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Magda Carneiro Sampaio

Magda Carneiro Sampaio: In defense of children

Eduardo CesarMagda Carneiro Sampaio is a pediatrician who admits her preferences with confidence: “I love babies. Thankfully, we have enough people here at the hospital to treat the older children and teenagers,” she says. Her scientific interests complement her personal preferences. Ever since her first steps as a researcher, she wanted to understand the immunological development of children from the first days of life. Uniting pediatrics and immunology, she is a professional capable of reconciling intense clinical activity with experimental laboratory research.

Dr. Sampaio came from Recife in 1973, after graduating from the Federal University of Pernambuco (UFPE), to do her residency at the Hospital of the University of São Paulo School of Medicine (HC-USP) and, three years later, began her doctorate, advised by veteran immunologist Charles Naspitz, of the Federal University of São Paulo (Unifesp), to concentrate on immunology applied to pediatrics. Placed in the beginning of her career at the HC-USP Children’s Institute (ICR), she spent 15 years at the Institute of Biomedical Sciences (ICB) working in collaboration with Luiz Trabulsi on pioneering research on immunology in breast milk before returning to the ICR in 2005. Today she is the Chairperson of the Institute’s Board.

One of the first individuals in Brazil to work in the field of primary immunodeficiencies, Dr. Sampaio is one of the developers of a project that seeks to make the diagnosis of children more humane and safe, advising physicians to pay increased attention in clinical and physical examinations of patients instead of the usual long list of laboratory tests. She was also one of the coordinators of a project that advocates new pediatrics procedures for children who could live up to 100 years or more, with the objective of early prevention of chronic diseases in adults and the elderly.

Her passion for medicine was not passed on to her two daughters. One is a historian with a PhD dissertation ready to be defended at USP. The other is an actress and singer of children’s songs. The researcher spoke to FAPESP about children, medicine and science in the interview below.

You always have some ambitious project in sight. What’s the latest?
One of the latest, of an educational and social nature, is the “Child-friendly diagnostic professional.” The objective is to reduce the negative impact of diagnostic procedures on the child, especially the youngest. This project has three aspects. The first, in which I was more involved, aims to reduce the amount of blood collected from children. It is common to take several tubes of blood, and this is hard on children. A 2 kg infant has a very small amount of blood, less than 200 milliliters (ml), about one medium-sized cup. The volume of blood to be collected is determined by the type of analysis, irrespective of the age and weight of the patient. To carry out the analysis itself, only a tiny amount of blood is required. The problem is in what is called the pre-analytical phase, involving collection and preparation of the material, which still requires a lot of blood. The main reason for blood transfusions in young children who are hospitalized is because of the excessive amount of blood removed. So much is removed that some must be replaced. At the ICR, we systematically began using much smaller tubes than those commonly used [shows the common tube and another much smaller tube]. It’s about 90% smaller. For almost all types of automated analysis [the big tube], the volume collected is much higher than the amount of blood or other material required by the equipment. The conventional blood count tube, for example, requires 4.5 ml of blood. We are now collecting 0.5 ml and even that is a lot, because we use 5 microliters for the exam! Some better hospitals already use this system, but the general hospitals with pediatric wards do not yet. We are starting to disseminate the idea that blood is being wasted, and this could affect the clinical treatment of pediatric patients.

Immunology applied to pediatrics
Federal University of Pernambuco (UFPE) (undergraduate degree), 1973 University of São Paulo (USP) (residency 1974-1975 and PhD 1976-1978) World Health Organization (postdoctoral research), 1983
Children’s Institute, USP School of Medicine
Scientific production:
126 articles in international journals, 2 books, 28 doctoral students advised

What are the other aspects of this project?
The second is to reduce the radiation to which the child is exposed during imaging studies. I’m talking about clinical pathology, imaging tests, which are very important. Some radiation is innocuous, while other types are potentially very dangerous, those using ionizing radiation. The principal source is X-rays. Both an English and an Australian reference demonstrate the risk of X-rays and CT scans, which use large numbers of X-rays to generate images. The two studies, involving large numbers of children and adolescents, show a higher risk for developing leukemia, lymphomas and brain tumors in people exposed to radiation.

