Human Pratices & Integrated
The UFMG_UFV Brasil team aimed in 2022 to develop a solution to a local problem that is one of our biggest problems: helminth infections. As one of the most important neglected tropical diseases, these infections are a problem mainly because our governments have failed to eradicate them, even with proper treatments and well-known prevention methods. This is strongly related to the fact that most of the affected population is poor and suffers from the lack of public policies that endorse universal access to basic sanitation and health care [1]. As an aggravating factor, the COVID-19 pandemic interrupted numerous interventions and programs to eliminate and control these diseases, such as research and treatment of cases. The most vulnerable groups became even more exposed to infectious diseases due to a lack of access to health, education, quality food, drinking water, basic sanitation, and housing [2]. Therefore, our team saw the possibility of solving a local problem, while the project's development could help to raise social awareness about our current situation. Our project focuses on improving the quality of human life beyond the absence of diseases. With that in mind, our work must start with a human-centered design. For this purpose, we talked to numerous people from every perspective and point of view so that our project could be validated in different areas.
Understanding the Problem
To approach such a delicate problem, we need to understand how the disease remains prevalent in our country and who’s still affected by it. We did a series of interviews with different people (government officials, health departments, NGOs, indigenous and others) to fully trace the profile of the problem so that we could develop the most effective and responsible project possible.
First, we focused on contacting the government (Surveillance of Zoonoses of the Brazilian Ministry of Health) to fully understand how the fight against this disease is currently being done through the Brazilian health system. This contact clarified many aspects of combatting helminth infections. Still, we realized that if we wanted to develop a human-centered design, we should get more in touch with one of the affected communities.
We found that São João das Missões, the city with the lowest HDI of the Minas Gerais state (state of our team), were one of the cities with a high prevalence of the diseases, especially in the Xakriabá indigenous community. Hence, we decided to contact the Health Secretary of São João das Missões, Jonesvan Pereira, who explained the situation in the community. We were astonished to hear about the conditions people live in, which are conducive to developing helminthiases and malnutrition.
With the help of Jonesvan, we also contacted NGOs ("Médicos do Mundo" and "Amigos de Minas") that used to provide health care and food distribution in the community. This helped us understand how contact with indigenous people could be made and how we could articulate new solutions.
In partnership with the NGOs, we also carried out a humanitarian mission in the indigenous community - on two different days. There, we were able to have direct contact with the population and perceive, in person, how the environment is conducive to the development of parasitic diseases: little to no sanitation infrastructure, scarce access to drinkable water, food distribution, and medical care.
It's also important to say, that while contacting historically persecuted people our team needed to pay extra attention to ethics and values. With care to respect for cultural differences, we talked to them to exchange knowledge and understand their beliefs and perceptions.
We made sure to understand the point of view of every person in this context - we got a perspective from the federal government, the city’s health secretary, an indigenous nurse, parasitology researchers, health professionals, NGOs, and even visited the community. This made it possible to fully understand the problem and develop an effective, responsible, ethical, and human-centered design.
Click the buttons below to see how each conversation helped understand the problem and impacted our project.
Objectives
To better understand the current panorama of geohelminthosis in Brazil from the point of view of health institutions, from current problems to possible solutions.
Who was interviewed?
Marcelo Yoshida Wada, General Coordinator for Surveillance of Zoonoses and Vector-Transmitted Diseases - Ministry of Health. Other professionals were also present at the meeting.
Outputs
The meeting was held to obtain more information about the Brazilian landscape of geohelminthiases and how our group could help with some of the current challenges. Here are the main topics aborded:
According to the professionals, there are a series of goals of the sustainable development objective (SDG), whose third goal is the elimination of geohelminthiases.
About the organization of health institutions in the fight against geohelminthiasis: the endemic areas are the responsibility of the SISPCE control program (Information System of the Schistosomiasis Surveillance and Control Program, which also monitors endemic geohelminthiases). The treatment (diagnosis and treatment) is mainly conducted by SUS (Unified Health System), the Brazilian public and free health system.
The main problems currently in endemic regions are: difficulty in installing an effective surveillance system capable of accurately quantifying the number of infected people, lack of basic sanitation, difficulty in better incorporating primary care in more remote communities, and lack of specific funding for combating geohelminthiasis.
Regarding the treatments adopted, chemoprophylactic treatment is currently carried out using albendazole in a chewable tablet for specific age groups, but without a therapeutic alternative. The other treatments will depend on the epidemiological characteristics, so the treatment is more general in regions with a higher prevalence. Still, it will always depend on the cost-benefit.
