delighted to be here - on the invitation of Tumani Corrah; I am contracted in effect to spend 75% of my time working for the Unit as Head of Researcher Training and Development, but I still have 25% of a job in the UK doing other things for Head Office.

The groundworkThe Unit - and institutions in Africa generally - have been good over the last decade in developing PhD students, Foundation and BSc skills. We’ve been less good at developing people at the postdoctoral level – particularly Africans. One of my passions is to help the Unit play its role in strengthening the cadre of West African or African postdocs, particularly the people who will go on and lead research programmes.

I want to see this Unit recognised as a leading player and the preferred regional partner in researcher training: building on the things we are already good at; addressing the things we are not so good at; building on our existing partnerships and making new partnerships in the region and internationally. Of course this Unit’s got links with many institutions; some of these are probably a bit ad hoc in relation to training, and maybe we can lift them up a level, and present the Unit as a place with something to offer, rather than just requesting help. I am well aware that we are in discussion with the University of Westminster; we have also had good relationships with Kingston and Manchester, mainly focused around Foundation degree level, BScs and some PhDs. I am wondering whether we can pull together these institutions as a bigger package...

[As part of this process], I am talking to people here about what works well and the perceived gaps, [although of course] I won’t necessarily be able to meet everyone’s expectations. I have already learnt it will be important to work with the Leadership Board, to make sure we have clearer policies and structures for researcher training and.

Where we’ll be in a year’s timeI am setting up a development centre targeted to PhDs and postdocs. [The idea] is to help them up their skills, not just as researchers, but

also as managers of people and resources, and in gaining grants and fellowships, and able later to be leaders in a variety of roles. We’ll also be running a series of workshops in a year’s time, from which I will have had feedback – so let’s say the first year is a pilot.

This time next year we will be welcoming the first one or two of the three new MRC-LSHTM West African Fellows and helping them to establish in The Gambia. I will be working with Tumani Corrah and Peter Piot (Director, LSHTM) to establish these Fellowships. They will MRC Fellowships, not Unit employee positions, and we aim to attract two outstanding early postdocs from the region and one from Europe or the UK. We shall expect them to be great role models for aspiring scientists.

....And – maybe this is a bit rash at this early stage of appointment - I will also have helped the Leadership Board to raise an extra £1 million from training and development funders or donors yet to be identified....

It’s a tremendous privilege to be here – and it’s very refreshing for me personally to be developing my own career even at my age. I hope it’s a signal to people that careers are in our own hands not in other people’s.


TRAINING

Investigating TB where it matters the most

Leopold Tiencheu from Cameroon recently defended his PhD at the London School of Hygiene & Tropical Medicine, his thesis titled ‘Understanding differences between host response to Mycobacterium tuberculosis and Mycobacterium africanum.’ Leopold’s background is in biochemistry and molecular biology. Why did he detour into TB immunology? Here we find out.

A researcher’s beginningsDuring my Master’s studies at the University of Yaoundé1 Cameroon (2007), I was introduced to TB research; the aim of my project was to characterise specific mutations in genes, conferring drug resistant to M. tuberculosis isolates, using a PCR based dot-blot hybridization technique. They’d already published data on this work reveals differences in the pattern of specific mutations conferring drug resistance to M. tuberculosis isolates from two different geographical regions and I found this very interesting.

After my Master’s I did a year’s internship in the mycobacteria laboratory of Centre Pasteur (Cameroon), followed by a job with the Global Viral Forecasting Initiative, where I developed SOPs and participated to establish a molecular biology lab to investigate immerging zoonotic viruses. During this time I was also actively applying for international PhD fellowships...

Transition

The MRC full time PhD studentship was actually one of several international offers I received. But what really attracted me was the topic: TB. Firstly, because of my Master’s project; secondly because I was very interested in understanding the interaction of bacteria with the host. The Unit’s reputation was also one of the reasons I chose the MRC – and the fact that the MRC studentship involved collaboration with LSHTM as my host university.

However, embarking on a PhD in immunology with a background in biochemistry and molecular biology was always going to be a challenge, so I had to read a lot, and I took a three month course on Immunology of infectious diseases at the start at the LSHTM...

