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Consensus document aids schistosomiasis management
After malaria, human schistosomiasis is the parasitic disease with the highest morbidity and mortality worldwide. An estimated 236 million people are infected. Most are in sub-Saharan Africa. Complications lead to the deaths of 300,000 people each year. Pilot studies point to a high rate of underdiagnosis, whether in the sub-Saharan immigrant population residing in Spain or among individuals affected by outbreaks of autochthonous transmission (as happened in the 2003 case of four Spanish farmers who bathed in an artificial irrigation pool in Almería).
The “Consensus Document for the Management of Schistosomiasis in Primary Care” was recently published in the journal Atención Primaria [Primary Care]. Its aim is to establish clear recommendations so that primary care clinicians will be able to diagnose, manage, and treat this disease. The document was prepared by professionals who belong to the following five scientific societies: the Spanish Society of Family and Community Medicine, the Spanish Society of General Practitioners and Family Doctors, the Spanish Society of Primary Care Physicians, the Spanish Society for Pediatric Infectious Diseases, and the Spanish Society of Tropical Medicine and International Health (SEMTSI).
Agustín Benito Llanes, PhD, is the director of Spain’s National Center for Tropical Medicine (Carlos III Institute of Health) and the president of the SEMTSI. He told Univadis Spain, “The consensus document is invaluable for the management of cases imported by migrant populations coming from endemic areas and in the prevention of possible outbreaks in our country, especially urinary schistosomiasis.” He went on to explain, “This diagnostic strategy, which is also recommended by the European Centre for Disease Prevention and Control (ECDC), must be viewed in the context of the general management of patients with imported eosinophilia – eosinophilia being a condition that indicates that the individual may have a disease caused by a parasitic worm. I do know that primary care has been greatly affected and impacted by the pandemic, but new e-consultation and telemedicine models are making it possible for hospital specialists and primary care specialists to quickly get in touch with each other and work closely together. This technology can play a critical role in the shared care of patients with these types of diseases.”
The document recommends that serologic screening for schistosomiasis be considered for the following patients: asymptomatic individuals who have come from endemic regions and were exposed to freshwater sources; those who present with symptoms consistent with those of the disease; and patients for whom clinical exams or lab tests suggest acute schistosomiasis (eosinophilia is usually a sign). Screening for chronic schistosomiasis is indicated if the necessary resources for diagnosis and treatment are not available. The following considerations support screening asymptomatic individuals: the high prevalence of parasitic infection among migrants from endemic regions and among people who have traveled to those places; and the possibility of preventing serious complications and secondary transmissions.
The working group recommends that all at-risk individuals undergo screening, no matter how long it’s been since they were last in an endemic zone. This is because the parasites can live for over a decade. If primary care physicians don’t have access to diagnostic tests or to treatments, patients should be referred to specialists with experience in tropical diseases. A definitive diagnosis is made through the detection of blood fluke eggs in urine, stool, or body tissues. Through such detection, the species responsible for infection can be identified.
Primary care difficulties
To prevent and control the disease, the European health authorities recommend serologic screening of at-risk population groups. Because primary care is usually the first point of contact with the health care system for these infected patients, primary care physicians must know the main characteristics of schistosomiasis and be provided with the necessary means for its diagnosis and treatment. Yet physicians in health care centers face significant limitations when it comes to identifying and treating these patients.
Joaquín Salas, MD, director of the Tropical Medicine Unit at Poniente Hospital in El Ejido (Almería) and the document’s first author, explained these difficulties. “In Spain, we currently have the problem where the care of migrant patients varies greatly between the different autonomous communities – and even within an autonomous community, depending on geographical areas. This variability is caused, in large part, by the number of migrants that they serve. In places that have a large sub-Saharan migrant population, there are health centers that have gotten to a point where they’re able to request serologic testing for schistosomiasis. Unfortunately, in many instances, this testing is still only available to specialists. The objective of documents like ours is to make not only physicians but also managers aware of the importance of diagnosing and treating this disease as early as possible. Raising awareness is complicated, to a large extent, by the lack of knowledge about this disease – something that’s seen with many other ‘neglected diseases’ which primarily affect the poorest people in poor countries.”
Dr. Llanes explained that an autonomous community can individually approve serologic screenings and incorporate them into its primary care programs, regardless of whether they can be approved at the state level. He pointed out that this is what happened with Chagas disease. “To prevent vertical transmission, a protocol for pregnant women was implemented by several communities; it’s about to be approved on a national level.”