Can exposure be reduced?
Yes. First, you must use ultrasound whenever possible, because this type of radiation is harmless. It has been used for over 30 years with fetuses during pregnancy, with no reports of problems. But we have some situations, for example when exploring the chest, in which ultrasound is not helpful, and conventional radiography and CT scans are the best. However, it must be made very clear that a CT scan should be requested for a child only under exceptional circumstances given the enormous amount of radiation needed to generate the images. Another investigation method is MRI, using radio waves, which are considered non-ionizing. But the machine is costly and the time required to obtain the images is enormous, requiring the child to sit still for a long period, which is difficult, hence the need for sedation or even anesthesia in some cases. Then comes the third aspect, which is to humanize care to accommodate the patient and minimize procedures using anesthetics and sedation, which are obviously risks, however small. The principle is that doctors should remember the importance of the clinical exam. Today, what were once supplementary have now become the principal exams! There has been a true inversion in the logic of medical diagnoses, which should be based on the formulation of a diagnosis based on clinical data, obtained from the medical history [interview with the patient] and physical examination. Supplementary, laboratory or imaging tests are ordered if needed to confirm or rule out hypotheses.

Health professionals will therefore need to return to examining the patient carefully.
They have to take their time and pay attention, which begins with talking to the family. A well-taken medical history is very important. What worries me most is that today’s families think that if a list of tests has not been requested, if the child is not X-rayed, the doctor did not do his or her job. And it is exactly the opposite. Good treatment involves the clinical history and a careful physical examination, and then additional tests are unnecessary in most pediatric visits. A truly absurd thing happens to children with chronic respiratory problems, such as bronchial asthma, who are subjected to at least one radiograph for every crisis! They fail to identify the causes and triggers of the problem and treat the symptoms, always based on an X-ray, which almost always shows what a good auscultation would have easily revealed. Therefore, the “Child-friendly diagnostic professional” program is primarily an education program for health professionals and the public. We have to remind physicians that radiation is dangerous, that you should not overexpose the patient, and that you can take less blood for the really necessary analyses, among other measures. Also, families need to be aware of the risks of an X-ray, not to mention the financial costs. Health care is becoming impossibly expensive.

Have you already implemented this project here at the Children’s Institute?
We began implementing the program in March 2012, after its unanimous approval by the Board. Modifying the lab was simple, it was just a matter of calibrating the machines. The small tubes, called pediatric, cost more, which was an additional expense of R$8,000 per month, which is not much given the benefits to our little patients. For X-rays, we purchased a tomography machine that emits lower radiation doses, but they are still very high, and we are now installing the first MRI equipment in the hospital. We are expanding the use of ultrasound, which is beginning to be used by pediatricians themselves in the emergency room and intensive care units, without involving radiologists. The “Diagnostic Professional” is a collective, including the radiologists, clinical pathologists and nurses who help humanize pediatric care, in addition to our colleagues in neonatology. The team also includes a lawyer, Gustavo Mônaco, a professor at the USP Law School specializing in the rights of children and adolescents. He wants to turn some of these measures into laws.

What else are you working on?
In October we launched the site (The ABCs of Pediatric Health), which addresses health issues during the first two decades of life and is written for families. I had an old dream of making an educational site to also provide some information for healthy children, or those suffering from simple diseases that are not usually treated by the ICR. “Dr. Google” does not answer all questions and there is the important issue of whether the information it returns is both safe and reliable. Much of the information available on the internet is linked to an interest in selling something, even in health. It took us a long time to get the site up due to lack of financial resources, because we did not want the support of pharmaceutical or food companies, to avoid conflicts of interest. Finally, the dream is coming true within the Pediatric and Adolescent Health Research Support Program (NAP CriAd), based at the ICR, which chose to use the site as its communication channel. At the ICR we have a team of pediatricians and other top-level professionals with renowned experience involved in the project. Our only commitment is to scientific knowledge and the desire to provide a service to society, even as a form of gratitude for the quality education that the contributors received at free public universities, mostly the USP School of Medicine. We were able to hire journalist Juliana Lanzuolo through the ICR. She manages the project with great enthusiasm, along with fellow journalist Samia Prates.

What is the profile of the children treated at the institute?
Here we treat the minority of children with rare, serious, complex illnesses: 85% of the children are estimated to be completely healthy, while 15% may have a chronic disease, the most common being mild bronchial asthma. Before, the most common disease in the Brazilian pediatric population was dental caries, which affected more than 50% and has fallen very rapidly in recent decades. Second are the rising obesity rates. We went from malnutrition to obesity very quickly. Third are mild behavioral and neurological disorders, such as difficulties in learning, attention and hyperactivity. We have 240 beds in two hospitals: the Children’s Institute and Itaci [Institute for Pediatric Cancer Treatment], which is our oncology-hematology service, where we provide hematopoietic cell transplants. We see about 8,000 patients per month in outpatient and emergency-room visits, mostly for serious, complex and rare chronic diseases. We perform an average of 200 surgeries per month, especially liver and kidney transplants and congenital malformation surgery. The children we treat come from all over Brazil.

