Three years ago, Jesús Tilano went to a hospital in a heavily forested valley in Colombia with large open wounds on his nose, right arm and left hand. He was diagnosed with leishmaniasis, a parasitic disease that spreads through the bite of the female sand fly and plagues poor people who work in fields or forests in developing countries.
He was prescribed a drug that required three injections a day for 20 days, each extremely painful. Mr. Tilano, 85, had to make repeated expensive bus trips into town to get them. Then his kidneys began to fail, which is a common side effect of the drug, as well as heart failure and liver damage.
“The cure is worse than what I had before,” Mr. Tilano said.
Leishmaniasis is a terrible disease, with terrible treatments that have hardly changed in a century. The medicine Mr. Tilano took was first given 70 years ago. All treatments are some combination of painful, toxic, expensive, or difficult to administer, requiring an inpatient hospital stay or daily visits for a month.
Among the so-called “neglected tropical diseases,” many experts believe that leishmaniasis is in a class of its own in terms of underdevelopment, in the 120 years since it was first identified, to help two million people infected by it each. year.
Now, finally, that is beginning to change: When Mr. Tilano’s grandson Andrés Tilano, 14, contracted leishmaniasis last year, he was treated at a clinic in Medellín, with an experimental therapy that cured the his infection within a few days.
The treatment he received was one of several developed by the Program for the Study and Control of Tropical Diseases, known as PECET, a small research institute based at the University of Antioquia in Medellín. In its effort to find new treatments for leishmaniasis, the program has partnered with the Drugs for Neglected Diseases Initiative, or DNDi, a nonprofit research and development organization based in Geneva.
All of the experimental treatments that researchers are testing are less toxic, burdensome or expensive than what currently exists. But a huge hurdle still stands in the way of getting them to the millions of people who need them.
None of the new treatments have been tested in a large-scale trial, or approved by Colombia’s drug regulator, or adopted into national treatment guidelines. When a drug is manufactured by a pharmaceutical company, the company shepherds it through an expensive and time-consuming regulatory process.
But there’s no money to be made in a drug for a condition that disproportionately affects the poor, and academic or public health institutions rarely have the resources to push a drug through the end of the process, Marcela said. Vieira, a Brazilian intellectual property. lawyer with expertise in drug development and access.
The global drug development system has long favored private sector companies that can bankroll experiments and diseases that make it hard for people to pay for treatments. New research on diseases such as leishmaniasis is increasing coming from the public sector and academic institutions in middle-income countries, particularly Brazil, South Africa, India, Cuba and China, said Ms. Scallops. The Covid-19 pandemic, which has moved low- and middle-income countries to the back of the line for vaccines and therapeutics, has helped spur new investment in building drug development and production capacity.
“We have to do it, because no one else is going to do it for us,” said Dr. Juliana Quintero, a specialist in leishmaniasis and researcher at PECET.
The program’s research labs sit on six floors in a large brick building at the University of Antioquia in Medellín. On the ground floor, Dr. Quintero the patients who arrive on buses from rural towns. He knew that few could afford to stay in the city for a month of injections; he wanted a treatment that he could take home to them, preferably by mouth. Because funds for drug development for leishmaniasis are so scarce, he hopes for something that will work for each of the 22 family parasites that cause variations of the disease in tropical countries around the world. .
Leishmaniasis researchers took inspiration from the region’s Indigenous people: A drug they were testing, a gel applied to wounds, came from a plant used by Indigenous people to fight the parasite. The experimental treatment that cured Andrés Tilano is called thermotherapy, and it resembles the traditional folk remedy of burning wounds. In his clinic, Dr. Quintero of a hand-held device that emits heat at 50 degrees Celsius, or 122 degrees Fahrenheit, over the wound, killing the parasite inside.
Now, prescribed by Dr. Quintero said the two treatments developed by his institute are being given to patients under the so-called compassionate use model, since they have not yet been approved or registered by the Colombian government.
