Leishmaniasis: sickness without borders
January 10, 2017
Valter Luiz, a 63-year-old Brazilian, died last January, taken by leishmaniasis. He is officially the first human being to have succumbed to the disease in the Brazilian state of Paraná, specifically in Foz do Iguaçu, the last town in Brazil before the border with Argentina. “Valter was hospitalized on Monday, and on Friday he died. It happened out of nowhere. We didn't understand. No one told us about this disease, leish ..., something,” sighs the sister-in-law of the deceased, Tereza de Jesus Fernandez Batista.
Leishmaniasis, also known as black fever, is a parasitic disease transmitted by a small fly, the phlebotomine sandfly. Just like the tiger mosquito, the vector of dengue and zika, the female phlebotomine sandfly feeds on blood. When it bites, it injects a parasite of the Leishmania genus, which attacks the vital organs, the skin, and the mucous membranes.
Visceral leishmaniasis, the most severe form of the disease, is manifested by bouts of fever, weight loss, anemia and an enlarged liver and spleen. And this is what happened to Valter Luiz. However, the physicians who treated him did not make the correct diagnosis. The Fernandez family were on their way to the cemetery when they learned the true cause of the death, by telephone. "Before, they said it was acute leukemia," says Ms. Fernandez.
It is probable that the case of Valter Luiz is only the tip of the iceberg. The disease is so little known that very few physicians consider it in their diagnoses. Unlike dengue, leishmaniasis does not make the headlines. And this in spite of the fact, according to the World Health Organization (WHO), that 20,000 to 30,000 people die each year from different forms of the disease worldwide. Brazil has been particularly hard hit by the visceral form with an average of 3,500 new cases per year, with a total of 48,720 cases between 2001 and 2014, according to the Pan American Health Organization.
On the southern border of Brazil, adjoining Paraguay and Argentina, the number of cases has also constantly increased. The border area between the three countries currently has the highest prevalence of visceral leishmaniasis in Latin America, says Dr Oscar Daniel Salomon, Director of the National Institute of Tropical Medicine (INMeT), based in Puerto Iguazú, the Argentinean sister city of Foz do Iguaçu.
This disease is often associated with poverty and unsanitary conditions, but the Fernandez family is clear proof that the parasite does not discriminate by social class. Far from the red dirt roads, stray dogs and heaps of garbage, the family lives in a wealthy neighbourhood of Foz do Iguaçu recently built on land that was once part of a vast forested area.
"The emergence of the disease is explained not by poverty, but the entry of humans into the virgin forest and deforestation, land use change and urbanization," says Dr Salomon.
Unlike the tiger mosquito, the phlebotomine sandfly, also simply known as the sandfly, does not breed in stagnant water but in organic matter left on the ground. It lives in carpets of dead leaves, stumps, and rotten fruit that has fallen to the ground. In its natural forest environment, the insect feeds on the blood of wild animals, but now that towns have encroached on its territory, it resorts to the most easily available source of fresh blood: domestic dogs and humans.
Dr Salomon has been monitoring leishmaniasis since it first appeared in Argentina in the 1980s. "Although efforts have been made to contain the epidemic, from the outset in the 1990s there have been more than 1,000 cases of cutaneous leishmaniasis in Argentina [Editor's note: another form of the disease that causes lesions on the skin, especially purulent ulcers]. As for visceral leishmaniasis, this formerly rural phenomenon has rapidly become urban," he explains.
The first case of visceral leishmaniasis in Argentina was recorded in 2006. The victim was an eight-year-old boy from the province of Misiones, which borders Brazil. Since then, the number of cases has multiplied year on year. In 2008, 34 cases were registered in this province, 4 of which were fatal, and in 2012 the parasite extended its range to a second province. Four years later, it claimed victims in four Argentinean provinces, especially among children under the age of 15.
Concerned, Argentinian scientists alerted their Brazilian and Paraguayan colleagues. A multinational monitoring operation was set up. With the support of Canada's International Development Research Centre (IDRC), researchers are now working to improve prevention and control in view of the emergence and spread of the disease in border areas.
From dogs to humans
Essentially, a tropical disease, leishmaniasis is moving to temperate zones and urban centres, following the migration flows of humans, and especially their dogs, which are the main reservoirs of the parasite outside the forest.
This was the case with Mel, one of the four female dogs who lived with Valter Luiz. Like many other dogs, she remained asymptomatic. But any phlebotomine sandfly that bit her could easily transmit the disease to the rest of the family. The Fernandez family discovered that the dog was a carrier of the parasite shortly after the death of Valter Luiz. To protect her other masters, the poodle had to be put down.
Dr Eliane Maria Pozzolo, a veterinarian in Dr. Salomon's team, monitors the progress of the epidemic, neighbourhood by neighbourhood. Today, her rounds take her to a disadvantaged area of Foz do Iguaçu where she regularly sets sandfly traps and takes blood samples from the dogs to check if the parasite is present.
As soon as she arrives, a resident comes to meet her. Marinha, one of the resident's dogs, is dying. "I think that she has the disease, the leish ... whatever it is," she says. A gaping wound is consuming the little dog's ear. For Dr Pozzolo, there is no doubt it is leishmaniasis. Marinha has to be put down.
