The most popular theory for the cause of death has been malaria.  Alexander had traveled to part of India where malaria was common, and some of his symptoms do indeed match the disease.  With malaria, the patient experiences chills which cause shaking, as Alexander is said to have done, and they develop a high fever, which comes and goes every few days for a week or so.  Alexander is described as initially having a fever which abated until he relapsed a few days later.  Malaria can also induce delirium and periods of unconsciousness, which it also seems Alexander suffered.  And in cases where malaria is fatal, the cause of death is usually a ruptured spleen: an agonizing condition that would result in excruciating pain in the area of the stomach, such as described in Alexander’s case.  For years, malaria was widely accepted by historians as the cause of death, until a tropical disease specialist, Dr James Maynard of London University, examined the accounts of Alexander’s fatal illness in the 1970s.  He concluded that if the ancient reports were reliable, then Alexander could not have died from malaria.    

Dr Maynard seriously doubted that Alexander had suffered a ruptured spleen.  If his spleen had ruptured when he was struck down with pain at the banquet, as the malaria theory supposed, then the pain would not have subsided overnight and abated for some days, as the sources report.  Alexander would have been in persistent agony until he died from internal hemorrhaging.  Moreover, the pain would have been on the left side of the stomach and not beneath it, as described. The other way that malaria victims can die is when diseased blood cells clog the brain tissue of the patient.  Dr Maynard found no evidence that Alexander had died in this way either, as the condition would have been accompanied by severe headaches which are not mentioned once by any of the sources.  In fact, Dr Maynard was certain that Alexander not have contracted malaria at all.

Malaria is a disease carried by certain mosquitoes that can infect a person with a bite. These mosquitoes live in jungle and tropical locations, but not in desert regions such as central Iraq where Alexander died.  However, two years earlier Alexander had been in an area of India where malaria was common.  Nevertheless, Dr Maynard seriously doubted that Alexander could have contracted the illness there.  The disease can remain dormant in the bloodstream for anything up to ten months from the time of the initial exposure.  Someone who fails to exhibit symptoms after that time is probably not infected: certainly not after two years.  Bouts of malaria, lasting some days, can and do recur, so it is possible that Alexander had previously suffered from the illness since he left India.  However, Alexander’s life from the time he was in India is well documented but there is no report whatsoever of a previous illness of this kind.

With the malaria diagnosis in question, in 1998 a team from the University of Maryland in the USA suggested that Alexander had died of typhoid.  Typhoid causes chills, high fever and delirium, from which Alexander appears to have suffered.  However, so do many other illnesses.  What convinced the team that he had specifically died of typhoid was the description Plutarch gives of the state of preservation of Alexander’s body after his apparent death.  One symptom sometimes associated with typhoid is a condition known as ascending paralysis: muscle paralysis which starts at the feet and moves slowly up the body.  Patients with this condition can eventually appear dead and, in the days before modern medicine, some unfortunate victims of typhoid were even buried before they had actually died.  As Plutarch reported that Alexander’s body failed to show any signs of decomposition for days, the team proposed that the king had been suffering from paralysis caused by typhoid and was actually still alive.

However, the typhoid theory failed to address many of the symptoms and circumstances associated with Alexander’s death.  To begin with, typhoid is caused by salmonella typhi bacteria which is transmitted by food or water contaminated by an infected person, or by sewage containing the germs.  As such, there would almost certainly have been an epidemic of the disease when Alexander fell sick.  However, there is nothing in any of the historical accounts to suggest such outbreak in Babylon at the time.  Secondly, salmonella typhi is an intestinal bug which causes severe diarrhea and abdominal pain.  Beside the fact that diarrhea is not mentioned in the historical accounts, Alexander’s pain is reported to have been in the area of his stomach and not his bowl which would have been the area of discomfort if he had typhoid.  In fact, the University of Maryland team proposed that Alexander’s stabbing pain suggested that he had died of a perforated bowel, which is often the cause of death in cases of typhoid fatality.  Even if the sources are wrong about the location of Alexander’s pain, a perforated bowel would have left him in constant agony until he died, rather than recovering for days as the accounts all describe.

Perhaps the most obvious possible cause of Alexander’s death to consider is alcohol poisoning.  Not only is he reported as having been a heavy drinker, on the day he was taken ill Alexander had been consuming large quantities of strong wine.  Intense pain in the area of the stomach is a symptom of alcohol poisoning and unconsciousness is inevitable. Alexander did suffer stabbing pains in his stomach and was unconscious shortly after.  If Alexander had suffered from the toxic effects of alcohol to the point where he was in excruciating agony, as is reported, then the lining of his stomach would have been so inflamed that he would also be vomiting violently and would not be able to hold down food or liquid for many hours or even days.  If Alexander was a chronic alcoholic, as has been suggested, then this condition would be extremely serious.  Unable to hold down any alcohol, Alexander would soon suffer from dangerous withdrawal symptoms.

Serious alcoholics suffer severe withdrawal symptoms known as delirium tremens, or DTs for short.   Unless the alcohol intake is lessened gradually, or substituted by modern drugs, the person experiences fevered agitation, extreme anxiety, delirium, hallucinations and severe trembling.  Moreover, delirium tremens also include grand mal seizures that sometimes lead to death.  All of these, or similar symptoms, seem to have been suffered by Alexander.  However, as DTs occur because the body has been denied the alcohol it has become dependent upon, they do not begin until enough alcohol has left the system – usually not for twenty-four hours or more.  Even with an extremely high metabolism, DTs would not occur until at least six hours after the last drink; and even then they would be the less severe effects, such as anxiety, agitation and some shaking.  The more extreme conditions - delirium, hallucinations and seizures - would not occur until many hours later.  However, Alexander was suffering from all these symptoms the night he was taken from the banquet.  In fact, the trembling and agitation are recorded while he was still drinking.  Whatever Alexander was suffering from on the night of the banquet it was not DTs, and alcohol poisoning itself would not cause such symptoms.  Alcohol poisoning either results in complete unconsciousness or a state of stupor in which the nervous system is dangerously sedated for hours: the victim is in precisely the opposite condition to one which would produce the writhing seizures and delirium which Alexander is said to have suffered. In fact, the major effect of alcohol poisoning is continual vomiting.  Death often results from the victim choking on their own vomit or, in the days before intravenous drips, from dehydration.  Even though Plutarch does say that Alexander suffered a violent thirst on the night he was taken ill, not once does he or any of the other historical sources once mention vomiting or even nausea as one of Alexander’s symptoms.

A new theory proposed in 2003 by two U.S. scientists, John Marr, an epidemiologist at the Virginia department of health, and Charles Calisher of Colorado State University, proposed that Alexander had died of West Nile Virus.   One of the main features of the West Nile virus is that it begins with weakness of the muscles which Alexander does not appear to have suffered from.  In fact, most damming to the theory is that, as Massimo Galli of the University of Milan pointed out, "West Nile Virus is a relatively young virus and reduces the probability of incidental infections of humans before 1,000 years ago.”