Researchers develop vaccine for deadly leptospirosis bacteria

In addition to having a major impact on the health of vulnerable populations, leptospirosis is an economically important health problem, making it a significant challenge. Currently there are no effective control measures for this disease, which remains a neglected tropical disease

Leptospirosis is an important health problem that has been neglected because it occurs among the poorest populations of the world. Although relatively unknown in the developed world, it is a growing scourge in poor environments across Latin America, Africa and Asia. Leptospirosis has a high incidence in certain areas, and, without treatment, it can cause kidney and liver damage and even death – the risk of death in the most severe cases can reach 40%. To date, there is no vaccine for human use against the disease and its development is a challenge. But this reality can change. A Yale research team has developed a vaccine that prevents disease while nearly eliminating deadly bacteria from the body. The article titled “Vaccination With Leptospira Interorgan PF07598 Gene Family-Encoded Virulence Modifying Proteins Protects Mice From Severe Leptospirosis and Reduces Bacterial Load in the Liver and Kidney”  was published in the journal Frontiers in Cellular and Infection Microbiology.

The team, led by the professor of infectious diseases at the Department of Internal Medicine of the Yale School of Medicine (YSM), Dr. Joseph Vinetz, used the genome design to identify exotoxin from the protein secreted by Leptospira as the prime suspect for death by leptospirosis. They showed that in preclinical models, vaccination with the toxin cured the disease, and an antibody neutralized the toxins. “We recently discovered that Leptospiral VM proteins are secreted exotoxins. The current paper shows that these proteins are antigenic targets of cross-serovar protective immunity in a mouse model of lethal leptospirosis,” explains Dr. Vinetz.

The researchers tested the hypothesis that immunization of mice with a family of proteins called VM proteins would protect against a lethal infection and reduce the burden of bacteria in the liver and kidneys. With this, they found that vaccinated mice were protected from lethal infections and that the bacteria load on these organs was reduced. According to Dr. Vinetz. This is the first time that a specific recombinant protein confers cross-protective immunity against leptospirosis in mice models the  details that the next step is to test in other animal models and in cattle and recalls that the pathway towards a leptospirosis vaccine for humans is long, expensive and demanding. “This process is starting now, and we hope one day to test it on humans,” he says. Asked why there is no vaccine yet, Dr. Vinetz clarifies that as the diagnosis of the disease is still insufficient, what makes the commercial argument for its development complicated.

Burden of leptospirosis in the world

Works by the World Health Organization (WHO) Reference Group on Leptospirosis Epidemiology have estimated (a few years ago) that there are more than 1 million cases per year with a mortality rate of ~5-20%. Dr. Vinetz emphasizes that this is undoubtedly an underestimated number. Also according to him, the burden of the disease falls mainly on poor people in tropical environments around the world, for which there are no effective diagnostic tests available. “Testing for leptospirosis remains difficult and is not available in most places due to lack of commercial interest. Molecular testing is very effective, accurate and efficient, but it is also expensive and requires substantial resources. Such resources are not efficient in rich countries and are not available in poor regions, concludes Dr. Vinetz. In addition, patients with leptospirosis are often misdiagnosed, as symptoms can be mistaken for malaria, dengue or other diseases. Currently there are no effective control measures against the disease.

The occurrence is related to precarious health infrastructure conditions and the incidence is expected to increase in the coming decades, when the number of people living in favelas in the world may reach two billion by 2030. In addition to extreme weather events, intense seasonal rains, rapid urbanization, inadequate sewage and sanitation, the possibility of major epidemics in urban communities is worsening.

Basic sanitation can be recognized as a constitutional right

The Constitution and Justice Commission (CCJ) approved, on July 6, unanimously, the Proposed Amendment to the Constitution (PEC) 2/2016, which modifies article 6 of the Brazilian Constitution to make the service a social right, as well as education, health, work, housing, leisure, food, social security and security. The amendment will also be submitted to two rounds of discussion and voting in the Senate.

The survey “Saneamento e Doenças de Veiculação Hídrica – ano base 2019”, released by the Trata Brasil Institute in October 2021, based on data from the National Sanitation Information System (SNIS), showed that 100 million Brazilians do not have access to the sewage collection service and 35 million are not supplied with treated water. Also according to the Institute, each Brazilian Real (R$) invested in sanitation generates savings of R$ 4 in the health area.

Indicators of the study also revealed the overload of the health system with 273,403 hospitalizations for waterborne diseases, which exposed the consequences of the lack of basic sanitation. The number represents an increase of 30 thousand hospitalizations compared to the previous year (2018). The incidence was 13.01 cases per 10,000 inhabitants, generating expenditures of R$ 108 million in Brazil, according to DataSUS. The list of waterborne diseases – which is directly related to the lack of water and sewage treatment – is long: leptospirosis, Escherichia coli diarrhea, amoebiasis, Giardiasis, cholera, bacterial dysentery, hepatitis A, schistosomiasis, typhoid fever, ascariasis, dengue, rotavirus, toxoplasmosis, schistosomiasis, skin and eye infections, among others.

About the disease

Leptospirosis is an acute febrile infectious disease caused by a diverse group of spirochetes called leptospires. A wide range of mammals, including rats, harbor bacteria in their kidneys and release them into the environment through urine. Humans and animals can become infected after coming into contact with contaminated water or soil. The incubation period, that is, the time interval between transmission and the onset of signs and symptoms, can vary from 1 to 30 days and usually occurs between 7 and 14 days after exposure to risk situations. In the early stages, symptoms include high fever, nausea, muscle pain (mainly in the calf) and jaundice. In the most severe phase, the person presents hemorrhage, pulmonary bleeding and renal failure. The treatment is done with simple antibiotics, such as penicillin.

Leptospirosis is severe and has emerged as an important cause of pulmonary hemorrhage and acute renal failure in developing countries. Death occurs in 10% of patients and up to 70% may develop hemorrhagic forms of the disease. The Leptospira family of bacteria consists of 64 species with 300 different varieties (called serovars). This makes the development of a vaccine challenging because researchers need to find a common feature of the bacterium that will trigger an immune response.