Be sure to check out the slideshow presentation Malaria's toll on Mariam within this article at MinnPost.com
No one saw the mosquito that wrecked little Mariam Nagita's life.
The first sign that the high-spirited tot was in serious trouble was her hot forehead. Fever was consuming her small body. She begged for fruit to eat, so her grandmother cut up a mango.
As Mariam sank her teeth into a slice of the sweet fruit, she dropped to the floor in convulsions.
That was four years ago. And Mariam, now eight, has never since spoken, walked or fed herself.
Mariam was the victim of double bad luck: First, that mosquito gave her malaria. Second, it was cerebral malaria, a form of the disease that is so severe it often kills children or leaves them with lasting brain damage.
Her case and others like it have inspired doctors from Minnesota, Michigan and Uganda to collaborate on a major effort to spare African children from the tragic consequences of cerebral malaria.
The best thing anyone could do for these kids is to prevent them from getting malaria in the first place, said Dr. Chandy John, who directs the University of Minnesota's Global Pediatrics Program. And many groups are working in Uganda and other countries to distribute bed nets and other safeguards against the mosquito-borne disease.
"But as these efforts are rolled out, there still are millions of kids who are getting malaria, so we need to do more for them," said John, one of several Minnesota doctors and medical students who are shuttling between Minneapolis and eastern Africa to work on that cause.
Malaria kills an African child every 30 seconds, according to the World Health Organization.
The killer comes in the form of a one-cell parasite called plasmodium. Its accomplice is the female Anopheles mosquito who hunts for blood to nurture her eggs. As the mosquito feeds from victim to victim, she picks up the parasite from one person and injects it in another.
U.S. taxpayers and private donors have launched a major thrust to help save children from the disease. The Bush administration alone has committed more than $1.2 billion to the fight with the ambitious goal of slashing malaria-related deaths in half in 15 countries including Uganda.
Mariam's case provides one example of where the American dollars are going.
During the first week or so after the mosquito bit Mariam, no one could have noticed any difference in her. Except for a bout of whooping cough, she had been as healthy as any four-year-old can be. Jumping rope was her passion. Her pride was registering to go to the school where her older brothers had learned the magic of reading.
Mariam was visiting her grandmother when the fever and convulsions hit. Her family took her to a local clinic for medicine. But the seizures got worse, and the little girl slipped in and out of consciousness.
When she recovered briefly one day to see her worried brother, Ashiraf, hovering over her, she said, "Ashiraf, leave me."
Those were the last words she ever spoke.
She sank deep into a coma and the family rushed her to Mulago Hospital in central Kampala. When she woke nine days later, she was blind, deaf and unable to move her arms and legs.
Once loose in Mariam's body, the parasite had morphed through stages that enabled it to evade her immune system, infect her red blood cells and eventually clog the capillaries that carried blood to her brain and vital organs.
That devastating sequence once threatened people in the United States and other temperate countries but it was largely eliminated during the 20th Century. Now malaria is a disease of the tropical regions, home to many of the poorest people on earth. It sickens more than 300 million people a year and kills at least a million.
Ninety percent of the deaths occur here in sub-Saharan Africa, mostly among young children. Like Mariam, many of those who survive have lasting brain damage.
Those are the kids that drew Minnesota doctors to Kampala in a search for the reasons malaria sometimes attacks the brain and central nervous system.
Far away and nearly malaria free, Minnesota may seem an unlikely platform for staging this battle against a scourge of the tropics.
But John chose Minnesota as his base in 2005 precisely because it offered such an opportunity. The son of doctors from India, he was born in the United States and raised with a strong sense of global mission.
"My parents always instilled this idea that we were very lucky to have what we have and that the most important thing was to look out for people who have less than we have," he said.
After finishing medical school at the University of Michigan, John worked in Bangladesh, Nigeria, Laos and other countries.
"Malaria was a problem in all of those places," he said.
Help from Minnesota
The misery and death he and other doctors saw called for a proactive approach — not just treating the disease but also contributing to research that might spawn better outcomes if not cures. A colleague convinced him Minnesota was a place where he could do both.
"In the Twin Cities, there are a lot of people doing great global health work," John said.
Immigrants, including children who arrive through international adoptions, can take some of the credit. As thousands of them flocked to Minnesota, many carried conditions that called for sophisticated understanding of maladies that strike in far-away places. Others drew attention to dire shortages of health care in the countries they had left.