Brazil suffers from a delicate situation where the prevalence of diseases occurs mainly because of the lack of primary sanitary conditions. The lack of a proper surveillance system also makes it difficult to understand the current scenario, which leads to the conclusion that there is an underdetection of cases. These factors also led to the conclusion that to understand the problem and develop effective solutions, it is necessary to get in touch with the affected populations, even more, if we consider that health conditions vary significantly between Brazilian regions. For this, we chose to research São João das Missões, the city with the lowest HDI in the state of Minas Gerais (state of our team).
Objectives
To better understand the situation of helminth diseases in the city with the lowest HDI in the team’s state (Minas Gerais), with high rates of prevalence.
Who was interviewed?
Jonesvan Pereira - Health Secretary of São João das Missões.
Xakriaba Land Map View. [3]
Outputs
Jonesvan Pereira Oliveira told us about hospitalizations due to parasitic diseases, with a severe aggravation by malnutrition, which, although gradually decreasing, still exists and coexists with infections. The indigenous community Xakriabá of the municipality has an extremely precarious basic sanitation structure, without a structure of bathrooms and sewage system, lack of piped water, and the need for water supply by water trucks. The population also has few socioeconomic resources, requiring government assistance (Bolsa Família, at the time). There is a lack of medical care in these communities, which makes the voluntary action of doctors and health professionals in the region even more important.
The population that suffers from parasitic diseases is mainly indigenous, and the main reason for the prevalence of these is the precarious basic sanitation structure and lack of prevention measures. We decided to make a partnership with the Health Secretary of the city, so we could visit and perform a voluntary action in the indigenous community.
Objectives
To clarify the health conditions in the Xakriabá community and study possibilities of intervention, get approval from community leaders, and better understand the population's scenery from the perspective of a native indigenous nurse.
Who was interviewed?
Geovanio is a nurse in the indigenous village Brejo do Mata Fome. He is also the son of Domingos Xakriabá, the indigenous leader of the Xakriabás.
Outputs
We scheduled a meeting with Geovanio to discuss the Xakriabá reality in São João das Missões.
According to him, it is estimated that around 12,000 indigenous people live in the region, distributed in 35 villages. However, the SESAI (Special Secretariat for Indigenous Health) had only one nutrition professional and two doctors active in primary care centers, evidencing the overload of health professionals working in these communities. In addition, there is still a certain resistance on the part of the inhabitants to seek medical care outside the village, relying primarily on traditional medicine.
Malnutrition is one of the region's population's greatest evils, and the deficiency of iron and other vitamins in affected patients is notorious. Verminous is also a problem in the region, accompanied by the high suicide rate plagues these communities.
According to Geovane, indigenous children have appropriate access to public education with one school per village, which integrates Brazilian basic education subjects and traditional knowledge of the Xakriabá community. Some projects are even carried out aimed at the linguistic rescue of the Akwen dialect. However, it would be important that in the case of carrying out educational practices, we use a very clear, didactic, and simplified language to ensure better understanding and fewer constraints on the part of the lay population.
Like it was said in other interviews, the community suffers from very precary basic sanitary conditions. Geovanio lead us to understand how we could approach with an educational intervention in the community, considering the peculiarities of the population. The fact that there are so little professionals present in the primary care centers, endorses that the surveillence in the region is poorly made. Also, we could understand that malnutrition is actually one of the main problems of the population.
Objectives
To understand how a voluntary action could be developed, in a partnership with one of the NGOs that act in the region.
Who was interviewed?
Álan Jahel is the coordinator of “Médicos do Mundo”, and an active volunteer from the “Amigos de Minas”, both NGOs that have worked in the Xakriabá community, in São João das Missões. He is a dentist, and has extensive experience volunteering in actions involving vulnerable populations.
Outputs
Álan explained how the voluntary services worked at this region. He described the activities carried out in the NGOs missions, the care that must be taken during work, and how the organization is carried out.
Objectives
To organize our actions in the upcoming voluntary action and understand better the scenery of the population from the point of view of a voluntary.
Who was interviewed?
Marlene is the co-founder and coordinator of the NGO "Amigos de Minas", having extensive experience involving voluntary actions in vulnerable populations, especially in the Xakriabá community in São João das Missiões.
Outputs
Marlene gave us further clarifications about the following actions of the NGO Amigos de Minas in São João das Missões and our next steps to complete our registration as volunteers in the team. She also commented on the importance of donations of hygiene items, clothes, toys, housing construction, and renovation, among other necessary services. One fact about the infrastructure of these places is the absence of toilets in most homes, people walking barefoot, and raising pigs without spatial restrictions, all contributing to higher rates of geohelminthiasis.
