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Wednesday, September 23, 2020

Professor Keith McAdam

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Keith McAdam is Emeritus Professor of Clinical Tropical Medicine at the London School of Hygiene and Tropical Medicine.  He has been associate international director for Africa at the Royal College of Physicians in London and is currently helping with the foundation of a new College of Physicians for East, Central and Southern Africa.  He has been visiting professor at several universities and has served on various charity and research funding boards. He is currently on the international board of AMREF Health Africa, is a member of the Academic Alliance for Aids Care and Prevention in Africa and a trustee of BBC Media Action Trust.  He was medical advisor to the UK Parliamentary Select Committee on Aids and a member of the Nuffield Council on Bioethics working party on ‘The ethics of healthcare related research in developing countries’. The president of Uganda, Yoweri Museveni presented him with an Award for Distinguished Service to the People of Uganda.  He has 250 publications in medical and scientific journals. On-going research includes: in Tanzania, the Agents of Change programme to assess the impact of Namweza, a novel life-skills training programme for people living with HIV; and in UK, evaluation of the effect of listening to familiar music on wellbeing and quality of life of people living with dementia (Music for my Mind). Below, he talks with Standard editor, Sainey Darboe.

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You have spent your working life in the field of tropical medicine. Where did that interest come from and how did you get started?

I grew up in Uganda, where my father was a surgeon, did my schooling in Kenya and went on to study medicine at Cambridge University and the Middlesex Hospital in London.  After training in Internal Medicine in London, I spent 3 years at the Institute of Medical Research in Papua New Guinea working on amyloidosis, a fatal condition that was very common there, as a complication of various inflammatory diseases including leprosy, malaria and filariasis (elephantiasis).  This gave me an abiding interest in the mechanisms of inflammation (causing fever, swelling, redness and pain); these are symptoms and signs that occur in many infectious diseases.  Having become an expert on amyloidosis, I spent two years 1975-77 at the Immunology Branch of the US National Cancer Institute in Bethesda developing my laboratory and clinical research focus on inflammation, cytokines, acute phase proteins, autoantibodies and the increasingly complex causes of amyloidosis.  This continued over the next 7 years in Boston as a clinical scientist in the Department of Medicine at Tufts New England Medical Center, from which I was recruited to the London School of Hygiene and Tropical Medicine and its associated clinical base at the Hospital for Tropical Diseases.

 

As Professor of Medicine at the London School of Hygiene and Tropical Medicine what area of work did you cover?

I was Professor of Clinical Tropical Medicine at the London School of Hygiene and Tropical Medicine, from 1985-2004.  For the first ten years of that time I was based in London during a period of great change at LSHTM when many small departments were reorganized into four large departments.  I led the Department of Clinical Sciences, which incorporated Tropical Medicine and Microbiology (and later Parasitology and Tropical Epidemiology were merged in too).  I brought with me a focus on inflammatory proteins (SAA and C-Reactive Protein) and the immunology of Leprosy.  However in this new setting my colleagues and I were successful in winning research grant funding to study specific aspects of the new epidemic of AIDS; particularly the opportunistic infections that occurred in people whose immune system was being destroyed by HIV.  Research was started in the department to work on the commonest opportunistic infections that affected the lungs (Tuberculosis), brain (Cryptococcus) and gut (Cryptosporidium).  This involved not only basic research in London on mechanisms of disease but also clinical research studies in Zambia and Kenya.  Others in the department had interests in immunity to infectious diseases including viruses (Hepatitis viruses, Herpes viruses and Epstein Barr Virus), bacteria (cholera, meliodosis), parasites (malaria and leishmaniasis) and fungi.

 

Why is the word hygiene included in the title?

Hygiene does sound a bit old-fashioned, doesn’t it!  It implies many of the disciplines involved with Public Health nowadays.  This includes topics such as how to ensure supplies of clean water, hand washing to reduce diarrhoeal illnesses, immunisation and prevention of infectious diseases; reducing mosquito bites and malaria through use of impregnated mosquito nets; reducing fly-borne illnesses such as trachoma by building latrines.

 

 

You were for eight years the Director of the Medical Research Council in Fajara. What is the background to the MRC’s involvement in The Gambia and when did that involvement start?

The MRC Laboratories was founded in The Gambia back in 1947 when the WWII British Army Hospital was handed over to Medical Research Council. Its main unit was at Fajara on the Atlantic Road where clinical services provided much appreciated care to the local population and sophisticated laboratories supported all the unit’s activities.  Field stations were later established at Keneba (Nutrition studies), Farafenni (demographic surveillance area with studies on reproductive health and malaria including mosquito studies in Walikunda), Basse (initially for work on schistosomiasis, later pneumococcal and malaria vaccine trials), and Caio, Guinea Bissau (for HIV2 studies).  In each centre clinical care of patients was provided and those who participated in research studies were obviously followed very closely. 

The MRC Unit in The Gambia is financed by the UK Government and it represents the UK’s single largest medical research investment in a developing country. 