But there’s another obstacle to treating schistosomiasis. At the moment, the recommended antiparasitic treatments (e.g., praziquantel) are considered foreign medications. This makes it difficult for primary care physicians and specialists to have access to them. Even so, Dr. Salas believes “that in some places, pharmacy units facilitate things in such a way that physicians who prescribe those treatments are able to obtain them quite quickly and with less red tape. Be that as it may, ideally, the medication would be available in our country’s pharmacies, and it could be prescribed without these kinds of bureaucratic obstacles. The same thing happened with ivermectin, which is used, among other things, to treat strongyloidiasis, and which, for a few months now, has been on the market without restrictions. We hope the same will happen soon with praziquantel.”
Increasing risk
Although schistosomiasis is not endemic to Spain, various factors are contributing to an increase in the number of cases within its borders. Dr. Salas said that “without a doubt, climate change and global warming are influencing the expansion of vectors – mosquitoes, ticks, snails – that can transmit, to places like Europe, diseases referred to as ‘tropical.’ In the case of schistosomiasis, it’s been shown that Bulinus snails, intermediate hosts for Schistosoma, have adapted perfectly to Almería here in Spain and to the French island of Corsica, where winters are more and more temperate. But not only is this adaptation due to climate change, those same snails have acquired specific capabilities that allow them to better tolerate temperatures lower than those they initially had in the areas where they’re from in sub-Saharan Africa. To sum up, the colonization of new territories is due as much to a change in the climate – temperatures gradually rising – as to adaptations of the vectors themselves.”
Dr. Llanes noted that “the case involving the farmers in Almería shows that the vectors in Europe can, in fact, transmit the disease, basically because Schistosoma haematobium, human, can develop hybrids with schistosomes of cattle origin, Schistosoma bovis – hybrids that can be transmitted through European snails. This is what happened with the outbreak in Corsica, its vector being the freshwater snail Planorbarius metidjensis – as I said, shown to be implicated in Corsica’s significant outbreak, to which subsequent cases are still being traced. Obviously, the effects of climate change – temperatures rising and extreme meteorological phenomena increasing – on the infections transmitted by vectors are of the utmost importance and, together with the process of globalization, are what makes us consider these types of conditions to be emerging diseases or emerging infections.”
This article was translated from Univadis Spain. A version appeared on Medscape.com.
After malaria, human schistosomiasis is the parasitic disease with the highest morbidity and mortality worldwide. An estimated 236 million people are infected. Most are in sub-Saharan Africa. Complications lead to the deaths of 300,000 people each year. Pilot studies point to a high rate of underdiagnosis, whether in the sub-Saharan immigrant population residing in Spain or among individuals affected by outbreaks of autochthonous transmission (as happened in the 2003 case of four Spanish farmers who bathed in an artificial irrigation pool in Almería).
The “Consensus Document for the Management of Schistosomiasis in Primary Care” was recently published in the journal Atención Primaria [Primary Care]. Its aim is to establish clear recommendations so that primary care clinicians will be able to diagnose, manage, and treat this disease. The document was prepared by professionals who belong to the following five scientific societies: the Spanish Society of Family and Community Medicine, the Spanish Society of General Practitioners and Family Doctors, the Spanish Society of Primary Care Physicians, the Spanish Society for Pediatric Infectious Diseases, and the Spanish Society of Tropical Medicine and International Health (SEMTSI).
Agustín Benito Llanes, PhD, is the director of Spain’s National Center for Tropical Medicine (Carlos III Institute of Health) and the president of the SEMTSI. He told Univadis Spain, “The consensus document is invaluable for the management of cases imported by migrant populations coming from endemic areas and in the prevention of possible outbreaks in our country, especially urinary schistosomiasis.” He went on to explain, “This diagnostic strategy, which is also recommended by the European Centre for Disease Prevention and Control (ECDC), must be viewed in the context of the general management of patients with imported eosinophilia – eosinophilia being a condition that indicates that the individual may have a disease caused by a parasitic worm. I do know that primary care has been greatly affected and impacted by the pandemic, but new e-consultation and telemedicine models are making it possible for hospital specialists and primary care specialists to quickly get in touch with each other and work closely together. This technology can play a critical role in the shared care of patients with these types of diseases.”