Marlene detailed how to interact with the Xakriabá people, including in relation to education and science.
Objectives
To get feedback on how to approach an indigenous community with science and education from the point of view of a synthetic biologist, ex-igemmer, and descendant of an indigenous mother.
Who was interviewed?
Maria Astolfi is a synthetic biologist and biological software developer. At 15 years old, Maria co-founded the first synthetic biology lab from the Amazon rainforest to engineer biodiversity into sustainable technologies. Maria was the first Brazilian woman engineer at Ginkgo Bioworks (Boston, USA) and is now a Ph.D. Student at Beckley University. Maria is committed to the global development of synthetic biology, where she co-founded the Brazilian SynBio Association. She is also the daughter of a scientist and an indigenous from the Amazonas, Brasil.
Outputs
She helped us to connect science and the indigenous community, telling us about her previous experiences. She tells us the importance of not carrying out a single action without obtaining the consensus from community leaders, always respecting cultural differences.
Maria also emphasized that, in the case of developing activities for the indigenous community, it should never be a one-time project. For projects to make a difference, they need planning and responsibility. Based on this, we developed an action plan that can be seen on the Humanitarian Mission page.
Objectives
To get feedback about our solution mechanism and understand the view of a specialist about the anthelmintic resistance problem and what should be done to overcome it.
Who was interviewed?
Luis Fernando Viana Furtado is a professor in UEMG and Doctor of Science with a concentration in Helminthology. He has experience in parasite genetics and molecular biology, focusing on genetic markers of anthelmintic resistance and molecular variability, and neglected tropical diseases in general.
Outputs
He explained to the team members that the lack of investment was a crucial factor in the absence of the development of new drugs for helminthic diseases. He talked about the current anthelmintic resistance scenery in livestock that creates economic losses and the mass administration of drugs caused that to the animals. Additionally, he explained the relationship between mass drug administration, a control method recommended by the World Health Organization, and the occurrence of anthelmintic resistance in human parasites. Furthermore, he emphasized the importance of creating new drugs against these parasites.
He also gave feedback about our project design and told us we had an interesting idea. Still, we had to think about some logistical problems: would our chassis be able to colonize the human intestine? Would our chitinase be able to destroy chitin from every parasitic stages? How would our probiotic be able to kill different nematodes, if they have different sizes and characteristics? After receiving this feedback, the team discussed these questions and concluded that we would only be able to answer them after experimental tests.
Humanitarian Mission
Given the presented socioeconomic situation, the team saw in the missions promoted by the NGO Amigos de Minas the possibility of a joint action with the following purposes: to bring scientific and health knowledge to the population, to assist the non-profit organization in the development of its humanitarian activities, in addition to understanding the reality experienced by the inhabitants, to develop the implementation of our project efficiently and conscientiously. We also developed an action plan, as recommended by Maria Astolfi. Check it out here.
Designing a Solution
After understanding the main problems, it's time to design our solutions. Hence, there is not much the team can do to solve the currently socioeconomic situation of vulnerable populations. However, we have approached the problem with a synthetic biology view.
As discussed in the previous interviews, the treatment for the disease is preventive chemotherapy. And, over time, we have noticed that drug resistance has become a frequent problem, and infections are increasingly persistent. On top of that, malnutrition has increased in underdeveloped countries, often associated with high contamination by helminths.
With synthetic biology, we can look directly at the problem, proposing more effective solutions to control helminth infections and assisting in the recovery of intestinal health and nutritional status.
In the following interviews, we contacted specialists to help design our solution in the best way possible.
Click the buttons below to see how each conversation with experts impacted our project.
Objectives
Get feedback about the genetic design of our solution.
Who was interviewed?
Fernando Ariel Genta is a researcher at the Oswaldo Cruz Foundation (FIOCRUZ) in Rio de Janeiro, with experience in Biochemistry and Molecular Biology of Insects and Enzymology. Maiara do Valle Faria Gama is doctorate by the Stricto Sensu Graduate Program in Parasitic Biology at the Oswaldo Cruz Institute.
Dr. Maiara Gama
Outputs
They clarified some questions about possible problems with chitins, and what the solutions would be. They raised possibilities of using other organisms to carry out the transformation, mainly yeasts and fungi because they would provide better secretion efficiency. However, we did not choose yeasts and fungi, and the main reason is the lack of specialized people in our laboratories and our supervisor's know-how. They brought questions that contributed to the discussion, decision-making, and project development.
Objectives
Understand which criteria we should use to choose the chitinases from the literature, since we needed help deciding the best chitin. Get feedback about our genetic design: protein secretion and post-translational modifications.