 

What were the principal areas of research that the MRC was engaged in, in The Gambia while you were director?

The unit’s research concentrated on communicable diseases of direct concern to The Gambia and the African continent, for the purpose of minimising the burden of illness and mortality in the country and the developing world as a whole. It also conducted research in nutrition, reproductive health and non-communicable diseases.

For the eight years I was seconded from LSHTM to West Africa (1994-2003) to be Director of the Unit in The Gambia, we had a broad research portfolio in infectious and tropical diseases, including programmes on malaria, HIV, hepatitis B and other viruses, TB, nutrition, pneumonia, reproductive health and non-communicable diseases. In each programme we worked closely with the Gambian government and all research proposals were reviewed and approved by the Joint Gambia Governmen-MRC Ethics Committee.

 

 

What were the major breakthroughs in research while you were there?

The largest research studies while I was working at the MRC Unit were vaccine trials that established the effectiveness of the vaccine and led to implementation in public health interventions in The Gambia and elsewhere in developing countries.  These large trials tested vaccines against: Hepatitis B, the commonest cause of cancer in West Africa; two large vaccine trials against the commonest causes of pneumonia in children (Haemophilus influenzae, type b –Hib and Streptococcus pneumoniae – pneumococcus); and more preliminary vaccine trials against malaria and tuberculosis.  New vaccines, comprising recombinant constructs and different adjuvants, designed to stimulate specific immune responses were evaluated and found to be safe.  The first trials of the current GSK malaria vaccine were conducted in The Gambia.

We established new programmes in TB, reproductive health and non-communicable diseases and defined the extent of these conditions in The Gambia.  We particularly focused on conditions that affected family health in the community.  In infectious diseases we engaged in studying the protective immune responses to the causative organism with the goal of finding a protective vaccine.  All diseases have a genetic component that defines the disease spectrum in different individuals and we studied the genetic susceptibility to common conditions in West Africa.

We recruited staff with health economics skills to help establish the cost and benefit of introducing research findings into public health policy and practice.  New anti-malarial medicines were evaluated, including one of the first trials employing combinations of artemesinins with other anti-malarial agents, combinations that are still widely used to treat drug resistant parasites that are now found in most parts of Africa.

We set up a large West African collaboration to study tuberculosis.  This involved a case-contact design in which the households of people who were diagnosed with TB were compared with people in a nearby household without any TB. Using new diagnostic tests we were able to follow household members that had been exposed to Mycobacterium tuberculosis the causative bacteria, and define those who had been infected but did not develop disease and those who went on to develop the disease tuberculosis, requiring drug treatment for six months.  We studied babies to understand the immune responses to the EPI childhood vaccines and found that BCG given at birth had a beneficial stimulatory effect on the responses to other vaccines given at the same time or even later.

The reproductive health programme focused on ways to reduce the unacceptably high levels of maternal mortality, particularly those deaths resulting from post-partum haemorrhage.  The beneficial effects of misoprostol in reducing bleeding were evaluated.  A screening programme for early detection of cervical cancer was initiated and the immune response against the causative viruses studied. The sexual health behavioural intervention programme, ‘Stepping Stones’, developed in East Africa, was adapted for use in Muslim communities in West Africa.  Projects on the blinding disease trachoma caused by Chlamydia  trachomatis, included a seminal study to reduce the fly population that spreads this bacteria; providing pit latrines reduced the transmission of the infection.  

The non-communicable diseases (NCD) programme was ahead of its time, establishing baseline prevalences for high blood pressure, obesity, diabetes and asthma in urban and rural communities.  The pattern showed that urban lifestyles led to a higher NCD burden, with some geographic variation within The Gambia.  These studies were timely as there is now a growing epidemic of hypertension, diabetes, obesity in most urban communities worldwide.  A retrospective study of cause of death in Banjul for the previous 50 years showed a change in disease patterns over time.

 

What do you feel most proud of in terms of the MRC’s achievements in The Gambia?

The close collaboration between the MRC and the Gambia Government has been a major factor in the success of this very productive investment in medical research.  The MRC is one of the largest employers in the country and provides health care to many families in The Gambia.  The MRC Unit has done much research that is relevant to the health needs of people living in The Gambia and in other countries with limited resources.  Many Gambian families have benefitted from participating in research studies and often the research findings have been put into policy and public health practice both in The Gambia and more widely in Africa.  The Gambia Government-MRC Ethics Committee has reviewed all research to ensure that the benefit of the research outweighs any potential risk.  Many staff have benefitted from training and I took a special interest in placing training and capacity building high on the agenda of the Unit.  Collaborations with leading researchers and institutions internationally inspired many excellent collaborators from all over the world to help and to work in The Gambia.  Having a critical mass of excellent staff in different disciplines allowed for a buzz of inspirational creativity in the Unit.  Many young staff that joined the MRC Unit were greatly influenced by the experience and continued to work in medical research and public health internationally. Many Gambians had long-term careers at the MRC Laboratories and were encouraged to participate in lifelong learning, doing courses in The Gambia and internationally and with much focus on on-the-job training.  We were all proud of the recognition of the Unit, in The Gambia, elsewhere in Africa and internationally as a centre of excellence for research, training and in the provision of healthcare.  Moreover many lifelong friendships and collaborations were born in The Gambia.

