Malaria's Last Stand is an expository look at the ongoing burden of one of humanity's oldest diseases. Staff writer Kaleigh Rogers travelled to Tanzania to capture the scope of malaria's impact on the road to elimination. Read more here.
The first time Dr. John Lusingu got malaria, he was 16. His immune system was completely naïve to the parasite, and it hit him hard, racking his body with fever, rigors, joint pain, diarrhea, and blurred vision. He had to be hospitalized.
Lusingu was treated and recovered, but soon after, he suffered another malaria infection. Then another. For the next 12 years, Lusingu continued to suffer repeated bouts of malaria every year, up to ten times a year.
Now 50 years old, Lusingu has had malaria more than 50 times in his life. In Tanzania, where he lives, this is the norm.
In fact, for most of Tanzania, 16 is late to be getting your first bout of malaria. Throughout the country, the disease is still endemic, killing up to 80,000 people every year, with children under five at some of the greatest risk. But Lusingu grew up in Kilomeni, a small town tucked in the Pare Mountains, some 5,500 feet above sea level. Mosquitoes, which carry the malaria-causing parasite, don't thrive at high altitudes, where the temperatures are cooler.
"When someone had fever there, it was usually pneumonia or maybe flu, but there was nothing like malaria," Lusingu told me as we drove across the Tanzanian countryside, a few hours south of the mountain range where he grew up.
At 16, Lusingu moved to the lowlands—to Moshi, at the foot of Mount Kilimanjaro—for high school. Though he had a bednet he could sleep under to protect him from hungry mosquitoes, he didn't like it; The white color reminded him of the funeral palls used to cover dead bodies in his hometown.
"Why would I want to sleep under something like that?" he thought at the time.
After his first bout of malaria, he quickly got over his superstition and started to sleep under the net, but it only helped so much. Slowly, the yearly malaria episodes began to taper off, and in his second-last year of medical school, at the age of 28, Lusingu had his final episode of malaria. After dozens of infections, his body had finally built up enough immunity to be asymptomatic when the parasite breaks in. He hasn't gotten sick from malaria since that day, 23 years ago.
This acquired immunity—hard-won but common among healthy adults in malaria endemic countries—is what gives researchers hope that an effective malaria vaccine is possible. If exposing the body to the parasite enough times makes you immune, there must be a way to artificially provoke that response. Lusingu is intimately familiar with this hope. Not only has he become immune after countless bouts of malaria (he couldn't precisely say how many times he's been sick), but he is also a principal investigator on our most advanced malaria vaccine candidate: RTS,S.
At the start of the rainy season in 1965, Lusingu was born to parents he describes as "poor peasants." That same year, the earliest seeds of the vaccine he would one day work on were already beginning to sprout. We have no vaccines for parasites, so when scientists began trying to create one for malaria, they started with what we knew: methods that have worked for bacteria and viruses.
First, researchers tried killing the early stage parasite (called a sporozoite) and injecting that into the body, to see if it was enough to provoke an immune response. This strategy, called an inactivated vaccine, is effective for some microorganisms (we have vaccines like this for polio and pertussis), but for malaria it didn't really work. There was some immune response when they tried it out on birds, but not with rodents or monkeys.
"There's not going to be one tool that is going to solve the malaria epidemic. It's a combination of strategies."
So researchers tried injecting a live, but weakened, version of the sporozoites, and this worked a little better. Eventually, scientists were able to figure out that a protein the sporozoites produce called circumsporozoite protein (CSP) was an antigen—it provoked an immune response. They sequenced it and set about trying to find a way to use it to make a vaccine. Though other strategies for a malaria vaccine have emerged since then, this CSP-focused approach was the first, and led to the development of RTS,S.
By the time Lusingu graduated medical school in 1994 and his bouts of malaria had faded away, the early versions of RTS,S were being tested in humans. But despite his personal experience with the disease, the new doctor was not yet interested in working on a malaria vaccine.
"I wanted to become a surgeon," Lusingu told me. "But I found that it was not a good thing because the supplies and equipment in the hospital were not always available. So I decided to do something where I could work with great passion, and to begin with I worked on HIV/AIDS."
But after accepting a position at Tanzania's National Institute of Medical Research in 2000, Lusingu was asked to instead focus on malaria. For two years, he studied the immunology and epidemiology of the disease. He got married and had two children, a daughter and a son. In 2002, Lusingu moved to Denmark to work on a PhD in Health Sciences from the University of Copenhagen, adding Danish to his growing list of spoken languages—his local village dialect, Swahili, French, and English. His family stayed behind, but eventually he was able to bring them to Denmark too.
"My children kept getting sick with malaria, so I asked if I could bring them there," Lusingu recalled.
After earning his PhD, Lusingu returned to the NIMR and started working on the vaccine trials for RTS,S, which were about to be tested in children around the continent. Early proof of concept trials had shown the vaccine to be safe in adults and children, and gave hopeful signs of effectiveness. In 2001, pharmaceutical company GlaxoSmithKline partnered with PATH, a global health nonprofit, to begin developing the vaccine in earnest (the partners later gained support from the Bill and Melinda Gates Foundation). By 2007, the phase II trial of the vaccine had shown promising results: The number of episodes of malaria experienced by vaccinated children each year was cut by 66 percent compared to the control group (which did not receive the vaccine). But that study only looked at 214 children.
