Medical historians like Thomas Short, Lazare Rivière and Charles Creighton gathered descriptions of catarrhal fevers recognized as influenza by modern physicians[1][2][3][4][5] attacking populations with the greatest intensity between 1557 and 1559.

[12] In the summer of 1557 parts of Europe had just suffered outbreaks of plague,[2] typhus,[2] measles,[13] and smallpox[13] when influenza arrived from the Ottoman Empire and North Africa.

Because it afflicted entire populations at once in mass outbreaks, some contemporary scholars thought the flu was caused by stars,[11] contaminated vapors brought about by damp weather,[18][11] or the dryness of the air.

[19][11] Ultimately the 1557 flu lasted in varying waves of intensity for around four years[7][20] in epidemics that increased European death rates, disrupted the highest levels of society, and frequently spread to other continents.

The flu pandemic first reached Europe in 1557 from the Ottoman Empire[21] along trade and shipping routes connected to Constantinople,[21] brought to Asia Minor by infected travelers from the Middle East.

On land, influenza spread north from the Ottoman Empire over Wallachia to the Kingdom of Poland and Grand Duchy of Lithuania before moving west into continental Europe.

The Sicilian Senate asked a well-known Palermitan physician named Giovanni Filippo Ingrassia to help combat the epidemic in an advisory capacity, which he accepted.

[13] German medical historian Justus Hecker writes that the young population of Padua had been reeling from a dual outbreak of measles and smallpox since the spring when a new illness, featuring extreme cough and headache, began to afflict the citizens in late summer.

[26] The disease, often called coqueluche by the French,[27][28] caused a severe outbreak in Nîmes that featured a fast onset of symptoms like headaches, fevers, loss of appetite, fatigue, and intense coughing.

[30] Italian physician Francisco Vallerioli, known as François Valleriola, was a witness to the epidemic in France and described the 1557 flu's symptoms as featuring a fever, severe headache, intense coughing, shortness of breath, chills, hoarseness, and expulsion of phlegm after 7 to 14 days.

"[16] Flu blighted the army of Mary I of England by leaving her government unable to train sufficient reinforcements for Henry Manners, 2nd Earl of Rutland to protect Calais from an impending French assault,[35] and by January 1558 the Duke of Guise had claimed the under-protected[36] city in the name of France.

One of the commissioners for the surrender of Calais found Sir William Pickering, former knight-marshal to King Henry VIII, "very sore of this new burning ague.

Influenza began to move north through England, felling numerous farmers and leaving large quantities of grain unharvested[44] before it reached London around mid-late October.

Queen Mary and Archbishop of Canterbury Reginald Pole, who had both been in poor health before flu broke out in London, likely died of influenza within 12 hours of each other on 17 November 1558.

Doctor John Jones, a prominent 16th Century London physician, refers in his book Dyall of Agues to a "great sweat" during the reign of Mary I of England.

[55] British medical historian Thomas Short wrote that "At Mantua Carpentaria, three miles outside of Madrid, the first cases were reported...There it began with a roughness of the jaws, small cough, then a strong fever with a pain in the head, back, and legs.

[67] The Native American Cherokee appear to have been affected during this wave,[68] and it may have spread along newly established trade routes between Spanish colonies in the New World.

[70] Missionaries like the Society of Jesus in Brazil founder Manuel da Nóbrega continued to preach, host mass, and baptize converts in the New World even when symptomatic with contagious illnesses like influenza.

Baptism rates in native communities were deeply connected with outbreaks of disease,[70] and missionary policies of conducting religious activities while sick likely helped spread the flu.

Egypt, which had been conquered by the Ottoman Empire around 40 years prior, became an access point for influenza to travel south through the Red Sea along shipping routes.

[citation needed] The Kingdom of Portugal had supported the Abyssinian (Ethiopian) Empire in their war against the Ottoman expansion of the Habesh Eyalet and sent aid to their emperor, including a team with Andrés de Oviedo in 1557 who recorded the events.

[73][72] Because of the epidemic Ottoman soldiers were soon recalled back to the ports, even though the emperor had been slain, and shortly afterwards Gelawdewos's brother Menas ascended to the Abyssinian throne and converted from Islam to Christianity.

Contemporary physicians to the 1557 flu, like Ingrassia, Valleriola, Dodoens, and Mercado, described symptoms like severe coughing, fever, myalgia, and pneumonia that all occurred within a short period of time and led to death in days if a case was to be fatal.

[50][24][58] Infections became so widespread in countries that influences like the weather, stars, and mass poisoning were blamed by observers for the outbreaks, a reoccurring pattern in influenza epidemics that has contributed to the disease's name.

Prior to greater research being conducted into influenza in the 19th century, some medical historians considered the descriptions of epidemic "angina" from 1557 to be scarlet fever, whooping cough, and diphtheria.

But the most striking features of scarlet fever and diphtheria, like rashes or pseudomembranes, remain unmentioned by any of the 1557 pandemic's observers and the first recognized whooping cough epidemic is a localized outbreak in Paris from 1578.

[75] These illnesses can resemble the flu in their early stages but pandemic influenza is distinguished by its fast-moving, unrestricted epidemics of severe respiratory disease affecting all ages with widespread infections and mortalities.