The use of genetic tools can help diagnose and treat infectious diseases and cancer
These devices, which cost 13.9 million Brazilian reais, were distributed to central laboratories in the 26 states and the Federal District – and helped monitor the evolution of the Coronavirus and the behavior of different variants of the pathogen in different waves of cases. Hospitalizations and deaths.
After the most critical phase of the health crisis, experts are now discussing how to leverage the potential of genetic sequencing for the benefit of public health and science in Brazil.
“With the decrease in demand associated with Covid-19, the use of these genetic sequencing technologies should be carefully considered,” explains Ligia da Vega Pereira, Professor of Genetics at the University of São Paulo (USP).
“Before 2021, we did not have the capacity, infrastructure, staff and logistics to perform molecular testing in the Unified Health System (SUS),” notes Dr. Rodrigo Guendalini, scientific advisor at the Oncogia Institute, an NGO focused on cancer patients and their families. .
“Now that we have everything installed, this is an opportunity we cannot miss,” he adds.
“The challenge now is how to keep the entire workflow fast and cost-effective,” adds virologist Anderson F. Brito, scientific researcher at the Instituto Todos Bella Saude (ITpS).
The debate about how to utilize these tools in different fields opens up some possibilities: sequencers could continue to monitor the behavior of different viruses, but there are proposals to use them in analyzing some types of cancer or in detecting rare tumors. Diseases.
In these cases, a proper diagnosis can make a big difference in guiding preventive strategies or determining the best treatment.
Understand below how to use these machines and what are the plans for using them in the future.
Extended monitoring
In response to a question from BBC News Brazil about these genetic sequencing devices, the Ministry of Health confirmed the purchase of 27 devices of this type in 2021.
The federal government paid for 24 of these machines at a cost of R$12.5 million.
The other three were acquired “through an international organization” at a cost of R$1.4 million.
“In total, R$13.9 million was spent,” the ministry explained in a note sent to the report.
“The sequencers were intended for the Central Public Health Laboratories (Lacen) of the 27 federal units that make up the SISLab network and which support health surveillance in Brazil.”
These central laboratories are considered the reference for each country in diagnosing diseases. Samples from patients suffering from a suspicious condition are sent to these places, as it is necessary to perform specific tests that help determine the cause of these discomforts.
Installing new genomic technologies requires a series of modifications, such as revamping the infrastructure to house the sequencers and training specialists to operate them correctly.
“In other words, we are not just talking about purchasing equipment. It was necessary to organize the whole chain of operations, train the teams, provide supplies…” says Gwendalini, who also works at Oncologia D’Or.
From the world’s point of view, all this acquired knowledge remained a kind of “legacy” of the epidemic.
But how does the Ministry of Health use – or plan to use – all this genetic potential going forward?
According to the memo sent to BBC News Brazil, the sequencers have begun to be used “to study the genomes of other pathogens of public health importance, such as dengue and chikungunya viruses.”
“Since implementation, 15,601 Sars-Cov-2 genomes have been generated [o coronavírus causador da covid-19]557 dengue virus genomes and 415 chikungunya virus genomes. “In 2023 alone, 5,020 genomes were generated, adding to the numbers of SARS-CoV-2 and arboviruses (dengue and chikungunya).”
Sequences of viruses transmitted by mosquito bites Aedes aegypti It is also part of a pilot project implemented in the states of Amazonas, Ceará, Goiás, Paraná, São Paulo and Minas Gerais.
The ministry also plans to establish a Center for Genomic Intelligence (Cigen), “which will enable the development of bioinformatics software to solve biological problems for free and independently, such as identifying variants of circulating pathogens and antimicrobial resistance genes, modeling agent behavior and epidemics, among others.”
“The current goal is to capitalize on this legacy and apply it to other diseases of public health importance,” the text concludes.
Brazil spent more than R$10 million on purchasing genetic sequencers
Expanding possibilities
For Gwendalini, the sequence numbers announced by the Ministry of Health – 5,000 genomes in 2023 – are good news, because they indicate that the machines are not standing still.
“But it is possible to do much more than that. With these 27 pieces of equipment in operation, it is possible to perform thousands and thousands of sequences every month.”
The oncologist suggests that some of these devices could be used in pilot projects for cancer sequencing in SUS.
“We can implement cancer genetic counseling services, where 10 or 15 genes are selected that completely change the therapeutic approach and allow for very effective preventive strategies,” he says.
The doctor adds: “We already know of some mutations that change the lives of entire families and reduce the risk of cancer by more than 80%.”
This is the case, for example, in genetic changes that appear in the BRCA1 or 2 genes and are associated with the development of tumors in the breasts and ovaries.
