What is Sickle Cell Disease?

The reason our millions of red blood cells that carry life-sustaining oxygen from the lungs to the rest of our bodies are red is that they contain large amounts of a red-colored protein molecule called hemoglobin.  It’s hemoglobin that picks up oxygen in the lungs and deposits it elsewhere.

Normal hemoglobin inside a red blood cell is liquid, like a bag of soup.  It flows freely so that normal red blood cells containing it are round and pliable and can navigate tiny blood vessels without getting stuck.

Proteins like hemoglobin are chains of amino acids programmed by our genes.  A single mutation of the gene that produces hemoglobin causes a subtle change in the hemoglobin protein that causes it to line up to form rigid needles.  The affected red blood cells develop an elongated shape resembling a scythe – hence the designation of “sickle cell” – and now form log jams in the blood circulation.  The impeded blood flow deprives tissues of oxygen resulting in severe pain and organ deterioration. These are the clinical hallmarks of sickle cell disease. It is a major cause of death of children under age five in developing countries where the disease is prevalent.  The main cause of death is infection to which sickle cell disease sufferers are greatly susceptible.

The transformation of red blood cells from their normal to a sickle shape only occurs when essentially all of the hemoglobin is abnormally affected.  This condition requires that one has inherited the mutated sickle cell gene from both parents. When someone has one sickle cell gene and one normal gene, a circumstance known as “sickle cell trait,” the red cells function perfectly normally, and the affected persons have no symptoms, although if they mate with a partner who has the trait, they may produce sickle cell disease offspring.

If a double dose of sickle cell genes is highly lethal, why didn’t the mutant sickle cell gene disappear?  The answer is that sickle cell trait protects those who have it from dying of a severe form of malaria – for reasons we simply don’t understand.  So, nature sacrifices individuals with sickle cell anemia to sustain the much greater number of persons carrying the trait. Therefore, it’s no surprise that sickle cell disease tracks geographically with the distribution of malaria – in Africa, India and the Middle East.

While currently no cure exists for sickle cell disease applicable to developing nations, relatively simple interventions can prevent death and treat the manifestations of sickle cell disease.  These measures include certain vitamins, vaccination against infections, prophylactic antibiotics and avoidance of dehydration. A few drugs have been developed that reduce the frequency of sickle cell disease symptoms, and recent work has shown that it’s feasible to administer them in Africa.  Employing these strategies, however, requires making the diagnosis of sickle cell disease by obtaining a blood sample and testing it – and doing so is a challenge in rural areas of developing countries for the following reasons.

First, awareness of the disease is poor, despite its prevalence.  The symptoms caused by sickle cell disease overlap those of malaria and other endemic maladies.  

Second, the diagnosis requires sophisticated equipment, not available or even usable in remote rural villages lacking electricity.  

Third, the dispersion of patients throughout vast rural hinterlands rarely in contact with health centers precludes transferring blood samples from infrequent patient encounters to centers able to make the diagnosis.  

What is needed is a “point-of-care” test that allows the healthcare worker to make a diagnosis on the spot and enroll the patient into an intervention program.  

Options has established partnerships that have come up with just such a test that simply rapidly and inexpensively generates a point of care diagnosis.  All it requires for power is an automobile battery. One of the partnerships was with the Department of Chemistry of Harvard University that developed the test in synchrony with a device company. Options connected them to dental and medical colleagues at the National Zambian Dental Training School and University Teaching Hospital, Zambia’s largest academic health center respectively.  The Harvard chemists and the device manufacturer validated the test with known sickle cell disease patients. In 2017, Options and these partners field tested the device at a remote rural health center in Zambia on 500 people who gathered for a dental prevention project. The test highly reliably diagnosed patients who were referred to the health center for further management.

Having now shown that applying dental prevention to round up persons subsequently diagnosed with sickle cell disease with the point-of-care test, Options’ ambition is to take the combined strategy of oral health prevention and sickle cell disease diagnostic screening into the rural areas of the entire country of Zambia.  This project will entail coordinating efforts of the device maker, the Zambian Dental Training School, University Teaching Hospital, the Zambian Ministry of Health, the Zambian Health Council and potential corporate donors of toothbrushes, toothpaste, fluoride varnish and other supplies.  Although corporate donations have been generous in the past, Options will need to raise funds to sustain the scale of the envisioned program.