For example, in November 2010, Dr. Jeffery K. Taubenberger of the National Institutes of Health discovered the earliest proof of sickle-cell disease while looking for the virus of the 1918 flu during the autopsy of an African-American soldier.

[2] There have been calls to reclassify sickle cell trait as a disease state, based on its malignant clinical presentations.

With regards to the actual concentration of hemoglobin in the circulating cells, the alleles demonstrate co-dominance as both 'normal' and mutant forms co-exist in the bloodstream.

[citation needed] The significance of the sickle-cell trait is that it does not show any symptoms, nor does it cause any major difference in blood cell count.

The trait confers about 30% protection against malaria [clarification needed] and its occurrence appears to have risen tremendously in Africa, India and the Middle East.

[20] [5] [21] Whole genome sequence analysis has identified a single origin of the sickle trait, with one haplotype ancestral to all sickle-cell variants.

[26] While more research is necessary on the topic, the correlation found between individuals with sickle cell trait and an increased risk of sudden death appears to be related to microcirculatory disorders, during exercise.

[27] In recent years the NCAA has partnered with the ACSM and issued a joint statement, warning athletes about both the prevalence and the potential risk factors of sickle cell trait.

[28][29] The inflammation and leakage of intracellular material resulting from muscle cell necrosis releases a particular protein, myoglobin, into the blood stream.

[31] In endurance-trained individuals with sickle cell trait the presence of alpha-thalassemia has been shown to act protectively against microvasculatory distress before, during, and after exercise.

Specifically to sickle cell trait, cramping occurs in the lower extremities and back in athletes undergoing intense physical activity or exertion.

[29][30] Individuals with known positive sickle cell trait status experiencing significant muscle weakness or fatigue during exercise should take extra time to recover and hydrate before returning to activity in order to prevent further symptoms.

Among these preventative measures are proper hydration[25] and gradual acclimation to conditions such as heat, humidity, and decreased air pressure due to higher altitude.

[28][29][32] Gradual progression of exertion levels also helps athletes' bodies adjust and compensate, gaining fitness slowly over the course of several weeks.