The projectThere are two main strains that cause tuberculosis in The Gambia – and West Africa as a whole: M. tuberculosis (Mtb) and M. africanum (Maf). Maf causes up to 40% of all TB cases in The Gambia and is restricted to W Africa. The epidemiological data suggests that

Maf exposed individuals take longer to develop active disease compared to those exposed to Mtb. Also patients infected with Maf are more likely to be severely malnourished, HIV infected and older compared to Mtb. This led us to hypothesise that Maf may be less virulent compared to Mtb. Blood samples were collected from TB patients before and following treatment, in the lab this blood were challenged with bacteria components and the responses were assessed using immunological techniques. We were trying to understand how the body is able to control Maf better than Mtb; ultimately such information can be used to design better interventions.

This study involved collaboration with Professor Stefan Kaufmann’s laboratory at the Max Planck Institute for Infection Biology, Berlin, Germany and Leiden University Medical Center, The Netherlands where further experiments were done on the samples.

One of the most interesting things I’ve found is that before treatment, there are few differences between Mtb- and Maf-infected patients. But following treatment Mtb-infected patients recover better than Maf patients. This may suggest that those infected by Maf have an immune profile that makes them more susceptible to disease induced by a less virulent strain and also prevents them from responding adequately to treatment compared to Mtb patients. Another reason could be that in comparison to Maf, Mtb is capable to cause disease in people with a stronger immune profile who recover faster when the bacteria is clear from the system by treatment.

This data also suggests that the current treatment regimen might be sub-optimal for Maf-infected patients, which may explain why they don’t recover as fast. There are really good hypothesis-driven findings in the study; this is exciting in terms of writing grants, and currently I am pursuing some of these results.

Some of the hurdles...The course of treatment for TB lasts six months, the first two months being the


TRAINING

intensive treatment period, followed by the continuation period. After two months most patients are healthier and continued their treatment but some didn’t want to continue with the study and some transferred from the study area. So I ended up recruiting more patients to compensate for those lost to follow up.

Another challenge was getting reagents! Being based here was a great opportunity, but sometimes you’d have to wait two or three months to get them from abroad. Being able to borrow reagents from other researchers has been a saving grace for me because otherwise I might still be doing my PhD...

Looking aheadOne essential priority now (as well as identifying postdoc opportunities) is the wellbeing of my family. I would like to thank my wife, Peggy-Estelle

who accepted to join me in The Gambia: she has been very supportive throughout. And my son Mark Donel who had to bear with my coming home late because of my work and absence during travels.

I got a lot of support from my supervisors Dr Martin Ota (MRC) and Professor Hazel Dockrell (LSHTM), and I’d like to thank them very much.

I’d also like to thank Jayne Sutherland, Bouke de Jong, all the members of the TB immunology group and the TB diagnostic lab; Professor Kampmann and the Unit leadership...by engaging in capacity building its making a unique difference in the lives of many young African scientists including me. I learned a lot – and there’s no doubt that the MRC has what it takes to address key scientific questions and deliver quality science.

Science: it’s something I really love

Mustapha Bittaye, trainee scientific officer with the Primaquine (malaria drug) trial, re-joined the Unit recently, having gained a first class degree in Biomedical Sciences and graduating as the best undergraduate student in the Biosciences programme from the University of Westminster. Mustapha’s history with the MRC goes back 10 years; here he traces his path and shares his thoughts for the future.

My beginningsI joined the Unit in 2003 as a lab technician in Keneba. Whilst there, I enrolled on the MRC in-house Certificate in Biomedical Sciences; from there I progressed to the Diploma, graduating as best student. Before completing my Diploma I joined the Malaria Programme as a senior laboratory technician based at MRC Fajara; I spent a year there before getting a full time BSc scholarship from the University of Westminster to study Biomedical Science.

Forays into cancer researchMy final year project at Westminster was on breast cancer. I had no experience in cancer research - my experience was centred on infectious diseases. I was awarded a bursary to attend the British Science Festival, where I met pioneers in cancer research. I also had the opportunity to go to the Birmingham Cancer Institute, relate with cancer researchers and increase my knowledge in that area. I had a very good supervisor who leads the ‘Against Breast Cancer’ research group at Westminster; and after my project I was given another bursary to go back and get this work published.