The document recommends that serologic screening for schistosomiasis be considered for the following patients: asymptomatic individuals who have come from endemic regions and were exposed to freshwater sources; those who present with symptoms consistent with those of the disease; and patients for whom clinical exams or lab tests suggest acute schistosomiasis (eosinophilia is usually a sign). Screening for chronic schistosomiasis is indicated if the necessary resources for diagnosis and treatment are not available. The following considerations support screening asymptomatic individuals: the high prevalence of parasitic infection among migrants from endemic regions and among people who have traveled to those places; and the possibility of preventing serious complications and secondary transmissions.
The working group recommends that all at-risk individuals undergo screening, no matter how long it’s been since they were last in an endemic zone. This is because the parasites can live for over a decade. If primary care physicians don’t have access to diagnostic tests or to treatments, patients should be referred to specialists with experience in tropical diseases. A definitive diagnosis is made through the detection of blood fluke eggs in urine, stool, or body tissues. Through such detection, the species responsible for infection can be identified.
Primary care difficulties
To prevent and control the disease, the European health authorities recommend serologic screening of at-risk population groups. Because primary care is usually the first point of contact with the health care system for these infected patients, primary care physicians must know the main characteristics of schistosomiasis and be provided with the necessary means for its diagnosis and treatment. Yet physicians in health care centers face significant limitations when it comes to identifying and treating these patients.
Joaquín Salas, MD, director of the Tropical Medicine Unit at Poniente Hospital in El Ejido (Almería) and the document’s first author, explained these difficulties. “In Spain, we currently have the problem where the care of migrant patients varies greatly between the different autonomous communities – and even within an autonomous community, depending on geographical areas. This variability is caused, in large part, by the number of migrants that they serve. In places that have a large sub-Saharan migrant population, there are health centers that have gotten to a point where they’re able to request serologic testing for schistosomiasis. Unfortunately, in many instances, this testing is still only available to specialists. The objective of documents like ours is to make not only physicians but also managers aware of the importance of diagnosing and treating this disease as early as possible. Raising awareness is complicated, to a large extent, by the lack of knowledge about this disease – something that’s seen with many other ‘neglected diseases’ which primarily affect the poorest people in poor countries.”
Dr. Llanes explained that an autonomous community can individually approve serologic screenings and incorporate them into its primary care programs, regardless of whether they can be approved at the state level. He pointed out that this is what happened with Chagas disease. “To prevent vertical transmission, a protocol for pregnant women was implemented by several communities; it’s about to be approved on a national level.”
But there’s another obstacle to treating schistosomiasis. At the moment, the recommended antiparasitic treatments (e.g., praziquantel) are considered foreign medications. This makes it difficult for primary care physicians and specialists to have access to them. Even so, Dr. Salas believes “that in some places, pharmacy units facilitate things in such a way that physicians who prescribe those treatments are able to obtain them quite quickly and with less red tape. Be that as it may, ideally, the medication would be available in our country’s pharmacies, and it could be prescribed without these kinds of bureaucratic obstacles. The same thing happened with ivermectin, which is used, among other things, to treat strongyloidiasis, and which, for a few months now, has been on the market without restrictions. We hope the same will happen soon with praziquantel.”
Increasing risk
Although schistosomiasis is not endemic to Spain, various factors are contributing to an increase in the number of cases within its borders. Dr. Salas said that “without a doubt, climate change and global warming are influencing the expansion of vectors – mosquitoes, ticks, snails – that can transmit, to places like Europe, diseases referred to as ‘tropical.’ In the case of schistosomiasis, it’s been shown that Bulinus snails, intermediate hosts for Schistosoma, have adapted perfectly to Almería here in Spain and to the French island of Corsica, where winters are more and more temperate. But not only is this adaptation due to climate change, those same snails have acquired specific capabilities that allow them to better tolerate temperatures lower than those they initially had in the areas where they’re from in sub-Saharan Africa. To sum up, the colonization of new territories is due as much to a change in the climate – temperatures gradually rising – as to adaptations of the vectors themselves.”
