A new Yale study may help with the future treatment of a little-known but deadly disease common in tropical climates.
Researchers at the Yale School of Public Health, in collaboration with scientists at Brazil’s Oswaldo Cruz Foundation and the Brazilian Ministry of Health, have identified a potential key cause of many fatalities related to leptospirosis, a rat-borne bacterial disease common in urban slums. According to the study, the disease affects about 1 million people each year and causes about 60,000 deaths per year.
The findings of the study indicate that many leptospirosis-related deaths may be related to the inability of the immune system to produce a certain immune protein called cathelicidin. The study, titled “Cathelicidin Insufficiency in Patients with Fatal Leptospirosis,” was published in the journal Plos Pathogens on Nov. 3.
“I think the major accomplishment of this study for us, as scientists, as researchers, for the scientific community, is one more piece of information of how and why that disease causes death,” said Elsio Wunder, one of the lead authors of the study.
To carry out the study, researchers took blood samples from leptospirosis patients admitted to a network of hospitals in the Brazilian city of Salvador. According to Albert Ko, another lead author of the study, researchers then analyzed the blood samples of each patient through a process called transcriptomics, looking at RNA in each sample to find differences in immune responses between patients who had survived and patients who had died.
In total, blood samples from 16 patients were analyzed. The study found that the three patients who had died had significantly lower levels of the immune protein cathelicidin, as well as a more severe inflammatory response.
“We saw that the patients that actually died of the disease had lower levels of cathelicidin, which is a peptide that actually is described to be antimicrobial, so it helps to kill bacterial pathogens in general during the infection process,” Wunder said.
Ko said that to further analyze the role of cathelicidin in patient survival, researchers injected lethal doses of Leptospirosa interrogans bacteria into separate groups of hamsters that had previously been injected with either cathelicidin or water.
According to the study, while all of the hamsters died within 14 days, the hamsters injected with the cathelicidin enjoyed much better protection from the disease, with several surviving longer than their the hamsters that had received only water.
“That was important not only to prove that cathelicidin is an important [protein] to protect people against death, but also to provide an insight that perhaps this may be a good way to treat these patients who come down with these life-threatening manifestations,” Ko said.
Moving forward, the researchers hope that the findings of their study may soon yield new treatments for patients with potentially fatal manifestations of leptospirosis. Both Ko and Wunder said they hope that cathelicidin will be administered to patients as a treatment for the disease. According to Ko, more animal trials are required to determine the correct dosage for humans, followed by human trials.
Nevertheless, many researchers realize that they could face certain challenges in treating the disease, given the nature of leptospirosis, Ko and Wunder said.
Both researchers described leptospirosis as a “neglected” disease. According to Wunder, few people want to invest money in leptospirosis treatment, as it primarily affects poor people in urban slums.
“It happens among poor people, whether they’re poor, rural-based subsistence farmers or urban slum dwellers,” Ko said. “It’s off the map, so pharmaceutical companies, research institutions, have not invested in these neglected tropical diseases.”
According to the World Health Organization, every year leptospirosis affects about 10 out of each 100,000 people living in tropical climates.