Eight years ago, Arafa Salim thought she was on the verge of death. “The doctors who were treating me didn’t know how to deal with it, my bone marrow couldn’t produce blood. I needed a lot of transfusions to save my life,” she said.
Salim, who has sickle cell disease, a genetic blood disorder that can result in severe anaemia, had survived a real scare. Her story is not uncommon. More than 10,000 children with sickle cell disease die each year before they reach their fifth birthday, in Tanzania, East Africa. If they survive childhood, the average life expectancy is just 35 years old.
Often described as an “invisible condition”, sickle cell disease is widely misunderstood. The inherited blood disorder causes red blood cells to change from a smooth flowing doughnut shape to the eponymous sickle. It limits the way the body distributes oxygen, having a huge impact on the lives of those diagnosed. The health implications are severe, and can range from the narrowing of blood vessels resulting in regular episodes of extreme pain, to disrupted blood flow, which can cause damage to muscles, bones and organs.
Throughout Salim’s childhood, doctors had told her she might not live to see her teenage years. “I remember people saying that I wouldn’t reach 12 years, but look at me now, I am 32 years old,” she said.
Living with pain
The Tanzanian sickle cell advocate grew up in the country’s economic capital and largest city, Dar es Salaam, nestled along a natural harbour on the Indian coast. Salim was the fourth of seven children in her family, and the first to be diagnosed with the disease, when she was just eight months old.
It wasn’t until she was in her early teens, however, that Salim first started to understand the impact of the disease. “As a kid I didn’t really understand the pain. It was only when I grew older that I realised the seriousness and extent of sickle cell disease,” she said. Salim turned to her mum for information. “I’m sure she always thought I was too young to know all about those complications, but I started to learn more about it on my own.”
“There is still a lot of misunderstanding surrounding the disease. It’s extremely hurtful when people think one is exaggerating the pain involved,” she said. “You learn to mask it, but the pain never goes away.”
It was this very need for education and a wider awareness of how sickle-cell patients behave, which motivated Salim to start her own non-profit organisation in 2010. With support from friends and family, she set up the Sickle Cell Disease Patients Community of Tanzania (SCDPC), working closely with the capital’s largest medical school, MUHAS, and the country’s referral hospital, Muhimbili National Hospital.
Over the last nine years, she has helped “bridge gaps of ignorance about the disease and its transmission” through raising awareness and outreach activities, as well as building confidence and support in health and research programmes.
She emphasises the challenge is not only about awareness, but also about teaching the community how to treat sickle cell patients. “We’ve carefully and slowly worked on sensitising people about sickle cell disease as it affects many in Tanzania,” she said. As part of her ongoing awareness campaign, Salim volunteers at the hospital. Working alongside medical staff, she runs different activities, such as arts and crafts workshops during clinic days, and speaks to fellow patients.
As well as regular group meetings for patients, fundraising events, and supporting families with sickle cell patients to apply for health insurance, the organisation also regularly visits schools. Salim recalls difficult times during her education when teachers and fellow pupils would not understand her behaviour. Like many who suffer from sickle cell disease, Salim mentions how she would tire quickly in class, be prone to thirst, and occasionally be bullied.
“Literally children would say, ‘Look your eyes are so yellowish, are you a genie?’ I would respond that I had sickle cell,” she said, referring to the jaundice sickle cell patients can suffer from, which results in a yellowing of the whites of the eyes.
Despite facing many obstacles, Salim completed her school studies, and in 2012, received a degree in Business Administration from the Learnit Institute of Business and Technology, University of Greenwich. Salim is determined to fulfil her dreams of working as a full-time health professional. “I always wanted to work in healthcare and save lives. I believe I will accomplish this dream,” she states.
Approximately five per cent of the world’s population carries trait genes for haemoglobin disorders, mainly, sickle-cell disease and thalassaemia. Nearly 90%of the global sickle cell disease population lives in three countries: Nigeria (85,000), the Democratic Republic of Congo (42 000) and India (38 000), and where the disease affects up to two per cent of the population, and the sickle cell trait is as high as 10 to 30%.
Tanzania (11 000) is the third worst affected country in Africa, where without intervention, at least 50% of patients are at risk of dying in childhood. However, cost-effective interventions have the potential to reduce childhood mortality by up to 70%.
Through Salim’s close work with the Muhimbili sickle cell programme, she has witnessed and been a part of, one of the biggest success stories in African science in recent years.
Established from the modest surroundings of a small hospital office in 2004, Professor Julie Makani, in collaboration with colleagues, has developed a biomedical research and healthcare programme, which is now one of the largest sickle cell disease cohorts in the world.
“Sickle cell disease is the single most important genetic cause of childhood mortality worldwide,” said Makani, who has dedicated her career to saving the lives of people with sickle cell disease. “Yet despite this, the ongoing research is not commensurate to the burden.”
Most of what is known about the genetic basis of this inherited disease comes from studies of US-based or UK-based African-Caribbean populations. Makani, one of the continent’s most prominent physicians, is determinedly working to change this. “There are very few programmes that are based in Africa, and integrated in African-led institutions,” said Makani, who looked across Africa and abroad for inspiration, and was certain they could run a successful research programme in Tanzania.
With limited infrastructure and basic sickle cell treatments such as blood transfusions and medications already in place at the hospital, Makani was keen to integrate research efforts with the necessity to provide good healthcare, training and education. She built a programme which actively supported women. “Our team is made up of over 60% women, with 90% in leadership roles,” she said. “This is not something that has happened naturally, and we actively work to increase the number of women in science and medicine. It is wonderful to see and be part of this.”
