Two children have now contracted the parasite -- while playing in freshwater lakes and ponds this summer. The latest case is a 12-year-old boy in Florida -- where some officials are now warning families to take precautions.
High water temperatures and low water levels are the ideal breeding ground for this brain-eating amoeba. Health officials in Florida are now issuing a warning "to be wary when swimming, jumping or diving in fresh water" with these conditions.
It's rare, but the amoeba can go up the nose and into the brain, causing parasitic meningitis.
Zachary Reyna, 12, is battling the disease in Miami Children's Hospital after contracting it while knee boarding in fresh water near his home.
"He's fighting and he's strong, he's really really strong," said brother Brandon Villarreal.
On Facebook, his brother says Zachary had surgery to remove pressure from his brain. At a vigil Tuesday - cheers of support from Zachary's baseball teammates.
"Everybody needs to keep praying and stay positive," said teammate Trace Burchard.
Nearly everyone who gets the infection dies. In the past 50 years, only three people have survived. Most recently, 12-year-old Kali Hardig, who's out of a coma and now in fair condition at Arkansas Children's Hospital.
"That I'm going to get to take kali home some day is amazing," said mom Traci Hardig.
Doctors credit her amazing survival - in part – to an experimental anti-amoeba drug. The Centers for Disease Control has sent the drug to Miami to treat Zachary. And just as friends and family had prayed Kali Hardig would be the third person to survive this horrible infection, Zachary's supporters hope he'll be next.
"He can be number four, that's what we're hoping for, for him to be number four," said Villarreal.
"Up to Kali's case, there were only two reported survivors," said Dr. Mark Heulitt, one of the doctors who treated her. "Now, Kali's the third."
There have been nearly 130 cases reported in the United States since 1962, according to the Centers for Disease Control and Prevention. Before Kali, there was only one known U.S. survivor, plus another nonfatal case documented in Mexico.
Kali's mother, Traci Hardig, brought her to Arkansas Children's Hospital with a nasty fever on July 19 - not long after Kali went swimming at a water park in central Arkansas.
The state Department of Health has said that now-shuttered park, which features a sandy-bottomed lake, is likely where Kali came into contact with the amoeba.
Initial symptoms usually start within one to seven days and may include headache, fever, nausea and vomiting. The disease progresses rapidly, and other symptoms can include stiff neck, confusion, loss of balance, seizures and hallucinations.
Moreover, the infection destroys brain tissue and can cause brain swelling and death.
So, in Kali's case, doctors cooled her body down to try to reduce the swelling. They also won clearance to treat her with a breast-cancer drug, Heulitt said.
"She wound up being on the ventilator for over two weeks," Heulitt said. But she's since made incredible progress.
Kali can now breathe on her own. Though she can't talk yet, she's able to write her name and respond to doctors and her family. And tests show no signs of the parasite in her system.
She still has weeks of rehabilitation ahead of her, but for now, her family is celebrating her triumphs.
"We've went from being told that our little girl wouldn't survive this amoeba to now they're saying that Kali is going to be the third survivor and going to get to go home," Traci Hardig said.
Hardig, who lives in the nearby suburb of Benton, beamed as she talked the strength and perseverance Kali has shown in the past few weeks.
It's not hard to see where Kali gets it from. While Kali has been recovering from her rare case of meningitis, Traci Hardig has been battling breast cancer.
"It's kind of a battle to decide that you want to put your health on hold because you want to totally focus on Kali, but I know I have to try to get myself better too, because Kali's coming home and I'm going to get to take care of her," she said.
But Hardig doesn't dwell on her own challenges. Instead, she thanks the people around the world who have sent prayers and good wishes to Kali, and she's trying to raise awareness for Zachary.
"We're praying for him to be survivor number four," Hardig said.
The Associated Press contributed to this report.