Dr. Llanes noted that “the case involving the farmers in Almería shows that the vectors in Europe can, in fact, transmit the disease, basically because Schistosoma haematobium, human, can develop hybrids with schistosomes of cattle origin, Schistosoma bovis – hybrids that can be transmitted through European snails. This is what happened with the outbreak in Corsica, its vector being the freshwater snail Planorbarius metidjensis – as I said, shown to be implicated in Corsica’s significant outbreak, to which subsequent cases are still being traced. Obviously, the effects of climate change – temperatures rising and extreme meteorological phenomena increasing – on the infections transmitted by vectors are of the utmost importance and, together with the process of globalization, are what makes us consider these types of conditions to be emerging diseases or emerging infections.”
This article was translated from Univadis Spain. A version appeared on Medscape.com.
After malaria, human schistosomiasis is the parasitic disease with the highest morbidity and mortality worldwide. An estimated 236 million people are infected. Most are in sub-Saharan Africa. Complications lead to the deaths of 300,000 people each year. Pilot studies point to a high rate of underdiagnosis, whether in the sub-Saharan immigrant population residing in Spain or among individuals affected by outbreaks of autochthonous transmission (as happened in the 2003 case of four Spanish farmers who bathed in an artificial irrigation pool in Almería).
The “Consensus Document for the Management of Schistosomiasis in Primary Care” was recently published in the journal Atención Primaria [Primary Care]. Its aim is to establish clear recommendations so that primary care clinicians will be able to diagnose, manage, and treat this disease. The document was prepared by professionals who belong to the following five scientific societies: the Spanish Society of Family and Community Medicine, the Spanish Society of General Practitioners and Family Doctors, the Spanish Society of Primary Care Physicians, the Spanish Society for Pediatric Infectious Diseases, and the Spanish Society of Tropical Medicine and International Health (SEMTSI).
Agustín Benito Llanes, PhD, is the director of Spain’s National Center for Tropical Medicine (Carlos III Institute of Health) and the president of the SEMTSI. He told Univadis Spain, “The consensus document is invaluable for the management of cases imported by migrant populations coming from endemic areas and in the prevention of possible outbreaks in our country, especially urinary schistosomiasis.” He went on to explain, “This diagnostic strategy, which is also recommended by the European Centre for Disease Prevention and Control (ECDC), must be viewed in the context of the general management of patients with imported eosinophilia – eosinophilia being a condition that indicates that the individual may have a disease caused by a parasitic worm. I do know that primary care has been greatly affected and impacted by the pandemic, but new e-consultation and telemedicine models are making it possible for hospital specialists and primary care specialists to quickly get in touch with each other and work closely together. This technology can play a critical role in the shared care of patients with these types of diseases.”
The document recommends that serologic screening for schistosomiasis be considered for the following patients: asymptomatic individuals who have come from endemic regions and were exposed to freshwater sources; those who present with symptoms consistent with those of the disease; and patients for whom clinical exams or lab tests suggest acute schistosomiasis (eosinophilia is usually a sign). Screening for chronic schistosomiasis is indicated if the necessary resources for diagnosis and treatment are not available. The following considerations support screening asymptomatic individuals: the high prevalence of parasitic infection among migrants from endemic regions and among people who have traveled to those places; and the possibility of preventing serious complications and secondary transmissions.
The working group recommends that all at-risk individuals undergo screening, no matter how long it’s been since they were last in an endemic zone. This is because the parasites can live for over a decade. If primary care physicians don’t have access to diagnostic tests or to treatments, patients should be referred to specialists with experience in tropical diseases. A definitive diagnosis is made through the detection of blood fluke eggs in urine, stool, or body tissues. Through such detection, the species responsible for infection can be identified.
Primary care difficulties
To prevent and control the disease, the European health authorities recommend serologic screening of at-risk population groups. Because primary care is usually the first point of contact with the health care system for these infected patients, primary care physicians must know the main characteristics of schistosomiasis and be provided with the necessary means for its diagnosis and treatment. Yet physicians in health care centers face significant limitations when it comes to identifying and treating these patients.
Joaquín Salas, MD, director of the Tropical Medicine Unit at Poniente Hospital in El Ejido (Almería) and the document’s first author, explained these difficulties. “In Spain, we currently have the problem where the care of migrant patients varies greatly between the different autonomous communities – and even within an autonomous community, depending on geographical areas. This variability is caused, in large part, by the number of migrants that they serve. In places that have a large sub-Saharan migrant population, there are health centers that have gotten to a point where they’re able to request serologic testing for schistosomiasis. Unfortunately, in many instances, this testing is still only available to specialists. The objective of documents like ours is to make not only physicians but also managers aware of the importance of diagnosing and treating this disease as early as possible. Raising awareness is complicated, to a large extent, by the lack of knowledge about this disease – something that’s seen with many other ‘neglected diseases’ which primarily affect the poorest people in poor countries.”