Isadora Ramos Hobold, who lives less than 1 km from the Luiz family, also lived with an infected dog. The little girl's vital organs were already affected when physicians identified the parasite. "A few more days without treatment and we would have lost her," sighs her mother, Daniela.
Seven months earlier, Isadora had spent four weeks in the hospital for what was then believed to be dengue. The physicians now concede that it was leishmaniasis, and that they hadn’t recognized it at the time.
"Health care professionals need to be better trained so that they think about leishmaniasis when they have a patient. Without it, they cannot make a quick diagnosis and save sufferers," says Dr Eliane Maria Pozzolo. Dr Salomon's team has launched an awareness-raising campaign for medical professionals on both sides of the border. The team has also set up a training course in molecular biology to teach laboratory technicians how to detect the parasite.
This is because if physicians suspect the disease during the clinical examination, they must ask for parasitological or blood tests to confirm the diagnosis. However, the parasite is frequently not detected until it is well established. "It depends a lot on the experience of the professional looking down the microscope," says Dr Esteban Couto, a physician and infectiologist at INMeT.
For the visceral leishmaniasis, the Brazilian branch of Dr Salomon's team has pushed for the adoption of the ELISA test based on the detection of antibodies in the blood. It was this method that saved little Isadora's life. "In Paraná, the test has now been adopted as standard. We hope that this will be the case in all the countries participating in the project [Brazil, Argentina, Paraguay, and Uruguay]," says Dr Pozzolo.
However, this test does not work for the cutaneous leishmaniasis more common on the other side of the border in Argentina. In this case, a skin sample must be taken from the edge of the lesion to identify the presence of the parasite. Here too, however, asking for an examination is key.
"They did five or six tests before we knew it was this disease. I had to stop working for more than seven months," says Mauro Urnao, sitting on a long wooden bench near his kitchen garden. His body is covered with dozens of scars. Cutaneous leishmaniasis is not normally lethal, but it leaves permanent, sometimes disfiguring marks.
"They looked like cigarette burns and liquid oozed out of them," explains Mauro Urnao. "My nose became huge. I looked like a circus clown. My fingers began to swell. My hands were all deformed. I wasn't able to touch anything."
Owner of an agricultural smallholding, this day-labourer lives modestly with his wife and his six-year-old son in a tiny wooden hut without running water and backed by forest. "When the doctor came here the first time, Mauro greeted him from a distance, hiding his hands under his arms. He didn't want to show them. He was ashamed," says his wife Walquiria Perera de Souza.
Towards a durable solution
After a month of treatment, Mauro Urnao was able to return to the fields. "Things are much better. Look, I can even take a little beer," he smiled, raising his glass before caressing his accordion. Still covered with scars, his fingers have become less swollen and he is once more able to press the keys of his instrument.
To treat the cutaneous form of the disease, as with visceral leishmaniasis, physicians prescribe an antiparasitic that is administered by a painful daily intramuscular injection. Used successfully for almost a century throughout the world, the treatment, which lasts a month, has proved its worth. However, because of its cardiac, renal, and pancreatic toxicity, it requires close follow-up and is contraindicated in some patients. "It's very invasive, but we have nothing better yet," says Dr Couto, who eventually treated Mauro Urnao.
In fact, in spite of many decades of research, it has not yet been possible to successfully develop a vaccine or preventive treatment for leishmaniasis in humans. But for Dr Salomon, the solution is not to be found in a laboratory test tube.
"With a vaccine, we may be able to reduce the problem, but we cannot eradicate it," he warns. There is a tendency to medicalize healthcare that leads us to place too much confidence in pharmaceuticals, and that makes us believe that there is a medicine for everything."
This is why his team wishes to address the source of the problem: the rapid urbanization of infested areas. Since it is impossible to eradicate the risk or to move people away from these areas, Dr Salomon recommends changing lifestyles and empowering public and private stakeholders "who change the land, potentially causing an outbreak of leishmaniasis. They should look out for the appearance of insects and protect exposed people, especially workers, in particular by offering them good health insurance," he argues. His team has been engaged in discussions with forestry companies, unions, and elected representatives.
"These are time-consuming, yet sustainable changes. We believe that the success of a public health policy depends on the solidarity of communities and governments that care about social equity," concludes the Argentinean scientist.
The research project described in this article and the production of this report were made possible with the support of the International Development Research Centre.
An immune system hacker
Leishmania is a tiny, yet extremely virulent protozoan parasite composed of a single cell. It is able to manipulate the white blood cells that normally protect the body by ingesting all infectious agents that enter it. Leishmania thus hijacks the host's entire immune system.
Leishmaniasis in figures (Source: WHO)
- 98 countries where the disease is endemic
- 1.3 million new cases every year
- 20,000 to 30,000 fatalities
- 350 million persons at risk
- 90% of visceral leishmaniasis cases are reported in Bangladesh, Brazil, Ethiopia, India, Sudan, and South Sudan.
- 95% of leishmaniasis cases occur in the Americas, the Mediterranean Basin, the Middle East, and Central Asia
- 20 species of leishmania parasites
- 90 species of the vector, phlebotomine sandflies
The original French version of this article was published in the December 2016 issue of Québec Science.