A PhD opportunity was offered to me; the idea was to design a cancer-related project

that would somehow benefit the people of The Gambia. But given my long term attachment to the MRC, my aspirations and the MRC’s objectives - which are centred around infectious diseases - I decided to rejoin the Unit and look at the opportunities available in those areas.

FutureI want to be a molecular biologist, and I’d like to have completed my PhD in five years’ time. I see myself being an independent scientist in future, generating ideas that will drive the Unit forward.

In 2003 I had a scholarship to read medicine in Russia; that’s when I joined the Unit. But I met a lot of people here and my inspiration grew, starting from the certificate course. I’m so much into science now – it’s something I really love, discovering my natural talent.

I’d like to thank the Unit for giving me the opportunity. And I’d like to offer a word of inspiration to the young ones: Don’t give up. Do your best, try to be the best, stay focussed and committed, and opportunities will come your way. That’s the advice I got from Professor Tumani Corrah...


TRAINING

Finding a home away from home in Basse

Amulai Touray

The West African Health Organisation, with its headquarters in Burkina Faso, has sent a number of young health research professionals from the sub-region to spend time at MRC Unit, The Gambia under their Young Professional Internship Programme.

The programme aims to equip qualified ECOWAS citizens (Economic Community Of West African States) with knowledge, practical skills and experience for the sustainable management of health issues in the sub-region.

Meet Ablo P Wachinou from Benin Republic who started his placement based at Basse Field Station in January 2013.

About AbloI completed my medical studies in 2005 at the School of Medicine of Cotonou (Benin). From 2005 to 2007, I worked for the National Tuberculosis Programme in Benin as a general practitioner. Then I moved to Togo to do my specialization in Pulmonology at the Mixed Faculty of Medicine and Pharmacy of Lome, completing in 2011. I returned to Benin to work as a Pulmonologist at the National Hospital for Tuberculosis and Lung Diseases. Because of my high interest in research, I attended many training courses, meetings and conferences both in Benin and internationally.

Has the internship been useful so far?Of course! Firstly, I have met many energetic, enthusiastic people who surprise me every day with their motivation and commitment. Secondly, looking at the background of this institution, its contribution to research in West Africa and the whole world, it is definitely the place to be for a young researcher like me. Thirdly, some of the Unit’s current research is directly related to my interests (infectious lung diseases); working on such projects at the MRC will be very helpful to me in future.

Being based in Basse makes it difficult to attend some of the training activities, since most of them take place at Fajara. But I’m delighted to have this chance, and I am sure that will be useful to me in my career.

What are your internship goals?My main goal is to acquire practical skills and experience in health research in an international research institute; specifically I want to learn how to implement and manage a research project. My last objective, but not the least is to improve my English (Benin is a French speaking country). We all know that English is the main research language, and for me it is important to speak English well.

What are your future plans?After my internship, I hope to return to Benin to take up a position as a lecturer and researcher in the Faculty of Medicine. I will also be working to realise one of my dreams: to create a research institute for tuberculosis and lung diseases in my country in the not too distant future. I have been told that the MRC is seeking to extend its collaboration with other institutions in the West African region and I really want to be a part of that.

Final wordI would like to acknowledge MRC Unit, the Gambia Unit through the Unit Director, Professor Tumani Corrah. The first time I met Professor Corrah, we had an amazing conversation that I think I will never forget; it reinforced my conviction to become a researcher. I would like to thank Dr Stephen Howie, the Child Survival Team Leader, and the supervisor of my internship who permitted me to work with his team. I want to thank my mentor Dr Bernard Ebruke, all the MRC staff of Basse, and the nurses at the Health Centre whose courtesy and daily motivation is to me like a gift that has helped me not to miss my country too much! And finally I want to acknowledge the West African Health Organization which has given me this marvellous opportunity for capacity building in research.


TRAINING

Equipping Project Managers

Marie Rose Thorpe

In its fourth and final year, the EDCTP-funded West African Nodes of Excellence for TB, AIDS and Malaria (WANETAM) continues to build the capacity of its West African network through various cross-discipline training activities.