Dr. Llanes explained that an autonomous community can individually approve serologic screenings and incorporate them into its primary care programs, regardless of whether they can be approved at the state level. He pointed out that this is what happened with Chagas disease. “To prevent vertical transmission, a protocol for pregnant women was implemented by several communities; it’s about to be approved on a national level.”
But there’s another obstacle to treating schistosomiasis. At the moment, the recommended antiparasitic treatments (e.g., praziquantel) are considered foreign medications. This makes it difficult for primary care physicians and specialists to have access to them. Even so, Dr. Salas believes “that in some places, pharmacy units facilitate things in such a way that physicians who prescribe those treatments are able to obtain them quite quickly and with less red tape. Be that as it may, ideally, the medication would be available in our country’s pharmacies, and it could be prescribed without these kinds of bureaucratic obstacles. The same thing happened with ivermectin, which is used, among other things, to treat strongyloidiasis, and which, for a few months now, has been on the market without restrictions. We hope the same will happen soon with praziquantel.”
Increasing risk
Although schistosomiasis is not endemic to Spain, various factors are contributing to an increase in the number of cases within its borders. Dr. Salas said that “without a doubt, climate change and global warming are influencing the expansion of vectors – mosquitoes, ticks, snails – that can transmit, to places like Europe, diseases referred to as ‘tropical.’ In the case of schistosomiasis, it’s been shown that Bulinus snails, intermediate hosts for Schistosoma, have adapted perfectly to Almería here in Spain and to the French island of Corsica, where winters are more and more temperate. But not only is this adaptation due to climate change, those same snails have acquired specific capabilities that allow them to better tolerate temperatures lower than those they initially had in the areas where they’re from in sub-Saharan Africa. To sum up, the colonization of new territories is due as much to a change in the climate – temperatures gradually rising – as to adaptations of the vectors themselves.”
Dr. Llanes noted that “the case involving the farmers in Almería shows that the vectors in Europe can, in fact, transmit the disease, basically because Schistosoma haematobium, human, can develop hybrids with schistosomes of cattle origin, Schistosoma bovis – hybrids that can be transmitted through European snails. This is what happened with the outbreak in Corsica, its vector being the freshwater snail Planorbarius metidjensis – as I said, shown to be implicated in Corsica’s significant outbreak, to which subsequent cases are still being traced. Obviously, the effects of climate change – temperatures rising and extreme meteorological phenomena increasing – on the infections transmitted by vectors are of the utmost importance and, together with the process of globalization, are what makes us consider these types of conditions to be emerging diseases or emerging infections.”
This article was translated from Univadis Spain. A version appeared on Medscape.com.
Precision medicine vs. antibiotic resistance
Diversity is an omnipresent element in clinical practice: in the genome, in the environment, in patients’ lifestyles and habits. Precision medicine addresses the variability of the individual to improve diagnosis and treatment. It is increasingly used in specialties such as oncology, neurology, and cardiology. A personalized approach has many objectives, including to optimize treatment, minimize the risk of adverse effects, facilitate early diagnosis, and determine predisposition to disease. Genomic technologies, such as massive sequencing techniques, and tools such as CRISPR-Cas9 are key to the future of personalized medicine.
Jesús Oteo Iglesias, MD, PhD, a specialist in microbiology and director of Spain’s National Center for Microbiology, spoke at the Spanish Association of Infectious Diseases and Clinical Microbiology’s recent conference. He discussed various precision medicine projects aimed at reinforcing the fight against antibiotic resistance.
Infectious diseases are complex because the diversity of the pathogenic microorganism combines with the patient’s own diversity, which influences the interaction between the two, said Dr. Oteo. Thus, the antibiogram and targeted antibiotic treatments (which are chosen according to the species, sensitivity to antimicrobials, type of infection, and patient characteristics) have been established applications of precision medicine for decades. However, multiple tools could further strengthen personalized medicine against multiresistant pathogens.
