Forty-six people were found dead after being abandoned in a tractor-trailer on a remote back road in San Antonio in the latest tragedy to claim the lives of migrants smuggled across the border from Mexico to the U.S. Sixteen people were hospitalized, including four children.

A city worker heard a cry for help from the truck shortly before 6 p.m. Monday and discovered the gruesome scene, Police Chief William McManus said. Hours later, body bags lay spread on the ground near the trailer as a grim symbol of the calamity.

San Antonio Mayor Ron Nirenberg said the 46 who died had “families who were likely trying to find a better life.”

“This is nothing short of a horrific human tragedy,” Nirenberg said.

It’s among the deadliest tragedies to have claimed thousands of lives of people attempting to cross the U.S. border from Mexico in recent decades. Ten migrants died in 2017 after being trapped inside a truck that was parked at a Walmart in San Antonio. In 2003, 19 migrants were found in a sweltering truck southeast of San Antonio.

The home countries of the immigrants and how long they were abandoned on the side of the road was not immediately known.

South Texas has long been the busiest area for illegal border crossings. Migrants ride in vehicles through Border Patrol checkpoints to San Antonio, the closest major city, from which point they disperse across the United States.

A city worker at the scene on a remote back road in southwest San Antonio was alerted to the situation by a cry for help shortly before 6 p.m. Monday, Police Chief William McManus said. Officers arrived to find a body on the ground outside the trailer and a partially opened gate to the trailer, he said.

Hours later, body bags lay spread on the ground near the trailer as a grim symbol of the calamity. Bodies still remained inside.

Of the 16 taken to hospitals with heat-related illnesses, 12 were adults and four were children, said Fire Chief Charles Hood. The patients were hot to the touch and dehydrated, and no water was found in the trailer, he said.

“They were suffering from heat stroke and exhaustion," Hood said. "It was a refrigerated tractor-trailer, but there was no visible working AC unit on that rig.”

Those in the trailer were part of a presumed migrant smuggling attempt into the United States, and the investigation was being led by U.S. Homeland Security Investigations, McManus said.

Three people were taken into custody, but it was unclear if they were definitively connected with human trafficking, McManus said.

Big rigs emerged as a popular smuggling method in the early 1990s amid a surge in U.S. border enforcement in San Diego and El Paso, Texas, which were then the busiest corridors for illegal crossings.

Before that, people paid small fees to mom-and-pop operators to get them across a largely unguarded border. As crossing became exponentially more difficult after the 2001 terror attacks in the U.S., migrants were led through more perilous terrain and paid thousands of dollars more.

Heat poses a serious danger, particularly when temperatures can rise severely inside vehicles. Weather in the San Antonio area was mostly cloudy Monday, but temperatures approached 100 degrees.

Some advocates drew a link to the Biden administration’s border policies. Aaron Reichlin-Melnick, policy director at the American Immigration Council, wrote that he had been dreading such a tragedy for months.

“With the border shut as tightly as it is today for migrants from Mexico, Guatemala, Honduras and El Salvador, people have been pushed into more and more dangerous routes. Truck smuggling is a way up,” he wrote on Twitter.

Stephen Miller, a chief architect of former President Donald Trump’s immigration policies, said, “Human smugglers and traffickers are wicked and evil” and that the administration’s approach to border security rewards their actions.

Texas Gov. Greg Abbott, a Republican running for reelection, was blunt in a tweet about the Democratic president: “These deaths are on Biden. They are a result of his deadly open border policies.”

Migrants - largely from Mexico, Guatemala, Honduras and El Salvador - have been expelled more than 2 million times under a pandemic-era rule in effect since March 2020 that denies them a chance to seek asylum but encourages repeat attempts because there are no legal consequences for getting caught. People from other countries, notably Cuba, Nicaragua and Colombia, are subject to Title 42 authority less frequently due to higher costs of sending them home, strained diplomatic relations and other considerations.

U.S. Customs and Border Protection reported 557 deaths on the southwest border in the 12-month period ending Sept. 30, more than double the 247 deaths reported in the previous year and the highest since it began keeping track in 1998. Most are related to heat exposure.

CBP has not published a death tally for this year but said that the Border Patrol performed 14,278 “search-and-rescue missions” in a seven-month period through May, exceeding the 12,833 missions performed during the previous 12-month period and up from 5,071 the year before.