Is it zika or is it dengue?

Meet Cássio Souza, a Brazilian scientist from the state of Rio Grande do Norte, who is studying dengue and zika virus infections in his PhD. He currently divides himself between researching these viruses, working on the COVID-19 testing task force, giving talks, and finding a bit of time to have some fun.

What did you want to be when you grew up? Cássio Souza first wished to be a marine biologist, because he wanted to dive and see the underwater world. Afterwards, he thought about becoming a doctor at the Air Force, because he wanted to fly and heal people. But it was the career as a biomedical scientist that won him over. He tells that, “as a child, whenever I got any toy, my greatest interest was not to play with it, but to take it apart to see what it looked like inside.” Later, this curiosity turned into discovering how the human body and diseases worked. But that is not all that influenced him to be where he is today, as a Ph.D. candidate in Biochemistry and Molecular Biology. Throughout his life, other influences led him to become interested in the social function of science. He believes that “all knowledge is valid, but it only becomes solid, tangible if it changes someone’s life for the better”. So, combined, his curiosity and social engagement found a perfect fit in the study of infectious diseases.

The Brazilian scientist is interested in diseases caused by viruses and germs, especially those that are more common in socioeconomically vulnerable communities, the so-called neglected diseases. “The social stigma of carrying a “poor people disease” is maintained by more than just the absence of treatment or good medical care. It is also pervaded by the lack of interest and investment in research and development to combat these diseases,” he explains. Despite the lack of resources for studying these illnesses, Cássio luckily found a place to do his research: the Institute of Tropical Medicine at the Federal University of Rio Grande do Norte (IMT-UFRN). The institute is in Brazil, and it is where he studies dengue and zika infections.

Two viruses that belong to the same family are the causes of these diseases. Both dengue and zika viruses can be transmitted by mosquitoes of the genus Aedes, the best known being Aedes aegypti. When these infections occur, they both lead to similar symptoms, such as body aches and fever. And according to the Oswaldo Cruz Foundation, these infections are present in several countries in South and Central America, Africa, and Southeast Asia. However, dengue has also been detected in the US and some European countries. So, in summary, these viruses have “more than 60% structural similarities, with epidemiological characteristics, transmission vectors, and clinical manifestations also being similar”, explains Cassio. But are the differences between these two agents and their infections that are the target of the scientist’s studies.

Global distribution of dengue and zika viruses. Adapted from Wu et al, 2018.

Most of the time, both zika and dengue infections lead to mild symptoms. These are treatable with rest, hydration, and medicines for fever and pain. But both diseases can develop into more severe clinical cases, which are distinct and depend on the virus. There are two main complications caused by zika that are worrying. One of them is congenital zika syndrome. In these cases, pregnant women who contract the zika virus can pass it to the baby still inside the belly. As a consequence, “the affected children are born with microcephaly, i.e. with a head smaller than normal, because of errors in the formation of the bones of the head and the brain. This causes a lot of problems for the child’s development,” clarifies Cassio. The other is Guillain-Barré Syndrome, which is “a type of disease that affects the nerves (…) and the person ends up losing movement little by little, and may not even be able to breathe, because the muscles that move the lungs may become paralyzed,” he explains. In the case of dengue fever, when the infection worsens, it causes severe abdominal pain, vomiting, and bleeding gums. Without medical help, it can even lead to death. Thus, because of these more severe phases of zika and dengue infections, it is important to identify which virus the person has been infected with. With this information, the patient can then receive the most appropriate treatment. Also, for disease control purposes, we need to know which virus is most common in certain areas. With this knowledge, public health policies are better planned to meet local demands.

But it is hard to differentiate between these two infectious agents. Especially based only on the symptoms, as we saw above. And the most common laboratory test doesn’t solve the issue. In this test, the goal is to identify if the organism already has a type of protein produced when we have an infection. In other words, antibodies. The human body is essentially capable of making specific antibodies for each kind of virus or germ that we contact. “This is how it works: if a person has antibodies against Zika in their blood, it is because at some point they had contact with this virus”, clarifies Cássio.