One of the principal goals of WANETAM is to develop the technical (human) capacity that will enable scientists in West Africa to conduct clinical trials to international GCP standards. To support this, the project management course PRINCE2 was identified as one that combines both theory and practice and would give project managers a number of customisable tools to enhance project management, an essential support in conducting clinical trials. Accredited by the Association for Project Management (APM) Group, the 5-day Foundation and Practitioner training culminated in working with case studies to ensure a sound understanding of the PRINCE2 methodology.

The twenty-five participants were selected by a training committee from the partner collaborators of WANETAM and WANETAM Plus and came from Benin, Burkina Faso, Mali, Nigeria, Senegal and The Gambia. Participants were divided into 2 groups and the training was provided by Victor Fashoro, in association with the ILX Group from 29th April to 10th May 2013.

With pleasure, we can report that the WANETAM and WANETAM Plus consortium now has a number of certified project managers as all participants have been accredited with the PRINCE2 Foundation Certificate.

When asked in a feedback survey how the knowledge and skills would be used in their work, one participant wrote, “...managing the risk throughout the life of projects, better control of project activities and keeping documents for future reference.” Additionally, the PRINCE2 method has given each training participant the customisable tools that they can use in managing their projects in order to have better control over the various activities, which will go towards strengthening the project management capacity of the WANETAM network.

Moussa Lingani, a clinical trial coordinator said “I hope this is just the beginning of a new era of well trained project managers! I'm thankful to the Gambian people for this nice stay and to all other people living there”


TRAINING

Gambia Unit scientists lead training in Malawi

MRC joined forces with the Wellcome Trust to run an Advanced Course on the ‘Molecular Approaches to Clinical Microbiology in Africa’ at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi - 25th May to 1st June 2013.

This one-week intensive course is held biennially and draws participants from across Africa selected to represent researchers who require the knowledge of genome-based techniques for their new or on-going projects.

The course content is designed to be in tune with developments in clinical microbiology, not just in Africa but across the globe. Genome-based techniques are revolutionising the routine practice of the identification and characterisation of pathogens, opening many new opportunities and challenges in all areas of clinical microbiology from routine diagnosis to basic research.

Dr Martin Antonio was course instructor and co-organiser of the workshop, assisted by Eunice Machuka and Sheikh Jarju. The MRC Gambia Unit team taught molecular methods used in the MRC Molecular Microbiology group for the identification and characterization of pneumococcal, and meningococcal as well as single locus (MLST) and whole genome analysis.

Nurudeen Ikumapayi and Nat halie MacDermott (MRC Unit, The Gambia) also attended the course, which aims to provide clinical microbiologists and laboratory scientists working in Africa with a concise yet

comprehensive overview of the latest research and practice in this area, with an emphasis on how these techniques can be applied day-to-day in the African setting, especially when resources are limited.

The course combined an understanding of the latest research techniques and theoretical approaches with practical methods to provide a foundation-level of understanding of the philosophy, methods and vocabulary of molecular techniques for those primarily trained in culture-based microbiology.

The next course is scheduled to take place at KEMRI in 2014. MRC Unit, The Gambia will host the course in 2015.

Martin Antonio, Eunice Machuka and Sheikh Jarju


Quality Initiatives at MRC Unit, The Gambia

Nana Tawiah and Tisbeh Faye-Joof

Given the increasing competition to attract funding for research, a Quality approach to our work has become inevitable. The Unit’s aim is to attain and maintain an effective Quality Management System (QMS) that conforms to the requirements of International Quality Standards including, ISO 15189, Good Clinical Practice (GCP), Good Clinical Laboratory Practice (GCLP) and MRC’s Good Research Practice (GRP). In our quest to get the laboratories 1SO 15189 accredited in April/May 2014, several initiatives have been undertaken.

QUALITY ASSURANCE

ISO 15189 LaunchApril 9th 2013 marked the official launch of the Unit’s campaign to achieve the International Quality Standard 1SO 15189. The launch was led by the Unit Director, Professor Tumani Corrah. The Quality Manager, Nana Tawiah gave a presentation on sustaining our commitment to our vision and mission, making reference to the Unit’s Quality Policy Statement. An overview of the Quality Standards (GCP, GCLP, GRP and ISO15189) and important milestones were highlighted. The launch was wrapped up with a quiz, which was won by Tisbeh Faye-Joof; the prize was a Samsung dual sims mobile phone. A similar ISO 15189 launch is scheduled to take place in Basse and Keneba.

