The new research takes into account prior outbreaks of similar viruses, mosquito transmission patterns, climate conditions, virus incubation periods, and the impact of herd immunity - which occurs when a high percentage of a population becomes immune to an infection.
Herd immunity can extinguish an outbreak when so many people become immune - either naturally or through vaccination - that the virus no longer spreads efficiently.
The researchers also calculated the potential impact of economic factors.
According to study co-author Alex Perkins of University of Notre Dame, women in poorer areas are at greater risk for Zika because they are less likely to have screens on their windows and air conditioners - two factors that have a major influence on reducing exposure to mosquitoes that carry Zika.
Given all these parameters, they estimate that up to 1.65 million women of childbearing age in Latin America and the Caribbean are at risk of contracting Zika in the first wave of the outbreak.
"That is a cumulative number over the course of roughly the first two to three years of the outbreak," Perkins said. "We consider that to be an upper limit of what might be possible."
Perkins said the estimate puts tens of thousands of babies at risk of developing the birth defect microcephaly or other issues related to being exposed to Zika in the womb.
The model also predicts that Brazil will have three times more infections than any other affected country, due to its size and suitability for transmission.
U.S. health officials have concluded that Zika infections in pregnant women can cause microcephaly, a birth defect marked by small head size that can lead to severe developmental problems in babies.
The connection between Zika and microcephaly first came to light last fall in Brazil, which has now confirmed more than 1,600 cases of microcephaly that it considers to be related to Zika infections in the mothers.
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