How is Pediatrics of the Future coming along?
In 2005 we started a project called “A new pediatrics for children who will live 100 years or more.” Its focus is early prevention of chronic degenerative diseases in adults and the elderly that are known to start early. The main focus is on families who are already at risk for certain diseases, such as coronary heart disease and obesity. Osteoporosis, for example, appears after the age of 50, but must be prevented at an early age, because most bone mass is formed in the first 20 years. Thus, it is the pediatrician who must guide prevention. This is a broad project to change the pediatrician’s approach, because her action will have an impact throughout the patient’s life. In this project we worked mostly in collaboration with the Pernambuco Mother-Child Institute (IMIP). Last year, together with a doctor there, João Guilherme Bezerra Alves, we drew up a summary for the pediatricians containing the 10 most important recommendations for people to reach 90 or 100 years of age in good health: 1) prenatal care, 2) breastfeeding, 3) establishment of healthy eating habits from the start, 4) monitoring of growth and development, 5) prevention of infections, in particular through vaccines, 6) encouragement of physical activity and discouragement of a sedentary lifestyle, 7) prevention of smoking, alcoholism and drug use, 8) early identification of hypertension, diabetes, dyslipidemia, and a tendency towards osteoporosis , 9) prevention of mental health problems, and 10) education for violence prevention. The last is a very Brazilian issue, but it kills many young people. Many of the issues addressed in this project are not related to our own research. We gathered and reviewed other studies, so it is a translation of the concepts and results of good studies applied to medical practice.

You seem to like very young children a lot.
It’s true, I love babies. Thankfully, we have enough people here to treat the older children and teenagers. What interests me most is the beginning of life. I never tire of treating the babies. They enchant me, even after 40 years in the profession. The beginning of life is almost always very tumultuous in terms of infections. Children suffer from them during the first two years, and we know now that some have slower immune system development. The subject that most intrigues me is immunological immaturity and how nature has invented ways to provide immunity by passing antibodies through the placenta and through breast-feeding.

When you studied medicine, were you already interested in this?
No. My first passion was the host-pathogen relationship and immunology. Only later did I fall in love with children’s development, which is something extraordinary. I studied medicine in Recife, at UFPE, and part of the internship [5th and 6th year of medical school] was at IMIP. I then applied to do my residency here at the Hospital das Clínicas (HC) because I wanted to study pediatric immunology and in Recife the area was not yet well developed. And then I never left. At the time my professors and colleagues told me to not go into pediatrics because I cried a lot when seeing children malnourished from lack of food. They said I was not emotionally equipped to work in the area. I don’t know if I overcame that, probably not, but I’m here. I’ve always felt great pity for patients. I could never do any procedure because I have very little manual dexterity and I’m afraid of making people suffer. On the other hand, I’m good at diagnosis. I love to understand phenomena. It’s no wonder I went to the ICB.

When did you go to the ICB?
After graduation, I spent two years in residence at HC-USP and then went straight into the doctoral program in 1976. The pediatrics professor Eduardo Marcondes knew of my interest in immunology and couldn’t find anyone to advise me at USP. At the Paulista School of Medicine, which had not yet been integrated into Unifesp, he found Charles Naspitz who introduced the study of pediatric allergies and immunology in Brazil. A very generous person, Naspitz became accredited at USP solely for my sake, although he already had many students. I used the lab at the Paulista School of Medicine and the asthmatic patients were at the ICR. I would arrive here early, examine the children, collect blood and go to work there. It was a very rich experience. I finished my PhD at the end of 1978, set up the allergy and immunology department at the ICR, and went to the ICB in 1989 because I wanted to do basic research and have a teaching career. Here at HC I was just a doctor, although I had already defended a thesis at the associate professor level. I worked in immunology for 15 years, from 1989 to 2004, before deciding to return. I continued to be fascinated by clinical work and wanted to see patients with primary immunodeficiencies, an area which has developed greatly since the 1990s.