ISO 15189 awareness sessionTraining of Managers, Quality Steering Group (QSG) members and Internal Auditors on the ISO 15189 Quality Standard took place on 16th April 2013. The group was introduced to the ISO 15189 standard and the Unit’s QMS. This group oversees compliance with requirements of the QMS in their respective departments, disseminating the meaning of Quality throughout the Unit.

GCLP Accreditation InspectionIn the week commencing 22nd April 2013, Tim Stiles (Qualogy Limited)

conducted a GCLP audit of the Clinical Laboratories, Serology and TB Diagnostics. He also visited Biomed, Archives and the Biobank. The purpose of the audit was to ensure that the Clinical labs are maintaining the GCLP standard and that the standard has improved from last year in all the labs audited. The outcome of the audit was that the Clinical laboratories maintained their GCLP accreditation while Serology and TB Diagnostics have attained accreditation for the first time. This is another milestone in our quality initiatives, but the Unit needs to move to the next phase through continuous improvement. The re-inspection cycle is agreed to be every 2 years.

Internal Auditors’ Training in Auditing Skills On 25th and 26th April, twenty volunteers/nominees were trained in auditing skills by

Tim Stiles and Nana Tawiah through interactive lectures and workshops. Internal auditors form a very crucial part of the QMS. Following the training, Internal Auditors are expected to conduct comprehensive auditing of the Unit’s activities, which is needed to achieve ISO 15189 accreditation. Internal Auditors will help increase support in implementation of quality standards at the department and Unit levels.

How to Implement ISO 15189 Training on how to implement the ISO 15189 standard took place from 6th to 10th May (for staff of laboratories) and 13th to 14th May (for staff of Finance, Procurement and Purchasing, Health & Safety, Biobank and Biomed). The training was delivered by the Clinical Laboratories Manager, Ameh James, supported by Gibril Bah, Boto Jaiteh (Clinical labs) and members of the Quality Department. The training was in the form of interactive lectures and practical sessions aimed at showing the step by step implementation of the standard. The senior members of staff who were trained are expected to be committed to implementing the standard and to providing step-down training to all staff in their respective departments.

Assuring Quality in the labs: Back row from left: Tim Stiles, Ameh James, Saffiatou Darboe, Patrick Owiafe, Gibril Bah, Tisbeh Faye-Joof, William Dei-Alorse. Front row from left: Davis Nwakanma, Jacob Otu, Ebrima Nyassi, Ousman Secka, Nana Tawiah


Ecole Francaise students visit the laboratoriesTwenty students aged 14-17 from the French School visited the laboratories at Fajara recently. The visit, coordinated by Trachoma group leader, Dr Sarah Burr, included demonstrations by Simon Correa of the malaria group and hands-on practice with microscopes.

UTG Medical Students visit Fajara Recently, final year medical students from the University of The Gambia’s Faculty of Medicine & Allied Health Sciences visited the MRC’s Fajara campus. The students were given a tour of the laboratories by Research Laboratories Manager, Ousman Secka and an overview of the Unit by Professor Tumani Corrah.

A growing number of UTG-trained clinicians are joining the MRC. Those currently working at the Unit include Dr Bully Camara (Pregnanzi project); Dr Abdou Sillah (African European TB Consortium); and Dr Bintou Jallow (Medical Officer, Clinical Services Department).