Makani emphasises that with more than 300 000 babies born every year with sickle cell disease, the vast majority of these in Sub-Saharan Africa, advances in treatment are not coming fast enough. Sickle cell disease was the first genetic disorder to be described, more than a century ago, yet until recently there was only one chemotherapy drug, hydroxyurea (hydroxycarbamide). In large parts of Africa, the drug is not available in public or private pharmacies and, when accessible, is not affordable for most patients.
“There are very few studies looking at the use of hydroxycarbamide in Africa”, said Makani. “But in the absence of evidence, we should not delay the use of the drug.”
As word spread through patient communities and more clinicians became aware of the sickle cell programme, people started travelling long distances from across the country for appointments and referrals. Makani and her team worked on developing health guidelines and training which could be used by medical staff and scientists in other hospitals. Within ten years, these were successfully adopted at a national level by the Tanzanian Ministry of Health in 2014.
“We slowly evolved into one of the biggest centres in the world for sickle cell treatment with more than 45 000 patients and 12 years of data,” said Makani, who won the Royal Society’s Pfizer Award in 2011. “We’ve built something that is valuable in Africa and it is really gratifying to see local and international investment.”
Building a biomedical resource
The Muhimbili sickle cell programme is now one of the world’s most valuable biomedical resources for the disease. The wealth of longitudinal and genetic data the team has amassed over a period of 12 years is impressive. It consists of 75 000 recorded visits from more than 10 000 individuals, patients both with and without sickle cell disease.
Through collaboration with local and foreign partners including the University of Oxford, King’s College London, and with funding from the Wellcome Trust, the programme has been able to build a biorepository, storing years of biological samples including DNA, red cells, plasma and serum from more than 5,000 sickle cell patients.
The partnership has paid dividends, and in 2014, the research teams from Muhimbili, King’s College London and Wellcome Trust Sanger Institute (WTSI) carried out one of the first genome-wide association studies in sickle cell disease in Africa, looking at more than 1,200 individuals in Tanzania. In sickle cell disease populations outside Africa, research has shown how genetic variations can influence the ability to produce foetal haemoglobin (a type of haemoglobin that reduces disease severity) by as much as 50%, but knowledge of this effect in African populations is scant.
Samples were gathered in Tanzania and genotyped at the WTSI, with the genome-wide scan carried out by the UK-based team, and the subsequent data analysis conducted jointly by researchers in Africa and the UK. The study identified the prevalence of genetic variants involved in sickle cell anaemia in the Tanzanian population and how that compares with other populations. It also revealed suggestive additional variants, which can now be studied further by the research community in the search for interventions for sickle cell anaemia in patients in Africa and worldwide.
Makani believes we’ll soon start seeing more targeted, personalised medicines being developed to treat people with the same genetic mutation, but tailored to adapt to different environmental, geographic and lifestyle factors. With the rapid advances in gene editing, including the use of CRISPR/CAS9 technologies, the possibility of finding a cure for sickle cell disease is increasing. Last year saw the first successful treatment of a sickle cell patient using gene therapy.
“If we can find a cure for a single-gene disorder such as sickle cell disease, this could be a model for curing other diseases with more complex genetic basis such as cancers, diabetes mellitus and Alzheimer’s,” said Makani. “Even with infectious conditions like malaria and HIV, there is no doubt genetic factors have a role, with some people more genetically susceptible to becoming infected or experiencing more serious symptoms.”
In recent years, several different networks and consortia have sprung up to share scientific knowledge and experiences of sickle cell disease across different African countries. These include the Sickle in Africa Consortium which will soon span 20 research sites in 15 countries, with the goal to collaboratively reduce the public health burden of sickle cell disease in Africa, and ultimately find a cure. Another initiative, SickleGenAfrica, is looking at the relationship between sickle cell disease, malaria and haemolysis, and will be the first initiative to set up sickle mouse studies in Africa. Makani formed the Sickle Cell Foundation in Tanzania to promote and support the creation of nationwide sickle cell centres, run public awareness campaigns, as well as work with patient advocacy groups like Salim’s. She has watched one successful advocacy campaign after another bring attention and resources to other disorders, such as HIV, but sickle cell remains less well known.
“If you look at HIV and the advocacy around that, it is incredibly sophisticated,” said Makani. “It would be great if we could have the same level of advocacy around sickle cell disease. The sickle cell disease patient community is growing. We recognise the importance of patients not just as participants but as partners in advocacy.”
Makani and Salim are optimistic about the future of sickle cell disease. They hope that in a country like Tanzania, where the population has risen from 25 million in 1990 to 60-million today, sickle cell testing can soon become a part of standard healthcare, blood supply for transfusion is adequate, and hydroxyurea can be available to many. Both cite new-born screening programmes as important to identifying the children at risk early and prevent complications. This has worked well in high-income countries such as the US, where new-born screening has reduced mortality rates in under-fives by more than 70 per cent.
Despite a second drug, Endari, being approved in 2017 for sickle cell patients five years and older, Makani still has only one aim in mind – curing sickle cell disease. “We hope to start carry out bone marrow transplants, participate in gene therapy trials and contribute to the evidence, with the hope we’ll find a cure for the disease.”
Salim concludes: “A good day for us would be a sickle cell free generation, where no more babies are born with sickle cell disease. We’ll continue this fight until we reach our goal.”