Cold Case solved. Another mystery is off the books ' although this one took over four hundred years.

We're talking about Francesco de' Medici, the Second Grand Duke of Tuscany, and his second wife, Bianca, who both died in 1587 after 11 days of suffering. The death certificates say they died from malaria.

However, it didn't take long for rumors to suggest otherwise – that the couple had been poisoned by Francesco's brother, Cardinal Ferdinando, with whom he had long standing disagreements. Coincidentally, Ferdinando had visited the couple just before they fell ill.

To set history straight: In 2004, Francesco's bones, along with those of his first wife and his father, were unearthed. Since no one knows where Bianca was buried she couldn't be included in the study.

In 2006, an analysis of the bones found arsenic which seemed to support the poison theory. Except ' arsenic was commonly used in embalming. Instead, the latest study by Gino Fornaciari supports the official cause of death ' malaria.

He tested Francesco's bone samples for the presence of Plasmodium falciparum proteins. These are malarial proteins the parasite would have left in its victims.

Since the bone samples were over 400 years old, it was likely the proteins did not survive.

Yet they did. The tests were positive for two malarial parasite proteins – proving he died from malaria. Neither Francesco's father nor his first wife tested positive, which supports their role as negative controls in the study since they had died from other causes.

Malaria was endemic in Central Italy at the time, so it's not surprising Francesco and Bianca became infected. Plasmodium falciparum is the most dangerous type of malaria.

It causes infected red blood cells to sludge in capillaries, killing pockets of tissue in the brain and other organs.

Solving this mystery exonerated one man of a shameful crime.