Authors: Colin Michie, Brianna Braithwaite, Raquel Kaizer Jasmin Millon, Oriena Mensah
Malaria caused sickle cell to develop
Before history was recorded, the survival of humankind was determined by disease. Food was often limited; lifespans were short. Many infants died, most often from infection by malaria. Predators and malnutrition will have killed many of our early ancestors, but countless youth died of malaria.
Malaria is spread by mosquitoes. The parasite lives in their salivary glands. When a host insect injects saliva to prevent their blood meal clotting, they also inject malarial organisms. The parasite lives inside red cells. This is a comfortable spot for a parasite because there is a lot of protein food available as haemoglobin. So the parasite multiplies, breaks out of one red cell, invades another. This cycle of eat, break, eat and break causes fevers. Sometimes, the fever repeats on a regular basis as thousands of red cells break at the same time. Malaria parasites can spread to the liver, the brain, or be eaten at the next mosquito meal, so they can move to another human (or perhaps a nearby ape).
Our predecessors that survived had to have something special – something that protected their red cells from the assaults of malarial parasites. Those with genetic defences had families that acquired their protective genes. Whole populations became better at surviving as they collected genetic protections against mankind’s common killer. Malaria was a major force that altered human genes. Let’s look at some of those genetic defences.
Different haemoglobins, including sickle cell
Those with sickle cell trait are more likely to survive infections with malaria. The sickle cell mutation is unusual in that it involves a change in just one pair of molecules in the DNA helix (on chromosome 11) and one amino acid difference in the haemoglobin molecule. These tiny changes make the haemoglobin a bad meal for parasites.
Other types of haemoglobin such as C, D or E, or the thalassemias also make it difficult for parasites to survive. The malarial receptor on the surface of the red cell, known as the Duffy antigen, disappeared completely from those living in Africa. This prevents easy entry of parasites into red cells. Enzymes such as G6PDase that might help parasite growth were lost too.
Sickle cell trait is the term applied to those with one gene for sickle haemoglobin. Those with two genes, one from each parent, have sickle cell anaemia. If both parents have the trait, there is a 25% chance that they will have a child with sickle cell anaemia, a 50% chance that they will have sickle cell trait and a 25% chance they will have no sickle haemoglobin at all.
Once humans migrated away from areas where infants were killed by malaria, these various genetic defences became less relevant. Some of the defences disappeared over the generations. Others remain. As malaria has been treated and mosquitoes controlled, some of the genetic defences have become a problem.
Why does the sickle cell gene cause illness?
Sickle cell haemoglobin makes crystals that cause red cells bend, from rounded discs into rigid and fragile banana-shapes. Banana-shaped cells have two major problems. First, they tend to stick to the lining and block small blood vessels. This is referred to as vaso-occlusion. Second, they break easily too, living for a few weeks rather than the usual three to four months. This is called haemolysis.
These two problems have a series of consequences. The damage to small blood vessels reduces blood flow to the local tissues. This often causes pain – particularly in bones such as the ribs or vertebrae. Over time, it can also cause other damage including stroke and kidney damage. Damaged blood vessels become inflamed and this makes the whole process recur. Shorter red cell lifespans cause anaemia and the breakdown of red cells causes jaundice. The combination of inflammation and problems with blood flow in small vessels makes patients prone to infection as normal defence mechanisms in the form of white cells and immune proteins do not work so efficiently.
Why is sickle cell variable?
Sickle cell is rarely a problem in small infants under six months of age. Why are these particular patients protected? As a foetus, we make a special type of haemoglobin – foetal haemoglobin – which is particularly effective in collecting oxygen in the mother’s placenta. Foetal haemoglobin is turned off in most of us once we are born, as other types of haemoglobin.
From a global perspective, sickle cell anaemia is variable in severity. Significant proportions of sickle cell patients in the Middle Eastern countries have mild disease, with few crises. It was found those with mild or moderate sickle disease in this part of the world had raised levels of foetal haemoglobin. Details of sickle cell trait and various haemoglobins and of other factors that can moderate the impacts of sickle cell disease can be found at: https://www.cdc.gov/ncbddd/sicklecell/toolkit.html
What treatments are available for sickle cell?
Life expectancy for those with sickle cell has increased steadily for 50 years. One of the most important steps takes place here on St. Martin. Babies with sickle cell are identified and carefully followed. On average, two infants are expected to be born each year on the island with sickle cell anaemia. They are given regular antibiotic and vaccines to protect them from infection as well as folic acid to help them make new red cells. They are encouraged to drink extra fluids, stay warm and avoid infection. They should see a specialist doctor regularly.
Medications for sickle cell have been used to increase foetal haemoglobin. Hydroxyurea or hydroxycarbamide increases foetal haemoglobin and reduces the sickling of red cells. It has been found effective and safe in patients of all ages. Treatments with hydroxyurea, blood transfusion or bone marrow transplantation or even genetic treatments to increase foetal haemoglobin need to be considered for some children. The care of all with sickle cell anaemia is greatly helped by support groups and networks. These are well developed on Jamaica and St Lucia: It would be useful to re-awaken the Sickle Cell Foundation on St. Martin. The roles played by foundations in the research and care of sickle cell anaemia internationally have been large and the Caribbean has been a leader in developing these.
What can you do for sickle cell?
It is important that all of us understand this problem. Globally, it is a common disorder and so we need to understand how to help reduce the risk of crises in sickle cell sufferers. This curse of malaria will not leave our species, but at least we can tackle it carefully with sound knowledge.
The following are some useful resources:
joingens.com/sickle-cell/sign-up (sponsored by Novartis)