Over 300,000 babies are born with sickle cell anaemia each year, more than three quarters of them in sub-Saharan Africa (1). It is often said that the vast majority of these babies do not survive into adult life. But what is the evidence for this statement and, if you have sickle cell, does your chance of survival depend on where you are born?
The best way of looking at mortality rates in early life is to undertake a cohort study. In these studies, all babies with sickle cell disease are identified at birth and then this “cohort” is carefully followed up to see what happens over the subsequent years. It is important to identify all the affected babies, to make sure that missing some doesn’t skew the figures, and it is also important to make sure that none of the babies are lost to follow up, so that the figures reflect the true outcome for all the children. These are difficult and time consuming studies to undertake and none have been conducted, in those resource poor countries in Africa, where sickle cell is most prevalent. They have however been successfully completed in the UK, in the USA and in Jamaica.
The cohort studies in the Caribbean were pioneering. The Jamaican study in 1995 (2) reported a mortality rate for children with sickle cell anaemia of 26% by age 15 years. This was halved to 11% by introducing penicillin prophylaxis and parental health education. The next study, in 2004, from the USA, based in Dallas Texas (3) reported a 15% childhood mortality rate, with 85% of children surviving to 18 years of age. This compared favourably with a previous study from the USA, in the 1970’s, which found that 50% of children with sickle cell anaemia died. The most recent study from the UK (4) in 2007 found that 99% of children in East London survived to 16 years of age, a mortality rate of only 1%. These cohort studies demonstrate that in well resourced health services, where money and expertise are readily available, deaths in childhood from sickle cell disease can be virtually eliminated. The Jamaican study, in particular, showed how relatively simple interventions can have dramatic beneficial effects.
Cohort studies are not feasible in much of Africa, because of the time and expense involved. How then does the survival of babies with sickle cell disease in Africa compare with the results from the developed world? Are there other sources of evidence that we can use to give an indication of this?
In a prospective study a large group of children with sickle cell anaemia are collected and carefully followed up over several years. This is easier to do than a cohort study but unfortunately only provides very limited information. The children recruited to the study are inevitably selected and may not include any children from the first year of life or from rural areas, among whom mortality is likely to be highest. Such studies will therefore, in all likelihood, underestimate mortality rates. An example of such a study was reported from Dar-es-Salaam, Tanzania in 2011 (5). The authors found that out of a total study population of 1,516 children with sickle cell disease, only 5.7% died during the follow up period. However, many children may have died before they made contact with the hospital, since the average age at recruitment to the study was as high as 8 years, and a large number of individuals, 209 or 12.1% of the study population, were lost to follow up. So, this surprising low mortality rate of about 6% is almost certainly a gross underestimate.
A better way of looking at mortality rates is a cross-sectional study. In these investigations individuals with sickle cell anaemia, in a large population, are grouped into age bands. If there is no excessive mortality in childhood then the number of children, teenagers and adults with sickle cell anaemia would be about the same in each age group. This is a relatively easy study to undertake and many such surveys have been published from Africa. All the African studies show that the number of individuals with sickle cell anaemia drops off quite rapidly in the higher age bands, and that by the teenage years there is a mortality rate of between 60 and 90% among children with Hb SS, compared with children with Hb AS or Hb AA. A famous study from Garki, in rural northern Nigeria (6), published in 1979 when there was virtually no effective health care, calculated that almost all children with Hb SS disease died before the age of 5 years.
It is clear from the figures that there is a massive discrepancy between the chances of surviving childhood if you live in London compared with if you live almost anywhere in sub-Saharan Africa. In London, childhood survival is virtually certain, whereas in sub-Saharan Africa the majority of children with sickle cell anaemia die before they are 5 years old. Medical and nursing intervention really does make an enormous difference to the lives of children with sickle cell in the first few years of life. There is some evidence that the survival of children with sickle cell anaemia is slowly improving, especially in African cities and a recent study from The Republic of Benin (7) demonstrated a ten fold reduction of childhood mortality based on newborn screening and early diagnosis.
So, what is needed to change this desperate situation. Firstly, and most importantly, babies with Hb SS need to be identified and diagnosed when they are born in order to start preventative treatments as soon as possible. Secondly, because we know that most early deaths are due to infection, babies need to start infection prevention treatment immediately after birth with regular penicillin, anti-malaria measures and a childhood vaccination programme. Thirdly, resources are needed to educate the parents about sickle cell so that they know what to look for and when they should bring their children to the clinic or hospital.
These three simple measures have been shown to be absolutely key in reducing early mortality rates. Universal newborn screening for sickle cell is expensive and requires considerable laboratory expertise but, the other components, penicillin, anti-malarial tablets, impregnated bed nets, vaccines and health education are potentially affordable. A cheap, bedside screening test for sickle cell disease which could be applied to newborn babies, would go a long way to making this a practicable intervention. There needs to be a concerted effort to implement this programme in the countries of sub-Saharan Africa to reduce this terrible waste of young lives.