When Lusingu came on board, it was time to test the vaccine on a much larger group.
Lusingu told me that in the Kipare language spoken in Kilomeni, his home town, the word for mosquito is ngilingili. Then he smiled and leaned forward, repeating the word quickly until it slurred together into one long trill—ngilingilingilingili—mimicking the familiar, whining buzz of a mosquito in flight.
We were on our way to a village outside of Korogwe, part of the Tanga region in the northeast part of the country, to visit a family that had participated in the phase III trial of RTS,S. Along the drive, Lusingu pointed to the vast sisal plantations that once brought prosperity to the region, before the plant (used to make fabric) was abandoned in favor of cheaper synthetic materials. We talked about the investments the Tanzanian government has made in infrastructure like the paved roads we were driving on, which connect the country's four corners. We stopped at a produce stand and Lusingu insisted I try a fresh, sticky orange.
Though not as burdened as some areas of Tanzania, this part of the country still sees hundreds of thousands of cases of malaria each year. When I arrived, it was the end of the rainy season, and the sky still opened up for intense downpours in the middle of the afternoon heat, causing puddles to pool and gutters to overflow. The combination of heat and rain is ideal for malaria-spreading mosquitoes, which propagate in as little as half an inch of standing water and thrive in temperatures between 60 and 90 degrees Fahrenheit.
When we arrived in the village of Chang'ombe, I met Bahati Bakari, 44, and her six-year-old daughter Jamila. Jamila was the only one of Bakari's four children to participate in a trial, because she alone was in the right age range (participants were children between 6 weeks and 17 months of age). During the trial, Bakari told me Jamila still got sick a few times, but tested negative for malaria each time—she was just getting typical colds. Her other children weren't so lucky.
"Her brother and sisters had several episodes of fever—on a monthly basis in the rainy season—which most of the time tested positive for malaria," Bakari told me. "It's scary for me when they're sick because they have such a high fever."
Even among those immunized, Jamila was particularly lucky. The Phase III trial began in 2009, with more than 15,000 patients enrolled across seven sub-Saharan African countries. There were two age cohorts, 6–12 weeks and 5–17 months at the time of first vaccination, randomized into control or treatment groups. The children were monitored over the next four years and at first the vaccine was fairly effective, reducing the number of malaria bouts a child had annually by half in the first year. But its effectiveness waned over time, and by the end of the four years, the vaccine was only 39 percent effective in the older cohort, and 27 percent effective in the younger group.
This may not seem encouraging, but it's important to remember that each time a child gets sick with malaria, it puts him or her at new risk of severe malaria or death. If we can cut down the number of times a child gets sick each year by even a third, it could save hundreds of thousands of lives.
"One of the biggest challenges you have facing malaria endemic communities is emerging resistance to drugs and insecticides, so there's a need to develop additional tools to help with the malaria fight," said Dr. Chris Odero, a malaria specialist working on the RTS,S vaccine project for PATH. "This is just the first generation vaccine. Of course, there's potential to improve and make it better. But for malaria there is no magic bullet. There's not going to be one tool that is going to solve the malaria epidemic. It's a combination of strategies."
The RTS,S results were enough to convince the World Health Organization. In October, the international organization recommended moving forward with pilot projects to test the feasibility of rolling out the vaccine on a large scale, with 100,000 to 200,000 people enrolled. At the moment, the WHO is considering applications from countries that have applied to participate. Tanzania is among those applicants.
Unlike many diseases, malaria doesn't disproportionately plague the poor. Even Jakaya Kikwete, the former president of Tanzania who focused much of his administration on fighting the disease, told me he had malaria just a few months ago—he had travelled to the countryside and didn't have a bednet. He's also seen up close the toll it can take.
"I lost my younger brother, the one born after me, from malaria. He was three years old. I was five," Kikwete said at a press dinner in May. "It's a personal issue for me. I've seen so many people die from malaria."
In the parts of the world where it still festers, malaria has left scars on every life, which helps to explain why those fighting the disease have dedicated decades to the work. Lusingu's children are now teenagers, planning to go to college in the US, Canada, or Europe. The doctor said he too once dreamed of continuing his work in the West, but he's remained in his homeland. Right now, he does ongoing long-term monitoring of the kids who were in the Phase III trial and is awaiting the start of the pilot project, one of the final hurdles to clear before RTS,S can be administered across Africa.
Before we part ways, he tells me one last personal story. One evening, when Lusingu was still in primary school, his older brother Joseph collapsed on the road near his house. Joseph, eight years older, was already in high school in the lowlands, and was travelling home when he suddenly passed out. When he awoke, he was delirious.
"He started shouting, shouting," Lusingu recalled, shaking his head. "He was brought back home. My mother was crying. My dad ran to find rural medical aid. Rural medical aid came and said, 'this is malaria.'"
It was the first time Lusingu saw the disease first hand. Joseph was treated and recovered, and went on to become a doctor as well. But the quinine—the drug used to treat malaria back then—left him with lifelong tinnitus.
"When he's in a very quiet place," Lusingu told me. "He can still hear a buzzing."
Travel expenses while reporting this series were funded through a fellowship provided by the International Center for Journalists and Malaria No More.