Three years ago, Jesús Tilano went to the hospital in a densely 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 a female sand fly and affects poor people who work in the fields or forests of developing countries.
He was prescribed medication that required three injections a day for 20 days, each of which was extremely painful. Mr. Tilano, 85, had to make several expensive bus trips to the city to collect them. Then his kidneys began to malfunction, which is a common side effect of the drug, as is heart failure and liver damage.
“The cure was worse than what I had before,” Mr. Tilano said.
Leishmaniasis is a terrible disease, with terrible treatments that have barely changed in a century. The medicine Mr. Tilano took was first administered 70 years ago. All treatments are a combination of treatments that are painful, toxic, expensive, or difficult to administer, requiring hospitalization or daily visits for a month.
Among “neglected tropical diseases,” many experts believe that leishmaniasis is in a class of its own in terms of the lack of progress, in the 120 years since its identification, to help the two million people who have contracted it. year.
Now, finally, that is starting 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 his infection in a few days.
The treatment he received is 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 efforts to seek 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 experimental treatments evaluated by researchers are much less toxic, onerous or expensive than those that currently exist. But there still remains a major obstacle to overcome in order to transmit them to the millions of people who need them.
None of the new treatments have been tested in a large-scale trial, approved by Colombia’s drug regulator, or adopted into national treatment guidelines. When a drug is made by a pharmaceutical company, the company will guide it through a costly and time-consuming regulatory process.
But there is no money to be made from a drug for a disease that overwhelmingly affects the poor, and academic or public health institutes rarely have the resources to push a drug all the way through the process, said Marcela Vieira, a Brazilian intellectual property specialist. lawyer with expertise in the development and access to medicines.
The global drug development system has long favored private sector companies that can finance experiments and diseases that affect people with money to pay for treatments. More and more new research into diseases such as leishmaniasis is from the public sector and academic institutions in middle-income countries, particularly Brazil, South Africa, India, Cuba and China, Ms. Vieira said. The Covid-19 pandemic, during which low- and middle-income countries have been relegated to the back of the line when it comes to vaccines and treatments, has helped spur new investments in strengthening vaccine development and production capacity. drugs.
“We have to do it, because no one will do it for us,” said Dr. Juliana Quintero, a leishmaniasis expert and PECET researcher.
The program’s research laboratories are located on six floors in a bulky brick building at the University of Antioquia in Medellín. Downstairs, Dr. Quintero sees patients arriving by bus from rural towns. She knows that few people can afford to stay in town for a month of vaccinations; she wants a treatment she can send home, ideally one she can take orally. Because funds for leishmaniasis drug development are so scarce, she hopes to find something that will work for each of the family’s 22 parasites that cause variations of the disease in tropical countries around the world.
Leishmaniasis researchers have taken inspiration from the region’s indigenous people: One of the drugs they are testing, a gel applied to the lesions, is derived from a plant that indigenous people use to fight the parasite. The experimental treatment that Andrés Tilano treated is called thermotherapy and resembles the traditional indigenous treatment of burning the lesions. In his clinic, Dr. Quintero used a handheld device that radiated heat at 50 degrees Celsius, or 122 degrees Fahrenheit, above the lesion, killing the parasite deep down.
Today, Dr. Quintero prescribes two treatments developed by his institute and provides them to patients under a so-called compassionate use model, because they have not yet been approved or registered by the Colombian government.
Mr. Tilano and his grandson suffered from cutaneous leishmaniasis, which is the mildest form of the disease. It can progress to mucosal leishmaniasis, when the parasite infects tissues such as those inside the nose. Another species of parasite migrates to the spleen, liver or bone marrow and causes what is called visceral leishmaniasis.
Untreated, the visceral form of the disease is fatal in more than 95 percent of cases; it kills around 6,000 people each year, most in Africa and Asia. The number of deaths has declined significantly in recent years, mainly due to advances in the detection and treatment of leishmaniasis in India, where it is known as kala-azar.
Because existing treatments are very expensive and difficult to obtain, Dr. Quintero said, few patients complete the course. This creates a newly drug-resistant parasite, which another sandfly can pass on to its family or other members of its community. When Dr. Quintero went to visit Mr. Tilano at his home not long ago, she met his daughter and granddaughter, who bore large circular scars from injuries that had eventually healed.
Mr. Tilano’s son Luís, a lumberjack who had become something of a local expert on the disease, asked Dr. Quintero to accompany him to the banks of the Cauca River to see a neighbor who he thought might also suffer from leishmaniasis. After crossing a field of curious cattle and a steep riverbank, she crawled through the twisted vines of a fig tree and encountered a group of older women panning for gold at the water’s edge. The neighbor, María de las Mercedes González, 55, had large lesions on her face and Dr. Quintero used the flashlight on his cell phone to try to determine if the parasite had already spread into the cartilage of her nose.
“Imagine an animal so small that a single bite can cause such a problem: it’s a very irritating little creature,” Ms. González said after Dr. Quintero explained the risk she faced without treatment and announced that she would have to spend $10,000. pesos (about $2.50, more than she usually earns in a day of mining) to travel to town daily for treatment. The medicines, at least, would be free thanks to Colombia’s public health system.
DNDi, the nonprofit, screened more than 2.5 million compounds – a standard first step in drug development – to come up with five chemical structures that appeared, in initial laboratory tests, to work against parasite responsible for leishmaniasis. But of those five, only one or two will advance to larger clinical trials, said Jadel Kratz, who leads the organization’s drug discovery work in Latin America.
Early discovery and preclinical studies cost between $10 million and $20 million, he said, while early small clinical trials for safety and some signs of effectiveness could cost another $6 million. The final phase, a large patient trial to test whether the drug works, costs a minimum of $20 million, far more than public and university research teams can fund.
“It is a huge risk for local research if only multinational companies can do this work,” said Dr. Iván Darío Vélez-Bernal, who recently retired as director of the PECET research institute.
But DNDi’s focus on leishmaniasis and the work of researchers in a network including India, Colombia and Brazil are starting to bear fruit. Today, five drugs are in phase 1 trials and another in phase 2, which is unprecedented in the history of the disease.
It is unclear when or how the drugs will move to the next phase of the process. Medicines flowing out of public sector institutions tend to languish without advocates, said Ms. Vieira, a researcher at the Center for Global Health at the Graduate Institute of International and Development Studies in Geneva.
Drugs that come from public health agencies in Brazil or India are often very different from those developed by a pharmaceutical company in an industrialized country, Dr. Kratz said: The scientists who create them think about access from the start , knowing that whatever they design will have to be delivered by a health system with limited resources.
In Colombia and neighboring Brazil, leishmaniasis mainly affects farmers, loggers and miners, people whose work puts them in regular contact with the sandfly. But climate change is causing the fly’s habitat to spread rapidly, and Dr. Quintero finds himself treating cases from semi-urban areas more frequently. During Colombia’s long civil war, which took place largely in the jungle, the parasite also sickened soldiers, who accounted for up to half of cases nationwide. So the military was eager to find a treatment and helped test some experimental drugs.
The Colombian government is now missing an opportunity by not funding the phase 3 trial of PECET’s experimental therapies, Ms. Vieira said.
“The trials are expensive, but it’s a lot less than they’ll pay for a treatment if it’s developed by a for-profit company, or for all the things they already have to pay for, for sick people and who have no money. access to treatment,” she said.