Mr. Tilano and her grandson had cutaneous leishmaniasis, which is a less severe form of the disease. It can progress to mucosal leishmaniasis, when the parasite infects tissue such as the inside of the nose. Another species of parasite migrates to the spleen, liver or bone marrow and causes what is called visceral leishmaniasis.
If untreated, the visceral form of the disease is fatal in more than 95 percent of cases; it kills an estimated 6,000 people each year, most of them in Africa and Asia. The death toll has dropped significantly in the past few years due to advances in the detection and treatment of leishmaniasis in India, where it is known as kala-azar.
Because current treatments are so expensive and difficult to obtain, Dr. Quintero, few patients complete the course. That creates a new drug-resistant parasite, which another fly can transmit to its family or to others in its community. When Dr. visited Quintero at Mr. Tilano’s house not long after, he met his daughter and grandson, with large circular scars from the wounds that had finally healed.
Mr. Tilano’s son Luís, a lumberjack who became a local disease expert, asked Dr. Quintero to accompany him down to the banks of the Cauca River to see a neighbor who he thought also had leishmaniasis. After navigating a farm of exotic cattle and a steep river bank, he crawls through the twisted vines of a fig tree and meets a group of old women panning for gold at the water’s edge. Neighbor María de las Mercedes González, 55, had large wounds on her face, and Dr. Quintero uses his cellphone’s flashlight to try to determine if the parasite has moved to the cartilage in his nose.
“Imagine a very small animal that with one bite could cause such a problem: It is a very annoying little creature,” said Ms. González after Dr. explained. Quintero the risk he faces without treatment, and broke the news that he had to spend 10,000 pesos (about $2.50, more than he usually earns in a day of mining) to make the daily trip to the city for treatment. Medicines, at least, will be free through Colombia’s public health system.
DNDi, the nonprofit organization, screened more than 2.5 million compounds — a common first step in drug development — to come up with five chemical structures that seemed, in initial lab tests, like they might work. these against the parasite that causes leishmaniasis. But of those five, only one or two will progress to larger clinical trials, said Jadel Kratz, who runs the organization’s drug discovery work in Latin America.
Early detection and preclinical studies would cost $10 million to $20 million, he said, while getting through the first small clinical trials for safety and some signs of effectiveness could be another $6 million. The final phase, a large trial in patients to test whether the drug works, will cost at least $20 million — more than the public and academic research groups can fund.
“It is a big risk for local research if only multinational corporations can do this work,” said Dr. Iván Darío Vélez-Bernal, who recently retired as director of PECET, the research institute.
But DNDi’s focus on leishmaniasis, and the work of researchers in a network that includes India, Colombia and Brazil, is beginning to bear fruit. Now there are five drugs in Phase 1 trials, and another in Phase 2, which is unprecedented in the history of the disease.
It’s unclear when or how the drugs will make it to the next stage of the process. Medicines that come out of public sector institutions tend to languish without a champion, Ms. Vieira, who is a researcher at the Global Health Center at the Graduate Institute of International and Development Studies in Geneva.
Medicines that come from public health organizations in Brazil or India often differ in fundamental ways from those developed by a pharmaceutical company in an industrialized country, Dr. Kratz: The scientists who created them thought about access from the beginning, knowing that whatever they designed had to be delivered by a low-resource health system.
In Colombia and neighboring Brazil, leishmaniasis mainly affects farmers, loggers and miners — people whose jobs bring them into regular contact with the sand fly. But climate change is causing the fly’s habitat to spread rapidly, and Dr. Quintero himself treated more often cases from semi-urban areas. During Colombia’s long civil war, most of which was fought in the jungles, the parasite also sickened soldiers, accounting for half of the country’s cases. So the army was keen to find a cure, and helped test some of the experimental drugs.
The Colombian government is missing an opportunity now by not funding Phase 3 trials for PECET’s experimental therapies, Ms. Scallops.
“The tests are expensive but it’s less than what they would pay for a treatment if it was developed by a for-profit company, or all the things they already have to pay for, for people who are sick and no access to treatment,” he said.
