Can we prevent sickle-cell disease? The Manchester Project

Graham R. Serjeant, Contributor

Act I, Scene I. A mother with a young baby has just learnt that the child has sickle-cell disease, diagnosed by newborn screening. After explanation of the genetics and learning that abnormal genes must be inherited from both parents to have an affected child, the mother responds, "Why did nobody tell me that I carried this gene? If I had known, I might not have had this child."

This mother is right. To have a child affected by sickle-cell disease, abnormal haemoglobin genes must be inherited from mother and father. In Jamaica, babies with homozygous sickle-cell (SS) disease are born most commonly when both parents carry the sickle-cell gene (sickle-cell trait), but even then there is only a one-in-four chance at each pregnancy that the child will be affected. There is still a three out-of-four chance that the baby will be healthy, having either the normal AA genotype or, like the parents, carrying the sickle-cell trait. Apart from knowing the risks, the problem is that, currently, we cannot predict when the one-in-four chance will occur. In some families, that one-in-four chance has occurred in the first five pregnancies and all five children have had SS disease. In Jamaica, in addition to the 10 per cent with the sickle-cell trait, other abnormal haemoglobin genes such as HbC (3.5 per cent of Jamaicans) and beta thalassaemia (1.5 per cent of Jamaicans) may also give rise to babies with forms of sickle-cell disease.

Overall, one in every 150 births in Jamaica has some form of sickle-cell disease. Most of these abnormal genes are relatively easy to detect and people who carry these genes should be given this information so they may factor this into the other decisions in their choice of partner. Prevention, if possible, is much better than having to treat established disease, and we know that the disease can be prevented if one parent is normal.

Act I, Scene II: The Manchester Project seeks to address this issue. We ask the question that if senior-school children are informed that they carry one of these abnormal genes, will this information affect their reproductive decisions and prevent births of babies with sickle-cell disease? The proposal was submitted to the minister of health in November 2006 and, following discussions with the Ministry of Health and the Ministry of Education, the project was finally approved in mid-2007.

Act I, Scene III: The scene changes to the offices of the Southern Regional Health Authority on Brumalia Road in Mandeville, where the project was allocated a room on the ground floor to establish a diagnostic laboratory. Detection of HbS and HbC is relatively simple, with routine tests such as haemoglobin, electrophoresis and appropriate confirmatory tests. Detection of the beta thalassaemia trait is more difficult because this does not cause abnormal haemoglobin but reduces the amount of haemoglobin within the red cells so full haematology is necessary to measure the haemoglobin, red-cell count, size and amount of haemoglobin in the red cells. If these indices suggest beta thalassaemia, additional tests are needed, and then final confirmation must be done by DNA analysis. Everything was in place in the laboratory by the end of December 2007.

Act I, Scene IV: The scene now changes to the 15 secondary schools in Manchester (including Spaldings and Knox high schools just across the border in Clarendon). Illustrated lectures on sickle-cell disease, problems and inheritance are given to students in fifth and sixth forms (generally aged 16-18 years), all are given a 'Dear Parent' letter to take home with information about the study and giving them the opportunity to opt out, talks are given to the parent-teacher associations and arrangements made with the staff to set up screening sessions. A team of three experienced blood-takers visits the schools and up to 250 samples may be taken in a two- to three-hour screening session.

abnormal genes

Then, back to the laboratory for tests needed to detect the abnormal genes. Permanent laminated cards are produced for every student detailing their haemoglobin genotype and whether they are at risk of having a child affected by sickle-cell disease in the future. The cards are returned to the teachers for distribution, and all carriers of abnormal genes are offered individual counselling and the opportunity to ask questions. Each year, approximately 2,600 students complete these procedures, but how will we know whether this affects their decisions?

Act II, Scene I: We must screen the babies as they are born to detect cases of sickle-cell disease. This confers great benefit on affected babies and has become routine in the United States and the United Kingdom, and increasingly in other societies. So the babies benefit from having the diagnosis made early, but we also need this information to see whether the frequency of affected babies decreases over the years, as our informed students become parents. Newborn screening is complicated by the high levels of babies' blood (foetal haemoglobin) at the time of birth, but can be readily achieved by high-pressure liquid chromatography (HPLC). These machines are expensive, but the Manchester Project has been fortunate to have two machines donated, one from England and one from South Africa. Each is capable of analysing a blood sample every three minutes.

Screening was commenced at Mandeville Regional Hospital in August 2008, at Percy Junor and Hargreaves Memorial hospitals in January 2009, and in May Pen and Black River hospitals from January 2010. Each year, the project now screens 8,000-9,000 babies in the Southern Region, with the detection of approximately 50 babies with sickle-cell disease who are followed in sickle-cell clinics at Mandeville Regional Hospital. It is too early to state whether the frequency of affected births is declining. The project is currently funded until 2012 by the National Health Fund and the Alcoa Foundation, but it will be vital that the newborn screening continues as part of the Ministry of Health's regular services.

Act III, Scene I: What is the relevance of the Manchester Project? If empowering the students with knowledge of their haemoglobin genotype does reduce the frequency of affected births, this will have considerable benefit for the families in reducing the distress of coping with a sick child, and it will have major implications for health-care planning since it can be calculated that each sickle-cell patient currently costs the Jamaican health service in excess of J$1 million in a lifetime.

But are there implications beyond this? Look at sub-Saharan Africa, where based on birth rates and known frequencies of the sickle-cell trait, estimates suggest that more than 250,000 babies are born each year with the disease. The scale of this public-health problem far outstrips the available resources, with the result that the average survival is likely to be less than five years in Africa compared with 55 years in Jamaica. African countries are unlikely to ever have the resources to provide optimal health care for these children, and prevention of affected births must be an essential component in controlling the disease. If the Manchester Project is successful, this model may have major implications for controlling the frequency of the disease in other developing societies.

Epilogue: Jamaica has led the world in many aspects of the management of sickle-cell disease. It was the first country to have extensive newborn screening when 100,000 babies were screened at Victoria Jubilee Hospital between 1973 and 1981. The Jamaican Cohort Study, based on follow-up of these children, has identified simple, cost-effective interventions to improve survival and the quality of life and Jamaica now has the greatest documented survival for adults with the disease. With generous funding from the National Health Fund and the Alcoa Foundation, hopefully, Jamaica will show the world how to reduce the frequency of babies born with the disease. That is the hope of the Manchester Project.

Graham Serjeant is chairman of the Sickle Cell Trust (Jamaica). Email feedback to columns@gleanerjm.com.