 

When you left The Gambia you went back to your roots in Uganda as director of the Infectious Diseases Institute in Kampala. What did that work involve?

After leaving The Gambia in 2003, I was privileged to be invited to be the founding director of a new Infectious Diseases Institute (IDI) in Uganda.  This institute had grown out of an Academic Alliance of 14 leading academics (9 from Uganda and 5 from North America) who wanted to make a difference in the care of people with HIV and Aids.  At that time antiretroviral drugs (ARVs) had only just become available in East Africa.  The incidence of HIV infection was very high and the death rate shocking; the coffin industry flourished.  The availability of ARVs at IDI brought a tsunami of demand for ARVS and care.  

With generous support from Pfizer, we recruited excellent staff in Uganda and internationally.  We were able to focus initially on establishing the essential infrastructure systems to support a major new institute, including sound financial systems (trusted by international funding agencies), clean water, reliable power supply, human resources practices and a strategic planning department that led the grants management activities.  The priority given to developing governance and management systems was an essential part of setting up the new institute and accompanied the building of the Institute at Makerere University, the first new building on the medical campus in 30 years.  IDI was set up as a company limited by guarantee, owned by the university, with autonomy in terms of financial management, HR practices and salaries.  

The clinical service soon cared for 10,000 people living with HIV, since availability of ARVs meant that most people were not dying from Aids but living with HIV.  The training programme initiailly focused on training of doctors, nurses, clinical officers and laboratory staff from Uganda and increasingly from other countries in Africa (including The Gambia), and later included programme managers and admin staff training in grants management and public health systems.  Initially short courses focused on clinical management of Aids, use of ARVs and laboratory tests.  Later we started training in the field with a systems approach to building public health in the community, including prevention of HIV transmission and malaria control.

Research was initially focused on following a large cohort of people living with HIV, their treatment and the natural history of their illnesses; then on the major opportunistic infections and their management; and on ensuring optimal adherence to treatment and criteria for switching to second and third line medicines.  We expanded to include research on implementation of public health interventions in delivery of health care for HIV, malaria and tuberculosis.  

The overwhelming demand for care exceeded our capacity, so we had to come up with a new paradigm for care of people living with HIV. Patients became known as ‘Mikwano gjaffe’ or ‘Our Friends’ in the local vernacular and the Friends organized activities in the clinic every day: music and dance, art and crafts, social and spiritual support, games in the clinic and entrepreneurial life skills training.  The clinic was transformed from a morgue to a market place.  Friends were encouraged to become change agents for their communities and a training programme (later called Namweza) was designed to teach life skills to help them in managing their complicated social networks.

 

When you now survey the area of global health, what do you see as the biggest challenges and do you feel optimistic that they will be met?

Infectious diseases are still a major cause of death and ill-health worldwide.  Ideally prevention by effective vaccines is the long-term goal and investment in creating and testing new vaccines remains an international priority.  Resistance to antimicrobials is of growing concern and investment in new medicines is another high priority but is very expensive; prevention of resistance can only be achieved by a worldwide coordinated effort not to misuse antimicrobials, both in humans and in veterinary practice.  Alternative combination treatments for malaria, HIV and tuberculosis remain a high priority because of emerging resistance to antimicrobials and the difficulty of adhering to long-term treatment.  An overlapping epidemic of diseases of lifestyle, the so-called non-communicable diseases (NCDs), is becoming a major health problem in less affluent countries; prevention should again be a priority but is difficult to implement: healthy diets and exercise are the key.  Changing behaviour remains a difficult goal and we need to come up with novel ways to achieve this both for prevention of communicable and non-communicable diseases.

 

What do you make of the spread of Ebola epidemic and the fact that MRC in The Gambia is to conduct Ebola tests in The Gambia?

The West African Ebola epidemic is very worrying.  The causative Filovirus is highly infectious and causes death in a frighteningly high proportion of people infected. It is transmitted from body fluids of people who are very sick or have died (contact with blood, urine, faeces, saliva, semen and washing of bodies after death is particularly dangerous). Healthcare personnel are at high risk of infection, so protective clothing is required to reduce the risk of infection in hospitals.  Recently some cases have been cured by giving affected patients specific antibodies to the virus, suggesting that perhaps treatment with serum from survivors might help to clear the virus; and in future a preventative vaccine could be effective.   The virus appears to be maintained in the bat population and new human outbreaks may occur by aerosol inhalation of bat guano that has dried in places where bats reside, for example big caves. Well-rehearsed public health guidelines need to be in place in all countries and diagnostic capability is critical to pick up infected cases early.  So it is highly commendable that the MRC Unit is taking on the diagnostic capacity for the country and more widely too.

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