We all spend a lot of time looking at the detail, but sometimes it is important to take a step back and look at the bigger picture.
During the 9th Sickle Cell and Thalassaemia Conference in London this autumn several speakers looked at the global burden of sickle cell and how it is managed in resource poor countries. The scale of the problem was overwhelming but what was inspiring was the innovative ways in which local medical services were beginning to tackle the problem.
Sickle cell, along with the thalassaemias, are inherited disorders which affect the haemoglobin molecule, found inside all of our red blood cells. A staggering 5% of the world’s population carry a mutation affecting one of the haemoglobin genes. Assuming a world population of 7.3 billion (July 2015), that equates to 365 million individuals around the world with an inherited haemoglobin disorder. These two conditions, sickle cell and thalassaemia, are therefore far and away the commonest single gene disorders to affect the human race.
Out of the 365 million individuals, how many are carriers of sickle cell? No one knows exactly, but in 2010 it was estimated that there were more than 100 million sickle cell carriers worldwide. The situation is complicated and these estimates are difficult because the sickle cell mutation is not uniformly distributed around the world. Sickle cell does not occur at all in some populations, such as in northern Europe, south east Asia or the indigenous peoples of the Americas. On the other hand, it is found at high frequency in people who live in sub-Saharan Africa, the Middle East and India. Often it is very common in these areas, in parts of west Africa a quarter of the population may be carriers.
In all, 65% of carriers are found in sub-Saharan Africa, 28% in Arabia and India, 7% in the Americas and 5% in Europe and Asia. Some specific figures for individual countries include: Jamaica 10% of the population (272,000), the UK 0.42% (250,000), Saudi Arabia 4.2% (1,210,860) and the USA 0.55% (1.5 million). These countries, except Jamaica, are all relatively low prevalence areas, no one appears to have attempted to find out how many carriers there are in high prevalence countries. For Nigeria, assuming a carrier rate of 25% and a population of 173.6 million, that would equate to nearly 43.5 million sickle cell carriers.
Of course, what we are really interested in is the number of people who have sickle cell disease, but there is, surprisingly, very limited data on this. In the USA there are estimated to be 90-100,000 with the disease and in the UK 12-15,000, but there is little information for any other countries, in particular for those where the mutation is most commonly found.
There is a problem here, however. There is a famous equation, “The Hardy-Weinberg” equation, which allows you to predict how many people there should be with the disease if you know the total population and the number of carriers. Surveys in Africa and elsewhere identified large numbers of carriers but very few with the disease, many fewer than were predicted by the Hardy-Weinberg. It soon became clear that the reason for this was that babies with sickle cell anaemia had a very high early mortality rate and as a result very few survived into later childhood or adult life. This means that counting the number of adults with sickle cell anaemia does not really give a fair estimate of the burden of the disease in that particular population.
A better way of estimating the disease burden is to look at the birth rate of babies with sickle cell disease. Unfortunately, only two countries in the world, the USA and the UK, have a universal newborn screening programme in place that picks up all affected babies at birth, although many other countries have more limited programmes. In the USA about 1,000 babies (1 in every 4,000 births) are born each year and in the UK about 320 (1 in every 2080 births). Estimates for France put the figure at 340 (1 in every 2415 births) and for Jamaica 166 (1 in every 300 births) annually. Both of these countries have selective newborn screening programmes, so these figures may be underestimates. Once again, however, we do not have good figures for countries with a high prevalence of the disease.
At the 9th Sickle Cell and Thalassaemia Conference Dr Frederic Piel from Oxford University used data from many different sources to calculate that in 2010, 305,800 babies with sickle cell anaemia were born throughout the world. He was also able to calculate that this number will increase by 32% to 404,200, in 2050. In his analysis just three countries account for 57% of all sickle cell anaemia births; they are Nigeria (91,000 increasing to 140,800 by 2050), the Democratic Republic of the Congo (39,700 increasing to 44,700) and India (44,400 falling to 33,900). In all 75% of all births with sickle cell anaemia occur in sub-Saharan Africa (just under 230,000 babies) and 2-3% of all babies born in sub-Saharan Africa will have sickle cell anaemia. Although these estimates are based upon a sophisticated analysis of a large database, Dr Piel noted that there were limitations in the calculations and the actual figures may well be higher.
However you look at the figures, whether the number of sickle cell carriers or the birth rate of babies with sickle cell anaemia, it is the countries of sub-Saharan Africa, particularly Nigeria and the Democratic Republic of Congo, which have the biggest disease burden, with India an often overlooked runner up.