What did you do at the ICB?
I worked a lot with placental transmission of antibodies and the immunology of human milk, both collected from mothers at the USP University Hospital. It was one of the most productive times of my career, because I had the opportunity to work directly with Professor Luiz Trabulsi. I was very lucky because he retired from Unifesp and went to work at the ICB just when I arrived there. Together, we studied how breast milk protects the child against bacterial diarrhea. In the 1980s there was already epidemiological evidence that breastfed children suffered less from diarrhea. We set up a line of research with in vitro models, simulating an infection, and we saw that, with breast milk, enterobacteria did not adhere to cells. Then we examined the antibodies and which bacteria antigens were critical in inhibiting microbial adherence, and thus infection. It was a very successful project. Trabulsi was the foremost expert in the country on pathogenic enterobacteria in infant gastrointestinal tracts. He always studied childhood diarrhea.

Did you try to develop a vaccine?
We were very close. We had the candidate antigens and knew that the vaccine would have to be live to colonize the intestine. We had identified a highly antigenic organelle that the bacterium uses to adhere to the intestine, and we were ready to express it in a probiotic, but there was strong resistance at that time, and still today, against genetically modified organisms. The vaccine was shelved because, beginning in the late 1990s, infectious diarrhea caused by Escherichia coli began to decline. This is not due so much to medicine, but rather to improved living conditions, sanitation and education. It was the physician Zilda Arns, of Pastoral da Criança [an entity of the Catholic Church focusing on child development], who taught mothers across the country to take quick action to prevent dehydration. She invented that spoon with a measure for salt and another for sugar, to be mixed in a glass of water, making an excellent oral rehydration drink. She took advantage of the fact that the Catholic Church is present throughout Brazil and did an exceptional job, which certainly saved thousands of lives. It was a very good time because we had a known epidemiological phenomenon, which is the protection that breastfeeding provides against infectious diarrhea, and we clarified why this happens. It was work at the frontier of knowledge at the time and resulted in many academic theses. My most-cited articles were written during that period. When Trabulsi died, I was already director of the ICB, my life was a little more complicated and I went back to the ICR.

Are you also interested in rare diseases?
As infectious diseases are controlled by sanitation and vaccines, children who have rare diseases survive longer, and we have to take good care of them. Among these diseases are primary immunodeficiencies or PIDs, which are almost all monogenic. Today, there are approximately 180 different PIDs. In March, we founded the Brazilian Consortium of Primary Immunodeficiency Reference and Training Centers (CoBID) with doctors and researchers from around the country. The idea is that a more advanced center can help other, less-advanced centers identify patients suffering from these conditions as early as possible.

Can you identify the problem in newborns?
It’s very difficult. The challenge is to recognize the most severe cases as early as possible, because for these children the only chance of survival is a hematopoietic cell transplant, from bone marrow or an umbilical cord, as soon as possible. They are known as “bubble kids,” because of the movie The boy in the plastic bubble from 1976. Today we know that there are already about 15 different genetic defects that lead to the same clinical picture of very serious infections in the first months of life. In some US states they already do a type of infant screening test to identify the problem and perform a transplant before children get sick.

What is the DORA network?
It is a network of university services in São Paulo involved with diagnosis and treatment of rare diseases. The objective of this São Paulo State Department of Health project is to divide diseases into groups based on patient clinical needs (neuromuscular, metabolic, nephrological, cardiological, immunological, etc..) and liaise between university hospitals that have specialists in these diseases. Treating rare diseases, almost all of which are genetic, is needed because the nosological profile of the population has been changing rapidly. We know that there are between 4000 and 5000 different rare diseases, and new discoveries are made all the time. In Brazil we do not know much about frequency, but in France 3% of the population has some rare disease. Primary immunodeficiencies affect one in 1,200 individuals from the general population and thus, as a group, are not so rare. Here many diseases are linked to the X chromosome. At the ICR, 75% of children diagnosed with PIDs before two years of age are boys.

What is the biggest problem in relation to rare diseases?
The fact that pediatricians who do primary care lack information. The strategy being developed in the DORA project is to disseminate warning signs for several groups of rare diseases. Our group developed a list of 12 warning signs of primary immunodeficiencies in the first year of life, particularly for severe infections, since the children have weak defenses. One goal of DORA is to connect colleagues on the front line to the nearest university hospitals. A web portal is being developed with the help of Professors at the USP Polytechnic School to facilitate the referral of patients who might have rare diseases to specialized centers. Patients with rare diseases suffer a lot going from one place to another until they find a medical service able to provide adequate diagnosis and treatment, if available. Rare diseases are also called orphan diseases.