Who was interviewed?
Sarah Sacks Thimoteo is a specialist with experience in Microbiology, Enzymology and Molecular Biology working mainly in the following themes: metagenomics, chitinases and biocontrol.
Outputs
When we talked to Sarah, we had done a bioinformatic analysis and were struggling to choose the best protein for the application of our project: killing human parasitic nematodes. We explained to her our concerns about selecting the right chitinase, and she explained the different classifications used for chitinase: exochitinase and endochitinase. Furthermore, she advised us to choose our chitinases considering the optimal pH, salinity, and temperature for the activity in the human intestine. She suggested using two chitinases together to obtain a synergetic effect: an endochitinase and an exochitinase. In addition, we discussed the best way to use the chitinases together: expressing in the same plasmid and the same bacterium or different plasmids and bacterium.
After this conversation, we decided to express two chitinases in different bacterium, to avoid the bacterial burden, and we understood the criteria that we should use to choose them. It was really helpful. She also advised us on possible challenges we would face: how to choose a signal peptide and the impact of possible post-translational modifications since we were thinking about using chitinases from fungi and secreting the chitinases in a bacterium.
Objectives
To know if our proposal to use a probiotic was the best way to help in the malnourishment.
Who was interviewed?
Maria do Carmo Peluzio is a full professor at the Federal University of Viçosa (UFV), and coordinates the Laboratory of Food Analysis and Nutritional Biochemistry/DNS/UFV. She has great experience with the study of the intestinal microbiota correlating with the use of probiotics in diseases and in the use of nutrients and foods with functional property claims in the prevention of chronic non-communicable diseases.
Outputs
When we talked to Maria do Carmo, we were uncertain if the probiotic for itself was enough to ease the effects caused by parasitosis and poor accession to nutrients. The team was even considering adding a pathway to express a vitamin. Still, the researcher explained that this wasn't a good plan since we have no idea of the bacteria's multiplication in the intestine, so it could easily exceed the dose. Therefore, it is very risky, and this idea was not considered.
Getting back to the benefits of probiotics, the teacher explained to us that these bacteria could produce metabolites that improve intestinal absorption and make metabolism homeostasis and their direct impact on the immune system. She also highlighted the matter of cognitive and physical development in children, which is affected by helminthiases and enhanced by probiotics. But she also warned us about the recommendation that children under two years old do not take probiotics, so our target public cannot cover this age group.
Finally, she stated that the cost of a probiotic is significantly higher than an anti-helminthic, so we need to find ways to make the process cheaper (like the bioreactor). But, on the other hand, the health benefits of our bio-drug combined with increased resistance are plausible arguments for the higher price.
Objectives
Understand the role of C. elegans as a model organism, using them as proof of concept for our research.
Who was interviewed?
Viviane de Souza Alves is a full professor at the Federal University of Minas Gerais (UFMG). She is one of the biggest references in the field of microbiology in Brazil and also one of the most active scientific disseminators, coordinating the @microUFMG project and the MicroBios podcast. Her research investigates the role of translational regulation in aging and immune response, microorganism-host interaction and activity of new bioactive compounds, using the invertebrate model Caenorhabditis elegans.
Outputs
Viviane helped us in explaining how we could use C. Elegans as a model organism. C. elegans is a tiny, free-living nematode found worldwide that has been used as a well-characterized invertebrate model in several areas of study. Its biology and cultivation techniques are already well established.
Given the biology of C. elegans, Dr Viviane suggests testing purified chitinases and chitinase-secreting bacteria as well, in eggs isolated from adults and in L1 and L4 stage larvae. In this essay, we should test the amount of chitinase as a helminthicide and verify its toxicity on helminths through its mortality, larval growth, motility, feeding rate, genes expression, biochemical assay, reproduction, and so on.
We made sure to understand if each part of our part were possible, so we could in fact develop a possible solution. Because of it, we also had to investigate the possibilities of implementation of our treatment, wich can be seen here.
References
[1] WORLD HEALTH ORGANIZATION: WHO. Soil-borne infections. Available in: https: //www.who.int/news-room/fact-sheets/detail/soil-transmitted-helminth-infections.
[2] Brazil. Ministry of Health. Health Surveillance Secretariat. Department of Communicable Diseases Surveillance. Practical Guide to the Control of Geohelminties. Brasilia, p. 33, 2018. Available in: http://bvsms.saude.gov.br/bvs/publicacoes/guia_pratico_controle_geohelmintiases.pdf.
[3] 1. Google Maps. (2022). Xakriaba Racharia. Map image. Retrieved from https://goo.gl/maps/jJW694dpcmVDDLDX8