Therapeutic drug monitoring, in which multiple pharmacokinetic and pharmacodynamic factors are considered, is a strategy with great potential to increase the effectiveness of antibiotics and minimize toxicity. Owing to its costs and the need for trained staff, this tool would be especially indicated in the treatment of patients with more complex conditions, such as those suffering from obesity, complex infections, or infections with multiresistant bacteria, as well as those in critical condition. Multiple computer programs are available to help determine the dosage of antibiotics by estimating drug exposure and to provide recommendations. However, clinical trials are needed to assess the pros and cons of applying therapeutic monitoring for types of antibiotics other than those for which a given type is already used (for example, aminoglycosides and glycopeptides).
One technology that could help in antibiotic use optimization programs is microneedle-based biosensors, which could be implanted in the skin for real-time antibiotic monitoring. This tool “could be the first step in establishing automated antibiotic administration systems, with infusion pumps and feedback systems, like those already used in diabetes for insulin administration,” said Dr. Oteo.
Artificial intelligence could also be a valuable technology for optimization programs. “We should go a step further in the implementation of artificial intelligence through clinical decision support systems,” said Dr. Oteo. This technology would guide the administration of antimicrobials using data extracted from the electronic medical record. However, there are great challenges to overcome in creating these tools, such as the risk of entering erroneous data; the difficulty in entering complex data, such as data relevant to antibiotic resistance; and the variability at the geographic and institutional levels.
Genomics is also a tool with great potential for identifying bacteria’s degree of resistance to antibiotics by studying mutations in chromosomal and acquired genes. A proof-of-concept study evaluated the sensitivity of different Pseudomonas aeruginosa strains to several antibiotics by analyzing genome sequences associated with resistance, said Dr. Otero. The researchers found that this system was effective at predicting the sensitivity of bacteria from genomic data.
In the United States, the PATRIC bioinformatics center, which is financed by the National Institute of Allergy and Infectious Diseases, works with automated learning models to predict the antimicrobial resistance of different species of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. These models, which work with genomic data associated with antibiotic resistance phenotypes, are able to identify resistance without prior knowledge of the underlying mechanisms.
Another factor to consider with regard to the use of precision medicine for infectious diseases is the microbiota. Dr. Oteo explained that the pathogenic microorganism interacts not only with the host but also with its microbiota, “which can be diverse, is manifold, and can be very different, depending on the circumstances. These interactions can be translated into ecological and evolutionary pressures that may have clinical significance.” One of the best-known examples is the possibility that a beta-lactamase–producing bacterium benefits other bacteria around it by secreting these enzymes. Furthermore, some known forms of bacterial interaction (such as plasmid transfer) are directly related to antibiotic resistance. Metagenomics, which involves the genetic study of communities of microbes, could provide more information for predicting and avoiding infections by multiresistant pathogens by monitoring the microbiome.
The CRISPR-Cas9 gene editing tool could also be an ally in the fight against antibiotic resistance by eliminating resistance genes and thus making bacteria sensitive to certain antibiotics. Several published preliminary studies indicate that this is possible in vitro. The main challenge for the clinical application of CRISPR is in introducing it into the target microbial population. Use of conjugative plasmids and bacteriophages could perhaps be an option for overcoming this obstacle in the future.
Exploiting the possibilities of precision medicine through use of the most innovative tools in addressing antibiotic resistance is a great challenge, said Dr. Oteo, but the situation demands it, and it is necessary to take small steps to achieve this goal.
A version of this article appeared on Medscape.com. This article was translated from Univadis Spain.
Diversity is an omnipresent element in clinical practice: in the genome, in the environment, in patients’ lifestyles and habits. Precision medicine addresses the variability of the individual to improve diagnosis and treatment. It is increasingly used in specialties such as oncology, neurology, and cardiology. A personalized approach has many objectives, including to optimize treatment, minimize the risk of adverse effects, facilitate early diagnosis, and determine predisposition to disease. Genomic technologies, such as massive sequencing techniques, and tools such as CRISPR-Cas9 are key to the future of personalized medicine.
Jesús Oteo Iglesias, MD, PhD, a specialist in microbiology and director of Spain’s National Center for Microbiology, spoke at the Spanish Association of Infectious Diseases and Clinical Microbiology’s recent conference. He discussed various precision medicine projects aimed at reinforcing the fight against antibiotic resistance.