The upshot is that the University of Minnesota Children's Hospital Fairview is one of the best venues in the United States for helping kids around the world. It is a rare place, John said, where medical workers can teach and learn while also doing research and treating patients at home and abroad.
In the cerebral malaria project, John works with Dr. Robert Opoka of Makerere University in Kampala and Michael Boivin, a neurophysiologist from Michigan State University. Their work is funded in part by the National Institutes of Health, the University of Minnesota and a Fulbright African Regional Research Award.
In a sprawling medical complex on a hill overlooking Kampala, a placard with the lettering "MU/UMN/MSU Cerebral Malaria Project" marks the door to the team's headquarters. Inside the cramped office, Minnesota medical student Phil Barbosa from Stillwater has added a homey touch of maroon and gold by decorating a wall above his desk with a U of M pennant.
Barbosa's assignment is largely desk work, but he can't help engaging with the kids who have been enrolled in the project's latest study.
"We have sadly lost one patient who was very, very ill when they came in," he said in a recent email. "All others though have pulled through and we will be following them for two years."
Losing a patient in this line of work is not unusual, said Opoka, who was working at another desk in the cramped office.
"One in five kids with cerebral malaria die," Opoka said.
The deadly nature of the disease was well known.
What this team has discovered is that one in four of the kids who survive have lasting problems with attention, memory and other cognitive skills.
That adds up to more than 200,000 children a year who may have significant long-term brain injury because of cerebral malaria, John said.
In some of the afflicted kids that complication is obvious. They are as devastated as Mariam.
For others, though, the lingering effects are more subtle. A malaria survivor might be a little slower in school, and no one had followed up to systematically to assess what had happened to their working memories, abilities to pay attention and other functions of learning.
"When children came out of their coma, it had been assumed they were OK," Opoka said.
Now, the team has tracked hundreds of kids who had been treated for cerebral malaria at Mulago Hospital in Kampala.
Looking at everything from CT scans to lab tests of body chemicals, they are searching for clues to why some children respond to malaria in ways that injure their brains. Some of the analysis is done in Minneapolis. But one of the team's goals is to train more Ugandans to do the work in Kampala and provide them with the resources they will need.
Meanwhile, emails fly almost daily between the project's workers in Minneapolis and Kampala.
If they could learn to manipulate the factors at play in a child struck by the disease they might have a shot at saving more lives — or, at least, sparing the survivors from brain damage.
One hope is to find drugs that can reduce the brain damage. Some drugs as readily available as aspirin and antibiotics might make a difference if children get them at the right time and in the right doses, John said.
"If we understand the factors that lead to it, in many cases there already are drugs out there that can turn down or in some cases turn up the levels of these factors depending on what direction we want them to go," John said.
Yet another goal is to help rehabilitate kids like Mariam for whom the damage already has been done. That part of the project involves sophisticated skills testing and therapy.
Families and therapy
Families like Mariam's are trained to get involved in the therapy.
Mariam's family lives on the slope of a hill just outside Kampala in a comfortable brick home where lace adorns the living room furniture and sunshine streams through the open front door.
On a recent afternoon, Mariam sat propped against a wall in that patch of sunlight. It's one of her favorite spots, said her mother, Namakula Garret.
The girl has grown almost to the size of a typical 8-year-old.
Nourishing that growth is painstaking work for the whole family and for Mariam too. Her mother and brothers prop her in a sitting position then spoon food into her mouth. Her favorites are plantains, rice, corn meal porridge and potatoes. They hold a bowl under her chin because some of the food invariably comes out, and they patiently push it back in.
A typical day starts with cleaning Mariam up. She is incontinent. Then her two brothers help her with the exercise therapy they learned through the medical project. They also take her for outings in a wheel chair the project provided.
They're making progress. Mariam has regained limited vision and hearing plus some movement of her arms. She has yet to say a word, but she does muster a small scream when she is hungry or upset.
Most effective of all, she has recovered her smile. And she uses it generously to reward her attentive helpers.
"I still look forward to hope for my daughter," Garret said.
Back at the project headquarters, though, Opoka said, "there is going to be very little further improvement."
Therapists are working toward a point where she may be able to feed herself, but that is as far as she is likely to go.
"She never will be the girl she was before she got sick," he said.
Maybe other children, though, could be spared from at least some of the devastation of cerebral malaria. That's the point of the research on Mariam and hundreds of others stricken with the disease.
Be sure to check out the slideshow presentation Malaria's toll on Mariam within this article at MinnPost.com