But, to start with, if these agents come from the same family, as is the case of dengue and zika viruses, the antibodies against them can also be similar. The scientist tells that “nowadays, the main method to diagnose zika and dengue searches antibodies against the [non-structural] protein 1 (NS1), and studies are showing high similarity between proteins NS1 from zika and dengue.” In both infections, such protein is released by the infected cells into the blood. In principle, this makes the sampling and detection of these molecules easier, which turns the diagnosis simpler. But it is like we are trying to distinguish between two different shades of blue. Both shades are different, but very similar, increasing the chances of identifying them wrongly. Molecularly speaking, this leads to an issue called cross-reaction. It happens when an antibody against one agent also has an attraction for another, giving false-positive results. So, more specific tests are needed to identify between zika and dengue. This is where one of Cássio’s projects can help. He gives us more details: “we tested different protocols and searched different antibody markers to improve the specificity of the tests, to reach a safer and more efficient way to do the diagnosis”. Since this study was not published and evaluated by other scientists yet, it is still not possible to share the results. But Cássio says that they are promising.

The researcher also works on another interesting project. This other one is also related to antibodies, but now focusing on the zika virus. Cássio explains: “antibodies (…) are carried by our blood even after the disease is over. This is important because if we are infected by the same virus again, these antibodies may help to fight the infection. And this can prevent that we get sick another time. Antibodies not only control infections, but they also help us to identify if a person is currently sick, or if they were infected in the past.” As we saw above, pregnant women can pass the zika virus to their babies still in their bellies. And this can lead to congenital zika syndrome. But what happens in the scenario where a mother got infected while pregnant and gave birth to a baby with this syndrome? Did she, after this first infection, produce antibodies able to protect her and an eventual fetus, in case she gets pregnant again? “If these mothers have these antibodies in their blood protecting them, the chances of having another baby with the syndrome are lower. The majority of studies show that these women have these antibodies, but they only checked this some months after the child was born.” In this unfinished work, Cássio and his colleagues look for the same antibodies. But this time, at a longer interval after the first pregnancy, when the mother got infected with zika. The goal is to know if these molecules remain in the body, protecting the women and the future baby, what could guarantee a longer immune memory.

Taking care of these two main projects, until one year ago, Cássio’s routine was quite different. “[It] included experiments, scientific meetings, and lectures from my Ph.D. program. (…) It used to be common to spend 10 to 12 hours straight at the university, (…) including weekends and holidays. Thousands of samples were tested, dozens of new protocols were established, in addition to giving help to my colleagues in their projects (…). With the COVID-19 pandemics, my routine changed completely. Nowadays, on top of the experiments and other activities of my Ph.D., I work at the testing taskforce of COVID-19 at the clinical unit of IMT-RN. This lab has offered an important service during this pandemics. Our team is currently taking charge of a big part of qPCRs [molecular tests] in the Brazilian state of Rio Grande do Norte. (…) Also, I still work as a clinical analyst in a private hospital laboratory at the capital,” tells Cássio. “I sacrificed a lot of my career as a scientist last year, my research projects are in second priority, as now the focus is to help to save the greatest number of lives. It is exhausting, and sometimes I panic, I’m afraid of not finishing my Ph.D., of affecting my career, but mainly because I cannot see an end to this critical situation. I cried many times of despair, of fear, of tiredness. But at the same time, it is gratifying. I learned tons in this last year, as a scientist and as a health worker (…). I am part of teams composed of excellent colleagues. I have been giving my best, either in the lab, or teaching and doing science communication. In the latter, talking about our working during the pandemics in events that I’m invited as a speaker.”

To pursue this arduous but rewarding career, the researcher reveals that his friends and co-workers, “young people like me, who are working hard to build their careers and are becoming brilliant professionals and recognized in their fields” are his main references. Besides, his master’s (Prof. Janeusa Souto) and doctoral (Prof. Selma Jerônimo) mentors are also his daily inspirations. “Because I see in them incredible examples of scientists”. Outside of work, Cássio loves cooking and dancing: “the kitchen is my corner of peace; whenever I need time to process something, or I want to celebrate something, or I want to do something nice for someone special, I immediately think of cooking. Dancing gives me an incredible feeling of freedom. I just close my eyes and let the music take me, without thinking about anything else. Especially if it is [Brazilian] funk or axé [another Brazilian rhythm].

To finish, I would like to thank Cássio and his team for the amazing work they are doing for the combat against the COVID-19 pandemics. Your work and dedication are tremendous. I also want to wish Cássio and his projects all the success in the world, and may he continue to do his best as a scientist, cook, and dancer! You can learn more about Cássio’s routine here.

Thanks a lot, Cássio, for sharing your story with us!

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