Infectious diseases are complex because the diversity of the pathogenic microorganism combines with the patient’s own diversity, which influences the interaction between the two, said Dr. Oteo. Thus, the antibiogram and targeted antibiotic treatments (which are chosen according to the species, sensitivity to antimicrobials, type of infection, and patient characteristics) have been established applications of precision medicine for decades. However, multiple tools could further strengthen personalized medicine against multiresistant pathogens.
Therapeutic drug monitoring, in which multiple pharmacokinetic and pharmacodynamic factors are considered, is a strategy with great potential to increase the effectiveness of antibiotics and minimize toxicity. Owing to its costs and the need for trained staff, this tool would be especially indicated in the treatment of patients with more complex conditions, such as those suffering from obesity, complex infections, or infections with multiresistant bacteria, as well as those in critical condition. Multiple computer programs are available to help determine the dosage of antibiotics by estimating drug exposure and to provide recommendations. However, clinical trials are needed to assess the pros and cons of applying therapeutic monitoring for types of antibiotics other than those for which a given type is already used (for example, aminoglycosides and glycopeptides).
One technology that could help in antibiotic use optimization programs is microneedle-based biosensors, which could be implanted in the skin for real-time antibiotic monitoring. This tool “could be the first step in establishing automated antibiotic administration systems, with infusion pumps and feedback systems, like those already used in diabetes for insulin administration,” said Dr. Oteo.
Artificial intelligence could also be a valuable technology for optimization programs. “We should go a step further in the implementation of artificial intelligence through clinical decision support systems,” said Dr. Oteo. This technology would guide the administration of antimicrobials using data extracted from the electronic medical record. However, there are great challenges to overcome in creating these tools, such as the risk of entering erroneous data; the difficulty in entering complex data, such as data relevant to antibiotic resistance; and the variability at the geographic and institutional levels.
Genomics is also a tool with great potential for identifying bacteria’s degree of resistance to antibiotics by studying mutations in chromosomal and acquired genes. A proof-of-concept study evaluated the sensitivity of different Pseudomonas aeruginosa strains to several antibiotics by analyzing genome sequences associated with resistance, said Dr. Otero. The researchers found that this system was effective at predicting the sensitivity of bacteria from genomic data.
In the United States, the PATRIC bioinformatics center, which is financed by the National Institute of Allergy and Infectious Diseases, works with automated learning models to predict the antimicrobial resistance of different species of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. These models, which work with genomic data associated with antibiotic resistance phenotypes, are able to identify resistance without prior knowledge of the underlying mechanisms.
Another factor to consider with regard to the use of precision medicine for infectious diseases is the microbiota. Dr. Oteo explained that the pathogenic microorganism interacts not only with the host but also with its microbiota, “which can be diverse, is manifold, and can be very different, depending on the circumstances. These interactions can be translated into ecological and evolutionary pressures that may have clinical significance.” One of the best-known examples is the possibility that a beta-lactamase–producing bacterium benefits other bacteria around it by secreting these enzymes. Furthermore, some known forms of bacterial interaction (such as plasmid transfer) are directly related to antibiotic resistance. Metagenomics, which involves the genetic study of communities of microbes, could provide more information for predicting and avoiding infections by multiresistant pathogens by monitoring the microbiome.
The CRISPR-Cas9 gene editing tool could also be an ally in the fight against antibiotic resistance by eliminating resistance genes and thus making bacteria sensitive to certain antibiotics. Several published preliminary studies indicate that this is possible in vitro. The main challenge for the clinical application of CRISPR is in introducing it into the target microbial population. Use of conjugative plasmids and bacteriophages could perhaps be an option for overcoming this obstacle in the future.
Exploiting the possibilities of precision medicine through use of the most innovative tools in addressing antibiotic resistance is a great challenge, said Dr. Oteo, but the situation demands it, and it is necessary to take small steps to achieve this goal.
A version of this article appeared on Medscape.com. This article was translated from Univadis Spain.
Diversity is an omnipresent element in clinical practice: in the genome, in the environment, in patients’ lifestyles and habits. Precision medicine addresses the variability of the individual to improve diagnosis and treatment. It is increasingly used in specialties such as oncology, neurology, and cardiology. A personalized approach has many objectives, including to optimize treatment, minimize the risk of adverse effects, facilitate early diagnosis, and determine predisposition to disease. Genomic technologies, such as massive sequencing techniques, and tools such as CRISPR-Cas9 are key to the future of personalized medicine.