When these mutations are discovered in a woman who has not yet had any health problems, it is possible to conduct more precise monitoring, with the help of periodic examinations, or even to perform preventive surgeries on tissues in which cancer cells could grow in the future. .
These strategies help reduce the likelihood of such a tumor developing — or at least allow the disease to be detected in the early stages, when the chance of a cure is much higher.
“There is no need to reinvent the wheel here: this is a model already applied in other countries and it is difficult to go wrong in Brazil,” says Gwendalini.
Pereira, who is also president of gent-t, a biotech startup that maps genomic data and works with precision medicine, points out that sequencers can still help diagnose rare diseases.
“We know very well the genetic basis of some of these diseases,” she says.
“Individually, these cases might be considered rare. But when you add many of them together, the numbers are significant.
The specialist explains that the diagnosis of some of these diseases has a direct impact on the quality of life and health of patients.
“In these cases, a genetic diagnosis explains what’s going on there,” she says.
The specialist points out that “many of these people go through a very long diagnostic journey, from one doctor to another, and only the sequence gives a conclusive answer.”
Pereira also realizes that these techniques could help understand the peculiarities of the Brazilian genome.
“In Brazil, we have an additional challenge, which is a mix of indigenous, European and African DNA,” she points out.
To give you an idea, changes in TP53 are the third most common cause of hereditary breast cancer in the country, after only mutations in BRCA1 and 2.
However, in other countries, it is very rare to find a variant in the TP53 gene.
Understanding the DNA of the Brazilian population can track the mutations and genetic sequences that are most common in the country
New and old viruses
Brito believes that leveraging these sequencers to conduct genetic surveillance of different viruses is strategic for the country.
“Recently, some Brazilian states have declared a health emergency due to an increase in hospitalizations of children infected with respiratory syncytial virus,” he explains.
This pathogen is among the most common causes of the common cold, which can cause more serious conditions in children.
“But we don’t know exactly whether the virus responsible for this latest outbreak has anything special or what variants are circulating, simply because that data doesn’t exist,” Brito says.
For a virologist, it is possible to use sequencers to perform comparative studies. This would allow us to better understand this and other viruses, opening possibilities to create a strategy to prevent new waves of cases, hospitalizations and deaths in the future.
Brito recalls another recent incident where genetic monitoring could have made a big difference: the Zika virus epidemic, which broke out in 2015 in Brazil and led to cases of microcephaly, where babies are born with their heads smaller than their normal size. .
About a year ago, he added, Zika cases were diagnosed as dengue in the country because of the similarity of symptoms. “No one knew this pathogen was spreading here,” he recalls.
He adds: “It would have been necessary for someone to have been surprised by the unusual increase in cases of microcephaly, to suspect something other than dengue fever, and to sequence the virus to find out what was different about it.”
Monitoring the arboviruses transmitted by the Aedes aegypti mosquito – dengue and chikungunya – is one of the projects that the Ministry of Health has already started.
Initial speed
Brito highlights that to create a genetic surveillance network with practical applications, it must be very well organized and make results available quickly.
During the pandemic, the virologist published a study with other experts that calculated the time between collecting samples from a patient with Covid-19 and publishing the sequence in databases. On average, this process took about 45 days in South America.
“This is immortality. When the information becomes available, it no longer calls for any practical action from a public health standpoint.”
In other words, the entire process – which includes collecting samples, sending them to laboratories, genetic sequencing, producing reports and publishing the results – needs to be very well coordinated across the country.
This would allow us to obtain a practical, real-time picture of the circulation of certain pathogens and the emergence of variants – and would serve as a basis for representatives of the Ministry of Health and state and municipal secretariats to take measures to contain or deal with transmission. With an increase in disease cases in a certain area of the country.
Practical example: Surveillance of the influenza virus that causes influenza. Sequencing samples from patients with this infection will allow us to know the details of the pathogen strains circulating. This information will help determine the composition of vaccines or even send equipment, professionals and resources to the most affected areas.
“But, again, this process has to be quick. Brito insists that it cannot take more than a month to convert a sample into genomic data.
“Therefore, investments should not focus only on genetic sequencers. It is necessary to think about all elements of the chain, as trained and experienced professionals.
“In this way, it is possible to respond quickly to deal with potential risks to public health,” the virologist concludes.
Pereira points out that, in addition to all the practical challenges, it is necessary to think of genetic surveillance as a source of knowledge that directly benefits public health.
“Only in this way these efforts will continue, so that the best use can be made of the investments already made and those yet to be made,” he says.
“To achieve this, it is necessary that these programs be a state project, and not a government initiative,” she concludes.
