Brazilian genomics breakthrough offers hope for leptospirosis control



Luisa Massarani

Rio de Janeiro



A team of Brazilian researchers has sequenced the genome of a bacterium which causes leptospirosis, a disease which infects over 100 000 people and causes 1000 deaths worldwide every year. The breakthrough has been hailed as a first step towards creating a vaccine against one of the world's most widespread zoonoses (diseases affecting both humans and animals).

"The research is important since ... it will open new opportunities for developing quicker and more precise diagnostic tests and vaccines for preventing leptospirosis," said Dr Carlos Morel from the Oswaldo Cruz Foundation, a biomedical research centre linked to Brazil's Ministry of Health.

The researchers, whose findings were published in the Brazilian Journal of Medical and Biological Research (2004;37:459-77), analysed the 4.6-million-base-pair genome of the strain of bacteria mainly responsible for the disease in Brazil, Leptospira interrogans serovar Copenhageni. The results of their research have pointed to the identification of candidate proteins for this purpose. Although leptospirosis can be treated with antibiotics, when left untreated it can lead to kidney damage, liver failure and, in extreme cases, death.

"We have already isolated 23 proteins ... that we consider potentially important for the development of a vaccine against leptospirosis," said Ana Lucia Tabet Oller do Nascimento, a researcher from Butantan Institute in São Paulo and lead author of the study. The 23 proteins were selected because of their ability to induce the production of antibodies in humans, explained Nascimento. "However, we need now to test if such antibodies are in fact protective against the disease," she added. The researchers are now analysing another 200 proteins.

Despite the success of their research, Nascimento estimated it would take around ten years to develop a vaccine or any other product offering protection against the disease.

"Nothing is done in the short term when we are talking about developing a vaccine, which includes several steps between the sequencing and the final product. To believe that genomics can shorten such a period of time is to believe in magic or miracles," said Morel who views genomics research as a potentially powerful tool for controlling developing country diseases.

Leptospirosis occurs worldwide in urban and rural areas and in both tropical and temperate regions, mostly in developing countries. It is contracted by humans through direct contact with the urine of infected animals or by contact with a urine-contaminated environment. The disease has been found in both wild and domestic animals including rodents, insectivores, dogs, cattle, pigs and horses. It is therefore an occupational hazard for those who work outdoors or with animals and a recreational hazard for those who swim or wade in contaminated waters.

The number of human cases worldwide is not well-documented. According to WHO, it probably ranges from 0.1 to 1 per 100 000 per year in temperate climates to 10 or more per 100 000 per year in the humid tropics. During outbreaks and in high-risk groups, 100 or more per 100 000 may be infected. In Brazil 4128 cases were recorded in 2000, according to the National Foundation of Health.

The science of genomics — the branch of genetics that studies organisms in terms of their full DNA sequences (or genomes) — has been accelerating in recent years with very positive implications for combating diseases afflicting developing countries, says the report Genomics and world health, published by WHO in 2002. However, according to the report, 80% of DNA patents in genomics between 1980 and 1993 are held in the US. Of the 1233 new drugs marketed between 1975 and 1999, only 13 were approved specifically for tropical diseases.

"In this regard, steps need to be taken to avoid the creation of a 'genomics divide,' to ensure that the benefits of the genomics revolution also accrue to developing countries and that ethical, legal and social implications are taken into account," said Dr Tikki Pang, Director of WHO's Research Policy and Cooperation department.

A resolution on genomics and world health adopted during the Fifty-seventh World Health Assembly, 17–22 May 2004, called upon WHO Member States to facilitate greater collaboration among the private sector, the scientific community, civil society, and other relevant stakeholders, particularly within the United Nations, in order to mobilize "more resources for genomics research targeted at the health needs of developing countries."

World Health Organization Genebra - Genebra - Switzerland