Happy 100th Birthday, MRC

� the identification of the dietary cause of rickets by Sir Edward Mellanby

� the discovery, in 1918, that influenza is caused by a virus

� the description of neurotransmission and the first neurotransmitter, acetylcholine, by Sir Henry Hallett Dale and Otto Loewi, leading to a Nobel Prize for Physiology or Medicine in 1936

� the development of penicillin by Sir Alexander Fleming, Sir Ernst Boris Chain and Lord Florey, gaining them the 19 45 Nobel Prize

� linkage of lung cancer to tobacco smoking by Sir Richard Doll and Sir Austin Bradford Hill in the British doctors study, published in 1956

� the discovery of the structure of DNA by James D. Watson, Francis Crick, Rosalind Franklin and Professor Maurice Wilkins. They would receive the 1962 Nobel Prize for Physiology and Medicine for their discovery

� the development of magnetic resonance imaging in 1973 by Professor Peter Mansfield and independently by Paul Lauterbur. This would lead to the 2003 Nobel Prize

� the co nducting of large studies in the 1970s and 1980s which established that aspirin can decrease the risk of cardiovascular disease

� the publication of the genome of C. elegans, the first multicellular organism to receive this treatment, in 1998

� the ongoing Heart Protection Study, showing benefits of primary prevention with simvastatin in patients at high risk for cardiovascular disease

� Dr Venki Ramakrishnan of the MRC Laboratory of Molecular Biology winning the Nobel Prize for Chemistry in 2009[ for showing how ribosomes, the tiny protein-making factories inside cells, function at the atomic level

� the discovery that early treatment of HIV-infected babies with anti-retroviral therapy can dramatically increase their chances of survival

� the development of a test for detecting infectious prions on surgical instruments which is more accurate than previous tests and 100 times faster

� the identification of the second ever genetic variant associated with obesity

� the finding that high quality surgery combined with a short course of radiotherapy can halve the rate of recurrence of colorectal cancer

Some of the major life changing discoveries by the Medical Research Council include:

In May this year the MRC’s Safety, Security, and Resilience Team entered the Continuity, Insurance and Resilience awards. Established in 1999, the awards recognise business continuity, security, resilience and risk professionals whose innovative strategies make them stand out above the rest. They are judged by an independent panel of experts for exceptional performance, service and results and are held in association with the City of London Corporation.

Mike Stephens of the MRC was ‘Highly Commended’ for his e-learning course on Research Continuity in the category ‘Business continuity initiative of the year’ sponsored by the City of London Corporation and London First. In the judges’ opinion it ‘successfully bridged the gap between operational business needs and academic research’.

The MRC’s Unit in The Gambia won top prize with Cambridge Risk Solutions for ‘Business continuity strategy through partnership’ sponsored by London First. Both MRC entries were up against stiff opposition from multinational companies with multi-million pound business continuity management budgets, making these achievements all the more notable. (Toni-Jo Henderson, Digital Communication Manager, MRC UK)

MRC Unit, The Gambia wins major Research Continuity Award

In the last few months, the Unit has said farewell to a number of colleagues who had spent many productive years working for the MRC. We extend our best wishes for the future to the following individuals:

Ousman Bojang Fatoumatta Samateh Famara Janneh Lamin Kambi

Ousman Jallow Joe Bangali Landing Sanyang Momodou Njie

Mustapha Faye Meta Jabbler Kollymam Joof Ida Bayo

Adetokunbo Bashorun Bakary Ceesay Siaka Badjie (Welder) Kulay Dampha

Musa Sawaneh Abdoulie Sanyang Ousman FM Barry Sonna Darboe

Ousman Joof Omar Badjie Abdou Krubally Fabakary Cham

Your Feedback Please!

Tama – the Newsletter of MRC Unit, The Gambia – is for everyone who is interested in our work and our community.

We are keen to receive feedback and suggestions for new features from our readers. So if you have any comments, please let us know.

Email: [email protected]

Medical Research Council Unit, The GambiaAtlantic Road, FajaraP. O. Box 273 BanjulThe Gambia

CommunicationsTel: 4495 442 Ext. 2306Email: [email protected]: www.mrc.gm © Medical Research Council 2013

TAMANEWSLETTERVOL: 12 ISSUE: 02 / 2013

EDITORIAL BOARD

Alison OffongYailouise Ndure

Kalilu DibbaTisbeh Faye-JoofSulayman Janneh

Elizabeth Stanley-BatchillyJoan Vives Tomas

Fanding P Njie

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TAMA | MRC Unit, The Gambia Newsletter | Vol. 12 | Issue ...cdn.mrc.gm/downloads/Tama_Vol12-Issue02_2013_LowRes.pdf · chickenpox substantially reduces the risk of varicella zoster