Jesús Oteo Iglesias, MD, PhD, a specialist in microbiology and director of Spain’s National Center for Microbiology, spoke at the Spanish Association of Infectious Diseases and Clinical Microbiology’s recent conference. He discussed various precision medicine projects aimed at reinforcing the fight against antibiotic resistance.
Infectious diseases are complex because the diversity of the pathogenic microorganism combines with the patient’s own diversity, which influences the interaction between the two, said Dr. Oteo. Thus, the antibiogram and targeted antibiotic treatments (which are chosen according to the species, sensitivity to antimicrobials, type of infection, and patient characteristics) have been established applications of precision medicine for decades. However, multiple tools could further strengthen personalized medicine against multiresistant pathogens.
Therapeutic drug monitoring, in which multiple pharmacokinetic and pharmacodynamic factors are considered, is a strategy with great potential to increase the effectiveness of antibiotics and minimize toxicity. Owing to its costs and the need for trained staff, this tool would be especially indicated in the treatment of patients with more complex conditions, such as those suffering from obesity, complex infections, or infections with multiresistant bacteria, as well as those in critical condition. Multiple computer programs are available to help determine the dosage of antibiotics by estimating drug exposure and to provide recommendations. However, clinical trials are needed to assess the pros and cons of applying therapeutic monitoring for types of antibiotics other than those for which a given type is already used (for example, aminoglycosides and glycopeptides).
One technology that could help in antibiotic use optimization programs is microneedle-based biosensors, which could be implanted in the skin for real-time antibiotic monitoring. This tool “could be the first step in establishing automated antibiotic administration systems, with infusion pumps and feedback systems, like those already used in diabetes for insulin administration,” said Dr. Oteo.
Artificial intelligence could also be a valuable technology for optimization programs. “We should go a step further in the implementation of artificial intelligence through clinical decision support systems,” said Dr. Oteo. This technology would guide the administration of antimicrobials using data extracted from the electronic medical record. However, there are great challenges to overcome in creating these tools, such as the risk of entering erroneous data; the difficulty in entering complex data, such as data relevant to antibiotic resistance; and the variability at the geographic and institutional levels.
Genomics is also a tool with great potential for identifying bacteria’s degree of resistance to antibiotics by studying mutations in chromosomal and acquired genes. A proof-of-concept study evaluated the sensitivity of different Pseudomonas aeruginosa strains to several antibiotics by analyzing genome sequences associated with resistance, said Dr. Otero. The researchers found that this system was effective at predicting the sensitivity of bacteria from genomic data.
In the United States, the PATRIC bioinformatics center, which is financed by the National Institute of Allergy and Infectious Diseases, works with automated learning models to predict the antimicrobial resistance of different species of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis. These models, which work with genomic data associated with antibiotic resistance phenotypes, are able to identify resistance without prior knowledge of the underlying mechanisms.
Another factor to consider with regard to the use of precision medicine for infectious diseases is the microbiota. Dr. Oteo explained that the pathogenic microorganism interacts not only with the host but also with its microbiota, “which can be diverse, is manifold, and can be very different, depending on the circumstances. These interactions can be translated into ecological and evolutionary pressures that may have clinical significance.” One of the best-known examples is the possibility that a beta-lactamase–producing bacterium benefits other bacteria around it by secreting these enzymes. Furthermore, some known forms of bacterial interaction (such as plasmid transfer) are directly related to antibiotic resistance. Metagenomics, which involves the genetic study of communities of microbes, could provide more information for predicting and avoiding infections by multiresistant pathogens by monitoring the microbiome.
The CRISPR-Cas9 gene editing tool could also be an ally in the fight against antibiotic resistance by eliminating resistance genes and thus making bacteria sensitive to certain antibiotics. Several published preliminary studies indicate that this is possible in vitro. The main challenge for the clinical application of CRISPR is in introducing it into the target microbial population. Use of conjugative plasmids and bacteriophages could perhaps be an option for overcoming this obstacle in the future.
Exploiting the possibilities of precision medicine through use of the most innovative tools in addressing antibiotic resistance is a great challenge, said Dr. Oteo, but the situation demands it, and it is necessary to take small steps to achieve this goal.
A version of this article appeared on Medscape.com. This article was translated from Univadis Spain.